Abstract: AIMS/HYPOTHESIS: We sought to identify determinants of progression from impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) to diabetes in high-risk screened individuals. METHODS: In general practices in Denmark, stepwise screening for type 2 diabetes mellitus in persons aged 40 to 69 years included a risk questionnaire, random blood glucose, HbA(1c), fasting blood glucose and an OGTT. The 1,821 individuals with IGT or isolated IFG (WHO 1999) were re-invited after 1 and 3 years. Follow-up data on glucose measurements were available in 1,510 individuals and additional clinical data in 1,002 collected at the 3-year visits. Regression models using interval censoring were used. RESULTS: Progression rates from IFG and IGT to diabetes over 3.5 years were 11.8 and 17.0 per 100 person-years, respectively and were particularly high in the first year. Baseline determinants of progression were: IFG: glucose measures, BMI [per kg/m(2), rate ratio (RR) 1.04 (95% CI, 1.01-1.08)] and triacylglycerol [per twofold increase, RR 2.19 (1.49-3.22)]; and IGT: glucose measures and known hypertension [RR 1.46 (1.11-1.93)]. Weight reduction and decreased triacylglycerol were inversely associated with development of diabetes in IFG individuals [per 1 kg/year, RR 0.81 (0.66-0.98) and per 1 mmol l(-1) year(-1), RR 0.08 (0.01-0.51), respectively], whereas in IGT participants only weight reduction was inversely associated [per 1 kg/year, RR 0.80 (0.67-0.96)]. CONCLUSIONS/INTERPRETATION: Higher levels of glucose measures, larger BMI, known hypertension and hypertriacylglycerolaemia are significant determinants of progression in high-risk screened individuals. Weight loss of 1 kg/year or reduction of hypertriacylglycerolaemia markedly reduced the risk of diabetes.

Abstract: AIMS/HYPOTHESIS: Recent genome-wide association studies have suggested that a polymorphism in GCKR, the gene encoding the glucokinase regulatory protein, is involved in triacylglycerol regulation. Our aim was to examine in large-scale studies the common GCKR rs780094 polymorphism in relation to metabolic traits (mainly fasting hypertriacylglycerolaemia) and traits related to pancreatic beta cell function. METHODS: The polymorphism was genotyped in 16,853 Danes using Taqman allelic discrimination. Association was analysed in case-control studies and quantitative trait analyses. We also analysed the possible interactive effect between the GCK -30G>A polymorphism and the GCKR rs780094 variant on metabolic traits. RESULTS: The minor GCKR A-allele of rs780094 is associated with an increased level of fasting serum triacylglycerol (p = 6 x 10(-14)), impaired fasting (p = 0.001) and OGTT-related insulin release (p = 3 x 10(-6)), reduced homeostasis model assessment of insulin resistance (p = 0.0004), WHO-defined dyslipidaemia (p = 6 x 10(-9)) and a modestly decreased risk of type 2 diabetes (p = 0.01). Significantly increased fasting serum insulin concentrations were demonstrated when analysing the GCK -30A and GCKR rs780094 G-alleles in an additive model. CONCLUSIONS/INTERPRETATION: The GCKR rs780094 polymorphism, or another variant with which it is in tight linkage disequilibrium, is likely to increase glucokinase regulatory protein activity to induce improved glycaemic regulation at the expense of hypertriacylglycerolaemia as reflected in the present study of 16,853 Danes. We also suggest an additive effect of GCK and GCKR risk alleles on plasma glucose and serum insulin release.

Abstract: Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.

Abstract: We evaluated variations in glucose measurements and the reproducibility of glucose tolerance classification in a high-risk screening setting in general practice. Screening for diabetes was performed in persons aged 40-69 years. Based on capillary fasting (FBG) and 2-h blood glucose (2 hBG) individuals with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT) and diabetes had a second test done after 14 days. Intra-individual coefficients of variation (CV) were estimated in each glucose tolerance class using the approximation CV(2)(x)=var(ln(x)). Bland-Altman plots with limits of agreement were made. In the total population, the CV(intra) was 7.9% and 13.8% for FBG and 2 hBG, respectively. Limits of agreement ranged from -1.15 to 1.67 mmol/l for FBG and from - 2.62 to 3.27 mmol/l for 2 hBG. One individual with IFG and 22.5% with IGT had diabetes at the second test, 76.1% with diabetes had this diagnosis confirmed, and about 30% with IFG and IGT had normal glucose tolerance at the second test. The expected values of repeated capillary blood glucose measurements were about+/-1 and+/-3 mmol/l for FBG and 2 hBG, respectively. Yet, 70% of high-risk prediabetic individuals were persistently classified with abnormal glucose regulation; diabetes was confirmed in 76% of the cases.

Abstract: OBJECTIVE: Three independent studies have shown that variation in the fat mass and obesity-associated (FTO) gene associates with BMI and obesity. In the present study, the effect of FTO variation on metabolic traits including obesity, type 2 diabetes, and related quantitative phenotypes was examined. RESEARCH DESIGN AND METHODS: The FTO rs9939609 polymorphism was genotyped in a total of 17,508 Danes from five different study groups. RESULTS: In studies of 3,856 type 2 diabetic case subjects and 4,861 normal glucose-tolerant control subjects, the minor A-allele of rs9939609 associated with type 2 diabetes (odds ratio 1.13 [95% CI 1.06-1.20], P = 9 x 10(-5)). This association was abolished when adjusting for BMI (1.06 [0.97-1.16], P = 0.2). Among 17,162 middle-aged Danes, the A-allele associated with overweight (1.19 [1.13-1.24], P = 1 x 10(-12)) and obesity (1.27 [1.20-1.34], P = 2 x 10(-16)). Furthermore, obesity-related quantitative traits such as body weight, waist circumference, fat mass, and fasting serum leptin levels were significantly elevated in A-allele carriers. An interaction between the FTO rs9939609 genotype and physical activity (P = 0.007) was found, where physically inactive homozygous risk A-allele carriers had a 1.95 +/- 0.3 kg/m(2) increase in BMI compared with homozygous T-allele carriers. CONCLUSIONS: We validate that variation in FTO is associated with type 2 diabetes when not adjusted for BMI and with an overall increase in body fat mass. Furthermore, low physical activity seems to accentuate the effect of FTO rs9939609 on body fat accumulation.

Abstract: OBJECTIVE: We evaluated the association of variants in the sterol regulatory element-binding factor 1 gene (SREBF1) with type 2 diabetes. Due to the previous inconclusive quantitative trait associations, we also did studies of intermediate quantitative phenotypes. RESEARCH DESIGN AND METHODS: We genotyped four variants in SREBF1 in the population-based Inter99 cohort (n = 6,070), the Danish ADDITION study (n = 8,662), and in additional type 2 diabetic patients (n = 1,002). The case-control studies involved 2,980 type 2 diabetic patients and 4,522 glucose-tolerant subjects. RESULTS: The minor alleles of rs2297508, rs11868035, and rs1889018 (linkage disequilibrium R(2) = 0.6-0.8) associated with a modestly increased risk of type 2 diabetes (rs2297508: OR 1.17 [95% CI 1.05-1.30], P = 0.003), which was confirmed in meta-analyses of all published studies (rs2297508 G-allele: 1.08 [1.03-1.14] per allele, P = 0.001). The diabetes-associated alleles also associated strongly with a higher plasma glucose at 30 and 120 min and serum insulin at 120 min during an oral glucose tolerance test (all P < 0.006) and the minor allele of rs1889018 with a surrogate measure of insulin sensitivity (P = 0.03). Furthermore, the diabetes-associated alleles associated with a modestly increased A1C level in the population-based Inter99 of middle-aged subjects and in the ADDITION study of high-risk individuals (P = 0.006 and P = 0.008, respectively). CONCLUSIONS: We associate sequence variation in SREBF1 with a modestly increased predisposition to type 2 diabetes. In the general population, the diabetes-associated alleles are discreetly associated with hyperglycemia presumably due to decreased insulin sensitivity. Because sterol regulatory element-binding protein-1c is a mediator of insulin action, the findings are consistent with the presence of a yet undefined subtle loss-of-function SREBF1 variant.

Abstract: Context: Hepatic lipase (HL) plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) by involvement in reverse cholesterol transport and the formation of atherogenic small dense LDL. Objective: To investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Since behavioral factors influence HL activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. Design: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n=6,070), the ADDITION Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n=8,662) and in additional type 2 diabetic patients (n=1,064) and glucose-tolerant control subjects (n=360). Result: In the Inter 99 study the A-allele of rs2070895 associated with a 0.057 (95% CI 0.039-0.075) mmol/l increase in fasting serum HDL-cholesterol (HDL-c) (P=8x10(-10)) supported by association in the ADDITION study (0.038 [95% CI 0.024-0.053] mmol/l per allele; P=2x10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (Pinteraction=0.002) since vigorous physically active homozygous A-allele carriers had a 0.30 (95% CI 0.22-0.37) mmol/l increase in HDL-c compared to homozygous G-allele carriers. Conclusion: In conclusion, we validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A-allele. This interaction may have potential implications for public health and disease prevention.

Abstract: AIMS/HYPOTHESIS: A genome-wide association study recently identified an association between common variants, rs1535435 and rs9494266, in the AHI1 gene and type 2 diabetes. The aim of the present study was to investigate the putative association between these polymorphisms and type 2 diabetes or type 2 diabetes-related metabolic traits in Danish individuals. METHODS: The previously associated polymorphisms were genotyped in the population-based Inter99 cohort (n = 6162), the Danish ADDITION study (n = 8428), a population-based sample of young healthy participants (n = 377) and in additional type 2 diabetes (n = 2107) and glucose-tolerant participants (n = 483) using Taqman allelic discrimination. The case-control study involved 4,104 type 2 diabetic patients and 5,050 glucose-tolerant control participants. Type 2 diabetes-related traits were investigated in 17,521 individuals. RESULTS: rs1535435 and rs9494266 were not associated with type 2 diabetes. Odds ratios (OR) were OR(add) 1.0 (95% C.I. 0.9-1.2; p (add) = 0.7) and OR(add) 1.1 (0.9-1.2; p (add) = 0.4), respectively, a finding supported by meta-analyses: OR(add) 1.0 (0.9-1.1; p (add) = 0.6) and OR(add) 1.0 (0.9-1.1; p (add) = 0.6), respectively. Neither rs1535435 nor rs9494266 were consistently associated with any of the tested type 2 diabetes-related metabolic traits. CONCLUSIONS/INTERPRETATION: Data from large samples of Danish individuals do not support a role for AHI1 rs1535435 nor rs9494266 as major type 2 diabetes variants. This study highlights the importance of independent and well-powered replication studies of the recent genome-wide association scans before a locus is robustly validated as being associated with type 2 diabetes.

Abstract: Aim: To evaluate the potential advantages of a constant overnight subcutaneous delivery of insulin in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetics. Methods: Ten type 2 diabetic patients treated with oral antidiabetic drugs without gaining sufficient glycaemic control were included in this three-period study. All patients received continuous subcutaneous insulin infusion (CSII) with a short-acting insulin analogue, 2 IU/h, for 8 h during three consecutive nights (period A). Based upon the results from period A, two additional dose regimens of three nights (period B and C) were studied in random order. Serum insulin aspart, human insulin and plasma glucose (PG) profiles were recorded. Results: In period A, fasting plasma glucose (FPG) was reduced from a mean +/- s.d. (mmol/l) value of 11.6 +/- 2.9 to 5.5 +/- 1.6 (p < 0.0001) during the first night. No additional lowering of FPG was seen the two succeeding nights. FPG narrowed as the range before the infusion was 7.3-15.2 mmol/l compared with 3.6-6.1 mmol/l on the last morning after infusion. The variability in PG profile during the first and the last night of CSII was small and not significantly different. The rising insulin aspart was mirrored by a decrease in human insulin. In period B and C, similar tendencies as for period A were seen. In period A, two patients each experienced one mild hypoglycaemic episode. Conclusions: CSII with an insulin analogue overnight effectively reduced FPG without occurrence of major hypoglycaemia in type 2 diabetic patients who fail to achieve glycaemic control on oral antidiabetic treatment.

Abstract: AIMS/HYPOTHESIS: To estimate the 1-year progression rates from both IFG and IGT to diabetes in individuals identified in a pragmatic diabetes screening programme in general practice (the ADDITION Study, Denmark [Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care]). METHODS: Persons aged 40-69 years were screened for type 2 diabetes based on a high-risk, stepwise strategy. At baseline, anthropometric measurements, blood samples and questionnaire data were collected. A total of 1,160 persons had IFG or IGT at baseline: 811 (70%) accepted re-examination after 1 year. Glucose tolerance classification was based on the 1999 WHO definition. At follow-up, diabetes was based on one diabetic glucose value of fasting blood glucose or 2-h blood glucose. RESULTS: At baseline, 308 persons had IFG and 503 had IGT. The incidence of diabetes was 17.6 and 18.8 per 100 person-years in the two groups, respectively. CONCLUSIONS/INTERPRETATION: IFG and IGT identified in general practice during a stepwise, high-risk screening programme for type 2 diabetes have high 1-year progression rates to diabetes. Consequently, intensive follow-up and intervention strategies are recommended for these high-risk individuals.

Abstract: AIMS: To examine the impact on health-related lifestyle of conducting a targeted stepwise diabetes screening programme. METHODS: A total of 4731 people aged 40-69 years were offered stepwise diabetes screening in part of the Danish arm of the ADDITION-study in the county of Aarhus, Denmark. The screening comprised two main steps: identification of high-risk individuals by a mailed risk score questionnaire, and subsequent testing of high-risk individuals by their general practitioner. Questionnaires on physical exercise [International Physical Activity Questionnaire (IPAQ), short form], smoking habits and alcohol consumption were mailed to the target population 1 month prior to the offer of screening, and at 12 months' follow-up. At follow-up, additional questions regarding perceived changes in dietary habits, smoking, alcohol consumption and exercise were included. Three pairs of comparison groups were analysed. RESULTS: One year after screening, smokers who underwent further testing reduced smoking by one daily cigarette more than people at low risk of diabetes. The rate of smokers was not reduced, and the result was not confirmed by data regarding perceived change. Alcohol intake and exercise were unchanged. Data on perceived changes showed that more people undertook increased exercise in the group at low risk than in the further examined group, but this was not seen when comparing high-risk attenders with non-attenders. Dietary habits were unchanged, except that slightly more people in the group with an abnormal test result reported increase of fruit and vegetable intake and reduction of fat intake compared with the group with a normal test result. CONCLUSION: Only minor and inconsistent impacts on lifestyle was observed 1 year after screening.

Abstract: AIMS: The intention was to investigate whether preventive health checks and health discussions are cost effective. METHODS: In a randomized trial the authors compared two intervention groups (A and B) and one control group. In 1991 2,000 30- to 49-year-old persons were invited and those who accepted were randomized. Both intervention groups were offered a broad (multiphasic) screening including cardiovascular risk and a personal letter including screening results and advice on healthy living. Individuals in group A could contact their family physician for a normal consultation whereas group B were given fixed appointments for health consultations. The follow-up period was six years. Analysis was carried out on the "intention to treat" principle. Outcome parameters were life years gained, and direct and total health costs (including productivity costs), discounted by 3% annually. Costs were based on register data. Univariate sensitivity analysis was carried out. RESULTS: Both intervention groups have significantly better life expectancy than the control group (no intervention). Group B and (A) significantly gain 0.14 (0.08) life years more than the control group. There were no differences in average direct (3,255 euro (3,703 euro) versus 4,186 euro) and total costs (10,409 euro (9,399 euro) versus 10,667 euro). The effect in group B is, however, better than in group A with no significant differences in costs. The results are insensitive to a range of assumptions regarding costs, effects, and discount rates. CONCLUSIONS: Preventive health screening and consultation in primary care in 30- to 49-year-olds produce significantly better life expectancy without extra direct and total costs over a six-year follow-up period.

Abstract: OBJECTIVE: In the present study, we aimed to validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) loci, as well as the intergenic rs9300039 variant. Furthermore, we aimed to characterize quantitative metabolic risk phenotypes of the four variants. RESEARCH DESIGN AND METHODS: The variants were genotyped in the population-based Inter99 cohort (n = 5,970), the ADDITION Study (n = 1,626), a population-based sample of young healthy subjects (n = 377), and in additional type 2 diabetic case (n = 2,111) and glucose-tolerant (n = 521) subjects. The case-control studies involved a total of 4,089 type 2 diabetic patients and 5,043 glucose-tolerant control subjects. RESULTS: We validated association of variants near HHEX/KIF11/IDE, CDKN2A/B, and IGF2BP2 with type 2 diabetes. Interestingly, in middle-aged people, the rs1111875 C-allele of HHEX/KIF11/IDE strongly associated with lower acute insulin response during an oral glucose tolerance test (P = 6 x 10(-7)). In addition, decreased insulin release following intravenous tolbutamide injection was observed in young healthy subjects (P = 0.02). Also, a reduced insulin release was observed for the CDKN2A/B rs10811661 T-allele after both oral and intravenous glucose challenges (P = 0.001 and P = 0.009, respectively). CONCLUSIONS: We validate that variants in the proximity of the HHEX/KIF11/IDE, CDKN2A/B, and IFG2BP2 loci associate with type 2 diabetes. Importantly, variations within the HHEX/KIF11/IDE and CDKN2A/B loci confer impaired glucose- and tolbutamide-induced insulin release in middle-aged and young healthy subjects, suggesting a role for these variants in the pathogenesis of pancreatic beta-cell dysfunction.

Abstract: AIM: To analyze the consequence of preventive health screenings and discussions on the utilization of secondary healthcare. METHODS: All 30- to 49-year-old residents registered with a general practitioner in the district of Ebeltoft, Denmark, were included (n = 3,464) in a randomized controlled trial with eight years' follow-up. A random sample of 2,030 subjects was selected for invitation (Invited). The remaining 1,434 persons were never contacted and served as external control group (Non-Invited). Persons accepting participation were randomly divided into one internal control group (Questionnaire) and two intervention groups. One intervention group was offered three health screenings (Health Screening) during the five years. The other intervention group were in addition offered a yearly health discussion with their general practitioner (Health Screening and Discussion). RESULTS: The rate ratio for hospital admissions was 0.97 (95% confidence interval 0.80 to 1.18) in the Invited group compared with the Non-Invited. The annual admission rates showed a significant trend (p = 0.0003) with a decrease four and five years after intervention launch for the Invited group compared with the Non-Invited. A similar trend was found when comparing the internal control group with intervention groups (p = 0.0016). CONCLUSIONS: A 30- to 49-year-old general population's utilization of secondary healthcare did not increase in response to a general health promotion offer. During the observation period a significant decline in annual hospital admission rates was seen.

Abstract: BACKGROUND: Motivational interviewing has been shown to be broadly usable in a scientific setting in the management of behavioural problems and diseases. However, data concerning implementation and aspects regarding the use of motivational interviewing in general practice is missing. AIM:To evaluate GPs' conception of motivational interviewing in terms of methods, adherence to and aspects of its use in general practice after a course. STUDY DESIGN: In a randomised controlled trial concerning intensive treatment of newly diagnosed patients with type 2 diabetes detected by screening, the GPs were randomised to a course in motivational interviewing or not. The study also included a third group of GPs outside the randomised controlled trial, who had 2 years previously received a similar course in motivational interviewing. SETTING: General practice in Denmark. METHOD: The intervention consisted of a 1.5-day residential course in motivational interviewing with 0.5-day follow-ups, twice during the first year. Questionnaire data from GPs were obtained. RESULTS: We obtained a 100% response-rate from the GPs in all three groups. The GPs trained in motivational interviewing adhered statistically significantly more to the methods than did the control group. More than 95% of the GPs receiving the course stated that they had used the specific methods in general practice. CONCLUSION: A course in motivational interviewing seems to influence GPs professional behaviour. Based on self-reported questionnaires, this study shows that the GPs after a course in motivational interviewing seemed to change their professional behaviour in daily practice using motivational interviewing compared with the control group. GPs evaluated motivational interviewing to be more effective than 'traditional advice giving'. Furthermore, GPs stated that the method was not more time consuming than 'traditional advice giving'.

Abstract: OBJECTIVE: To report 1-year results of newly developed method, guided self-determination (GSD), applied in group training (GSD-GT) for Type 1 diabetes patients with persistent poor glycaemic control. METHODS: GSD was designed on the basis of qualitative research to help patients develop life skills with diabetes using worksheets filled in at home and coached by nurses in mutual reflection. We randomized 18-49-year-old adults at a Danish university hospital to either 16 h GSD-GT in 2001 or to similar training 1 year later. Inclusion criteria: mean A1C> or =8.0% for at least 2 years, disease onset < or =40 years and insulin treatment from onset. RESULTS: Thirty GSD-GT patients and 20 controls completed the study. GSD-GT patients did better than control patients in terms of (a) increased autonomy support perceived from health professionals (p<0.01); (b) higher frequency of self-monitored blood glucoses (p<0.001); (c) increased perceived competence in managing diabetes (p<0.01); (d) fewer diabetes-related problems (p<0.05); and (e) improved glycaemic control (p<0.01). CONCLUSION: GSD was effective in improving life skills with diabetes, including A1C, over a period of 1 year. PRACTICE IMPLICATIONS: GSD is a worthy candidate for further research. We consider it adjustable to people with type 2 diabetes and other chronic conditions.

Abstract: AIMS/HYPOTHESIS: We assessed country-level and individual-level patterns in patient and provider perceptions of diabetes care. METHODS: The study used a cross-sectional design with face-to-face or telephone interviews of diabetic patients and healthcare providers in 13 countries from Asia, Australia, Europe and North America. Participants were randomly selected adults with type 1 or type 2 diabetes (n=5,104), and randomly selected diabetes-care providers, including primary-care physicians (n=2,070), diabetes specialist physicians (n=635) and nurses (n=1,122). Multivariate analysis was used to examine the relationships between outcomes and both country and respondent characteristics, and the interaction between these two factors. RESULTS: Providers rated chronic-care systems and remuneration for chronic care as mediocre. Patients reported that ease of access to care was high, but not without financial barriers. Patients reported moderate levels of collaboration among providers, and providers indicated that several specialist disciplines were not readily available to them. Patients reported high levels of collaboration with providers in their own care. Provider endorsement of primary prevention strategies for type 2 diabetes was high. Patients with fewer socio-economic resources and more diabetes complications had lower access (and/or higher barriers) to care and lower quality of patient-provider collaboration. Countries differed significantly for all outcomes, and the relationships between respondent characteristics and outcomes varied by country. CONCLUSIONS/INTERPRETATION: There is much need for improvement in applying the chronic-care model to the treatment and prevention of diabetes in all of the countries studied. Each country must develop its own priorities for improving diabetes care and comparison with other countries can help identify strengths as well as weaknesses.

Abstract: AIM: The aim of this study was to compare the effect of multiple mealtime injections of biphasic insulin aspart 30 (30% fast-acting insulin aspart in the formulation, BIAsp30) to traditional basal-bolus human insulin regimen (HI) on glycaemic control in patients with type 1 diabetes. METHODS: Twenty-three patients (eight women and 15 men) aged 44.8 (20.6-62.5) years (median and range) with a diabetes duration of 19.5 (1.6-44.6) years completed the study. All eligible patients were randomly assigned to BIAsp30 thrice daily supplied with bedtime NPH insulin when necessary, or basal-bolus HI for 12 weeks and then switched to the alternative regimen for another 12 weeks. The insulin dose adjustments were made by patients on the basis of advice from a diabetes nurse. At end of each treatment period, the patients attended two profile days, 1 week apart for pharmacodynamic and pharmacokinetic assessments. HbA1C was measured at baseline and at the end of each treatment period. A seven-point self-monitored blood glucose (SMBG) was obtained twice weekly. RESULTS: In comparison with HI, multiple mealtime injections of BIAsp30 resulted in a significant reduction in HbA1C[HI vs. BIAsp30 (%, geometric mean and range): 8.6 (7.4-11.4) vs. 8.3 (6.7-9.8), p = 0.013]. During treatment with BIAsp30, nighttime glycaemic control was significantly improved. Day-to-day variation in pharmacodynamics and pharmacokinetics and the rate of hypoglycaemia were not increased with BIAsp30 compared with HI. Conclusions: In type 1 diabetics, multiple mealtime administration of BIAsp30 compared with traditional basal-bolus human insulin treatment significantly improves long-term glycaemic control without increasing the risk of hypoglycaemia. Despite a higher proportion of intermediate-acting insulin, thrice-daily injections with BIAsp30 do not increase the day-to-day variations in insulin pharmacokinetics and pharmacodynamics.

Abstract: PURPOSE: Previous studies have shown that the progression of diabetic retinopathy to vision-threatening lesions may be related to the development of retinopathy lesions in specific retinal areas. The purpose of the present study was to examine whether the occurrence of retinopathy in these retinal areas is related to known risk factors for progression of retinopathy in type 2 diabetes. METHODS: A total of 377 randomly selected patients with type 2 diabetes underwent examinations which included measurement of blood pressure, haemoglobin A1c and cholesterol, and a full eye examination including fundus photography. The fundus photographs were digitized and a computer-assisted technique was used to quantify retinopathy lesions in the macular area, around the vascular arcades and in the retinal periphery. Only the number of microaneurysms/haemorrhages was sufficient for statistical analysis. RESULTS: Patients with retinopathy had significantly longer diabetes duration, and higher blood pressure and HgbA1c than patients without retinopathy. However, among the patients with retinopathy there was no correlation between these risk factors and the overall number of microaneurysms/haemorrhages or the number of these lesions in the local areas of the fundus studied. CONCLUSIONS: The localized distribution of retinopathy lesions does not correlate with known risk factors and background factors for the development of diabetic retinopathy in the early stages of the disease. Future improvements of grading systems for diabetic retinopathy should focus on a quantification of the overall number and dynamics of retinopathy lesions in the early stages of retinopathy and the regional distribution and dynamics of lesions in more advanced stages of retinopathy.

Abstract: OBJECTIVE: This study aims to describe the routine monitoring of lipids and the use of lipid-lowering medicine in people with type 2 diabetes in the period 2000-2002. MATERIAL AND METHODS: Data from the National Health Service Registry, the Regional laboratory database and the Danish National Hospital Registry have been used for identification and description of known diabetes in a background population of 649,177 citizens in the County of Aarhus, corresponding to 12% of the total Danish population. All data were collected for the period 1 January 2000 to 31 December 2002. RESULTS: A total of 14,644 people with type 2 diabetes were identified, 52% of whom were men. The mean age was 64 years and the mean duration of diabetes was 7 years. A total of 61% had a minimum of one measurement of total cholesterol in 2000 compared with 64% in 2002. Some 71% of the patients in 2000 compared with 66% in 2002 had a total cholesterol concentration above 5.0 mmol/l. The proportion of people with type 2 diabetes treated with a lipid-lowering drug increased from 15% in 2000 to 24% in 2002. For those who were treated with lipid-lowering medication 33% in 2000 and 42% in 2002 reached currently recommended targets of total cholesterol concentrations. CONCLUSIONS: The results of this study provide a realistic picture of the monitoring of cholesterol as part of diabetes care and found a tendency to increased adherence to guidelines. Even so, it seems as if more patients with diabetes could benefit from treatment with lipid-lowering medication.

Abstract: BACKGROUND: Motivational Interviewing is a well-known, scientifically tested method of counselling clients developed by Miller and Rollnick and viewed as a useful intervention strategy in the treatment of lifestyle problems and disease. AIM: To evaluate the effectiveness of motivational interviewing in different areas of disease and to identify factors shaping outcomes. DESIGN OF STUDY: A systematic review and meta-analysis of randomised controlled trials using motivational interviewing as the intervention. METHOD: After selection criteria a systematic literature search in 16 databases produced 72 randomised controlled trials the first of which was published in 1991. A quality assessment was made with a validated scale. A meta-analysis was performed as a generic inverse variance meta-analysis. RESULTS: Meta-analysis showed a significant effect (95% confidence interval) for motivational interviewing for combined effect estimates for body mass index, total blood cholesterol, systolic blood pressure, blood alcohol concentration and standard ethanol content, while combined effect estimates for cigarettes per day and for HbA(1c) were not significant. Motivational interviewing had a significant and clinically relevant effect in approximately three out of four studies, with an equal effect on physiological (72%) and psychological (75%) diseases. Psychologists and physicians obtained an effect in approximately 80% of the studies, while other healthcare providers obtained an effect in 46% of the studies. When using motivational interviewing in brief encounters of 15 minutes, 64% of the studies showed an effect. More than one encounter with the patient ensures the effectiveness of motivational interviewing. CONCLUSION: Motivational interviewing in a scientific setting outperforms traditional advice giving in the treatment of a broad range of behavioural problems and diseases. Large-scale studies are now needed to prove that motivational interviewing can be implemented into daily clinical work in primary and secondary health care.

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Abstract: BACKGROUND: Regular preventive health screenings are a feature of primary health care in several countries. Studies of the effect of regular preventive health checks have reported different results regarding primary health care utilization. OBJECTIVE: To analyse the effect of preventive health screening and health discussions on contacts to general practice. METHODS: A randomized controlled trial with all GPs in the district of Ebeltoft, Denmark. All middle-aged residents registered with a GP in the district of Ebeltoft were included (n = 3464). A random sample of 2030 subjects was selected for invitation to participate in health screening or health screening and discussions. The remaining 1434 subjects were never contacted and served as an external control group. Main outcome measure was number of daytime consultations in general practice. RESULTS: The annual rate ratios for daytime consultations showed a very clear time trend (P < 0.0001) with a high rate of contacts among invited compared with non-invited subjects during the first year (P = 0.001) followed by a gradual decrease to a lower level after eight years (P = 0.037). The total rate ratio for daytime consultations was 1.01 (95% CI 0.93 to 1.10). CONCLUSION: We observed no differences between the invited group and the non-invited group in any type of contact to general practice when the entire follow-up period was considered. There was a significant trend in rate ratios for daytime consultations with an initial rise followed by a gradual decrease in rate ratios. More investigations are needed to confirm and explore reasons for this trend.

Abstract: AIMS: To compare pharmacokinetic characteristics of two biphasic insulin aspart (BIAsp) formulations: BIAsp30 and BIAsp70 (30% and 70%, respectively, of fast-acting insulin aspart) during 15 days of multiple dosing (thrice daily). METHODS: A total of 22 patients with Type 1 diabetes (nine women, 13 men) aged 41.4 +/- 9.9 years (mean +/- sd) with a diabetes duration of 18.9 (2.3-40.3) years (median and range) completed the randomized, double-blinded, two-period crossover study. On day 1 and day 15 of each treatment period, 24-h serum insulin and glucose profiles were evaluated. Total area under the insulin aspart concentration-time curve (AUC(0-24 h)), AUC after dinner administration stratified into early (AUCdinner(0-6 h)) and intermediate-phase (AUCdinner(6-14 h)), maximum insulin concentration (Cmax), time to maximum insulin concentration (Tmax) after each meal were recorded. RESULTS: On day 15 BIAsp70 was associated with a shorter Tmax, and more than 40% elevated Cmax. Comparing with BIAsp30, AUC(0-24 h) and AUCdinner(0-6 h) were increased by 25% and 28%, respectively, but AUCdinner (6-14 h) was markedly lower for BIAsp70 [BIAsp30/BIAsp70: 1.9; 95% CI (1.42, 2.55)]. Similar findings were also observed on day 1. The fasting or pre-meal serum insulin levels on day 15 tended to be higher with BIAsp30, but the differences were not statistically significant. CONCLUSIONS The pharmacokinetic properties of BIAsp30 and 70 remain constant during 2 weeks of daily administration in patients with Type 1 diabetes. In comparison with BIAsp30, the administration of BIAsp70 results in a shorter time to and larger maximum insulin aspart concentration. Furthermore, total and early post-dinner insulin AUC were greater, whereas late-phase insulin exposure was lower with BIAsp70.

Abstract: BACKGROUND: The 12-lead electrocardiogram (ECG) is a common diagnostic test available to the GP in the evaluation of patients with cardiac complaints. In daily clinical practice it is important for GPs to know the sensitivity and specificity of their ECG interpretation skills. OBJECTIVES: The purpose of the present study was to evaluate the ECG interpretation skills of GPs and the value of automatic ECG recorder interpretations in general practice. METHODS: A total of 902 ECGs were recorded in a random sample of the population aged 31-51 years in the district of Ebeltoft, Denmark, from December 1991 to June 1992. They were interpreted automatically by an interpretive ECG recorder and by the GPs in the clinic in Ebeltoft, with a cardiologists interpretation as a gold standard. Sensitivity, specificity and predictive values of diagnoses were calculated. RESULTS: Overall, the sensitivity of abnormal diagnoses made by the GPs (69.8%) was significantly lower (P <0.001) than that of diagnoses made by the interpretive ECG recorder (84.4%). The overall specificity of abnormal diagnoses made by the GP (85.7%) was significantly higher (P <0.001) than that achieved by the interpretive ECG recorder (75.6%). CONCLUSIONS: GPs in this study were good at correcting false-positive diagnoses made by the interpretive ECG recorder. In order to avoid unfortunate reclassifications of true-positive to false-negative diagnoses, GPs are recommended to pay special attention to the diagnoses of ST-segment deviation, T-wave inversion or the presence of Q-waves made by interpretive ECG recorders, when ECGs are used in individual risk assessment.

Abstract: AIMS: To evaluate the effectiveness of an intensive educational and low-tech ergonomic intervention programme aimed at reducing low back pain (LBP) among home care nurses and nurses' aids. METHODS: In 1999, 345 home care nurses and nurses' aids in four Danish municipalities were studied. Participants in two municipalities constituted the intervention group and participants in the other two served as the control group. In the intervention group, participants were divided into small groups, each of which was assigned one specially trained instructor. During weekly meetings participants were educated in body mechanics, patient transfer, and lifting techniques, and use of low-tech ergonomic aids. In the control group, participants attended a one time only three hour instructional meeting. Information on LBP was collected using the Standardised Nordic Questionnaire supplemented with information on number of episodes of LBP and care seeking due to LBP during the past year. RESULTS: A total of 309 nurses and nurses' aids returned the questionnaire at baseline and 255 at follow up in August 2001. At follow up, no significant differences were found between the two groups for any of the LBP variables, and both groups thought that education in patient transfer techniques had been helpful. Within group changes in LBP status was not related to the intervention or to satisfaction with participating in the project. CONCLUSIONS: Intensive weekly education in body mechanics, patient transfer techniques, and use of low-tech ergonomic equipment was not superior to a one time only three hour instructional meeting for home care nurses and nurses' aids.

Abstract: AIM: A study was carried out to discover the views of Danish general practitioners on the possibility of intervening in their patients' lifestyles in general and on the obstacles to doing so, based on their experience of participating in a health promotion study. METHOD: A focus group interview was conducted with five general practitioners who had participated in "The Ebeltoft Health Promotion Study" to assess their views on their preventive role. RESULTS: The general practitioners have internalized the view advanced by society and the medical profession that they have an important role to play in preventing lifestyle-related illness. However, they are sceptical about the effectiveness of intervention and have ethical concerns about giving lifestyle advice. They are also somewhat irritated by the fact that patients are chiefly interested in having their health checked, rather than in following up by changing their behaviour. The general practitioners differ in their views as to when, and how actively, they should initiate discussions with individual patients to encourage them to change their lifestyles. CONCLUSIONS: If the medical profession and those responsible for overall health policy wish to make general practitioners change their behaviour towards their patients, it is important that they understand the aims, values, and working conditions of general practitioners that underlie their present attitudes and behaviour.

Abstract: INTRODUCTION: The aim was to evaluate the practices of routine management of dyslipidemia performed by general practitioners in a large geographic area. METHODOLOGY: Patients were identified by three or more plasma cholesterol measurements registered in the electronic laboratory information system (LIS) covering the total geographic area, and the study population was characterised by information from general practitioners' records, and from a questionnaire sent to the patients. Further information on ischaemic heart disease (IHD) was obtained from the National Hospital register, and information on prescriptions on lipid lowering medications from the National Health Service. PARTICIPANTS: A sample of 1163 subjects, monitored by 134 different general practices. RESULTS: One third of the patients monitored for dyslipidemia had IHD, and two thirds were monitored as part of primary intervention. Dietary counselling was reported by 76%, and 54% were treated with lipid-lowering medications. The treatment frequency was related to cardiovascular risk, increasing from 25% of those with the lowest risk to 72% of the patients with IHD. The treatment goal was not reached in 74% of the cases, but overall a 20% reduction in plasma cholesterol was achieved. CONCLUSION: Subjects monitored for dyslipidemia were relevantly monitored because of IHD or high risk of IHD, and initiated treatment of dyslipidemia was clearly related to the individual assessed risk of IHD. Only a minority reached the treatment goals (< 5 mmol/l), and the statin doses used were generally lower than the doses used in clinical trials.

Abstract: OBJECTIVE: To explore how persons with an elevated cardiovascular risk score (CRS) balanced health-related advice against the life they wanted to live or were able to live. SETTING: 2000 Danes aged 30-50 were invited to participate in a health-screening project in general practice. Screenings were conducted at baseline and after one and five years, and included among other screening procedures a calculation of CRS (see Figure 1). DESIGN: Participants with an elevated CRS were asked to participate in a qualitative semi-structured interview. They were selected by stratified purposeful sampling reflecting variations in age, sex. and perceived health. SUBJECTS: Nine men and five women aged 33-50 years. THEORETICAL FRAMES OF REFERENCE: Bandura's theory of self-efficacy and the Health Belief Model's consideration of individuals' cues to act against a health threat supported analysis. RESULTS: Being informed about an elevated CRS had a considerable impact on the informants. They initiated significant lifestyle changes, though only to a limited degree when such changes would affect their quality of life adversely. In cases where other results of the multiphasic screening were normal, interpreted as such, or if there were stressful circumstances in the informant's life, the elevated CRS receded into the background. INTERPRETATION: Doctors, who inform individuals about the impact of risk factors, need to know that the consequences and health advice are not always interpreted by laypeople as supposed by the medical culture.

Abstract: OBJECTIVE: To examine the correlates of patient and provider attitudes toward insulin therapy. RESEARCH DESIGN AND METHODS: Data are from surveys of patients with type 2 diabetes not taking insulin (n = 2,061) and diabetes care providers (nurses = 1,109; physicians = 2,681) in 13 countries in Asia, Australia, Europe, and North America. Multiple regression analysis is used to identify correlates of attitudes toward insulin therapy among patients, physicians, and nurses. RESULTS: Patient and provider attitudes differ significantly across countries, controlling for individual characteristics. Patients rate the clinical efficacy of insulin as low and would blame themselves if they had to start insulin therapy. Self-blame is significantly lower among those who have better diet and exercise adherence and less diabetes-related distress. Patients who are not managing their diabetes well (poor perceived control, more complications, and diabetes-related distress) are significantly more likely to see insulin therapy as potentially beneficial. Most nurses and general practitioners (50-55%) delay insulin therapy until absolutely necessary, but specialists and opinion leaders are less likely to do so. Delay of insulin therapy is significantly less likely when physicians and nurses see their patients as more adherent to medication or appointment regimens, view insulin as more efficacious, and when they are less likely to delay oral diabetes medications. CONCLUSIONS: Patient and provider resistance to insulin therapy is substantial, and for providers it is part of a larger pattern of reluctance to prescribe blood glucose-lowering medication. Interventions to facilitate timely initiation of insulin therapy will need to address factors associated with this resistance.

Abstract: OBJECTIVE: This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmaco-kinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes. METHODS: Twenty-three patients (8 women, 15 men) aged 44.8 (20.6-62.5) years (median and range) with diabetes duration of 19.5 (1.6-44.6) years and haemoglobin (Hb)A(1C) of 9.2% (8.1-12.3%) participated in the study, which consisted of 12-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA(1C) and insulin antibodies were also determined. RESULTS: Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75% (moderate vs high (%, median and range): 62 (15-74) vs 80 (75-89)). High levels of insulin antibodies resulted in about threefold increase in AUC((0 - 24 h)) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P < 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA(1C) were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies. CONCLUSIONS: In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies.

Abstract: AIMS: To examine patient- and provider-reported psychosocial problems and barriers to effective self-care and resources for dealing with those barriers. METHODS: Cross-sectional study using face-to-face or telephone interviews with diabetic patients and health-care providers in 13 countries in Asia, Australia, Europe and North America. Participants were randomly selected adults (n = 5104) with Type 1 or Type 2 diabetes, and providers (n = 3827), including primary care physicians, diabetes specialist physicians and nurses. RESULTS: Regimen adherence was poor, especially for diet and exercise; provider estimates of patient self-care were lower than patient reports for all behaviours. Diabetes-related worries were common among patients, and providers generally recognized these worries. Many patients (41%) had poor psychological well-being. Providers reported that most patients had psychological problems that affected diabetes self-care, yet providers often reported they did not have the resources to manage these problems, and few patients (10%) reported receiving psychological treatment. CONCLUSIONS: Psychosocial problems appear to be common among diabetic patients worldwide. Addressing these problems may improve diabetes outcomes, but providers often lack critical resources for doing so, particularly skill, time and adequate referral sources.

Abstract: AIM: To evaluate the degree of concordance between venous plasma glucose (PG) and capillary whole blood glucose (BG) in diagnosing Type 2 diabetes and to compare the prevalence of confirmed and unconfirmed Type 2 diabetes. METHODS: All 40- to 69-year olds without known diabetes listed with five general practices were invited for screening (2051 persons). People identified by screening as being at high risk for having diabetes (random BG (rBG) > or = 4.5 mmol/l or HbA1c > or = 5.9%) were examined using BG and PG. The main outcome measures were confirmed diabetes cases (one diabetic glucose value plus symptoms or two diabetic glucose values on two different days) and unconfirmed diabetes (one diabetic glucose value on the first day of testing). RESULTS: One thousand and twenty-eight (50%) accepted screening. Diabetes was confirmed by BG or PG in 22 patients (1.8%), and in 14 of these by both BG and PG. Four patients in whom diabetes was confirmed only by BG had unconfirmed diabetes by PG. Three of four people in whom diabetes was confirmed only by PG had unconfirmed diabetes according to BG. The prevalence of unconfirmed diabetes was 3.3% and the prevalence of confirmed diabetes 2.1%. CONCLUSION: Confirmed diabetes can be diagnosed by either BG or PG. BG seems more convenient than PG for use in general practice. The prevalence of confirmed diabetes was lower than the prevalence of unconfirmed diabetes.

Abstract: Fetal growth has been linked with increased risk of cancer and cardiovascular disease later in life. The insulin-like growth factor (IGF) axis has recently been proposed as a predictor of risk of subsequent cancer and cardiovascular disease. However, only few data are available on the possible association between fetal growth and levels of IGFs later in life. We examined the association between markers of fetal growth, i.e. birth weight, birth length and Ponderal Index, from birth records and serum IGF-I, IGF-II, and IGF binding protein 3 (IGFBP-3) levels in 545 middle-aged Danish men and women. We fitted separate multivariate models including birth weight, birth length, Ponderal Index and serum IGF-I, IGF-II, and IGFBP-3, respectively. After adjustment for age, alcohol intake, smoking, diabetes mellitus, systolic and diastolic blood pressure, serum total cholesterol and current height and weight, we found negative associations between birth weight and Ponderal Index, respectively, and serum IGF-II in men, i.e. the mean regression coefficients were -49.41 (95% CI: -87.06-11.77) (microg/l)/kg and -3.49 (95% CI: -6.73-0.25) (microg/l)/(kg/m3), respectively. Furthermore, in men birth weight was negatively associated with the (IGF-I + IGF-II)/IGFBP-3 and IGF-II/IGFBP-3 ratios, which are believed to be indicators of bioavailable IGF and IGF-II, respectively. However, no other associations were found in any of the models. Between 1 and 16% of the variance in serum IGF-I, IGF-II, and IGFBP-3, respectively, could be explained by the statistical models used in the analyses. We found very little support to the hypothesis of an association between fetal growth and the IGF axis throughout life.

Abstract: BACKGROUND: Randomised, controlled trials focusing on long-term psychological reactions to information about increased risk of coronary heart disease are scarce. DESIGN: A population-based randomised, controlled, 5-year follow-up trial was conducted in general practice. METHODS: In 1991, invitations were sent to 2,000 middle-aged people registered in the general practices in the district of Ebeltoft, Denmark. A total of 1,507 (75.4%) agreed to participate and were randomised into a control group and two intervention groups: one included health screening, a written feedback and an optional follow-up visit with the general practitioner; the other included health screening, written feedback and a planned 45-min follow-up visit with the general practitioner. The participants were informed at screening about their risk of developing coronary heart disease. Psychological distress was measured by the GHQ-12 before screening and at the 1 and the 5-year follow-up. RESULTS: Before the screening (0 year), 1 and 5 years after there were no significant differences in the GHQ-12 score between the control group and the two intervention groups. Nor were there any differences related to information about increased risk of coronary heart disease between scores obtained at the 1 and the 5-year follow-up. CONCLUSION: Middle-aged persons had no long-term psychological reaction after information about increased risk of developing coronary heart disease following a health screening in general practice evaluated by the GHQ-12, 1 year and 5 years after the examinations.

Abstract: OBJECTIVE: To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. RESEARCH DESIGN AND METHODS: A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. RESULTS: The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765-0.838) for the first half of the Inter99 population, 0.761 (0.720-0.803) for the second half of the Inter99 population, and 0.803 (0.721-0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P<0.0001). CONCLUSIONS: We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.

Abstract: OBJECTIVE: To develop a method to evaluate routine management practices concerning lipid-lowering treatment in patients with ischaemic heart disease (IHD) in a large geographic area. DESIGN: A register-based study linking information on IHD with cholesterol levels and prescriptions on lipid-lowering medications by personal registration number. Plasma cholesterol levels were collected from the electronic laboratory information system (LIS), and information on IHD from the Danish National Hospital Register (LPR). The extent of treatment was evaluated by information on prescriptions on lipid-lowering medications from the Danish National Health Service. SETTING: Evaluates treatment in both hospitals and primary care. SUBJECTS: Patients with IHD. RESULTS: In total 3477 patients <75 years were identified, and 43.7% had claimed prescriptions on lipid-lowering medications (01.01.2000-31.07.2000). In the whole population, 42% reached the goal for total cholesterol lower than 5 mmol L-1 set by European guidelines. In the 1521 patients treated with lipid-lowering medications 55% reached the goal. CONCLUSION: By use of registers it was possible to develop a method to evaluate and monitor current treatment practice for dyslipidaemia in a large geographic area. The method makes it possible to evaluate the impact of guidelines, changes in treatment procedures and to provide feedback to physicians. The study revealed that lipid-lowering treatment is still not sufficiently implemented in clinical practice even in patients with known IHD, and the used doses of statins are lower than those used in randomized clinical trials.

Abstract: OBJECTIVE: The aim of this study was to explore beliefs and attitudes about refusing health screening in general practice. METHODS: In 1991, in Ebeltoft, Denmark people aged between 30 and 50 years were invited to participate in a 5-year randomized, controlled, population-based project testing the value of health screenings and health discussions in general practice. In 1994, non-participants who declined the offered health screening but expressed willingness to be contacted in the future were asked to participate in a qualitative interview. They were drawn by stratified purposeful sampling which reflected variation in perceived health, body mass index, age and sex. The sample comprised six men and 12 women RESULTS: Some had not participated because they were busy, felt healthy or had recently been examined. The non-participants emphasized the limitations of health screening and did not want possible risk factors to be revealed, or their feeling of good health to be disturbed. They stressed the individual's own responsibility for maintaining good health and believed that a positive attitude promoted health. They would contact their GP if they had symptoms. CONCLUSION: Non-participants have rational views on risk factor testing and on their own responsibility for maintaining health. Non-attendance was due to a conscious choice which included consulting their own GP.

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Abstract: OBJECTIVE: To describe the occurrence of "health realists", "health pessimists" and "health optimists" in a non-patient population by identifying cases of concordance and discordance between doctor-evaluated health and self-evaluated health and to describe the distribution of selected life-style-related physiological risk factors among these health-groups. DESIGN: Comparative study. SETTING: Primary health care. SUBJECTS: 456 middle-aged persons registered with a general practitioner (GP) were after a general health screening invited to a health discussion. Prior to the health screening the participants had assigned their health status to one of five categories ranging from "very poor" to "excellent". After the health discussion the GP rated the participants' general health status on a visual analogue scale. On basis of this information patients were classified as "health realists", "health optimists" and "health pessimists". RESULTS: 54% of the participants could be classified as "good-health realists", 14% as "poor-health realists", 22% as "health optimists", and 10% as "health pessimists". "Poor-health realists" had the greatest accumulation of risk factors, followed by "health optimists", "health pessimists" and "good-health realists". Among the "health pessimists" there was a significantly higher risk score of future cardiovascular disease and poor physical endurance compared with the "good-health realists". CONCLUSION: Discordance between doctor-evaluated health and self-evaluated health was found in 32% of the cases studied. "Health pessimists" had more risk factors than "good-health realists" even though the GPs had rated their general health status as good in both cases.

Abstract: OBJECTIVES: This study aims to describe the use of routine screening for diabetic eye complications in a large population based cohort of type 2 diabetic patients in the County of Vejle, Denmark. Furthermore, it aims to identify characteristics of patients and general practitioners related to the frequency of eye examinations. METHODS: The type 2 diabetic population alive and resident in the County of Vejle on 1st January 1997. Data concerning eye examinations were collected from public data files for the period of January 1993 to December 1997. RESULTS: In a population of 4438 type 2 diabetic patients, 46% had had one annual eye examination in 1997 and 26% had not had a single eye examination within the last five years. Patient characteristics related to an eye examination included: treatment with insulin or oral hypoglycaemic agents, females and long duration of diabetes. The number of diabetic patients who had had an eye examination varied substantially between the general practices. The characteristics of general practitioners were not related to this variation. CONCLUSIONS: The results of this study indicate a great need for quality improvement of ophthalmologic service in diabetes care. To achieve this improvement, more focus should be given to cooperation between the general practitioners and the ophthalmologists.

Abstract: INTRODUCTION: The aim was to develop a method for continuous monitoring of routine practice of screening and monitoring of dyslipidaemia, and to present the present status of cholesterol screening and monitoring in a large well-defined geographic area in Denmark. METHODOLOGY: Population based register survey, based on the electronic laboratory information system (LIS) as primary data source. All lipid measurements from both hospitals and primary health care, were included for a five-year period (1995.8.1.-2000.7.31.), and civil registration number was used to separate measurements from subjects living in an area comprising 248,475 adult inhabitants. RESULTS: An increasing number of subjects was screened every year, and during the five-year period approximately 25% of the total population older than 16 years were screened for dyslipidaemia (61,102), and half the subjects between 60 and 69 years were screened. The proportion of measurements prescribed from general practice increased significantly from 62.2% to 66.8%. The fraction of laboratory request forms including LDL-cholesterol increased from 39.8% to 58.5%. The number of subjects monitored for dyslipidaemia, by three plasma cholesterol measurements during 1 1/2 years increased by 71%. CONCLUSIONS: The method adequately identified subjects monitored for dyslipidaemia, and provided important information on routine practice for screening and monitoring of dyslipidaemia.

Abstract: PURPOSE: To describe whether quantitative assessment of early changes in the morphology of retinopathy lesions can predict development of vision-threatening diabetic maculopathy. METHODS: We used a nested case-control study, and we studied 11 type 2 diabetes patients who had developed visual loss secondary to diabetic maculopathy. For each diabetes patient, we also studied three matched control patients who had been followed for a comparable period of time without developing visual loss. Fundus photographs describing the early development of retinopathy were digitized and subjected to a full manual quantitative grading on a computer monitor. Differences in the early development of retinal morphology were compared between the two groups. The outcome parameters were changes in the number and area of haemorrhages and exudates in different regions of the fundus, and the weighted distance of these lesions from the fovea and the optic disc. RESULTS: In patients who developed visual loss secondary to diabetic maculopathy there was significant early progression in the total area and number of haemorrhages and exudates. The haemorrhages had progressed in all retinal areas except the area around the optic disc and the temporal vascular arcades. The exudates had progressed temporally from the fovea and in the retinal periphery. CONCLUSIONS: The results suggest that a quantitative description of the regional development of early diabetic retinopathy may help in identifying patients who will later develop vision-threatening maculopathy.

Abstract: AIMS/HYPOTHESIS: The yield of screening programmes for Type 2 diabetes in the existing healthcare setting might be lower than anticipated from tests of screening algorithms in data from epidemiological surveys. Our aims were to evaluate the reliability of the algorithms and the effectiveness of a proposed stepwise screening programme for Type 2 diabetes in general practice. METHODS: The screening programme had four steps: (i) mail-distributed self-administered risk-chart; (ii) screening tests: random blood glucose (RBG) and HbA(1)c; (iii) diagnostic procedure 1 for fasting blood glucose (FBG) (if RBG >/=5.5 mmol/l or HbA(1)c >/=6.1%); and (iv) OGTT as diagnostic procedure 2 (if 5.6</=FBG<6.1 mmol/l or HbA(1)c >/=6.1%). Abnormalities of glucose metabolism were classified according to the WHO 1999 criteria, based on capillary whole blood. The subjects were all patients between 40 and 69 years of age ( n=60,926) who were registered in 88 general practices and had not been previously diagnosed with diabetes. RESULTS: A total of 11,263 individuals had a high-risk risk-score and attended the screening consultation (step 1 test-positive). Of these, 30.1% needed diagnostic tests (step 2 test-positive) and 27.2% of these needed an OGTT (step 3 test-positive). The test-positive proportions were equal to the proportions obtained in data from a population-based survey from Step 2 onwards, and the algorithms were thus reliable. The identification rate was only 19% of all prevalent undiagnosed diabetes according to a recently published prevalence estimate. This was due to a large dropout rate among high-risk individuals prior to entry into the programme. CONCLUSIONS/INTERPRETATION: Population-based mail-distributed stepwise screening for Type 2 diabetes in general practice is ineffective, despite reliable screening algorithms, primarily because many high-risk individuals fail to participate.

Abstract: PURPOSE: To determine the prevalence of diabetic retinopathy and the causes of visual impairment in an unselected population of type 2 diabetes patients, and to describe the risk factors for developing diabetic retinopathy in this population. METHODS: A total of 10 851 type 2 diabetes patients were identified in the county of Arhus. A representative sample of 378 patients underwent a routine ocular examination, including fundus photography. Blood pressure and serum haemoglobin A1c, total cholesterol, high density lipoprotein cholesterol, triglyceride and apolipoprotein a were measured. RESULTS: The prevalence of diabetic retinopathy in the type 2 diabetes population was 31.5%. In all, 2.9% had proliferative diabetic retinopathy and 5.3% had clinically significant macular oedema. Of the latter, 8/20 (40%) were newly identified and had not yet been laser-treated. There was a positive correlation between severity of retinopathy and duration of diabetes, HbA(1c), systolic blood pressure and treatment with insulin. None of the patients had social blindness (visual acuity < 0.1), but 15/378 (4.0%) had developed visual impairment (VA < 0.3). CONCLUSION: The prevalence of diabetic retinopathy and visual impairment in this unselected type 2 diabetes population was lower than anticipated from the existing literature, and causes other than diabetic retinopathy contributed significantly to the occurrence of visual loss. A substantial number of the patients with vision-threatening diabetic maculopathy had not been referred for timely photocoagulation treatment.

Abstract: OBJECTIVE: Mortality and incidence of cardiovascular disease have declined during the past 35-40 years. The dual aim of this study is to investigate whether the prevalence of electrocardiographic findings is low compared with older studies and to describe the prevalence of electrocardiographic findings in the Danish population, which has not been reported since 1981. DESIGN: Cross-sectional study based on electrocardiograms obtained from a random sample of the population in the district of Ebeltoft, Denmark, December 1991-June 1992. RESULTS: The age and sex stratified prevalence of abnormal electrocardiograms ranged from 6.8% (95% CI: 4.01-10.7%) in women to 15.0% (95% CI: 10.6-20.4%) in men aged 41-51 years. Men had significantly more electrocardiographic changes than women (p = 0.004). Frequent findings were signs of earlier myocardial infarction (3.1%; 95% CI: 2.1-4.5%), axis deviation (3.1%; 95% CI: 2.1-4.5%) and incomplete right bundle branch block (1.2%; 95% CI: 0.6-2.2%). CONCLUSION: Prevalence of ischemic electrocardiographic findings is low when compared with studies from the past 50 years.

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Abstract: AIMS: Screening for Type 2 diabetes has been recommended in several countries due to the increasing prevalence of diabetes. This review evaluates whether Type 2 diabetes is a disease that fulfils the criteria for screening set by the World Health Organization. METHODS: Literature search was performed on the literature bases MedLine, Pub Medical, NIDDK, Cochrane Library and CINAHL using the MeSH terms 'non-insulin-dependent-diabetes-mellitus' and mass screening. Using this strategy we identified studies specifically evaluating screening strategies and diagnostic tests for Type 2 diabetes. The evaluation of psychosocial consequences included studies related to other chronic diseases. This literature was used to evaluate whether the WHO criteria for screening were fulfilled. RESULTS: The papers were reviewed but a meta-analysis was not possible, as no randomized controlled clinical trials were performed in the area of screening. CONCLUSION: Type 2 diabetes does not fulfil the criteria for population-based mass screening. No screening and intervention studies have been performed, systematically evaluating the positive and negative effects of screening. Furthermore, intervention studies up until now have been restricted to clinically diagnosed patients with diabetes, and most of these have recruited patients with long diabetes duration and early complications. These groups will have a worse prognosis and thus probably show greater benefits of such intervention. Finally, the psychosocial and health economic consequences of screening and intervention for Type 2 diabetes are largely unknown. Thus, systematic screening and intervention trials should be encouraged, and meanwhile intensified case finding and opportunistic screening in high-risk groups should be performed.

Abstract: OBJECTIVES: To investigate the course of low back pain (LBP) in a general population over 5 years. DESIGN: Prospective population-based survey by postal questionnaires in 1991, 1992, and 1996. SETTING: The municipal of Ebeltoft, Denmark. SUBJECTS: Two thousand people aged 30 to 50 years, representative of the Danish population.Main outcome measure Number of days with low back pain during the past year. RESULTS: One thousand three hundred seventy were recruited of whom 813 (59%) were followed to 5 years. The responders could be divided into 3 groups with regard to LBP: no pain, short-term pain, and long-lasting/recurring pain. More than one third of people who experienced LBP in the previous year did so for >30 days. Forty percent of people with LBP >30 days at baseline remained in that group 1 and 5 years later, and 9% with LBP >30 days in year 0 were pain free in year 5. People with LBP in year 0 were 4 times more likely to have LBP in year 1, and 2 times more likely to be affected in year 5. CONCLUSIONS: Low back pain should not be considered transient and therefore neglected, since the condition rarely seems to be self-limiting but merely presents with periodic attacks and temporary remissions. On the other hand, chronicity as defined solely by the duration of symptoms should not be considered chronic.

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Abstract: AIMS: This study examined whether adverse social factors are associated with an increased rate of biological ageing in middle-aged subjects. METHODS: The authors investigated five markers of biological ageing in 690 subjects followed for five years in Ebeltoft, Denmark. Mean age at baseline was 40 years (range 30-50 years). These markers included repeated measures of pulse pressure, lung function, hearing, physical work capacity and a cardiovascular risk score. A zeta-score was calculated based on a factor analysis of the five markers used. The relative biological age was finally calculated in relation to chronological age in subgroups of different social class (occupation, educational level) and marital status, at baseline and after follow-up. RESULTS: Men and women from a higher social class appeared to be biologically younger than corresponding subjects from a lower social class (p < 0.001). This difference was still evident after 5 years of follow-up (p < 0.01) for men and women of different occupations and for women of different educational levels (p < 0.01). Married/cohabiting men were biologically younger than single men and this difference increased during the follow-up period in that the difference between groups at five-year follow-up was significant (p < 0.05). CONCLUSIONS: Middle-aged men and women from a higher social class showed signs of being biologically younger than their corresponding chronological age, while the opposite was found for men and women of lower social class. This discrepancy was still evident after five years of follow-up, and even tended to increase for single men. Differential ageing may thus be an important biological aspect of differences in health according to social class.

Abstract: AIM: Diabetes and glucose intolerance are diagnosed by measurement of glucose in blood. Glucose is usually measured as venous plasma or capillary whole blood and diagnostic criteria frequently provide equivalence estimates for these two methods. This study examined the relationship between glucose measured in capillary and venous samples collected at random, fasting and 2 h after oral glucose. METHODS: Simultaneous measurements of venous plasma and capillary blood glucose were performed on random samples in 609 people, fasting samples in 685 people, and 2 h after oral glucose samples in 463 people. Separate capillary and venous samples were collected each time. A variance component model was used to construct conversion algorithms between venous and capillary results. RESULTS: The relationship between venous and capillary glucose values varied, with venous plasma being higher than capillary blood for random and fasting samples but lower for sampling 2 h after oral glucose. Discrepancies were observed between measured capillary blood values and the published WHO capillary blood equivalence values for venous plasma values for all except a fasting venous value of 7.0 mmol/l. For example, for a fasting venous plasma glucose of 6.1 mmol/l the WHO equivalent value is 5.6 mmol/l, while the measured value was 5.2 mmol/l, and for a 2-h venous plasma glucose of 11.1 mmol/l the WHO value is 11.1 mmol/l, while the measured result was 11.7 mmol/l. CONCLUSIONS: These results highlight the difficulty in equating glucose levels from one sampling and measuring procedure to another, and raise uncertainties about current published equivalence values which could lead to misclassifications in glucose tolerance status.

Abstract: Previously, we proposed a model of the circuitry underlying simple-cell responses in cat primary visual cortex (V1) layer 4. We argued that the ordered arrangement of lateral geniculate nucleus inputs to a simple cell must be supplemented by a component of feedforward inhibition that is untuned for orientation and responds to high temporal frequencies to explain the sharp contrast-invariant orientation tuning and low-pass temporal frequency tuning of simple cells. The temporal tuning also requires a significant NMDA component in geniculocortical synapses. Recent experiments have revealed cat V1 layer 4 inhibitory neurons with two distinct types of receptive fields (RFs): complex RFs with mixed ON/OFF responses lacking in orientation tuning, and simple RFs with normal, sharp-orientation tuning (although, some respond to all orientations). We show that complex inhibitory neurons can provide the inhibition needed to explain simple-cell response properties. Given this complex cell inhibition, antiphase or "push-pull" inhibition from tuned simple inhibitory neurons acts to sharpen spatial frequency tuning, lower responses to low temporal frequency stimuli, and increase the stability of cortical activity.

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Abstract: INTRODUCTION: Both physical and psychosocial workplace factors are considered risk factors for low back pain (LBP). However, today, no consensus has been reached regarding the exact role of these factors in the genesis of LBP. MATERIAL AND METHODS: Questionnaire data were collected at baseline for 1,397 (and after five years for 1,163) men and women aged 31-50 years at baseline. LBP (any LBP within the past year; LBP < or = 30 days in total during the past year; LBP > 30 days in total during tha past year) was analysed in relation to physical workload (sedentary, light physical, and heavy physical work) using logistic regression and controlling for age, gender, and social group. The proportions af workers changing between the workload groups over the five-year period were analysed in relation to LBP status. RESULTS: A baseline no statistically significant differences in LBP outcomes were found for workers exposed to sedentary, light physical, or heavy physical work. This was true for both genders and all age and social groups. At follow-up these was a statistically significant dose-response association between any LBP and long-standing LBP during the past year and increasing physical workload at baseline, also after controlling for age, gender and social group. Subjects with a heavy physical workload at baseline changed significantly more often to sedentary work, if they had experienced LBP for more than 30 days out of the past year. DISCUSSION: Having a sedentary job might have a protective or neutral effect in relation to LBP, whereas having a heavy physical job constitutes a significant risk factor. Because og migration between exposure groups (the "healthy worker" effect), longitudinal studies are necessary for investigating the associations between physical workload and LBP.

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Abstract: OBJECTIVES: To investigate the impact of general health screenings and discussions with general practitioners on the cardiovascular risk profile of a random population of patients. STUDY DESIGN: A population-based, randomized, controlled, 5-year follow-up trial conducted in a primary care setting. POPULATION: The study group consisted of 2000 patients, randomly selected middle-aged men and women aged 30 to 50 years from family practices in the district of Ebeltoft, Denmark. Of these patients, 1507 (75.4%) agreed to participate. Patients were randomized into (1) a control group who did not receive health screenings, (2) an intervention group that received 2 health screenings, (3) an intervention group that received both the 2 screenings and a 45-minute follow-up consultation annually with their general practitioner. OUTCOMES MEASURED: Cardiovascular risk score (CRS), body mass index (BMI), blood pressure, serum cholesterol, carbon monoxide in expiratory air, and tobacco use. RESULTS: After 5 years, the CRS, BMI, and serum cholesterol levels were lower in the intervention groups compared with the control group. The improved outcome was greater in the baseline risk groups. The number of patients with elevated CRS in the intervention groups was approximately half the number of patients with elevated CRS in the control group. The difference was not a result of medication use. There was no difference between the group that received consultations after the screenings and the group that had health screenings alone. CONCLUSIONS: Health screenings reduced the CRS in the intervention groups. After 5 years of follow-up, the number of persons at elevated cardiovascular risk was about half that expected, based on the prevalence/proportion in a population not receiving the health checks (the control group). The impact of intervention was higher among at-risk individuals. Consultations about health did not appear to improve the cardiovascular profile of the study population.

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Abstract: INTRODUCTION: We investigated the impact of general health screenings and discussions with general practitioners on the cardiovascular risk profile of the population. MATERIAL AND METHODS: A population-based, randomised, controlled, 5-year follow-up trial conducted in a primary care setting. In total 2000 randomly selected men and women, aged 30-50 years, from family practices in the district of Ebeltoft, Denmark. Of these persons, 1507 (75.4%) agreed to participate, and were randomised into: (1) a control group who did not receive health screenings; (2) an intervention group that received two health screenings; or (3) an intervention group that received both the two screenings and a 45-minute follow-up consultation annually with their general practitioner. All were followed up after 5 years by questionnaires and health screenings. The outcome measures were: cardiovascular risk score (CRS), body mass index (BMI), blood pressure, serum cholesterol, carbon monoxide in expiratory air, and use of tobacco. RESULTS: After 5 years, the CRS, BMI, and serum cholesterol levels were lower in the intervention groups, as compared with the control group. The improved outcome was greater in the baseline risk groups. The number of persons with elevated CRS in the intervention groups was about half the number of persons with elevated CRS in the control group. The difference was not a result of medication use. There was no difference between the group that received consultations after the screenings and the group that had health screenings alone. DISCUSSION: Systematic health screenings reduce the cardiovascular risk score in a middle-aged population. After 5 years of follow-up, the number of persons at elevated cardiovascular risk was about half the expected. The impact of intervention is higher in at-risk individuals. Planned consultations about health did not appear to improve the cardiovascular profile of the study population.

Abstract: INTRODUCTION: This study aims to describe the use and the level of HbA1c and furthermore, to describe the pharmacological treatment of type 2 diabetes in the County of Aarhus, Denmark. MATERIAL AND METHODS: The County of Aarhus has a background population of 641,000 citizens. Data were collected from public data files for the period January 2000 to December 2000. Patients were classified as having type 2 diabetes if they were treated with diet alone, with antidiabetic tablets or, irrespective of treatment, if they were more than 40 years of age at time of diagnosis. RESULTS: In a population of 10,431 type 2 diabetics, 86% had a HbA1c measurement. Mean HbA1c was 7.48% (95% CI 7.45%-7.51%). A description of drug therapy showed that 66% had purchased a prescription for antidiabetic drugs, 63% for antihypertensive drugs and 14% for lipid-lowering drugs. 8% had purchased prescriptions for antidiabetics as well as antihypertensive and lipid-lowering drugs. DISCUSSION: In this study it was found that a large proportion of type 2 diabetics have a HbA1c measurement and several type 2 diabetics have a poor glycemic regulation. Few had purchased prescriptions for antidiabetics as well as antihypertensive and lipid-lowering drugs and most after a long duration of diabetes. It is concluded that there are possibilities for improving treatment of type 2 patients and that registers easily can be established to monitor the quality of diabetes treatment.

Abstract: OBJECTIVES: To evaluate changes in plasma cholesterol following health screening and health discussions in general practice. DESIGN: Randomised prospective population-based study conducted over a period of 5 years. SETTING: Primary care, all general practitioners (GPs) in a well-defined area. SUBJECTS: A random sample of inhabitants aged 30-49 years in January 1991, registered with a local GP was invited to participate. The participants (1507 persons, or 75.4% of the 2000 invited) were randomly allocated to two intervention groups and a control group. MAIN OUTCOME MEASURES: Plasma cholesterol, percentage of subjects with plasma cholesterol higher than 7 mmol/l. RESULTS: After 5 years of intervention, plasma cholesterol in the whole population was significantly lower in the intervention groups compared to the control group. The decrease was most pronounced (0.5 mmol/l) in subjects at high cardiovascular risk. The percentage of high-risk individuals with a cholesterol level higher than 7 mmol/l was significantly lower in the intervention groups compared to the control group (9.8% vs 6.2%, p = 0.04), corresponding to a 37% reduction. CONCLUSIONS: The study shows that the health checks had a measurable impact on plasma cholesterol levels, the most pronounced effect is seen among individuals at high cardiovascular risk.

Abstract: OBJECTIVE: The aim of the present study was to compare patient and GP priorities for general practice care. METHODS: A questionnaire survey was carried out in general practice in Denmark which included 900 consecutive patients aged over 18 years from 15 practices collected in 1995, and 919 randomly sampled GPs in 1999. The postal questionnaire, developed by the EUROPEP group, contained 40 questions about eight aspects of primary care. Participants were asked to state their priorities for each question ranging from "not at all important" to "most important". A reminder questionnaire was sent to non-responders after 2 weeks. Top priority percentages ("very/most important") were calculated for each question as were differences between participant groups. RESULTS: Questionnaires were answered by 771 (85.7%) patients and 584 (64.2%) GPs. Their priorities were highly correlated (r = 0.754, P < 0.001). Patients gave higher priority than GPs to availability and accessibility of the practice and seeing the same GP. The GP should be capable of providing information on illness, investigations and treatments and patient associations, and should know the patient's history and be regularly updated through courses. CONCLUSIONS: Patient and GP priorities for primary care were highly correlated. The higher priority awarded by patients than by GPs to specific aspects of primary care should be acknowledged when organizing and developing general practice.

Abstract: BACKGROUND: Prophylactic strategies to counter acquired hearing impairment may involve routine audiometric screening of asymptomatic working-age adults attending general practice for regular health checks. AIM: To evaluate the effect of adult hearing screening on subsequent noise exposure and hearing. DESIGN OF STUDY: A randomised controlled population-based study of health checks and health discussions in general practice. SETTING: The project was initiated in the district of Ebeltoft, Aarhus county, Denmark. METHOD: Intervention group participants' hearing thresholds were determined audiometrically at 0.5, 1, 2, 3, and 4 kHz in each ear. Participants were advised to get their ears checked if the average hearing loss exceeded 20 dB hearing level (dBHL) in either ear. Noise avoidance was emphasised when thresholds exceeded 25 dBHL bilaterally at 4 kHz. Follow-up included questionnaires and audiometry. RESULTS: Hearing loss was observed among 18.9% of the study sample at baseline. At the five-year follow-up we recorded no significant differences between the control and the intervention groups regarding subjective or objective hearing, or exposure to occupational noise. However, there was a tendency towards reduction in exposure to leisure noise among intervention participants (P = 0.045). Approximately 20% reported hearing problems; 16.5% reported tinnitus-related complaints; 0.8% used hearing aids; 35.0% reported frequent noise exposure; and occluding wax was suspected in 2.1%. CONCLUSION: Preventive health checks with audiometry did not significantly affect hearing, but leisure noise exposure tended to become less frequent. The poor effect may be ascribed to inadequate audiological counselling or a higher priority to other advice, e.g. on cardiovascular risk or lifestyle.

Abstract: INTRODUCTION: This study aims to describe the process of identifying people known to have diabetes through public data files, to validate this method, and to describe models for optimization of such identification processes. PATIENTS AND METHODS: In a study population of 303,250 citizens, the diabetics were identified by combining information from public data files with information from general practitioners. Data validity was checked by comparing the results of data searches in public data files against information from general practitioners and a random sample of diabetics. Two models were defined to optimize the use of public data files for identification of diabetics. In model A the minimum number of parameters needed to obtain a sensitivity as high as possible was identified. In model B the optimal combination of parameters needed to obtain a high positive predictive value combined with a high sensitivity was identified. RESULTS: A total of 5449 diabetics were identified. Of those 4438 (81%) were classified as Type 2 diabetics and 1011 (19%) were classified as Type 1 diabetics. The data validation revealed that one person was misclassified as a diabetic and 93 persons were misclassified as non-diabetics. In model A the identification parameters included: "prescription", "HbA1c", "chiropodist service" and "glucose service". In model B the optimal combination of parameters was identified as: minimum two HbA1c measurements, minimum one visit to a chiropodist, minimum one prescription or minimum one abnormal HbA1c during one year. CONCLUSION: Public data files are suitable for identification of both Type 1 and Type 2 diabetics. Models have been developed to identify diabetics and to promote the possibilities of long-term follow-up and quality assessment in an unselected diabetic population in a region.

Abstract: STUDY DESIGN: A population-based cross-sectional and 5-year prospective questionnaire study. OBJECTIVE: To investigate self-reported physical workload as a risk factor for low back pain. SUMMARY OF BACKGROUND DATA: Both physical and psychosocial workplace factors are considered risk factors for low back pain. However, today no consensus has been reached regarding the exact role of these factors in the genesis of low back pain. METHODS: Questionnaire data were collected at baseline for 1397 (and after 5 years for 1163) men and women aged 31--50 years at baseline. Low back pain ("any low back pain within the past year," "low back pain < or = 30 days in total during the past year," "low back pain > 30 days in total during the past year") was analyzed in relation to physical workload (sedentary, light physical, and heavy physical work) using logistic regression and controlling for age, gender, and social group. The proportions of workers changing between the workload groups over the 5-year period were analyzed in relation to low back pain status. RESULTS: At baseline no statistically significant differences in low back pain outcomes were found for workers exposed to sedentary, light physical, or heavy physical work. This was true for all age, gender, and social groups. At follow-up there was a statistically significant dose-response association between any low back pain and longstanding low back pain within the past year and increasing physical workload at baseline also after controlling for age, gender, and social group. Subjects with heavy physical workload at baseline changed statistically significantly more often to sedentary work if they experienced low back pain for more than 30 days out of the past year. CONCLUSIONS: Having a sedentary job might have a protective or neutral effect in relation to low back pain, whereas having a heavy physical job constitutes a significant risk factor. Because of migration between exposure groups (the "healthy-worker" effect), longitudinal studies are necessary for investigating the associations between physical workload and low back pain.

Abstract: In cortical simple cells of cat striate cortex, the response to a visual stimulus of the preferred orientation is partially suppressed by simultaneous presentation of a stimulus at the orthogonal orientation, an effect known as "cross-orientation inhibition." It has been argued that this is due to the presence of inhibitory connections between cells tuned for different orientations, but intracellular studies suggest that simple cells receive inhibitory input primarily from cells with similar orientation tuning. Furthermore, response suppression can be elicited by a variety of nonpreferred stimuli at all orientations. Here we study a model circuit that was presented previously to address many aspects of simple cell orientation tuning, which is based on local intracortical connectivity between cells of similar orientation tuning. We show that this model circuit can account for many aspects of cross-orientation inhibition and, more generally, of response suppression by nonpreferred stimuli and of other nonlinear properties of responses to stimulation with multiple gratings.

Abstract: OBJECTIVE: Impaired fetal growth has been linked with cardiovascular disease and different cardiovascular risk factors. Few studies have examined the association between fetal growth and urinary albumin excretion, an important predictor of vascular disease in both diabetic and non-diabetic subjects. MATERIAL AND METHODS: We examined the association between markers of fetal growth, ie, birth weight, birth length and Ponderal Index, from birth records and urinary albumin excretion in 545 middle-aged men and women who had taken part in a population-based follow-up study in the municipality of Ebeltoft, Denmark. The outcome was the urinary albumin-creatinine ratio. RESULTS: Three men (1.1%) and 10 women (3.6%) had a albumin-creatinine ratio above 2.5/3.5 mg/mmol, which is considered abnormal and diagnostic of microalbuminuria. The strength of the associations between birth weight, birth length, Ponderal Index and albumin-creatinine ratio were fitted in separate multivariate models, but no associations were found in any model. CONCLUSIONS: Our study did not support the hypothesis of an association between fetal growth and adult albumin-creatinine ratio. Studies with larger numbers of microalbuminuric subjects are required in order to further clarify the relationship between fetal growth and later renal function.

Abstract: OBJECTIVE: To describe the use and level of HbA1c in a large unselected Type 2 diabetic population in Denmark. In addition, to describe the characteristics of the patients and the general practitioners in relation to the monitoring of HbA1c. DESIGN: Data were collected from public data files for the period January 1993 to December 1997. SETTING: The County of Vejle with a background population of 342,597 citizens, 303,250 of whom were listed with participating general practitioners. PATIENTS: The Type 2 diabetic population alive and resident in the county on 1 January 1997. RESULTS: In a population of 4438 Type 2 diabetics, 73% had a minimum of one annual HbA1c measurement in 1997. No HbA1c measurement was associated with a long history of diabetes, diet treatment or old age. Poor glycaemic regulation was found in 65% of the Type 2 diabetics in 1997. Poor glycaemic regulation was associated with tablet or insulin treatment, age under 70 years and long history of diabetes. The interpractice variation was huge. CONCLUSION: The quality of HbA1c monitoring of Type 2 diabetics needs to be improved. Possibilities for improvement seem to be present.

Abstract: OBJECTIVE: The overall aims of the ADDITION study are to evaluate whether screening for prevalent undiagnosed Type 2 diabetes is feasible, and whether subsequent optimised intensive treatment of diabetes, and associated risk factors, is feasible and beneficial. DESIGN: Population-based screening in three European countries followed by an open, randomised controlled trial. SUBJECTS AND METHODS: People aged 40-69 y in the community, without known diabetes, will be offered a random capillary blood glucose screening test by their primary care physicians, followed, if equal to or greater than 5.5 mmol/l, by fasting and 2-h post-glucose-challenge blood glucose measurements. Three thousand newly diagnosed patients will subsequently receive conventional treatment (according to current national guidelines) or intensive multifactorial treatment (lifestyle advice, prescription of aspirin and ACE-inhibitors, in addition to protocol-driven tight control of blood glucose, blood pressure and cholesterol). Patients allocated to intensive treatment will be further randomised to centre-specific interventions to motivate adherence to lifestyle changes and medication. Duration of follow-up is planned for 5 y. Endpoints will include mortality, macrovascular and microvascular complications, patient health status and satisfaction, process-of-care indicators and costs.

Abstract: During the past decade, studies have shown an inverse association between birth weight and blood pressure and risk of coronary heart disease in adult life. From old public archives we were able to trace the birth records of 545 out of 905 persons (60.2%) aged 31-51 years who participated in the Ebeltoft Health Promotion Project in Denmark. We examined the associations between birth weight, length at birth, Ponderal Index and systolic and diastolic blood pressure. No associations were found for women. For men, the mean systolic blood pressure fell from 131.1 mmHg with a birth weight of less than 3300 g to 129.6 mmHg with a birth weight of more than 4000 g, and for diastolic blood pressure 81.6 mmHg to 80.3 mmHg, respectively. For men, the mean systolic blood pressure fell from 135.7 mm Hg with a birth length of 30-51 cm to 131.6 with a birth length of 55-62 cm, and for diastolic blood pressure 83.0 mmHg to 78.8 mmHg, respectively. The associations may reflect organ programming in fetal life.

Abstract: This paper aims to report changes in hearing sensitivity over five years in a rural population aged 31-50 years and to identify risk factors associated with hearing deterioration. The study is prospective and based on data from pure tone audiometry and questionnaires in the Ebeltoft Health Promotion Project in Denmark. A representative sample of 705 subjects had a complete follow-up, including audiometry. The median hearing deterioration was 2.5 dB at 3-4 kHz and 0 dB at 0.5-2 kHz. There was a high degree of individual variability in deterioration. The overall deterioration of hearing sensitivity of the population was largely predicted from the cross-sectional findings reported previously. In the analysis of risk factors, hearing deterioration was defined as an average deterioration 10 dB/5 years at 3-4 kHz in at least one ear. Deterioration was present in 23.5% of the sample. The 41-50-year-olds had a relative risk of deterioration of 1.32 (95% CI 1.01-1.73) compared with the 31-40-year-olds. Males had a relative risk of 1.35 (1.03-1.76) compared with females. The risk was not significantly elevated for a range of other possible risk factors confirmed by logistic regression analysis. In conclusion, deterioration in hearing sensitivity on population level can be predicted on the basis of cross-sectional findings. Hearing sensitivity deteriorated mainly at 3-4 kHz. The deterioration increased with age and was higher in males than in females. Other risk factors were not found. The present study does not support the hypothesis that hypertension or tobacco smoking is associated with deterioration in hearing.

Abstract: Type 2 diabetes mellitus is characterised by abnormal beta-cell function (present at the time of diagnosis) that is often associated with insulin resistance. An important and consistent pathophysiological finding is the failure to produce adequate increments in insulin secretion in response to carbohydrate intake. Therefore, insulin secretagogue therapy, particularly when focused on prandial glucose regulation, is a logical approach to treatment because it addresses one of the most fundamental pathophysiological aspects of the disease. However, the traditional secretagogues-the sulphonylureas--have long been associated with the unwanted effect of hypoglycaemia. This is particularly likely to occur when drugs with lengthy plasma half-lives, prolonged drug-receptor interactions, active metabolites or a reliance on renal clearance are used. The problem is most prevalent in elderly patients, where sulphonylurea-induced hypoglycaemia may be related to failure to comply with strict mealtimes or the need for supplementary food intake, often in the context of compromised renal function. Data from large-scale outcome studies demonstrate that when tight glycaemic control is achieved through aggressive antidiabetic therapy, late diabetic complications can be significantly reduced. However, the pursuit of stricter HbA1c targets with more aggressive interventions may increase the risk of hypoglycaemia. This is an irony because the clinical need to avoid hypoglycaemia and patients' apprehension of it present barriers to the achievement of beneficial glycaemic targets. However, an increased risk of hypoglycaemia may not be inevitable with insulin secretagogue therapy. The recently introduced carbamoylmethyl benzoic acid derivative, repaglinide, has pharmacological properties that are well suited to its intended role as a prandial glucose regulator. When taken prior to main meals, the rapid onset and relatively short duration of action of repaglinide aid disposal of the mealtime glucose load, without continued stimulation of pancreatic beta-cells in the postprandial fasting period. Repaglinide is also characterised by hepatic metabolism and elimination, which is an advantage in the context of impaired renal function. Prandial glucose regulation with repaglinide selectively increases insulin secretion, and hence limits glucose excursions, in the prandial phase. If a meal is omitted, so too is the corresponding dose. This more flexible approach to the management of Type 2 diabetes has a number of advantages when compared with the fixed daily dosing regimens of sulphonylureas, among them a reduced risk of hypoglycaemia--a benefit that is particularly marked in the context of missed or irregular meals.

Abstract: In 1997 a new prescription system was introduced in the Danish health care system. The pharmacist must now substitute a prescription with a cheaper version of the drug (either generic or original) unless the prescribing doctor indicates that substitution is not allowed in the specific case. The purpose of this study was to evaluate problems of the system and obtain the pharmacists' views on the system. The study was based on questionnaires to a representative sample of 75 pharmacists (a quarter of Denmark's pharmacists). The response rate was 72%. Half of the pharmacists were dissatisfied with the system, which primarily was due to the excessive workload imposed. In spite of this, about half the pharmacists wanted the system to be continued, because the overall purpose of finding the cheapest drug for the patient is good. Nearly all pharmacists thought that analogue substitution (substitution between drugs with the same overall effects but obtained by different means) should not be introduced.

Abstract: In 1997 a new prescription system was introduced in Denmark. The pharmacist must now substitute the prescribed drug with a cheaper version either by a generic prescription (G-substitution) or by an original prescription (O-substitution) unless the prescribing doctor indicates that substitution is not allowed in the specific case. The purpose of this study was to obtain the patients' view on the new prescription system and to identify any related problems. The investigation was based on structured interviews. The interview guide was designed as a questionnaire, which was validated and tested before use. The response rate was 82%. The study showed that 84% of the patients were satisfied with the system and 85% of the patients thought that it should continue. Eighty-three percent of the patients had tried another version of the substituted medicine earlier. Out of these, 6% had experienced more side-effects from the substituted medicine, and 10% felt that the substituted medicine had a weaker effect. There was one case of erroneous medical treatment as a consequence of the substitution system. Only few problems such as more side-effects or less effect of the substituted medicine was experienced by the patients. It can be concluded that the patients in general are satisfied with the new prescription system.

Abstract: OBJECTIVES: To investigate whether impaired fetal growth, measured by low birth weight and short birth length, is linked with raised levels of serum lipids and increased risk and mortality of coronary heart disease. DESIGN: The association between birth length, birth weight, Ponderal Index and total serum cholesterol was examined in 545 Danish men and women aged 31 to 51 years who participated in the Ebeltoft Health Promotion Project in Denmark. RESULTS: No associations were found in women. For men, a negative association was found between birth weight and serum total cholesterol, with a fall in mean serum total cholesterol from 6.03 mmol/l at birth weight below 3300 g to 5.64 mmol/l at birth weight above 4000. A similar association was found between birth length and serum cholesterol, with a mean value of 6.23 mmol/l at birth length below 51 cm and a mean value of 5.56 mmol/l at birth length above 54 cm. No associations were found for Ponderal Index. Between 3% and 8% of the variance in serum total cholesterol could be explained by the statistical models used in this study. CONCLUSION: Our findings support the hypothesis of a negative association between birth weight, birth length and elevated serum cholesterol in adult life, but only in men.

Abstract: AIMS: In 1997 a new prescription system was introduced in the Danish health care system. The pharmacist must now substitute a prescribed drug with a cheaper version, either generic (G-substitution) or original (O-substitution) unless the general practitioner (GP) indicates that substitution is not allowed. The purpose of this study was to obtain the GPs' views on the system and evaluate the problems related to the system. METHODS: The study was based on questionnaires to GPs developed via qualitative interviews with the GPs and afterwards pilot tested. RESULTS: Out of 300 GPs the response rate was 80%. The study showed that 61% of the GPs were dissatisfied with the system and thought that it should be removed. There were several reasons for this: the system was incomprehensible, the introduction and information about the system was insufficient and the extra workload was too heavy. All the GPs agreed that analogue substitution (substitution between drugs with the same effect obtained by different means) was medically unjustifiable and should not be introduced.

Abstract: BACKGROUND: The association between alcohol intake and liver disease is well known, but little is known about alcohol consumption and changes in liver-derived enzymes within 1 year. In a 1-year follow-up study we examined changes in liver-derived enzymes and their association with self-reported alcohol consumption. METHODS: We recorded liver-derived enzyme values, self-reported alcohol consumption, and potential confounder variables at base line and at a 1-year follow-up in a representative sample of 822 persons (aged 30-50 years) from the survey of The Ebeltoft Health Promotion Project in Denmark, by using questionnaires, health examinations, and blood samples. RESULTS: The prevalence of increased liver-derived enzyme values was 11.1% at base line and 11.8% at the 1-year follow-up. The incidence rate of increased liver-derived enzyme values was 5.1 per 100 person-years, and 34% of the cases of increased liver-derived enzyme values returned to normal within I year. We found an odds ratio of 4.0 for men and 8.0 for women of developing increased liver-derived enzyme values if alcohol consumption was more than 21 units a week. The risk seemed to be dose-dependent. CONCLUSIONS: The prevalence of increased liver-derived enzyme values in the population was high and increased slightly during the study period. There was a strong association between the incidence rate of increased liver-derived enzyme values and self-reported alcohol consumption in a dose-dependent relationship, also when adjusted for confounding by smoking and obesity. The persons with persistently increased enzyme values had a higher weekly alcohol consumption than the rest of the study population.

Abstract: BACKGROUND: The benefits of near-patient, point-of-care tests have not been fully examined. We have assessed the clinical, organizational, and economic outcomes of implementing a near-patient test for C-reactive protein (CRP) in general practice. METHODS: In a randomized crossover trial during intervention periods, general practitioners (GPs) were allowed to measure CRP within 3 min, using NycoCard(R) CRP. During control periods, they had to mail blood samples for CRP measurements to the hospital laboratory and received test results 24-48 h later. Twenty-nine general practice clinics participated (64 GPs), and 1853 patients were included in the study. Results were evaluated at both the level of participating GPs and the level of included patients. RESULTS: For participating GPs, the overall use of erythrocyte sedimentation rates (ESRs) decreased by 8% (95% confidence interval, 1-14%) during intervention periods, and the number of blood samples mailed to the hospital laboratory decreased by 6% (1-10%). No reduction in the prescription of antibiotics was seen. The proportion of study patients having a follow-up telephone consultation was reduced from 63% to 53% (P = 0. 0001), and patients with CRP concentrations >50 mg/L had their antibiotic treatments started earlier when CRP was measured in general practices (P = 0.0161). CONCLUSION: The implementation of the near-patient CRP test was cost-effective mainly on the basis of a reduction in the use of services from the hospital laboratory by GPs. If the implementation is followed by education and clinical guidelines, opportunities exist for additional reduction in the use of ESR and for a more appropriate use of antibiotics.Copyright 1999 American Association for Clinical Chemistry

Abstract: This paper focuses on problems attached to using scientific results in everyday clinical practice. Based on examples we raise the question: Are research results obtained under ideal scientific conditions, presented to health professionals and the public in a way that creates unrealistic expectations of the health services? We suggest that the clinical researcher, when reporting scientific results, should be obliged to consider technological aspects, i.e. the human and monetary cost, effectiveness, compliance, the expected consequence for the patient, professionals and society, and resources needed to accomplish it. Presented with these considerations, actors of the health care scene in terms of professionals, administrators, politicians and patients should be better suited to decide if implementation of a new treatment should take place. Such procedures will give the population and the politicians more realistic expectations of the contributions of medical science and the health services in general.

Abstract: The aims of this study were to describe the diabetic population and to evaluate the routine diabetic care in one general practice. All patients with recognized diabetes were included. Information was collected from each patient's record and from patients' and doctors' questionnaire. One hundred an fourty (1.8%) of the patients had recognized diabetes and 81% of these diabetes had non-insulin-dependent diabetes (NIDDM). According to the records, HbA1c had been monitored in 85% of the NIDDM patients in the preceding year and in 76% of the IDDM patients. The corresponding figures for albuminuria were 84% vs. 76%, for S-creatinine 74% vs. 81%, for S-cholesterol 37% vs. 24%, for weight 47% vs. 43%, for blood pressure 60% vs. 48%, for foot care 67% vs. 62% and for eye examination 76% vs. 75%. International targets for good control were obtained for HbA1c in 42% of cases, for weight in 23%, for blood pressure in 30% and for S-cholesterol in 40% at the last control. The results of the study indicate that there is a continuous demand for quality monitoring and improvement of diabetic care in general practice.

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Abstract: The objective of the present study was to describe the prevalence of subjective hearing problems and hearing impairment and to evaluate the relation between subjective hearing problems and audiometric thresholds, in a random sample of subjects aged 31-50 years. The study is cross-sectional and based on data from questionnaires (N = 1397) and pure tone audiometry (N = 905) in the Ebeltoft Health Promotion Project in Denmark. Hearing problems were significantly more prevalent in males than females. Males had significantly poorer average audiometric thresholds (0.5, 1, 2 and 4 kHz) in the better hearing ear (BE) and worse hearing ear (WE) than females. Average audiometric thesholds were poorer in the 41-50-year-old age group compared with the 31-40-year-old age group, the difference being most marked in males. Overall prevalence of hearing impairment (at least two threshold levels >25 dB HL) was 7.4% (95% confidence interval: 5.7-9.1%) in BE and 15.9% (13.5-18.3%) in WE. Prevalence of impairment > or = 25, > or = 35 and > or = 45 dB HL (average across 0.5-4 kHz): (BE) 3.4% (2.2-4.6%), 1.0% (0.3-1.6%) and 0.2% (0.0-0.5%); (WE) 11.6% (9.5-13.7%), 3.6% (2.4-4.9%) and 1.7% (0.8-2.5%). An interesting sex difference was noted as females were aware of hearing problems at an earlier stage of impairment than males. In conclusion, hearing impairment is fairly prevalent in this young rural population, less prevalent, however, than in the British National Study of Hearing. It is proposed that general practitioners should take a more active part in primary prevention, early detection of hearing impairment and early referral for rehabilitation.

Abstract: INTRODUCTION: We examined whether waist circumference and waist-to-hip circumference ratio were a better predictor for elevated alanine transaminase level than body mass index. METHODOLOGY: In a cross-sectional survey we examined body mass index, waist circumference, waist-to-hip ratio, alcohol consumption, and alanine transaminase level in a random sample of 903 men and women aged 30 to 50 years from The Ebeltoft Health Promotion Project in Denmark. RESULTS: Body mass index, waist circumference and waist-to-hip ratio explained an approximate 12% variation in alanine transaminase in men and 4% in women, whereas waist-to-hip circumference ratio explained a 2% variation in women. The risk of elevated alanine transaminase level in men, calculated as odds ratio, with a body mass index (kg/m2) above 30, or a waist circumference above 102 cm, or a waist-to-hip circumference ratio above 0.9 was 9.3 (95% confidence interval [CI], 3.6-24.1), 5.6 (95% CI, 2.5-12.5) and 2.7 (95% CI, 1.3-5.3) respectively, but there was no elevated risk among women. CONCLUSIONS: Waist circumference and body mass index were both predictors in men. Waist-to-hip ratio was also a predictor in men, but not as strong a predictor as waist circumference and body mass index. No association was found in women. This difference is probably explained by differences in the accumulation of intra-abdominal adipose tissue among men and women with the same degree of obesity.

Abstract: Conflicting data for predictive values for C-reactive protein (CRP) in its ability to distinguish between viral and bacterial diseases are reviewed. Study designs regarding setting, patient-mix, severity of disease and prevalence seem to determine the magnitude of predictive values. We have calculated predictive values for patients suspected of septicaemia, meningitis, appendicitis, cholecystitis, upper- and lower respiratory disease, acute sinusitis and acute otitis media, and revealed the highest predictive values among patients suspected for severe and generalized infections. More localized diseases have lower predictive values. We emphasize the importance of a study design where the circumstances resemble the real situations in which the test is supposed to be used. This will ensure the clinical applicability of predictive values for a diagnostic test.

Abstract: The aim of this study was to validate the results of diagnostic pure-tone audiometry performed in a typical practice setting by comparing with test results obtained in a standardized audiological setting in accordance with the ISO standards. In a single-blinded crossover design, 119 persons were tested (0.25-8 kHz) in both settings. The mean deviations as a function of frequency were in the order of less than 2 dB (0.5-4 kHz) and otherwise up to 4 dB; the practice setting representing the poorer thresholds. The validity of the practice audiometry at three criteria of hearing impairment (0.5-4 kHz) was characterized by sensitivity (82-100%), specificity (95-99%); positive predictive values (75-90%) and negative predictive values (98-100%) focusing on the better ear. It is concluded that pure-tone audiometry of appropriate validity can be performed in general practice and that it is useful in selecting patients with no need of further audiological examination. Guidelines are needed.

Abstract: Analysis for C-reactive protein (CRP) was introduced in the Vejle Hospital catchment area in 1987. During the next ten year period the use of CRP has increased to reach a stable level both on hospital wards, out-patient clinics and in general practice. While the use of erythrocyte sedimentation rate on wards has decreased correspondingly, this is not seen in out-patient clinics or in general practice. There are medical as well as practical reasons for this discrepancy. It is believed that the possibility of performing a CRP as a point-of-care test in the GPs office in the future will lead to a reduction in the number of analyses of erythrocyte sedimentation rate performed in general practice as well.

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Abstract: STUDY DESIGN: Cross-sectional data were collected in a postal questionnaire within the framework of a 5-year randomized, controlled, prospective, population-based study. OBJECTIVES: To investigate to what extent associations differ or concur when correlates of low back pain are rested against various subdefinitions of low back pain. SUMMARY OF BACKGROUND DATA: Numerous factors have been suspected to cause low back pain, but findings have not been constantly reproduced in epidemiologic studies. METHODS: Data were collected on 748 people reporting nonspecific low back pain some time during the year preceding the survey. Six correlates of low back pain (age, sex, marital status, attitude to a healthy life-style, self-reported physical activity at work, and smoking) were cross-tabulated against nonspecific low back pain and against four subgroups of low back pain. RESULTS: There was only one statistically significant strong association between the potential risk indicators and the nonspecific definition of low back pain, but several emerged when the low back pain group was split into subgroups. Different subgroups of low back pain did, indeed, relate differently to the various correlates. CONCLUSIONS: It is necessary to define some clinically relevant subgroups of low back pain to accelerate the search for causal mechanisms.

Abstract: OBJECTIVE: C-reactive protein (CRP) is a well-known diagnostic tool in general practice. The scope of this study was to assess how frequently CRP is used by general practitioners and to evaluate the reasons for using it. DESIGN: A retrospective part based on data from a laboratory database system, and a prospective part with a questionnaire-based registration. SETTING: 30 general practice clinics in the catchment area of Vejle County Central Hospital. SUBJECTS: Retrospectively, all patients from general practice serviced by the laboratory for one year. Prospectively, 1190 patients from whom a blood sample was taken for CRP-measurement during a 2 month study period. MAIN OUTCOME MEASURES: The frequency of using CRP and the reason requesting it; A) diagnosing a new disease, B) monitoring a well-known disease, or C) "screening". Furthermore; 1) infections, 2) chronic inflammatory disease, 3) malignant disease, or 4) others. RESULTS: CRP-measurements were ordered in 3.7% of all consultations in general practice and for 34.1% of all patients whose blood sample was analysed at the central laboratory. The use of CRP was as follows: A-1: 28.6%, A-2: 6.7%, A-3,4: 9.3%, B-1: 8.2%, B-2: 12.4%, B-3,4: 6.5%, C-1: 5.7%, C-2: 3.2%, C-3: 3.5% and C-4: 15.2%. Diagnosing a new (infectious) disease was the most frequent single reason for CRP-measurement. There was major interpractice variation. CONCLUSIONS: CRP is frequently used in general practice, mostly (65.4%) in the field of infections and chronic inflammatory diseases. Because of major interpractice variation, the most correct way of using CRP should be evaluated and guidelines should be provided.

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Abstract: BACKGROUND: Based on the increased consumption of alcohol in Denmark the aim of this study was to measure prevalence of abnormal liver-derived enzymes in a homogeneous Danish population and possible associations with alcohol consumption, smoking and body mass index (BMI). METHOD: In a representative population sample of 905 people (aged 30-50) from the baseline survey of the Ebeltoft Health Promotion Project in Denmark, we examined prevalence of abnormal liver-derived enzymes and its possible association with self-reported alcohol consumption, smoking and BMI, applying logistic regression analyses. RESULTS: In a significant proportion, 12% (women 8%; men 16%) of the cohort we found raised levels of liver-derived enzymes associated with moderate self-reported alcohol intake adjusted for BMI and smoking. If the intake was higher than moderate, i.e. > 28 units per week (one unit equals 12 g of alcohol), the odds ratio (OR) for raised liver enzymes increased further; S-gamma-glutamyltransferase (GGT) (OR: for women 24.4; men 18.4). S-aspartate-aminotransferase (ASAT) (24.2; 5.8) and S-alanine-aminotransferase (ALAT) (27.2; 3.0). Furthermore, daily smoking increased the risk of raised liver enzymes in women (OR: 3.4-4.2), and obesity (BMI > or = 30 kg/m2) in men showed a positive association with all three enzymes (OR: 3.0-9.0). CONCLUSIONS: The occurrence of raised liver-derived enzymes was frequent in the Danish population sample and associated with moderate self-reported alcohol consumption adjusted for BMI and smoking.

Abstract: In a representative population sample of 905 persons we examined the prevalence of raised levels of liver-derived enzymes and its possible association with self-reported alcohol consumption adjusted for smoking and BMI applying logistic regression analyses. A large proportion of 12% (women 8%; men 16%) presented raised liver-derived enzymes. Below 21 units per week (one unit equals 12 grams of alcohol) there was no association with self-reported alcohol consumption. However, the risk of abnormal liver enzymes increased with higher consumption for both sexes; if the intake was above 28 units per week, the odds ratio for raised liver enzymes increased dramatically. Whether this subclinical biochemical liver condition is an early marker of alcohol-related liver damage remains to be seen, but the long-term consequences of the reported alcohol consumption and the frequency of raised liver enzymes require follow-up.

Abstract: We have assessed the technical performance and robustness of NycoCard CRP Whole Blood, a near-patient test for C-reactive protein (CRP), when used in realistic daily routine situations in general practice clinics (GPC). Thirteen GPCs participated, five of them with technician staff. From 898 patients, split-sample measurements for CRP were made. Results from GPCs were compared with results from a turbidimetric laboratory method, traceable to international reference preparations (IFCC CRM 470). Results were evaluated in difference plots where the expected distribution, due to an estimated analytical variation, was compared with measured differences. Of all difference points, 91.5% (n = 819) were within a 95% prediction interval based on the imprecision of both methods. Mean bias (95% confidence interval) was -0.3 mg/L (-0.9 to 0.3). No differences in analytic quality were found between GPCs with technician staffs and GPCs without, and between test results obtained within the first and second week, compared with the rest of the study period. We find the test as good when used in GPCs as could be expected from laboratory testing, and consequently robust, which is a necessity for use in routine situations in general practice. General application of difference plots in test evaluations are discussed in detail.

Abstract: The acute effects of a single GH pulse have previously been studied in young males. It is, however, likely that both the metabolic effects and the pharmacokinetics of GH may differ between age groups and sexes. We studied 36 healthy, clinically nonobese adults of both sexes, who were divided into a young group (mean age, 29.6 yr) and an older group (mean age, 51.0 yr). On 2 separate occasions, they received an i.v. bolus of either GH (200 micrograms) or saline followed by blood sampling for 5 h. Glucose turnover was estimated by infusion of [3-3H]glucose, and indirect calorimetry was performed before and 2 h after the bolus infusions. Body composition (computed tomography scan and dual energy x-ray absorptiometry) was performed at baseline. Baseline levels of serum insulin-like growth factor I (IGF-I) was lower in older subjects, whereas circulating IGF-binding protein-1 and lipid intermediates were lower in males than in females. The area under the GH curve was lower in older subjects (young, 3978 +/- 1532 micrograms/L.24 h; older, 1144 +/- 79; P = 0.001), whereas the elimination half-life did not differ with age (young, 18.1 +/- 0.9 min; older, 16.4 +/- 0.8; P = NS). The MCR and apparent distribution volume of GH were higher in older subjects [MCR: young, 0.11 +/- 0.02 min/L; older, 0.19 +/- 0.01; P = 0.001; apparent distribution volume: young, 2.5 +/- 0.4 L; older, 4.5 +/- 0.3; P < 0.001). Both MCR and Vd correlated inversely with age and positively with indexes of adiposity. GH significantly increased lipid intermediates, but the response was higher in young subjects and males. By contrast, the ability of GH to acutely suppress IGF-binding protein-1 was more pronounced in older subjects and females. Serum levels of insulin and IGF-I did not differ significantly between GH and saline treatment groups. GH decreased the respiratory exchange ratio and increased resting energy expenditure, with no age or gender differences. A gradual decline over time in plasma levels and rate of turnover of glucose was recorded after both GH and saline. The following conclusions were reached. 1) The MCR and Vd of GH increase with age and correlate positively with fat mass. 2) Older subjects are responsive to the acute lipolytic effects of GH, but the response is higher in young subjects and in males. 3) Adipose tissue may be actively involved in the distribution and clearance of GH. 4) Age, sex, and body composition interact with GH in a complex manner, involving clearance, distribution, and metabolic actions of the hormone.

Abstract: OBJECTIVE: We carried out two studies (a and b) to assess general practitioners' attitudes towards a) regionally developed guidelines and b) guidelines developed by the Danish College of General Practitioners. DESIGN: a) A randomized study among all GPs in Aarhus county comparing their attitudes towards guidelines in general and towards regional multidisciplinary developed guidelines on Pap-testing for cervical cancer, and b) a survey among all Danish GPs on attitudes towards earlier submitted guidelines for diabetes Type 2. SETTING: GPs in Aarhus county and in all Denmark. SUBJECTS: a) Questionnaires sent to 370 doctors in Aarhus county, and b) to 3471 GPs in all Denmark. MAIN OUTCOME MEASURES: a) Attitudes to the known Pap guidelines compared with general attitudes. Themes in question were acceptance of guidelines, acceptance of multidisciplinary involvement, especially from the administrative staff, perceived effect on the consultation and the quality of care. In study b) remembrance of receiving, having read and used previous guidelines. Wishes with respect to future updates. RESULTS: a) GPs were very positive towards the Pap guidelines they knew, and only few resisted. The number of positive answers was significantly fewer when doctors were asked about guidelines in general. b) There was an overwhelmingly positive attitude towards guidelines from the College on diabetes care and other topics relevant to GP work. CONCLUSION: Danish GPs reported a very positive attitude towards the presented well-known guidelines on Pap testing and diabetes Type 2, and a fairly positive attitude towards hypothetical questions on guidelines in general.

Abstract: A study was carried out to investigate people's interest in participating in health check-up and in discussions about health with their own general practitioner, participants' health status, the proportion who received health advice following health check-up, and the lifestyle goals they set following discussion with their general practitioner. This study reports the baseline data from a five-year randomized, controlled, prospective, population-based study in general practices in Ebeltoft, Denmark. All general practitioners from the four practices in Ebeltoft and a random sample of 2,000 people aged between 30 and 50 years were invited to participate. Participants were randomly divided into three groups-one control group and two intervention groups. One intervention group was given a health check-up which included a range og tests (Table 2 and 3); this group received written feedback from the general practitioner. The other intervention group was also given a health check-up and written feedback, in addition, they were given the opportunity to attend their general practitioner to discuss health-promoting measures. A total of 1370 people participated in the study (69% response rate). Health advice was given to 76% of 905 participants following health check-up. Almost all of the 456 participants (96%) who were offered the opportunity of discussing their health with their general practitioner took up the offer: 64% of the 456 participants reported that they had decided to undertake lifestyle changes. Eleven of those who discussed their health with the doctor were referred to a specialist (2%). There was considerable interest in participating in health promotion. Three out of four of those who had a health check-up were given health advice. Two out of three of those who were offered a health talk with the general practitioner appeared willing to make relevant lifestyle changes. Longterm follow up is needed to determine effects and side effects of health check-up and health talks.

Abstract: OBJECTIVES: To investigate (a) whether there is a causal link between smoking and low back pain (LBP), (b) whether smoking is uniquely associated with symptoms in the lumbar spine and (c) the role of respiratory problems in the possible link between smoking and LBP. STUDY DESIGN: Data were collected through questionnaires in a cross-sectional study of a representative sample of the general Danish population, consisting of 1370 men and women aged 30-50 yr, with a response rate of 69%. BACKGROUND: In some epidemiological studies (mostly those of cross-sectional design) smoking has been associated with LBP; this association, however, is not consistently present in all reports. Several theories exist that attempt to explain a possible association between the two; only rarely have these theories been systematically tested. However, cross-sectional data can also be used to obtain answers to questions relating to causes and mechanisms. METHOD: A list of expectations was produced that related to three hypotheses previously forwarded in the epidemiological literature. The fit of the data in the present study was then considered in the light of these expectations. RESULTS: There is evidence in favor of a causal link between smoking and some definitions of LBP. Smoking was not uniquely associated with the lumbar spine. Respiratory symptoms seemed to be positively associated with LBP but only when linked with smoking. CONCLUSIONS: The clinical significance of these findings is limited, but it needs to be considered in future research. Abstinence from smoking may, however, be a useful means of primary prevention of certain types of LBP.

Abstract: STUDY DESIGN: Data were obtained in a Danish cross-sectional postal survey and compared with information from four methodologically similar studies conducted in some of the Nordic countries between 1977-1985. OBJECTIVES: The objectives were to estimate the lifetime cumulative incidence and the 1-year period prevalence of low back pain in the general population, to study whether there are any differences in the occurrence of low back pain according to age and sex, and to investigate whether low back pain is on the increase. SUMMARY OF BACKGROUND DATA: The prevalence of low back pain commonly is thought to be high, but estimates differ considerably between studies. It is also not known whether low back pain is more common in men or women or in certain age groups, and it is unclear whether the prevalence of low back pain has increased in the past years. METHODS: Prevalence estimates were established in a current study, and results then were adjusted to suit the age and sex criteria of four previous studies. RESULTS: Between 60-65% of 30- to 50-year-old men and women living in the Nordic countries reported at least one incident of low back pain during their lifetime, based on the information from four studies with a total sample size of 3513. The most likely 1-year period prevalence estimate is between 44-54%, based on two studies and a total sample of 2035 individuals. There was no consistent evidence favoring higher figures with increasing age or relating to any of the genders. No clearly observed time-related trend was noted. CONCLUSIONS: When data were examined from five methodologically similar studies on the 30- to 50-year-old Nordic population, there was reasonable consistency of prevalence figures. Thus, approximately 66% report having had low back pain at least sometime during their lifetime and approximately 50% sometime during the preceding year, with no significant differences relating to age or sex. The best method to investigate whether low back pain is on the increase might be through replicate studies.

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Abstract: BACKGROUND. There is increasing political pressure on the medical profession to approach welfare diseases, such as coronary heart disease and diabetes, through prevention. General practitioners are required to offer regular health checks to healthy people, in spite of the lack of scientific evidence for the universal need, usefulness and side effects of such an intervention. Randomized controlled trials are needed. AIM. A study was carried out to investigate people's interest in participating in health checks and in discussions about health with their own general practitioner, participants' health status, the proportion who received health advice following health checks, and the lifestyle goals they set following discussion with their general practitioner. This study reports the baseline data from a five-year randomized, controlled, prospective, population-based study in general practices in Ebeltoft, Denmark. METHOD. All general practitioners from the four practices in Ebeltoft and a random sample of 2000 people aged between 30 and 50 years were invited to participate. Participants were randomly divided into three groups--one control group and two intervention groups. One intervention group were given a health check which included being screened for cardiovascular risk factors, lung and liver function, fitness, sight and hearing and an optional test for the human immunodeficiency virus (HIV); this group received written feedback from the general practitioner. The other intervention group were also given a health check and written feedback; in addition, they were given the opportunity to attend their general practitioner to discuss preventive health. RESULTS. A total of 1370 people participated in the study (69% response rate). Health advice was given to 76% of 905 participants following health checks. Almost all of the 456 participants (96%) who were offered the opportunity of discussing their health with their general practitioner took up the offer; 64% of the 456 participants reported that they had decided to undertake lifestyle changes. Eleven of those who discussed their health with the doctor were referred to a specialist (2%). CONCLUSION. There was considerable interest in participating in health promotion. Three out of four of those having a health check were given health advice. Two out of three of those offered a health talk with the general practitioner appeared willing to make relevant lifestyle changes. Long-term follow up is needed to determine effects and side effects of health checks and health talks.

Abstract: In Denmark the co-operation between the primary and secondary health care system is organized through referrals. Recommendations for improving interaction between the diabetes team (diabetologists, diabetes nurses, dietitians, chiropodists etc.) at the diabetes clinic, and general practice have been prepared by a working party for the Danish National Board of Health. General recommendations: (a) Appointment of a liaison committee in each county consisting of general practitioners (GPs), diabetologists, administrators, etc. (b) Employment of a GP at the diabetes clinic to take care of improving communication, teaching, research, quality assessment, etc. (c) Referral of all newly diagnosed patients with Type 1 diabetes and younger or complicated patients with Type 2 diabetes to the diabetes clinic. More far-reaching forms of co-operation to be discussed in the liaison committees include: (a) Based upon his own knowledge of where to look for help to solve a specific health problem, the diabetic patient may on his own initiative consult either the diabetes clinic or general practice. (b) Provision of access to consult the diabetes nurse/dietitian at the diabetes clinic for instruction without a formal referral. (c) Patients treated solely in general practice and thus unknown to the diabetes clinic may be referred or reported systematically to the diabetes clinic.

Abstract: Albumin-creatinine ration (ACR) has been correlated to increased morbidity and mortality in diabetic as well as in nondiabetic populations. We investigated the albumin-creatinine ratio in 898 randomly selected persons aged 30-50 years, 471 women and 424 men (year 0). ACR was remeasured 1 year later in 811 (90%) of these persons (year 1). This was done in the framework of a prospective, randomized, population-based intervention trial evaluating the effect of health test and health conversations in general practice. The mean age of the study population was 39.8 (range, 30-51) years with a mean body mass index of 24.3 (15.9-44.3) kg/m2. The 50th, 95th, and 99th percentiles of ACR were 0.6, 2.0, and 5.0 mg/mmol at year 0 and 0.5, 2.0, and 5.3 mg/mmol at year 1. There was no significant difference between ACR values at year 0 and year 1. ARC values were slightly higher in women than in men, 0.6, (0.2-20.4) mg/mmol versus 0.5 (0.2-16.3) mg/mmol (p < 0.001, median and range). Albumin concentrations were slightly higher in men than in women 8.0 (2.0-196.0) mg/mmol versus 6.5 (2.0-121.0) micrograms/mL, p < 0.001. The correlation between ACR values measured year 0 versus year 1 was 0.43, p < 0.001 (Spearman rho). The agreement from year 0 to year 1 between normal ACR values (< or = 2.5 mg/mmol) and abnormal values (> 2.5 mg/mmol) were 0.33 expressed by Cohen's kappa.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: We re-examined 69 of the 70 patients entering the two independent Steno Studies of effects of improved metabolic control on progression of late diabetic complications. They were analysed according to an intent to treat after follow-up for 8 years (Steno Study 1) and 5 years (Steno Study 2). The glycaemic control had improved in the insulin infusion group compared with the conventional treatment group (mean HbA1c) by 2.0 +/- 0.6% vs 0.7 +/- 1.2 in Steno Study 1 and by 1.8 +/- 1.2% vs 0.4 +/- 1.3 (p less than 0.01) in Steno Study 2. In the insulin infusion groups three patients had died during episodes of ketoacidosis. These were not caused by malfunction of the insulin infusion pumps. In the conventional treatment groups, three patients suffered five cardiovascular events causing two deaths. From the sixth month of Steno Study 1 the annual change of the glomerular filtration rate was -3.7 (-5.4 to -2.0) ml.min-1.1.73 m-2 vs -1.0 (-2.1 to -0.1) (conventional vs insulin infusion group, mean (95% confidence interval, p less than 0.01]. The change in urinary albumin excretion was associated with the glycaemic control (n = 69, r = 0.49, p less than 0.0002). No progression was observed among 32 patients with low range microalbuminuria (30 to 99 mg/24 h).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH injections revealed no side-effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short-term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract: Since serum GH in normal subjects displays a circadian variation with a major and consistent surge after the onset of sleep we examined whether the time of GH administration in GH-deficient patients had any impact on its action. Eight GH-deficient patients all underwent 3 4-week study schedules in random order: 1) evening (2000 h) sc GH injections, 2) morning (0800 h) sc GH injections, and 3) no GH administration. At the end of each period the patients were admitted to hospital for 24-h measurements of hormones and metabolites. For comparison, 10 age- and sex-matched healthy untreated subjects were hospitalized once under identical conditions. Mean (+/- SE) GH availability, i.e. the area under the curve (AUC; micrograms per L/12 h) for 12 h after injection was significantly greater after evening injection than after morning injections [83.3 +/- 25.4 (evening) vs. 46.0 +/- 10.6 (morning); P less than 0.01]. This might be due to higher skin and sc temperatures when in bed. The 2000-0800 h AUC after evening injection was similar to the corresponding AUC in the reference group. Mean 24-h serum insulin-like growth factor-I levels (micrograms per L) were similar after evening (189.8 +/- 2) and morning (179.5 +/- 5.3) injections (P = 0.8), but the latter displayed a circadian variation suggesting that a steady state had not been reached. Both were significantly lower than the stable reference value (248.4 +/- 3.6 micrograms/L). Blood glucose profiles after morning and evening GH did not differ from that of the reference group, whereas blood glucose decreased when the patients received no GH (P less than 0.01). Daytime (0800-2400 h) insulin levels were increased after morning injections (P less than 0.05). Nighttime levels of lipid intermediates were below normal in the untreated state and after morning injection (P less than 0.05), whereas nighttime blood alanine tended to be above normal after morning GH injection (P = 0.08). Highly significant inverse relationships between circadian lipid intermediates and both blood alanine and lactate concentrations were observed in the reference group and in the patients after evening injections. These relationships disappeared after morning injections. We conclude that the metabolic effects of sc GH injections are clearly influenced by the time of administration and that the closest similarity to normal hormone and metabolite patterns and relationships is reached by GH injection in the evening in GH-deficient patients.

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Abstract: The episodic and pulsatile nature of GH secretion in normal man is well established. Studies in hypophysectomized rats have indicated that pulsatile administration of GH is superior to continuous infusion in promoting growth, but similar studies have not yet been conducted in human subjects. We compared three different iv GH administration schedules in six GH-deficient patients. They were hospitalized three times for 44 h on three occasions, separated by at least 4 weeks without GH treatment. On each occasion they received 2 IU GH, administered iv as either 1) two boluses (at 2000 and 0200 h), 2) eight boluses (at 3-h intervals starting at 2000 h), or 3) a continuous (2000-0200 h) infusion. Serum insulin-like growth factor-I (IGF-I) after eight boluses and that after continuous infusion were almost identical, with a steep increase reaching a peak at 2000-2400 h, followed by a steady decline. The total areas under the curve, expressed as mean levels (micrograms per L), were 147.6 +/- 11.8 (eight boluses) and 151.2 +/- 8.9 (infusion; P = NS). The change with time in IGF-I after the two-bolus regimen differed significantly from that in the other studies (P less than 0.001), displaying only a modest increase, as also reflected in a smaller area under the curve of serum IGF-I (125.3 +/- 8.7 micrograms/L; P less than 0.05). No differences in blood glucose, serum insulin, or plasma glucagon were observed when comparing the three studies. Both blood glucose and serum insulin tended to be elevated during the second night of each study. Almost identical fluctuations were recorded in lipid intermediates in the three studies, with nightly elevations being more pronounced on the first night. Alanine and lactate exhibited nearly identical patterns in the three studies and were characterized by low nocturnal levels. These data indicate that small but frequent iv boluses and continuous infusion of GH are equally effective in generating an increase in IGF-I in GH-deficient patients, whereas the same amount of GH given as two large boluses results in a significantly smaller increase in IGF-I. This could mean that a prolongation of the period during which serum GH is above zero in GH-treated subjects is just as essential as pulsatility for the growth-promoting effects of the hormone.

Abstract: Seven insulin-dependent diabetic patients (mean age 36 years and mean duration of diabetes 19 years) underwent intensified treatment with continuous subcutaneous insulin infusion (CSII) for one week. The patients were selected for the study due to long-standing hypergycemia in an endeavour to determine possible influence on retinal neurosensory function by even short-term near-normalization of blood glucose concentrations. During CSII treatment, near-normalization of the blood glucose levels was obtained (mean blood glucose concentration before treatment; 13.7 +/- 1.6 mmol/l-during treatment; 6.3 +/- 0.4 mmol/l. Recording of the oscillatory potentials by electroretinography and the macular recovery by nyctometry remained about the same in the course of this short-term treatment. Our study suggests that short-term strict metabolic control does not reverse the retinal neural abnormalities in long-standing insulin-dependent diabetes. Consequently; this regimen does not enable prediction of possible beneficial effect of sustained near-normoglycemic treatment.

Abstract: The aim of the present study was to look further into the question of local degradation of sc injected human GH in GH deficient patients. A comparison was made of serum GH levels after constant iv and sc infusion of the same amount of GH (33 ng.kg-1.min-1) in the same 9 GH deficient patients. A 3-h lag period was interposed between the iv and the sc infusion. Iv infusion was continued for 3 h. All 9 subjects subsequently received sc infusion for 19 h and five of them continued for additionally 24 h. The mean steady state serum GH level in the nine patients was 23.1 +/- 5.1 micrograms/l after iv and 6.8 +/- micrograms/l after sc administration (P less than 0.01). Extension of the sc infusion period in 4 of the subjects did not significantly alter the serum GH level (P less than 0.15), implying that a steady state was reached. The GH in the infusion system was stable throughout a 24-h period. We therefore conclude that sc injected GH is degraded locally to a substantial extent.

Abstract: Increasing doses of biosynthetic human GH (R-hGH) were given sc to seven GH-deficient patients for three consecutive 14-day periods (2, 4, and 6 IU/day at 2000 h), followed by 14 days of no GH therapy. At the end of each period each patient was hospitalized for frequent blood sampling from 2000 to 1100 h the following day. A dose-dependent increase in serum GH and serum insulin-like growth factor I (IGF-I) levels occurred. However, the time course of the serum IGF-I concentrations was different on the four occasions; there was a significant fall in the evening when no therapy was given (P less than 0.01), a significant increase after injections of 2 IU R-hGH, and constant levels during treatment with 4 and 6 IU R-hGH. Plasma glucose levels were within the normal range, with a significantly lower fasting level (at 0400 h) when no GH was given. Breakfast induced a plasma glucose rise when GH was administered, but no rise without GH, and a postprandial serum insulin response that was GH dose dependent. GH therapy increased serum FFA (P less than 0.05) and blood 3-hydroxybutyrate levels, but had no effect on blood alanine or lactate or serum triglyceride and cholesterol levels. We conclude that the serum IGF-I response to GH is dose dependent, and that a GH replacement dose of 2 IU/day (equalling 1.5 IU/m2.day) is insufficient to maintain normal diurnal serum IGF-I levels. Furthermore, a GH-independent diurnal variation in serum IGF-I in these patients is suggested. This GH preparation also has diabetogenic and lipolytic actions.

Abstract: The frequency and distribution of daytime biochemical hypoglycaemia (capillary blood glucose concentration below 3 mmol/l) was assessed in type 1 diabetic patients on conventional twice daily insulin therapy (n = 79) and on continuous subcutaneous insulin infusion (n = 20). Patients collected and mailed to the hospital blood for seven-point blood glucose profiles. For both treatment regimens the frequency of biochemical hypoglycaemia on individual days was inversely related to the median blood glucose concentration in a curvilinear manner (p less than 0.001). Hypoglycaemia was more frequent pre-prandially than post-prandially (p less than 0.01), and was evenly distributed during the day in patients on continuous subcutaneous insulin infusion. In patients on conventional therapy, however, pre-lunch hypoglycaemia was four times more frequent than pre-breakfast or pre-dinner hypoglycaemia (p less than 0.0001).

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Abstract: To determine possible quantitative changes of the blood-retinal barrier permeability in juvenile diabetics treated with continuous subcutaneous insulin infusion (CSII), we studied seven patients (three females and four males, mean age 36 years) with a mean duration of the disease of 19 years. The pump treatment was continued for seven to eight days and during the treatment mean blood glucose level decreased to near-normal values (before 13.7 mmol per liter - during 6.2 mmol per liter). There was no changes in retinal appearance during treatment. Determination of the blood-retinal barrier permeability showed no quantitative changes during the one week treatment with CSII (mean permeability before 7.6 10 divided by 7 cm/sec - mean permeability during 7.8 10 divided by 7 cm/sec). In order to quantitate possible long-term reversibility of break-down of the blood-retinal barrier we have design to extend the treatment period.

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Abstract: Thirty patients with insulin-dependent diabetes mellitus (IDDM) who had advanced background retinopathy were randomized to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 2 yr. The mean blood glucose and hemoglobin A1C (HbA1C) were significantly lower in the CSII group than in the UCT group. The mean blood glucose and HbA1C did not change from the first to the second year in either of the treatment groups in spite of less frequent home-monitoring of blood glucose and less frequent outpatient visits during the second year. Four patients in the CSII group and five in the UCT group developed proliferative retinopathy. However, a marginally significant trend was found toward more frequent improvement of retinal morphology in the CSII group (47%) than in the UCT group (13%). Beat-to-beat variation was found to deteriorate significantly with UCT compared with a nonsignificant improvement with CSII therapy. Vibration sense was unchanged in both treatment groups. It is concluded that near-normal blood glucose levels can be maintained with CSII therapy in spite of less frequent home-monitoring of blood glucose and outpatient visits. Furthermore, established background retinopathy may progress to proliferative retinopathy in spite of 2 yr of near-normal blood glucose levels. However, a marginally significant trend toward more frequent improvement of retinal morphology was found among CSII-treated patients compared with conventionally treated patients. Large-scale, prospective, randomized studies are needed to confirm these results.

Abstract: A double-blind cross-over study of the sc absorption of radiolabelled semi-synthetic human (SHI) and purified porcine (PPI) insulin was made. Absorption of both isophane (n = 10) and soluble insulin (n = 8) was studied. There was no significant difference between the disappearance from the injection site, the plasma free insulin concentrations, or blood glucose levels after sc injection of the isophane preparations. A faster disappearance of the soluble SHI (as judged from T/50 and AUC) was found (both P-values less than 0.01). However, no difference was observed between the plasma insulin concentrations at any time point (P less than 0.05). Blood glucose levels showed no statistical differences between the two soluble preparations. The data indicate minor differences between the pharmacokinetics of SHI and PPI, but these seem of no clinical importance.

Abstract: Long-term near-normal blood glucose regulation is possible with portable insulin pumps, and this treatment is acceptable to patients, but is also expensive. The pharmacokinetic difference between continuous subcutaneous insulin infusion and conventional injection therapy is discussed and can explain the difference between the obtained levels of blood glucose control. One-year near-normal blood glucose regulation cannot prevent the development of proliferative retinopathy in patients with established diabetic background retinopathy. Long-term large-scale prospective clinical trials are needed to evaluate whether strict metabolic control can prevent, delay, arrest, or even reverse microvascular complications. Furthermore, the side effects of the pump treatment need to be clarified before routine use of continuous subcutaneous insulin infusion. While awaiting these studies, the only indication for pump therapy in routine clinic is considerable glycaemic instability which is incompatible with leading a normal life.

Abstract: Where adjustments of diet, physical activity, and dosage of insulin are well known to diabetologists and diabetic patients, present-day knowledge of factors of importance to the pharmacokinetics of insulin is frequently ignored. The pharmacokinetics of insulin comprise the absorption process, the distribution including binding to circulating insulin antibodies, if present, and to insulin receptors, and its ultimate degradation and excretion. The distribution and metabolism of absorbed insulin follow that of endogenous insulin. The distribution and metabolism cannot be actively changed, except in the case of circulating insulin antibodies, which in rare cases also may cause insulin resistance. The use of insulin preparation of low immunogeneity will avoid or reduce this course of variation in action. The absorption process, the detailed mechanisms of which are still unknown, is influenced by many variables where some can be controlled, thereby reducing the intrapatient variability in insulin absorption, which may reach 35%, causing a corresponding metabolic lability. Besides the known differences in timing among different preparations, the size of dose, the injected volume, and the insulin concentration are determinants of absorption role. Fortuitous injection technique contributes to variance, as do changes in blood flow of the injected tissue. This may be induced by changes in ambient temperature, exercise of injected limb, or local massage. Regional differences are also due to differences in blood flow. Serum insulin peaks may peak up to 1 h after injection of soluble insulin into the thigh versus into the abdominal wall. Local degradation of insulin seems of less importance but may, in rare cases, be the cause of high insulin "requirements." Available evidence is reviewed and the importance of implementing the consequences in the daily care of the insulin-treated patient is emphasized.

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Abstract: One of the reasons for the variability of blood glucose regulation in Type 1 (insulin-dependent) diabetic patients is the huge variation in subcutaneous absorption of intermediate-acting insulin. We have investigated the variation in insulin absorption during continuous subcutaneous insulin infusion in eight such patients. The content of insulin in the subcutaneous tissue was measured using 125I-labelled insulin. The concentration of free serum insulin and blood glucose was followed from 1 h before and from 7 h after breakfast on two consecutive days. The amount of insulin absorbed during 24 h differed in all cases by less than 3% from the daily insulin dose given by the pumps. Mean insulin absorption rates and mean free insulin concentration showed peak values 30-90 min after meal bolus injections; this was sufficient to maintain near-normal blood glucose. Mean free serum insulin correlated strongly with disappearance of insulin from the subcutaneous tissue (r = 0.98). From the insulin absorption rates and free insulin concentrations during basal constant insulin infusion, the half-time of serum insulin was calculated as 6 min. Compared with the known large variability in the absorption of intermediate-acting insulin, continuous subcutaneous insulin infusion offers a precise and reproducible way of insulin administration resulting in post-prandial serum insulin peaks sufficient to maintain near-normal blood glucose levels. The half-time of serum insulin during subcutaneous infusion corresponds to values for intravenous infusion given in the literature, indicating that local degradation of insulin in subcutaneous tissue is of minor importance.

Abstract: 30 insulin-dependent diabetic patients with background retinopathy were randomised to conventional treatment (UCT) or treatment with continuous subcutaneous insulin infusion (CSII). They were followed prospectively for 1 year with fortnightly seven-sample home blood glucose measurements and retinal examinations every 6 months. Mean blood glucose and stable haemoglobin A1c during months 3-12 were significantly lower in the CSII than the UCT group. Retinal morphology deteriorated during the year with no significant differences between UCT and CSII groups. The frequency of deterioration was highest in the CSII group, especially among the 10 patients with best glycaemic control. Proliferative retinopathy developed in 3 patients--2 of these were CSII treated. Retinal function (oscillatory potential, macular recovery time, and posterior vitreous fluorophotometry) improved significantly with CSII treatment and deteriorated significantly with UCT. Changes in retinal function were most pronounced in patients with the best and the poorest regulated glycaemic control.

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Abstract: A total of 35 experiments in which insulin-dependent diabetics were connected to an artificial beta cell (Biostator) for feedback control of blood glucose during at least 24 h, were evaluated. Only 14 experiments, however, were available for analysis, since interruptions of more than 45 min/24 h in feedback control due to clots in analyser tubing occurred in those remaining. In these 14 experiments the 24-h insulin-infusion pattern was analysed. Basal insulin requirements (BIR), (between 01.00 and 04.00 hours) was found to be 0.178 +/- 0.044 (SD) mU/kg X min. Insulin requirements increased in the early morning (04.00-07.00 hours) to 0.231 +/- 0.084 mU/kg X min (P less than 0.01). A significant correlation between BIR and 24-h insulin requirement was found (r = 0.53, P less than 0.05). Insulin requirements per kJ following breakfast were higher than after lunch, 0.57 +/- 0.20 muU/kg X min X kJ versus 0.41 +/- 0.29 muU/kg X min X kJ (P less than 0.05).

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Abstract: Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A1c = 2.07 X mean blood glucose0.596, r = 0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.

Abstract: Ten randomly selected insulin-dependent diabetics with minimal betacell function were studied during treatment with an artificial betacell during two consecutive 24-hour periods. Patients were randomly served diabetic diet for one 24-hour period and average Danish food during the other 24-hour period. No significant (P greater than 0.05) difference was found between the mean blood glucose concentrations, nor insulin requirements on average Danish food compared to diet. However, the mean amplitude of glucose excursions was significantly higher on average Danish food than on diabetic diet (median 3.6 versus 2.7 mmol/l, P less than 0.05). Thus insulin-dependent patients not following their diabetes diet will show increased blood glucose fluctuations.

Abstract: Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.

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Abstract: The interaction between variation in insulin absorption and beta-cell function was studied as well as the possible relation between subcutaneous blood flow through the region of injection and the variability in insulin absorption. The results indicate that the dose of insulin, the type of insulin preparation and the local blood flow influence the insulin absorption. Residual endogenous insulin secretion, governed by the blood glucose values, serves as a modulator.

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Abstract: The absorption of monocomponent porcine 125I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125I-insulin dose. A significant correlation (p less than 0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.

Abstract: In a retrospective survey of 202 patients with acute cholecystitis 40 patients (19,8%) were found to have common duct stones. No close correlation between common duct stones and either serum bilirubin or serum alkaline phosphatase could be demonstrated. Therefore it was concluded that peroperative cholangiography is necessary in operations for acute cholecystitis.

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Abstract: In 1976 we reviewed a randomly selected cohort of 227 patients with duodenal ulcer first diagnosed in 1963. The cohort comprised cases diagnosed in both hospitals and general practice. Fifty patients had died, 12 had emigrated, and 154 (93%) of the remaining patients were interviewed. Fifty-seven medically treated patients had no symptoms, 44 had mild symptoms, and 19 had more severe symptoms. The remaining 34 patients had been treated surgically. Cases diagnosed in hospital had a more severe prognosis than those diagnosed in general practice. A random sample of 65 general practitioners and 78 medical and surgical gastroenterologists tried to predict the results of this study. The range of the predictions was very wide showing that individual prognostic estimates were highly unreliable. The mean prediction by all doctors differed little from the actual result, suggesting that the collective experience of the medical profession is more reliable. The predictions of general practitioners, physicians, and surgeons showed small systematic differences, presumably reflecting the different types of patients they treat.

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