Abstract: AIM/HYPOTHESIS: Leptin has been shown to regulate angiogenesis in animal and in vitro studies by upregulating the production of several pro-angiogenic factors, but its role in regulating angiogenesis has never been studied in humans. METHODS: The potential angiogenic effect of two doses of metreleptin (50 and 100Â ng/ml) was evaluated in vitro, using a novel three-dimensional angiogenesis assay. Fifteen healthy, normoleptinaemic volunteers were administered both a physiological (0.1Â mg/kg) and a pharmacological (0.3Â mg/kg) single dose of metreleptin, in vivo, on two different inpatient admissions separated by 1-12Â weeks. Serum was collected at 0, 6, 12 and 24Â h after metreleptin administration. Twenty lean women, with leptin levels <5Â ng/ml, were randomised in a 1:1 fashion to receive either physiological replacement doses of metreleptin (0.04-0.12Â mg/kg q.d.) or placebo for 32Â weeks. Serum was collected at 0, 8, 20 and 32Â weeks after randomisation. Proteomic angiogenesis array analysis was performed to screen for angiogenic factors. Circulating concentrations of angiogenin, angiopoietin-1, platelet derived endothelial factor (PDGF)-AA, matrix metalloproteinase (MMP) 8 and 9, endothelial growth factor (EGF) and vascular EGF (VEGF) were also measured. RESULTS: Both metreleptin doses failed to induce angiogenesis in the in vitro model. Although leptin levels increased significantly in response to both short-term and long-term metreleptin administration, circulating concentrations of angiogenesis markers did not change significantly in vivo. CONCLUSIONS/INTERPRETATIONS: This is the first study that examines the effect of metreleptin administration in angiogenesis in humans. Metreleptin administration does not regulate circulating angiogenesis related factors in humans. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT00140205 and NCT00130117. FUNDING: This study was supported by National Institutes of Health-National Center for Research Resources grant M01-RR-01032 (Harvard Clinical and Translational Science Center) and grant number UL1 RR025758. Funding was also received from the National Institute of Diabetes and Digestive and Kidney Diseases grants 58785, 79929 and 81913, and AG032030.
Abstract: Insulin resistance is closely associated with numerous metabolic disorders. Although studies have supported the importance of insulin resistance in carcinogenesis, the existing data have not established its relevance in the context of lung cancer. The aim of the present case-control study was to evaluate the association between insulin resistance and lung cancer after adjusting for possible confounders. Homeostasis model assessment of insulin resistance (HOMA-IR) and serum leptin and adiponectin levels were determined in 81 lung cancer cases and 162 age- and sex-matched controls; anthropometric and lifestyle variables were recorded. Mean HOMA-IR in the cases was more than 2-fold higher compared with the mean value of controls (P < .001). Among controls, HOMA-IR correlated positively with serum leptin (r = 0.16; P = .04), body mass index (r = 0.43; P = .0001), and waist-to-hip ratio (r = 0.21; P = .01) but negatively with serum adiponectin (r = -0.29; P = .0002). As expected, smoking was associated with an approximately 10-fold increase in lung cancer risk in multiple logistic regression models. A positive association between HOMA-IR, treated as continuous variable, and lung cancer (odds ratio [OR] = 1.52, 95% confidence interval [CI]: 1.16-1.99, P = .002, model 1) was demonstrated, which persisted after adjustment for somatometric and lifestyle variables (OR = 2.36, 95% CI: 1.00-5.55, P = .05, model 2). When serum adiponectin was also taken into account, the association seemed fairly robust (OR = 2.58, 95% CI: 1.11-6.01, P = .03, model 3); on the contrary, when serum leptin was added, the association remained positive, but lost its statistical significance (OR = 1.76, 95% CI: 0.78-3.98, P = .17, model 4). In the fully adjusted model, HOMA-IR was still positively, but only marginally, associated with lung cancer risk (OR = 2.02, 95% CI: 0.88-4.65, P = .10, model 5). Insulin resistance may represent a meaningful risk factor for lung cancer.
Abstract: The purpose of the study was to investigate the smoking habits of medical and other students and to explore the most important factors associated with students' smoking.
