ORIGINAL ARTICLE Leptin predicts the development of diabetes in Mauritian men, but not women: a population–based study S So ¨derberg 1,2 , P Zimmet 1 , J Tuomilehto 3 , P Chitson 4 , H Gareeboo 4 , KGMM Alberti 5 and JE Shaw 1 1 International Diabetes Institute, Melbourne, Australia; 2 Department of Public Health and Clinical Medicine, Cardiology, University of Umea˚, Umea˚, Sweden; 3 Department of Public Health, University of Helsinki, Helsinki, Finland; 4 Ministry of Health, Port Louis, Mauritius and 5 Department of Endocrinology and Metabolic Medicine, Imperial College, UK Objective: To determine if levels of the adipocyte-derived hormone, leptin, predict the development of type 2 diabetes. Methods: Population-based surveys were undertaken in the multiethnic nation of Mauritius in 1987, 1992 and 1998. Questionnaires, anthropometric measurements, and a 2-h 75-g oral glucose tolerance test were included. A cohort of 2330 participants who were free of diabetes, aged 25–79 years in 1987, and who were followed-up in 1992 and 1998 was studied. Serum leptin was measured in baseline samples. Glucose tolerance was classified according to WHO (World Health Organization) 1999 criteria. Results: In total, 456 subjects developed diabetes over 11 years with similar incidences in all ethnic groups (P ¼ 0.2). Baseline leptin correlated positively with anthropometric measurements, fasting and postload insulin and homeostasis model assessment indices (all Po0.001), and inversely with subsequent weight increase. Participants with incident diabetes had higher serum levels of leptin at baseline than those remaining nondiabetic (Po0.001). After adjustment for confounders, high leptin levels and high leptin/body mass index ratio were independently associated with incident diabetes over 11 years in men (odds ratio for top versus bottom quartile of leptin 2.18; 95% CI: 1.09–4.35), but not in women. Conclusion: We conclude that high leptin levels are associated with the future development of diabetes, and the association is independent of other factors in men, but not in women. International Journal of Obesity (2007) 31, 1126–1133; doi:10.1038/sj.ijo.0803561; published online 27 February 2007 Keywords: diabetes; leptin; prediction; epidemiology; population-based Introduction Obesity is related to reduced insulin sensitivity, hyperinsu- linemia and an increased risk of glucose intolerance. 1 The actual mediators increasing the risk of glucose intolerance in relation to obesity and the insulin resistance syndrome are not fully understood. 2 During the last decade, it has been established that fat tissue has many important metabolic and endocrine functions. Adipocyte-derived hormones such as leptin and adiponectin have been shown to be important regulators of insulin sensitivity, glucose tolerance, 3,4 vessel integrity 5,6 and lipid metabolism. 7,8 Leptin is important for the ‘communication’ between fat tissue and several metabolic pathways. Leptin deficiency in the ob/ob mice causes severe obesity, insulin resistance and the development of glucose intolerance. 9 In contrast, obesity in humans is characterized by high circulating levels of leptin owing to reduced sensitivity to leptin (leptin resis- tance) and leptin deficiency is a very rare cause of obesity in humans. 10 Flier 9 has suggested that leptin is important for the adaptation of metabolic and hormonal pathways during starvation and high levels may thus be physiologically inappropriate. This is supported by mounting experimental evidence showing that leptin may have detrimental effects on the cardiovascular system 6 and the insulin producing b- cell. 11 Indeed, we and others have shown that leptin is an independent predictor of type 2 diabetes 12 and cardiovas- cular disease 13 in men, but not women. Functional leptin receptors are expressed on the b-cell, 11,14 which could mediate effects on insulin secretion. Further- more, leptin relates experimentally to apoptosis of b-cells 15 Received 2 March 2006; revised 27 December 2006; accepted 16 January 2007; published online 27 February 2007 Correspondence: Dr S So ¨derberg, Department of Public Health and Clinical Medicine, Cardiology, Umea ˚ University Hospital, Umea ˚, SE-901 85, Sweden. E-mail: stefan.soderberg@medicin.umu.se International Journal of Obesity (2007) 31, 1126–1133 & 2007 Nature Publishing Group All rights reserved 0307-0565/07 $30.00 www.nature.com/ijo