Leptin predicts the development of diabetes in Mauritian men, but not women: A population-based study

Department of Dental Public Health, University of Helsinki, Helsinki, Uusimaa, Finland
International Journal of Obesity (Impact Factor: 5). 07/2007; 31(7):1126-33. DOI: 10.1038/sj.ijo.0803561
Source: PubMed


To determine if levels of the adipocyte-derived hormone, leptin, predict the development of type 2 diabetes.
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.
In total, 456 subjects developed diabetes over 11 years with similar incidences in all ethnic groups (P=0.2). Baseline leptin correlated positively with anthropometric measurements, fasting and postload insulin and homeostasis model assessment indices (all P<0.001), and inversely with subsequent weight increase. Participants with incident diabetes had higher serum levels of leptin at baseline than those remaining nondiabetic (P<0.001). 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.
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.

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Available from: George Alberti, Apr 16, 2014
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    • "Visceral obesity has been associated with insulin resistance (Yamashita et al., 1996). Indeed, it has been shown that leptin plays a role in modulating insulin action and sensitivity, and has been related to the emergence of insulin resistance and subsequent type 2 diabetes (Söderberg et al., 2007). Taking into account that the APOE3 genotype appears to more efficiently harvest dietary energy through fat deposition, we hypothesize that apoE3 isoform expression aggravates insulin resistance and subsequent type 2 diabetes following CPF exposure. "
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    ABSTRACT: Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Our recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Thus, we aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. We examined body weight status, food and water intake, lipid and glucose homeostasis, metabolic biomarkers concentrations, insulin levels and insulin resistance, and leptin and ghrelin profiles. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health. Copyright © 2015 Elsevier Inc. All rights reserved.
    Environmental Research 07/2015; 142:169-76. DOI:10.1016/j.envres.2015.06.036 · 4.37 Impact Factor
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    • "However, these studies have not adjusted for various body composition parameters. Soderberg et al. (29) demonstrated that leptin predicts development of diabetes in South Asian men in Mauritius independent of waist circumference and BMI. Therefore, it appears that adipokines in association with adiposity influence the development of diabetes. "
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    ABSTRACT: To investigate whether leptin and adiponectin are associated with body fat composition in a South Asian population independent of metabolic variables. Cross-sectional study. 150 South Asian men and women, between the ages of 45-79 years, in the San Francisco Bay Area without pre-existing clinical cardiovascular disease. Blood samples were obtained to measure glucose metabolism variables, lipid profiles and adipokines. Total body fat was determined using dual-energy X-ray absorptiometry. Abdominal computed tomography was used to measure subcutaneous, visceral and hepatic fat. Average body mass index (BMI) was overweight at 26.1±4.6 kg m(-2) and did not differ by sex. However, women had significantly more total body fat (P<0.001) and subcutaneous fat (P<0.001) than men, whereas men had significantly more visceral fat (P<0.001) and hepatic fat (P=0.04) than women. Women had significantly higher levels of adiponectin (P<0.01) and leptin (P<0.01). In sex-stratified analyses, leptin was strongly associated with all-body composition measures in women (P<0.05) as well as in men (P<0.05 except for hepatic fat), whereas there was an insignificant trend towards an inverse association between adiponectin and body composition in both women and men, which was significant in combined bivariate analyses. In multivariate analyses, leptin was strongly associated with all measures of adiposity, including BMI (P<0.001), total body fat (P<0.001), visceral fat (P<0.001) and hepatic fat (P=0.01). However, adiponectin's inverse association with adiposity was significantly attenuated by high-density lipoprotein (HDL), triglycerides and insulin resistance. The association between adipokines and diabetes was markedly attenuated after adjusting for body composition. Despite only modestly elevated BMI, South Asians have elevated levels of total and regional adiposity. Leptin is strongly associated with adiposity, whereas adiponectin's association with adiposity is attenuated by metabolic variables in South Asians. Adipokines in association with adiposity have an important role in the development of diabetes.
    International journal of obesity (2005) 08/2011; 36(6):810-6. DOI:10.1038/ijo.2011.167 · 5.00 Impact Factor
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    ABSTRACT: In humans with a loss of uricase the final oxidation product of purine catabolism is uric acid (UA). The prevalence of hyperuricemia has been increasing around the world accompanied by a rapid increase in obesity and diabetes. Since hyperuricemia was first described as being associated with hyperglycemia and hypertension by Kylin in 1923, there has been a growing interest in the association between elevated UA and other metabolic abnormalities of hyperglycemia, abdominal obesity, dyslipidemia, and hypertension. The direction of causality between hyperuricemia and metabolic disorders, however, is unceartain. The association of UA with metabolic abnormalities still needs to be delineated in population samples. Our overall aims were to study the prevalence of hyperuricemia and the metabolic factors clustering with hyperuricemia, to explore the dynamical changes in blood UA levels with the deterioration in glucose metabolism and to estimate the predictive capability of UA in the development of diabetes. Four population-based surveys for diabetes and other non-communicable diseases were conducted in 1987, 1992, and 1998 in Mauritius, and in 2001-2002 in Qingdao, China. The Qingdao study comprised 1 288 Chinese men and 2 344 women between 20-74, and the Mauritius study consisted of 3 784 Mauritian Indian and Mauritian Creole men and 4 442 women between 25-74. In Mauritius, re-exams were made in 1992 and/or 1998 for 1 941 men (1 409 Indians and 532 Creoles) and 2 318 non pregnant women (1 645 Indians and 673 Creoles), free of diabetes, cardiovascular diseases, and gout at baseline examinations in 1987 or 1992, using the same study protocol. The questionnaire was designed to collect demographic details, physical examinations and standard 75g oral glucose tolerance tests were performed in all cohorts. Fasting blood UA and lipid profiles were also determined. The age-standardized prevalence in Chinese living in Qingdao was 25.3% for hyperuricemia (defined as fasting serum UA > 420 μmol/l in men and > 360 μmol/l in women) and 0.36% for gout in adults between 20-74. Hyperuricemia was more prevalent in men than in women. One standard deviation increase in UA concentration was associated with the clustering of metabolic risk factors for both men and women in three ethnic groups. Waist circumference, body mass index, and serum triglycerides appeared to be independently associated with hyperuricemia in both sexes and in all ethnic groups except in Chinese women, in whom triglycerides, high-density lipoprotein cholesterol, and total cholesterol were associated with hyperuricemia. Serum UA increased with increasing fasting plasma glucose levels up to a value of 7.0 mmol/l, but significantly decreased thereafter in mainland Chinese. An inverse relationship occurred between 2-h plasma glucose and serum UA when 2-h plasma glucose higher than 8.0 mmol/l. In the prospective study in Mauritius, 337 (17.4%) men and 379 (16.4%) women developed diabetes during the follow-up. Elevated UA levels at baseline increased 1.14-fold in risk of incident diabetes in Indian men and 1.37-fold in Creole men, but no significant risk was observed in women. In conclusion, the prevalence of hyperuricemia was high in Chinese in Qingdao, blood UA was associated with the clustering of metabolic risk factors in Mauritian Indian, Mauritian Creole, and Chinese living in Qingdao, and a high baseline UA level independently predicted the development of diabetes in Mauritian men. The clinical use of UA as a marker of hyperglycemia and other metabolic disorders needs to be further studied. Keywords: Uric acid, Hyperuricemia, Risk factors, Type 2 Diabetes, Incidence, Mauritius, Chinese Ei saatavilla
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