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The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in ϳ4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. T he role of the newly described adipocyte-derived peptide adiponectin is still poorly understood. Nevertheless, its plasma concentration is decreased in patients with obesity, type 2 diabetes, or coronary artery disease (1,2). The treatment of diabetic animals with adiponectin has been shown (3,4) to improve insulin sensitivity. The adiponectin gene consists of three exons and two introns located on chromosome 3q27, where a diabetes susceptibility locus has been mapped (5,6). Single nucleotide polymorphisms (SNPs) of the adiponectin gene have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies (7-9), but these associations have not been seen in all studies (10,11). The aim of our study was to assess the effects of these polymorphisms on the 3-year evolution of features of the insulin resistance syndrome in a large Caucasian population of men and women, aged 30 -64 years, known as the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. The influence of baseline plasma adiponectin levels on the 3-year risk of developing hyperglycemia (impaired fasting glycemia or type 2 diabetes) was also estimated. RESEARCH DESIGN AND METHODSThe study population consisted of men and women, aged 30 -64 years, who participated in DESIR, a 9-year follow-up study that aims to clarify the Additional information for this article can be found in two online appendixes at http://diabetes.diabetesjournals.org. DESIR, Epidemiologic Data on the Insulin Resistance Syndrome; IFG, impaired fasting glucose; SNP, single nucleotide polymorphism; WHR, waistto-hip ratio.

Mutations in the translated part of the leptin gene (LEP) have been found in only two families. Nevertheless DNA polymorphisms in the LEP region are linked to extreme obesity. We previously found in the 5' region of LEP a polymorphism, G-2548A, associated with a differerce in BMI reduction following a low calorie diet in overweight women. Recently, this polymorphism was associated with extreme obesity in women. In this work, we genotyped a new sample from the general population including 314 normal weight (BMI < 27 kg/m2) and 109 overweight subjects (BMI > or = 27 kg/m2). The genotype and allele frequencies were significantly different between groups, with the G-2548 allele being more frequent in the overweight subjects (p < 0.01). In men, carriers of this allele had lower leptin concentrations adjusted for fat mass (p = 0.05). Our results indicate that variations at the leptin locus are associated with common obesity phenotypes, and not only with extreme obesity or the rare mendelian obesity syndromes.

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