Adiponectin is an adipose tissue-specific protein with insulin-sensitizing and antiatherogenic properties. Therefore, the adiponectin gene is a promising candidate gene for type 2 diabetes. We investigated the single nucleotide polymorphisms (SNPs) ؉45T/G and ؉276G/T of the adiponectin gene as predictors for the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial, which aimed to investigate the effect of acarbose compared with placebo on the prevention of type 2 diabetes. Compared with the TT genotype, the G-allele of SNP ؉45 was associated with a 1.8-fold risk for type 2 diabetes (95% CI 1.12-3.00, P ‫؍‬ 0.015) in the placebo group. Subjects treated with placebo and simultaneously having the G-allele of SNP ؉45 and the T-allele of SNP ؉276 (the risk genotype combination) had a 4.5-fold (1.78 -11.3, P ‫؍‬ 0.001) higher risk of developing type 2 diabetes compared with subjects carrying neither of these alleles. Women carrying the risk genotype combination had an especially high risk of conversion to diabetes (odds ratio 22.2, 95% CI 2.7-183.3, P ‫؍‬ 0.004). In conclusion, the G-allele of SNP ؉45 is a predictor for the conversion to type 2 diabetes. Furthermore, the combined effect of SNP ؉45 and SNP ؉276 on the development of type 2 diabetes was stronger than that of each SNP alone. Diabetes 54:893-899, 2005

Aim/hypothesis. We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor γ2 (PPAR-γ2; Pro12Ala) and in PPAR-γ coactivator 1α (PGC-1α; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. Methods. Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1α gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-γ2 gene was determined by the polymerase chain reaction-singlestrand conformation polymorphism analysis. Results. The Pro12Pro genotype of the PPAR-γ2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1α gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-γ2 gene, but only the carriers of the 482Ser allele of the PGC-1α gene were responsive to acarbose treatment. Conclusion/interpretation. We conclude that the Pro12Pro genotype of the PPAR-γ2 gene and the 482Ser allele of the PGC-1α gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.

We conclude that adiponectin has multiple effects on glucose, lipid and free fatty acid metabolism, and cytokines in offspring of T2DM subjects.

Abstract. Zacharova J, Todorova BR, Chiasson J.-L., Laakso M for the STOP-NIDDM Study Group

ZACHAROVA, JELENA, JEAN-LOUIS CHIASSON, AND MARKKU LAAKSO FOR THE STOP-NIDDM STUDY GROUP. Leptin receptor gene variation predicts weight change in subjects with impaired glucose tolerance. Obes Res. 2005;13:501-506. The leptin receptor (OB-R) gene is a promising candidate gene for type 2 diabetes, because leptin and its receptor play an important role in insulin secretion and the development of obesity. Therefore, we studied whether the pentanucleotide insertion polymorphism of the 3Ј-untranslated region (3ЈUTR) of the OB-R gene has an influence on the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the STOP-Noninsulin-Dependent Diabetes Mellitus trial. The STOP trial was a longitudinal, double-blind, placebo-controlled randomized trial that included 1429 subjects with IGT from high-risk populations. Using the restriction fragment length polymorphism method, we genotyped 770 subjects whose DNA was available for the insertion/deletion polymorphism of the 3ЈUTR of the OB-R gene. We did not find a relationship between the OB-R polymorphism and the conversion from IGT to type 2 diabetes (p ϭ 0.747). However, the insertion allele was associated with a significant reduction in weight (p ϭ 0.016), BMI (p ϭ 0.009), and waist circumference (p ϭ 0.006) in all subjects. Women carrying the I allele had a larger waist circumference change (p ϭ 0.036), whereas men lost more weight and had a greater decrease in BMI.The pentanucleotide insertion/deletion polymorphism in the 3ЈUTR of the OB-R gene did not influence the conversion to type 2 diabetes in obese patients with IGT. However, this polymorphism was associated with a significant weight change, suggesting that it may potentially modulate the risk for type 2 diabetes.