Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.

OBJECTIVE -To study the effect of body composition and adiponectin on insulin resistance and ␤-cell function in schoolchildren during puberty.RESEARCH DESIGN AND METHODS -Plasma adiponectin level and its relationships with insulin sensitivity and ␤-cell function were analyzed in 500 randomly recruited nondiabetic Taiwanese schoolchildren (245 boys and 255 girls) aged 6 -18 years in a national survey program for diabetes in 1999. Insulin resistance and ␤-cell function were evaluated by homeostasis model assessment (HOMA). Plasma adiponectin concentrations were determined with radioimmunoassay.RESULTS -Plasma glucose levels remained stable, whereas insulin resistance increased with a compensatory rise in ␤-cell function during this period. A transient drop of adiponectin level with a trough at 10 -12 years was found in boys but not in girls. This pubertal drop of adiponectin levels in boys coincides with the sharp rise in testosterone concentration. A negative correlation between testosterone levels and adiponectin concentration was also noted in boys (r ϭ Ϫ0.142, P ϭ 0.032). Plasma adiponectin levels correlated inversely with relative body weight, fasting insulin concentrations, and insulin resistance index by HOMA in boys aged 15-18 years and in girls aged 11-14 years. No association was observed between adiponectin levels and ␤-cell function by HOMA.CONCLUSIONS -There is a transient drop in the level of adiponectin during male puberty, correlated with the increase in testosterone level in boys. Plasma adiponectin levels were inversely correlated with obesity and insulin resistance in boys and girls during the pubertal period. Diabetes Care 27:308 -313, 2004T ype 2 diabetes, once considered to be a disease of adults, is now emerging in children and adolescents worldwide (1,2). In adults, both insulin sensitivity and ␤-cell function decline with aging. According to both crosssectional and longitudinal studies (3-5), these abnormalities are always found in the pre-diabetic state during development of type 2 diabetes. However, little is known about the evolution of the insulin resistance and ␤-cell function of children who are "growing" rather than "aging."Although children in their prediabetic state might share common pathogenesis in terms of insulin resistance and ␤-cell deterioration, the etiology of insulin resistance and the pattern of islet compensation under various stimuli for growth and development may differ markedly from those of adults. Much effort for elucidating transient insulin resistance during puberty has focused on sex steroids (6 -8), which, however, fail to explain the restoration of insulin sensitivity after puberty, when sex hormones have achieved and maintain adult levels. On the other hand, the growth hormone/ IGF-1 axis, a chronologically plausible culprit, is still controversial in its insulinantagonizing effects in children of different ages and sexes (9 -11). Given the tight, temporal coupling between growth and reproductive development, some common signals regulating adolescent growth ...

Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED.

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