The present study provides evidence of a role of ZAG gene in adipose tissue metabolism, with a close association with adiponectin gene expression in sc and visceral fat.

Chronic low-grade activation of the immune system may play a role in the pathogenesis of type-2 diabetes mellitus (T2DM). Interleukin-6 (IL6), a powerful inducer of hepatic acute phase response, has been implicated in the etiology of insulin resistance and T2DM. Recently, an IL6 promoter polymorphism (G/C) at position -174 was found to be associated with measures of insulin sensitivity. Because we have previously found an association between high IL6 levels and insulin resistance in both Pima Indians -a population with high rates of insulin resistance and T2DM -and Caucasians, we aimed to assess whether the IL6 promoter polymorphism is associated with T2DM in these populations. We genotyped the IL6 (-174) G/C polymorphism using pyrosequencing in 463 Native Americans and by PCR-RFLP in 329 Spanish Caucasians. Among the Spanish Caucasian subjects, there was a significant difference in genotypic distribution between diabetic and non-diabetic subjects (P=0.028); the GG genotype was more common in diabetic (0.40) than in non-diabetic (0.29) subjects. The G allele was much more frequent in the Native American sample, and among a sample of 143 cases and 145 controls, the GG genotype was significantly more common in diabetic subjects (P=0.019). When this sample population was stratified according to ethnic heritage, all 211 subjects who were of full Pima Indian heritage had the GG genotype, whereas in the 77 American Indian subjects with non-Pima admixture, T2DM was associated with IL6 genotype (P=0.001). These findings are consistent with a role for genetic determinants of inflammation in the development of T2DM in both Native Americans and Caucasians.

Insulin resistance is a feature of gestational diabetes mellitus (GDM). Inverse correlations between indexes of insulin sensitivity and serum markers of inflammation have been observed and, particularly, TNF-alpha has been shown to be associated with the appearance of insulin resistance in pregnancy. Mannose-binding lectin (MBL) is a protein member of the collectin family. Its deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. To test the hypothesis that a genetic predisposition to a proinflammatory state could favor the appearance of GDM during pregnancy, we studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105 consecutive GDM women and 173 healthy pregnant women. An association was found between G54D and GDM [odds ratio, 2.03 (1.18-3.49); P < 0.01], and this association remained significant when the presence of both mutated alleles was considered [odds ratio, 1.76 (1.04-2.96); P < 0.05] but not for the R52C. GDM patients who carried the G54D mutation required insulin therapy more frequently (56.4 vs. 30.4%, chi(2) =5.83; P = 0.027) and had heavier infants (3326.4 +/- 546.9 vs. 3087.5 +/- 395.5 g; P < 0.05) than GDM women homozygous for the wild-type allele. An inverse correlation in GDM patients between neonatal weight and plasma MBL levels (r = -0.320; P = 0.002) was found, remaining significant after adjustment for confounding variables. In conclusion, pregnant women bearing the G54D MBL allele have a greater risk for developing GDM and having heavier infants.

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The inverse correlation found between body fat and BMD in the first cohort indicates morbid obesity increases the risk of osteoporosis and we found a positive correlation with lean and fat mass before bariatric surgery and with lean mass after bypass surgery.