Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City.

BACKGROUND: Type 2 diabetes (T2D) is influenced by diverse environmental and genetic risk factors. Metabolic syndrome (MS) increases the risk of cardiovascular disease and diabetes. We analysed 14 cases of polymorphisms located in 10 candidate loci, in a sample of patients with T2D and controls from Mexico City. METHODS: We analysed the association of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARgamma, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS. The analysis included 519 subjects with T2D defined according to the ADA criteria, 389 with MS defined according to the AHA/NHLBI criteria and 547 controls. Association was tested with the program ADMIXMAP including individual ancestry, age, sex, education and in some cases body mass index (BMI), in a logistic regression model. RESULTS: The two markers located within the TCF7L2 gene showed strong associations with T2D (rs7903146, T allele, odd ratio (OR) = 1.76, p = 0.001 and rs12255372, T allele, OR = 1.78, p = 0.002), but did not show significant association with MS. The non-synonymous rs4994 polymorphism of the ADRB3 gene was associated with T2D (Trp allele, OR = 0.62, p = 0.001) and MS (Trp allele, OR = 0.74, p = 0.018). Nominally significant associations were also observed between T2D and the SIRT1 rs3758391 SNP and MS and the HHEX rs5015480 polymorphism. CONCLUSIONS: Variants located within the gene TCF7L2 are strongly associated with T2D but not with MS, providing support to previous evidence indicating that polymorphisms at the TCF7L2 gene increase T2D risk. In contrast, the non-synonymous ADRB3 rs4994 polymorphism is associated with T2D and MS.

Hypomagnesaemia and risk for metabolic glucose disorders: a 10-year follow-up study.

BACKGROUND: Although several lines of evidence suggest that hypomagnesaemia is a risk factor for developing type 2 diabetes, there are no studies regarding the association between hypomagnesaemia and the risk for developing impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Our objective was to examine the association between serum magnesium levels and the risk for developing IFG, IGT and type 2 diabetes. MATERIALS AND METHODS: A total of 1122 individuals (20-65 years of age) were enrolled between 1996 and 1997, and 817 individuals re-examined about 10 years later. New-onset IFG (5.6-7.0 mmol L(-1) fasting glucose), IGT (7.8-11.1 mmol L(-1) glucose 2-h postload), and type 2 diabetes were determined from the number of subjects who had these conditions at the second examination without evidence that they were present at the first one. The relative risk of new-onset metabolic glucose disorders and diabetes (dependent variables) was computed using Poisson regression model adjusted for age, sex, family history of diabetes, waist circumference and homeostasis model assessment for insulin resistance index. Serum magnesium levels of < 0.74 mmol L(-1) (independent variable) defined the exposed group. RESULTS: At baseline, 420 (51.4%) individuals had hypomagnesaemia. New-onset IFG and IGT was identified in 276 (33.8%) individuals. The relative risk for IFG, IGT and IFG + IGT was 1.11 (95% confidence interval, 0.5-5.1), 1.38 (95% confidence interval, 1.1-6.3) and 1.49 (95% confidence interval, 1.1-4.9), respectively. New-onset diabetes was identified in 78 (9.5%) individuals (relative risk 2.54; 95% confidence interval, 1.1-4.1). CONCLUSIONS: Hypomagnesaemia is independently associated with the development of IGT, IFG + IGT and type 2 diabetes, but not with the development of IFG.