Diabetic kidney disease (DKD) and retinopathy (DR) develop in a considerable number of subjects with Type 2 Diabetes (T2D) despite the achievement of the recommended targets for glycaemia and blood pr Show more
Diabetic kidney disease (DKD) and retinopathy (DR) develop in a considerable number of subjects with Type 2 Diabetes (T2D) despite the achievement of the recommended targets for glycaemia and blood pressure. Atherogenic dyslipidemia may play a relevant role, especially in T2DM women. We report our findings on the effect of diabetic dyslipidaemia, the HDL subclasses distribution and the common cholesteryl ester transfer protein (CETP)TaqIB variant on the incidence or the progression of DKD and DR in 97 T2D women, after a ∼9years of follow-up. At baseline, T2D women presented with low HDL-C levels and higher levels of large lipid rich α-1 (16.34mg/dl), α-2 (33.39mg/dl) and pre- α1 (4.81mg/dl) HDL subparticles. The CETP TaqIB polymorphism and baseline HbA1c, triglycerides, and HDL-C levels as well as specific HDL subpopulations were associated to the occurrence of RD after ∼9years of follow-up. At stepwise regression analysis, HbA1c, triglycerides and the less atheroprotective α-3 HDL particles were the only factors independently associated to the incidence of RD. These same variables were also associated with the progression from background to proliferative RD. BMI, LDL/HDL ratio and low levels of α-1 HDL particles were associated to the occurrence of DKD at univariate analysis, although BMI was the only significant predictor at stepwise multivariate regression analysis. In T2D women, atherogenic dyslipidemia as well as subtle modifications in lipoprotein particles profile are associated with incidence and progression of microvascular disease. Show less
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between bod Show more
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. Show less