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Dastani, Z., Hivert, M. - F., Timpson, N., Perry, J. R. B., Yuan, X., Scott, R. A., et al. (2012). Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet, 8(3), e1002607.
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5x10(-8)-1.2x10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3x10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3x10(-3), n = 22,044), increased triglycerides (p = 2.6x10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8x10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4x10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5x10(-13), n = 96,748) and decreased BMI (p = 1.4x10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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Sundling, V., Platou, C. G. P., Jansson, R. W., Bertelsen, G., Wollo, E., & Gulbrandsen, P. (2012). Retinopathy and visual impairment in diabetes, impaired glucose tolerance and normal glucose tolerance: the Nord-Trondelag Health Study (the HUNT study). Acta Ophthalmol, 90(3), 237–243.
Abstract: PURPOSE: The aim of the study was to describe the prevalence of visual impairment and retinopathy and to investigate risk factors for retinopathy in persons with diabetes, screen-detected diabetes, impaired glucose tolerance and normal glucose tolerance in a subpopulation of the HUNT study. METHODS: We used a sample (n = 163) from a population-based screening survey of hyperglycaemia, undertaken in 2004-2005 in Verdal, Norway. Baseline information was accessible through the second Nord-Trondelag Health Study (HUNT2), 1995-97. Data collection was made in 2005 and included patient history, refraction, visual acuity, cataract assessment and single-field, nonmydriatic retinal photography. Retinal photographs were graded independently by two graders blinded to patient information. Data were analysed with standard statistical methods, and p < 0.05 was considered significant. RESULTS: In all, 126 (77%) persons participated, 55% were women. The mean (SD) age was 59 (+/- 14) years. Four (3%) had correctable visual impairment, and none were visually impaired. Retinal photographs were gradable for both eyes in 109 (87%) participants. The prevalence of retinopathy was 11% in persons with known diabetes, 4% in persons with screen-detected diabetes, 3% in persons with impaired glucose tolerance and 10% in persons with normal glucose tolerance. Retinopathy was not associated with known history of diabetes or current glycaemic status. Nonfasting plasma glucose (in 1995-97) was an independent risk factor for retinopathy (in 2005), OR (95% CI) 1.5 (1.01, 2.13), p = 0.046. CONCLUSION: The prevalence of diabetic retinopathy in persons with diabetes in this study was low. Appropriate optical correction and regular eye examination can prevent unnecessary visual impairment in both persons with and without diabetes.
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