Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults. To identify genetic contributions in DR, we studied 2071 type 2 diabetics. We first conducted a genome-wide association study of 1007 individuals, comparing 570 subjects with ≥8 years duration without DR (controls) with 437 PDR (cases) in the Chinese discovery cohort. Cases and controls were similar for HbA1c, diabetes duration and body mass index. Association analysis with imputed data identified three novel loci: TBC1D4-COMMD6-UCHL3 (rs9565164, P = 1.3 × 10(-7)), LRP2-BBS5 (rs1399634, P = 2.0 × 10(-6)) and ARL4C-SH3BP4 (rs2380261, P = 2.1 × 10(-6)). Analysis of an independent cohort of 585 Hispanics diabetics with or without DR though did not confirm these signals. These genes are still of particular interest because they are involved in insulin regulation, inflammation, lipid signaling and apoptosis pathways, all of which are possibly involved with DR. Our finding nominates possible novel loci as potential DR susceptibility genes in the Chinese that are independent of the level of HbA1c and duration of diabetes and may provide insight into the pathophysiology of DR.

Type 2 diabetes mellitus (DM) is the most common single cause of end-stage renal disease. Albuminuria is the most commonly used marker to predict onset of diabetic nephropathy (DN) without enough sensitivity and specificity to detect early DN. This is the first study to identify urinary cyclophilin A (CypA) as a new biomarker for early DN.We recruited DM outpatients and healthy control subjects from January 2014 to December 2014. In this cross-sectional study, patients’ urine samples were collected to determine the expression of urinary CypA. We also treated mesangial (MES-13) and tubular (HK-2) cells with glucose or free radicals to observe the expression of secreted CypA in Western blot analysis.A total of 100 DN patients and 20 healthy control subjects were enrolled. All variables were matched. In univariate analysis, the concentration of urinary CypA correlated well with the progression of renal function. A significant increase in urinary CypA was noted in stage 2 DN and persisted in later stages. We could diagnose stage 2 DN using urinary CypA with a sensitivity of 90.0% and specificity of 72.7%. The area under curve was up to 0.85, indicating a good discriminatory power. In cellular models, MES-13 and HK-2 cells can both release CypA.Urinary CypA is a good biomarker for early DN detection in humans and it can be released from either mesangial or tubular cells. The underlying molecular mechanisms still need further clarification in cellular and animal studies.

Epicardial adipose tissue (EAT) is a metabolically active visceral fat, which secretes inflammatory cytokines and adipokines. In this study, our aim was to examine which measurements of EAT thickness by magnetic resonance imaging (MRI) could best help differentiate inflammatory status, classified by levels of high‐sensitivity C‐reactive protein (hs‐CRP), in obese men with metabolic syndrome (MetS). We prospectively enrolled 32 men with central obesity (waist circumference ≥90 cm) and at least two other MetS criteria. MRI examinations for measurements of EAT, subcutaneous fat, and abdominal visceral fat as well as recordings of anthropometric parameters and tests for serum inflammatory cytokines and adipokines were conducted. Subjects with MetS (N = 32) were divided into three subgroups: (i) low inflammatory status (hs‐CRP < 0.3 mg/dl, N = 8), (ii) intermediate inflammatory status (hs‐CRP 0.1–0.3 mg/dl, N = 15), and (iii) high inflammatory status (hs‐CRP >0.3 mg/dl, N = 9). EAT thickness at the right atrioventricular (AV) groove showed a significant linear trend among the three subgroups of MetS (P for trend = 0.004). High inflammatory status MetS subgroup had a significantly thicker right AV groove EAT than did the low inflammatory status MetS subgroup (19.3 ± 3.1 vs. 14.4 ± 3.3 mm, P = 0.015). In binary logistic regression analysis, right AV groove EAT thickness was an independent predictor for differentiating inflammatory status in MetS while abdominal visceral fat area and insulin‐resistance index were not. In conclusion, MRI measured EAT thickness at the right AV groove could be a useful marker for differentiating the inflammatory status in obese men with MetS.

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