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Background: The global epidemic of diabetes mellitus continues to grow and affects developed and developing countries alike. Intensive glycemic control is thought to modify the risks for vascular complications, hence the risks for diabetes-related death. We investigated the trend of diabetic vascular complication-related deaths between 2000 and 2016 in the global diabetes landscape. Methods: We collected 17 years of death certificates data from 108 countries in the World Health Organization mortality database between 2000 and 2016, with coding for diabetic complications. Crude and age-standardized proportions and rates were calculated. Trend analysis was done with annual average percentage change (AAPC) of rates computed by joinpoint regression. Results: From 2000 through 2016, 7,108,145 deaths of diabetes were reported in the 108 countries. Among them, 26.8% (1,904,787 cases) were attributed to vascular complications in damaged organs, including the kidneys (1,355,085 cases, 71.1%), peripheral circulatory (515,293 cases, 27.1%), nerves (28,697 cases, 1.5%) and eyes (5751 cases, 0.3%). Overall, the age-standardized proportion of vascular complication-related mortality was 267.8 [95% confidence interval (95% CI), 267.5–268.1] cases per 1000 deaths and the rate was 53.6 (95% CI 53.5–53.7) cases per 100,000 person-years. Throughout the 17-year period, the overall age-standardized proportions of deaths attributable to vascular complications had increased 37.9%, while the overall age-standardized mortality rates related to vascular complications had increased 30.8% (AAPC = 1.9% [1.4–2.4%, p < 0.05]). These increases were predominantly driven by a 159.8% increase in the rate (AAPC = 2.7% [1.2–4.3%, p < 0.05]) from renal complications. Trends in the rates and AAPC of deaths varied by type of diabetes and of complications, as well as by countries, regions and domestic income. Conclusion: Diabetic vascular complication-related deaths had increased substantially during 2000–2016, mainly driven by the increased mortality of renal complications. [ABSTRACT FROM AUTHOR]

In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57–3.96, P = 8.4×10−5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02–1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07–2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19–9.19, P = 0.0214) and 3.27(1.25–11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese. [ABSTRACT FROM AUTHOR]

Aims/Introduction Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon-like peptide ( GLP-1) might have immunomodulating effects. We hypothesize that GLP-1 receptor agonist, exendin-4, might reduce inflammatory response in type 2 diabetes. Materials and Methods Using peripheral blood mononuclear cells ( PBMC) sampled from 10 type 2 diabetes and 10 sex- and age-matched control subjects and supernatants from PBMC culture, the expression of phospho-mitogen activated protein kinase ( MAPK) signaling pathways in CD4+ T helper lymphocytes and monocytes was analyzed using flow cytometry. Cytokines/chemokines and superoxide anion before and after treatment with exendin-4 were measured by cytometric bead array and chemiluminesence assay, respectively. Results Compared with control subjects, PBMC from type 2 diabetes patients showed activated MAPK ( P38, c-Jun NH2-terminal protein kinase and extracellular signal-regulated kinase) signaling pathway, elevated superoxide anion, increased pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and chemokines ( CCL5/regulated on activation normal T-cell expressed and secreted and CXCL10/interferon-γ-induced protein 10). These changes were attenuated by exendin-4, possibly through the suppression of p38 MAPK. Conclusions These results suggest that exendin-4 might downregulate pro-inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective This report aimed to explore the association between the change of circulating interleukin-6 (IL-6) in patients and the development of type 1 diabetes mellitus (T1DM). Methods Four databases (PubMed, CNKI, WanFang and Civip) were used to search and list all clinical case-control studies about serum IL-6 level in T1DM patients between Jan 1, 2000 and Aug 31, 2016. Results A total of 20 case-control studies with 1238 T1DM patients and 742 healthy controls were included in this study. Compared to healthy controls, the serum content of IL-6 in patients with T1DM was significantly greater (overall: SMD, 1.49; 95% CI, 1.04 to 1.93; p < 0.001), and notably increased in all subgroup with different age, ethnic and disease duration (all p < 0.001). Furthermore, the analysis in subgroup exhibited that serum levels of IL-6 in the age greater than 20-year old (SMD, 1.64; 95% CI, 0.57–2.71; p < 0.001), the diseased duration among 0–10 years (SMD, 2.43; 95% CI, 1.42–3.44; p < 0.001) and the sorted American group (SMD, 1.68; 95% CI, 0.85–2.51; p < 0.001) were higher than those in control groups. Conclusions Patients with T1DM were found to be linked to elevated level of serum IL-6, which the age, ethnic and disease durations in T1DM patients had no effect on the serum IL-6 levels for promoting diabetes mellitus. [ABSTRACT FROM AUTHOR]