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.

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β(TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM).Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-αin T2DM patients versus healthy controls.Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (allp<0.001), the patients had increased serum levels of IL-6, TGF-β, and TNF-αbut decreased the percentage of peripheral CD4⁺CD25⁺Foxp3⁺Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4⁺CD25⁺Foxp3⁺Treg (p<0.001) and serum IL-10 level (p=0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4⁺CD25⁺Treg (p=0.360) and serum IL-17 level (p=0.459) were found in T2DM patients.Conclusions. T2DM patients have decreased the percentage of peripheral CD4⁺CD25⁺Foxp3⁺Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4⁺CD25⁺Foxp3⁺Treg number.

The aim of this study was used meta-analysis to investigate changes of serum tumor necrosis factor-alpha (TNF-α) in patients with type 1 diabetes mellitus (T1DM). Relevant literatures were identified from PubMed, Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from January 1, 1999 to September 30, 2016). Eligible reports were included for pooled analysis of serum TNF-α level and subgroup analysis was performed in relation with age, disease duration and ethnicity. A total of 23 articles (1631 T1DM cases, 1429 healthy controls) were included for this meta-analysis. Compared with the controls, the patients had significantly increased serum TNF-α level (P < 0.001). Similar results were also found among all subgroup analysis of different age, disease duration and ethnicity (with the exception of Asian) (all P < 0.05). Regression analysis indicated that age (P = 0.680), disease duration (P = 0.957), and ethnicity (P = 0.526) of patients were not significant impact factors for the high heterogeneity. The results were stable according to the sensitivity analysis and no publication bias existed in this meta-analysis. Serum TNF-α level in T1DM patients has significantly elevated among all age, disease duration and ethnicity groups.

The existing evidence indicates increased levels of transforming growth factor beta 1 (TGF-β1) in patients with type 2 diabetes mellitus (T2DM) and those with type 2 diabetic nephropathy (T2DN); yet no meta-analysis displays a reliable result. Here we conducted a meta-analysis to evaluate characteristic changes of TGF-β1 in T2DM and diabetic nephropathy. A systematic search was conducted for eligible studies, which reported the association of TGF-β1 withT2DM and T2DN patients, in PubMed, Wangfang, Chinese-Cqvip, and China National Knowledge Infrastructure database, from February 1, 1991 to December 15, 2015. The association of serum and urine TGF-β1 in T2DM and T2DN patients should be evaluated in case-control studies. The Newcastle-Ottawa Scale was used to access the quality of the included studies, and pooling data were synthesized as standard mean difference (SMD) and 95% confidence interval (CI). The collected data were synthesized according to Cochrane Handbook for Systematic Reviews criteria. Subgroup analysis was conducted by albuminuria and ethnicity. Regression analysis and sensitivity analysis were used to explore the sources of heterogeneity. Publication bias was judged by the Egger test. Sixty-three case-control studies of 364 T2DM patients (1604 T2DN patients) and 2100 healthy controls were included for meta-analysis. Compared with the controls, the cases had increased TGF-β1 levels in both serum (T2DM: SMD 1.78 μg/L; 95% CI 0.98–2.59, P < .001; T2DN: SMD 4.70 μg/L, 95% CI 3.55–5.85, P < .001) and urine samples (T2DM: SMD 1.27 pg/mg.creatinine, 95% CI 0.16–2.38, P < .001; SMD 1.19 ng/L, 95% CI 0.77–1.62, P < .001; T2DN: SMD 3.14 pg/mg.creatinine, 95% CI 2.15–4.13, P < .001; SMD 4.50 ng/L, 95% CI 3.16–5.83, P < .001). The increase of serum TGF-β1 persisted in patients with either microalbuminuria or macroalbuminuria (all P < .001) in Chinese and non-Chinese population. High heterogeneity exists in some comparisons and small-sample studies. Patients with T2DM and those with albuminuria, Chinese or non-Chinese, had increased serum and urine TGF-β1 levels.

The neuroendocrine hormone amylin, also known as islet amyloid polypeptide, is co-localized, co-packaged and co-secreted with insulin from adult pancreatic islet β cells to maintain glucose homeostasis. Specifically, amylin reduces secretion of nutrient-stimulated glucagon, regulates blood pressure with an effect on renin-angiotensin system, and delays gastric emptying. The physiological actions of human amylin attribute to the conformational α-helix monomers whereas the misfolding instable oligomers may be detrimental to the islet β cells and further transform to β-sheet fibrils as amyloid deposits. No direct evidence proves that the amylin fibrils in amyloid deposits cause diabetes. Here we also have performed a systematic review of human amylin gene changes and reported the S20G mutation is minor in the development of diabetes. In addition to the metabolic effects, human amylin may modulate autoimmunity and innate inflammation through regulatory T cells to impact on both human type 1 and type 2 diabetes.