The Effect of Diacerein on Type 2 Diabetic Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with Trial Sequential Analysis.

AIMS: To figure out the effect of diacerein supplementation on type 2 diabetes mellitus (T2DM). METHODS: An electronic search was processed on Pubmed, Embase, and Cochrane library for randomized controlled trials (RCTs) comparing the efficacy of diacerein with placebo on T2DM. The primary outcome was fasting blood glucose (FBG). Trial sequential analysis (TSA) was used to test the reliability of this pooled outcome. Secondary outcomes were glycosylated hemoglobin A1c (HbA1c), body mass index (BMI), lipid profiles, hematological indexes including hematocrit and platelet count, and systematic inflammatory level expressed as a C-reactive protein (CRP) level. Safety outcome was the rate of complications. The difference in continuous data was measured by mean difference (MD) and 95% confidence interval (CI), while the difference of dichotomous data was calculated by relative risk (RR) and 95% CI. A two-tailed P < 0.05 was regarded as statistically significant. RESULTS: Five RCTs with 278 participants were included. Compared with control, diacerein provided significant improvement on FBG (MD -0.52; 95% CI (-0.89~-0.14); P < 0.05 was regarded as statistically significant. P < 0.05 was regarded as statistically significant. P < 0.05 was regarded as statistically significant. P < 0.05 was regarded as statistically significant. P < 0.05 was regarded as statistically significant. CONCLUSION: Based on the current analysis, diacerein as an add-on treatment provided better glycemic control for T2DM but this benefit requires more verification. Compared with control, additional diacerein also lowered body weight and CRP level in T2DM, but increased the rate of gastrointestinal syndromes.

Contribution of birth weight and adult waist circumference to cardiovascular disease risk in a longitudinal study.

To determine the association of birth weight (BW) and waist circumference (WC) on cardiovascular disease (CVD). The longitudinal cohort study consisted of 745 participants who were able to provide their birth weight information and were followed from 2002 to 2014. During the follow-up, 83 events of CVD were confirmed. After adjusting for confounding factors, subjects with birth weight <2500 g were at a significantly increased CVD risk when compared to subjects with birth weight between 2500-3999 g (OR 2·47, 95%CI, 1·07-5·71). When high waist circumference (HWC), a measurement of adult obesity, was incorporated into stratifying factors according to presence or absence of low birth weight (LBW, birth weight <2500 g), adjusted CVD risk was significantly elevated in -LBW/+ HWC group (OR 1·94, 95%CI, 1·10-3·43) and marginally significantly increased in +LBW/-HWC group (OR 2·94, 95%CI, 1·00-8·64). CVD risk was highest in subjects with LBW and HWC (+LBW/+HWC), OR 4·74 (95%CI, 1·48-15·21). Higher waist circumference in adulthood is an especially strong risk factor for cardiovascular disease among those small at birth. In this cohort, birth size and adiposity in adulthood interact to predict events of cardiovascular disease.

Gender-related affecting factors of prediabetes on its 10-year outcome.

OBJECTIVE: To investigate the gender-related affecting factors of prediabetes on its 10-year outcome, in a longitudinal study. METHODS AND RESULTS: This longitudinal population-based study was performed in the Ping Liang community, Yangpu district, Shanghai, between November 2002 and October 2014. There were 334 participants with prediabetes enrolled in the final analysis. While a certain proportion of the prediabetic population progress to diabetes, the majority remain at the same level or even revert to normal glucose regulation. No gender difference was observed in the change of glucose regulation. However, results from an adjusted logistic regression analysis in males showed that physical activity was significantly associated with both elevated odds of reverting to normal glucose regulation (active vs inactive, OR 3.00, 95% CI 1.09 to 8.30) and developing diabetes (OR 0.34, 95% CI 0.13 to 0.92). Age, baseline 2 h glucose, triglycerides and smoking status were also risk factors significantly associated with diabetes development; while for females, waist circumference played a key role in the outcome. Every unit elevation of waist circumference was associated with lower odds of reverting to normal glucose regulation (OR, 0.94; 95% CI 0.89 to 0.98) and higher odds of progressing to diabetes (OR, 1.05; 95% CI 1.01 to 1.10). Baseline hypertension and family history of diabetes carried higher risk for developing diabetes as well. CONCLUSIONS: Physical activity in males and waist circumference in females are important factors predicting both progression to diabetes and regression to normal glucose regulation, indicating that more exercise for males and lower waist circumference for females are beneficial for prediabetes to achieve reversion.

Roles of SHARP1 in thyroid cancer.

SHARP1 is a basic helix­loop­helix transcription factor involved in various cellular processes, including proliferation and differentiation. The present study assessed the role of SHARP1 in the progression and invasion of thyroid cancer. PCR and western blot analysis demonstrated that in thyroid cancer tissues, SHARP1 was significantly downregulated at the mRNA and protein level compared with that in normal tissues. Furthermore, SHARP1 was downregulated in the TT and TPC­1 thyroid cancer cell lines compared with a normal thyroid cell line, while it was upregulated in other thyroid cancer cell lines. Overexpression of SHARP1 in TT and TPC­1 cells significantly inhibited the cell viability, migration and invasion in vitro. Furthermore, the protein and mRNA levels of HIF­1α were found to be decreased in TT and TPC­1 cells following forced overexpression of SHARP1. In addition, silencing of HIF­1α reduced the viability, migration and invasion of TT and TPC-1 cells. In conclusion, the present study indicated that SHARP1 acts as a tumor suppressor in thyroid cancer and that its downregulation may contribute to the proliferation, migration and invasion of thyroid cancer cells through mechanisms possibly involving HIF­1α, suggesting that SHARP1 may be an important therapeutic target for the treatment of thyroid cancer.

[The effect and pathophysiological mechanism of high free fatty acids(FfAs) on the cardiac structure and function].

OBJECTIVE: To study the pathophysiological links between elevated circulating FFAs concentration and the cardiac structure, and their function in obese insulin resistance rat model. METHODS: 4 weeks age male SD rats were fed with high-fat chow (OB) or standard laboratory chow (NC) respectively. Whole-body insulin sensitivity, the maximum velocity of myocardial contraction (+dp/dt(max)) and the maximum velocity of myocardial diastole (-dp/dt(max)) of intracardiac pressure, and myocardiac cell diameter (MCD) were measured. The concentrations of triglyceride (TG), FFAs and angiotensin II (Ang II) both in blood and in left ventricular portions of heart and the expressions of NF-kappaB, I-kappaB and iNOS in myocardium were analyzed. RESULTS: OB group developed obesity and left ventricular hypertrophy, and their insulin sensitivity was much lower than that of control group. Obese rats had higher plasma concentrations of TG, FFAs and Ang II. Accordingly, dramatic lipid deposition occurred within cardiomyocytes of obese rats, and the value of myocardiac Ang II was also increased. High-fat diet also induced a progressive decrease in values of +dp/dt(max) and -dp/dt(max). The higher expressions of NF-kappaB and iNOS in myocardium were observed in OB group, while IkappaB lower. Intramyocardial lipid deposition was associated with plasma FFAs concentrations (r = 0.80, P < 0.01). Intramyocardial FFAs concentration was associated with myocardial Ang II concentration (r = 0.74, P < 0.05) and changes in expressions of NF-kappaB (r = 0.86, P < 0.01), iNOS (r = 0.66, P < 0.05). The contractile dysfunction was associated with intramyocardial lipid deposition (r = -0.87, P < 0.01), Ang II (r = -0.52, P < 0.05) and expressions of NF-kappaB (r = -0.57, P < 0. 01), iNOS (r = -0.70, P < 0. 01). The diastolic dysfunction was associated with intramyocardial lipid deposition ( r = -0.85, P < 0.01), Ang II (r = -0.82, P<0.01) and expressions of NF-kappaB (r = -0.75, P < 0.01), iNOS (r = -0.78, P < 0.01). CONCLUSION: In obese/insulin resistance, state ectopic lipid accumulation in myocardium as the results of elevated circulating FFAs and TG concentration impairs cardiac systolic and diastolic functions. It is logical to deduce that ectopic lipid accumulation in myocardium may increase RAS activity and expressions of NF-kappaB, iNOS in myocardium, all of them have important roles to increase the risk of congestive heart failure in obese subjects.

[A study on the mechanism of islet cell insulin resistance in high-fat-diet obese rats].

OBJECTIVE: To study the changes of insulin signal transduction in islet cells of high-fat-diet rats with peripheral insulin resistance (IR). METHODS: Thirty male Wistar rats were randomly divided into 2 equal groups: high-fat-diet group and control group to be fed with high-fat food and normal food respectively. Twenty weeks after the rats were sacrificed. The contents of insulin and glucagon in homogenate of pancreas were detected during islet cell perifusion, and insulin receptor (IRc) and insulin receptor substrates (IRS-1 and IRS-2) were detected by immunohistochemistry. RESULTS: (1) The insulin sensitive index (ISI) was significantly decreased in the high-fat-diet rats in comparison with the normal rats, while the contents of glucagon in blood and in homogenate of pancreas were both significantly increased in the high-fat-diet rats (362 pg/ml +/- 58 pg/ml vs 291 pg/ml +/- 35 pg/ml; 442 pg/ml +/- 56 pg/ml vs 287 pg/ml +/- 48 pg/ml, both P < 0.05). (2) The glucose stimulated insulin secretion (GSIS) was impaired in the high-fat-diet rats. 16.7 nmol/L glucose could inhibit the glucagon secretion by the alpha cells of the normal rats, but not of the high-fat-diet rats. (3) The expression of IRc, IRS-1 and IRS-2 in islets was stronger in the peripheral cells (non-insulin secretion cells) than in the center cells (insulin secretion cells). The expression of IRc and IRS-2 was significantly decreased by 28% and 22% respectively in the high-fat-diet rats compared with the normal controls (both P < 0.01). CONCLUSION: High-fat-diet rats have impairment of insulin signal transduction in islet cells, which may contribute to the insulin resistance of islet alpha and beta cells and explain, at least in part, the dysfunction of the islet cells under peripheral IR.