From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion.

Glucose-stimulated insulin secretion from islet ß cells is mediated by KATP channels. However, the role of non-KATP K+ channels in insulin secretion is largely unknown. Here, we show that a non-KATP K+ channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of ß cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and ß cell failure in the long term.

Waist-to-height ratio is better than body mass index and waist circumference as a screening criterion for metabolic syndrome in Han Chinese adults.

Metabolic syndrome (MetS) is a major public health concern. Efficient screening requires criteria that are economical, easily accessible, and applicable for all populations. We aimed to compare the discriminating ability of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) for the diagnosis of MetS in a Han Chinese population.Demographic information, obesity indices, and results of biochemical tests were collected from a cross-sectional sample of 8084 individuals (3619 men and 4465 women, 18-79 years old) from Changping District, Beijing, China. Areas under receiver operating characteristic curves (AUCs) and adjusted odd ratios of 3 obesity indices were analyzed and their optimal cutoffs were determined.For women, the AUCs demonstrated that WHtR was significantly more powerful than BMI and WC (both P < .05) for predicting MetS [WHtR, 0.857 (0.846-0.868); WC, 0.849 (0.837-0.860); BMI, 0.808 (0.795-0.821)]. For men, WHtR was significantly better than BMI [P < .05; WHtR, 0.859 (0.846-0.871); WC, 0.855 (0.843-0.868); BMI, 0.815 (0.802-0.829)]. The optimal cutoffs for WHtR for discriminating MetS were 0.51 in both genders. Multiple logistic regression confirmed the positive association between WHtR and the risk of MetS. In the nonobese subgroup, WHtR was also superior to BMI and WC for predicting MetS in men (P < .05) and better than BMI in women (P < .05).Among the obesity indices analyzed here, WHtR was the best for predicting MetS in Han Chinese adults, especially in nonobese adults.

Efficacy of intermittent pneumatic compression for venous thromboembolism prophylaxis in patients undergoing gynecologic surgery: A systematic review and meta-analysis.

We sought to comprehensively assess the efficacy of Intermittent Pneumatic Compression (IPC) in patients undergoing gynecologic surgery. A computerized literature search was conducted in Pubmed, Embase and Cochrane Library databases. Seven randomized controlled trials involving 1001 participants were included. Compared with control, IPC significantly lowered the deep vein thrombosis (DVT) risk [risk ratio (RR) = 0.33, 95% confidence interval (CI): 0.16 - 0.66]. The incidence of DVT in IPC and drugs group was similar (4.5% versus. 3.99%, RR = 1.19, 95% CI: 0.42 - 3.44). With regards to pulmonary embolism risk, no significant difference was observed in IPC versus control or IPC versus drugs. IPC had a lower postoperative transfusion rate than heparin (RR = 0.53, 95% CI: 0.32 - 0.89), but had a similar transfusion rate in operating room to low molecular weight heparin (RR = 1.06, 95% CI: 0.69 - 1.63). Combined use of IPC and graduated compression stockings (GCS) had a marginally lower risk of DVT than GCS alone (RR = 0.38, 95% CI: 0.14 - 1.03). In summary, IPC is effective in reducing DVT complications in gynecologic surgery. IPC is neither superior nor inferior to pharmacological thromboprophylaxis. However, whether combination of IPC and chemoprophylaxis is more effective than IPC or chemoprophylaxis alone remains unknown in this patient population.

Contributions of renin-angiotensin system-related gene interactions to obesity in a Chinese population.

BACKGROUND: Gene-gene interactions may be partly responsible for complex traits such as obesity. Increasing evidence suggests that the renin-angiotensin system (RAS) contributes to the etiology of obesity. How the epistasis of genes in the RAS contributes to obesity is still under research. We aim to evaluate the contribution of RAS-related gene interactions to a predisposition of obesity in a Chinese population. METHODOLOGY AND PRINCIPAL FINDINGS: We selected six single nucleotide polymorphisms (SNPs) located in angiotensin (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AGTR1), MAS1, nitric oxide synthase 3 (NOS3) and the bradykinin B2 receptor gene (BDKRB2), and genotyped them in 324 unrelated individuals with obesity (BMI ≥ 28 kg/m(2)) and 373 non-obese controls (BMI 18.5 to <24 kg/m(2)) from a large scale population-based cohort. We analyzed gene-gene interactions among 6 polymorphic loci using the Generalized Multifactor Dimensionality Reduction (GMDR) method, which has been shown to be effective for detecting gene-gene interactions in case-control studies with relatively small samples. Then we used logistic regression models to confirm the best combination of loci identified in the GMDR. It showed a significant gene-gene interaction between the rs220721 polymorphism in the MAS1 gene and the rs1799722 polymorphism in the gene BDKB2R. The best two-locus combination scored 9 for cross-validation consistency and 9 for sign test (p = 0.0107). This interaction showed the maximum consistency and minimum prediction error among all gene-gene interaction models evaluated. Moreover, the combination of the MAS1 rs220721 and the BDKRB2 rs1799722 was associated with a significantly increased risk of obesity (OR 1.82, CI 95%: 1.15-2.88, p = 0.0103). CONCLUSIONS AND SIGNIFICANCE: These results suggest that the SNPs from the RAS-related genes may contribute to the risk of obesity in an interactive manner in a Chinese population. The gene-gene interaction may serve as a novel area for obesity research.