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Wu S.,Peoples Hospital of the Xinjiang Uygur Autonomous Region | Yi F.,Peoples Hospital of the Xinjiang Uygur Autonomous Region | Zhou C.,Community Medical Service Center | Zhang M.,Peoples Hospital of the Xinjiang Uygur Autonomous Region | And 9 more authors.
Journal of Diabetes | Year: 2013

Objective: To identify the optimal threshold of HbA1c and to evaluate the predictive performance of HbA1c levels in diagnosing diabetes and prediabetes in a middle-aged and elderly Han Chinese population from northwest China. Methods: In all, 3354 participants aged ≥40 years with no history of diabetes from northwest China were enrolled in the present cross-sectional study. All subjects underwent a 75-g oral glucose tolerance test (OGTT), as well as HbA1c testing. HbA1c thresholds for diagnosing diabetes and prediabetes were identified by the highest sum of sensitivity and specificity of each cut-off point, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy of the HbA1c threshold. Results: The mean (± SD) age of the participants was 57±8 years, and 70.75% were women. Based on results of the OGTT, 1347 (40.16%) subjects had impaired fasting glucose and/or impaired glucose tolerance, and 725 (21.62%) had diabetes. The area under the ROC curve for detecting undiagnosed diabetes and prediabetes by HbA1c levels was 0.810 (95% confidence interval [CI] 0.796-0.823) and 0.732 (95% CI 0.717-0.747), respectively. HbA1c threshold of 6.4% and 6.1% produced the highest sum of sensitivity (60.00% and 61.49%) and specificity (87.33% and 73.24%) for diagnosing diabetes and prediabetes, respectively. Conclusion: HbA1c is an effective and convenient method for diagnosing diabetes and prediabetes. HbA1c thresholds of 6.4% and 6.1% may be used as diagnostic criteria for diabetes and prediabetes, respectively, in the Han Chinese population living in northwest China. © 2013 Wiley Publishing Asia Pty Ltd and Ruijin Hospital, Shanghai Jiaotong University School of Medicine.

Xu M.,Harvard University | Xu M.,Shanghai Institute of Endocrine and Metabolic Diseases | Xu M.,Shanghai JiaoTong University | Qi Q.,Harvard University | And 5 more authors.
Circulation | Year: 2013

Background-Circulating branched-chain amino acids and aromatic amino acids were recently related to insulin resistance and diabetes mellitus in prospective cohorts. We tested the effects of a genetic determinant of branched-chain amino acid/ aromatic amino acid ratio on changes in body weight and insulin resistance in a 2-year diet intervention trial. Methods and Results-We genotyped the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 near the PPM1K gene in 734 overweight or obese adults who were assigned to 1 of 4 diets varying in macronutrient content. At 6 months, dietary fat significantly modified genetic effects on changes in weight, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) after adjustment for the confounders (all P for interaction ≤0.006). Further adjustment for weight change did not appreciably change the interactions for fasting insulin and HOMA-IR. In the highfat diet group, the C allele was related to less weight loss and smaller decreases in serum insulin and HOMA-IR (all P ≤ 0.02 in an additive pattern), whereas an opposite genotype effect on changes in insulin and HOMA-IR was observed in the low-fat diet group (P=0.02 and P=0.04, respectively). At 2 years, the gene-diet interactions remained significant for weight loss (P=0.008) but became null for changes in serum insulin and HOMA-IR resulting from weight regain. Conclusions-Individuals carrying the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improvement of insulin sensitivity than those without this allele when undertaking an energy-restricted high-fat diet. © 2013 American Heart Association, Inc.

Wu Y.-C.,Shanghai JiaoTong University | Su T.-W.,Shanghai Institute of Endocrine and Metabolic Diseases | Su T.-W.,Shanghai JiaoTong University | Zhang J.-F.,Shanghai JiaoTong University | And 4 more authors.
Journal of Diabetes | Year: 2015

Background: A comprehensive meta-analysis was performed to evaluate the comparative benefits of coronary artery bypass grafting (CABG) versus drug-eluting stents (DES) in patients with diabetes mellitus and severe coronary artery disease (CAD). Methods: A comprehensive literature search of PubMed, Embase, and ScienceDirect was undertaken. References cited with the papers were also checked to identify relevant articles. Results: In all, four randomized controlled trials, two prospective registries, and 11 retrospective studies were identified for review. Pooled analysis demonstrated that DES was associated with lower all-cause mortality at Day 30. However, there was no significant difference between CABG and DES in mortality at 12 months and at maximum follow-up. Furthermore, DES was associated with lower overall and major adverse cardiac and cerebrovascular events (MACCE)-free survival, as well as a higher incidence of myocardial infarction and repeat revascularization. In contrast, CABG was associated with an increased risk of stroke. Conclusions: For patients with diabetes mellitus and severe CAD, CABG is superior to DES in that it significantly improves overall and MACCE-free survival and reduces the incidence of myocardial infarction and repeat revascularization in the long term, although it is associated with greater perioperative risk and a higher incidence of stroke. Therefore, CABG should remain the gold standard for these patients. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Liu D.-M.,Shanghai JiaoTong University | Liu D.-M.,Shanghai Institute of Endocrine and Metabolic Diseases | Guo X.-Z.,Shanghai JiaoTong University | Guo X.-Z.,Shanghai Institute of Endocrine and Metabolic Diseases | And 11 more authors.
Osteoporosis International | Year: 2015

Summary: This meta-analysis aimed to investigate the associations between osteocalcin (Ocn) and fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c). It was revealed that both total Ocn and undercarboxylated Ocn (unOcn) were negatively related with FPG and HbA1c, and the association of unOcn with FPG was more pronounced in men. Introduction: The aim of this study was to investigate the strength of associations between Ocn and FPG and HbA1c using a meta-analysis approach. Methods: A search was carried out using the databases of PubMed, ISI Web of Science, and the Cochrane library from 2007 to 2014 to identify related studies. A pooled effect size with 95 % confidence intervals (CI) was derived. Results: The meta-analysis included 39 studies involving 23,381 participants. The overall correlation was −0.16 (95 % CI, −0.19 to −0.14) between total Ocn (tOcn) and FPG and −0.15 (95 % CI, −0.20 to −0.11) between undercarboxylated Ocn (unOcn) and FPG. In the analysis of the association between Ocn and HbA1c, the pooled correlation was −0.16 (95 % CI, −0.18 to −0.14) for tOcn and −0.16 (95 % CI, −0.23 to −0.08) for unOcn. The magnitude of the correlation between unOcn and FPG is significantly higher in men than in women (r = −0.18, 95 % CI, −0.21 to −0.14; r = −0.09, 95 % CI, −0. 13 to −0.05, respectively; P for interaction < 0.05). Similar trend was also found between unOcn and HbA1c but without significance (for men, r = −0.19, 95 % CI, −0.24 to −0.14; for women, r = −0.09, 95 % CI, −0.22 to 0.04, respectively; P for interaction > 0.05). No indication of significant publication bias was found in any method. Conclusions: This meta-analysis demonstrated that both unOcn and tOcn were similarly and negatively correlated with FPG and HbA1c in humans. The negative correlations between unOcn and glucose metabolism appear to be more pronounced in men than in women. © 2015, International Osteoporosis Foundation and National Osteoporosis Foundation.

Yang M.,Shanghai JiaoTong University | Ye L.,Shanghai JiaoTong University | Wang B.,Shanghai JiaoTong University | Gao J.,Shanghai JiaoTong University | And 9 more authors.
Journal of Diabetes | Year: 2015

Background: Type 1 diabetes mellitus (T1D) is a common autoimmune disease mediated by autoimmune attack against pancreatic β-cells. It has been reported that dysregulation of microRNAs (miRNAs) may contribute to the pathogenesis of autoimmune diseases, including T1D. The aim of the present study was to identify pathogenic miRNAs in peripheral blood mononuclear cells (PBMC) of T1D patients. Methods: Global miRNA and mRNA expression was profiled in PBMC from 12 patients with newly diagnosed T1D and 10 normal controls. Differently expressed miRNAs were validated in an independent set of patients and controls. The dynamic changes in miRNA and target gene expression were analyzed in T1D patients treated with either a short (6 months) or long (12-24 months) course of insulin. The association between miRNA expression and serum glutamic acid decarboxylase antibody (GADA) titers was also investigated. Results: Compared with normal controls, there were 26 miRNAs and 1218 genes differently expressed in PBMC of patients with newly diagnosed T1D. The greatest downregulation was for miR-146a (48% decrease; P<0.05). Expression of its target genes, predicted to be tumor necrosis factor receptor-associated factor 6 (TRAF6), B cell CLL/lymphoma 11A (BCL11A), syntaxin 3 (STX3) and numb homolog (NUMB), was upregulated. Moreover, T1D patients on long-course insulin and optimized glucose control had sustained low expression of miR-146. Interestingly, decreased miR-146a expression was significantly associated with high serum GADA titers (P<0.05). Conclusions: The results suggest that dysregulation of miR-146 expression in PBMC may be associated with the ongoing autoimmune imbalance in T1D patients. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

PubMed | Shanghai JiaoTong University, Louisiana State University, GenoVive, Shanghai Institute of Endocrine and Metabolic Diseases and 2 more.
Type: Journal Article | Journal: The Journal of nutrition | Year: 2015

Hepatic lipase (HL) plays a pivotal role in the metabolism of HDL and LDL. Recent genome-wide association studies have identified common variants in the HL gene (LIPC) associated with HDL cholesterol.We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial.We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30-70 y (61% women) who were assigned to high-fat (40% energy) or low-fat (20% energy) diets for 2 y. We measured serum concentrations of total cholesterol (TC), triglycerides, LDL cholesterol, and HDL cholesterol at baseline and 2 y of intervention.At 2 y of intervention, dietary fat modified effects of the variant on changes in serum TC, LDL cholesterol, and HDL cholesterol (P-interaction: 0.0008, 0.004, and 0.03, respectively). In the low-fat group, as compared to the G allele, the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [TC ( SE): -5.5 3.0, P = 0.07; LDL cholesterol: -4.8 2.5, P = 0.06] and a lower increase in HDL cholesterol concentrations ( SE: -1.37 0.69, P = 0.048), whereas an opposite effect in the high-fat diet group was evident [TC ( SE): 7.3 2.7, P = 0.008; LDL cholesterol: 4.1 2.3, P = 0.07], and there was no genetic effect on changes in HDL cholesterol concentrations (P = 0.54).Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults. This trial was registered at clinicaltrials.gov as NCT00072995.

Ren D.,Qingdao University | Sun K.,Qingdao University | Tian S.,Qingdao University | Yang X.,Qingdao University | And 5 more authors.
Journal of Biomechanics | Year: 2012

An increasing number of tissue banks have begun to focus on gamma irradiation and freeze-thaw in the reconstruction of anterior cruciate ligaments using allografts. The purpose of this study was to evaluate the biomechanical properties of human tendons after exposure to gamma radiation and repeated freeze-thaw cycles and to compare them with fresh specimens. Forty flexor digitorum superficialis tendons were surgically procured from five fresh cadavers and divided into four groups: fresh tendon, gamma irradiation, freeze-thaw and gamma irradiation+freeze-thaw. The dose of gamma irradiation was 25. kGy. Each freeze-thaw cycle consisted of freezing at -80°C for 7 day and thawing at 25°C for 6. h. These tendons underwent 4 freeze-thaw cycles. Biomechanical properties were analyzed during load-to-failure testing. The fresh tendons were found to be significantly different in ultimate load, stiffness and ultimate stress relative to the other three groups. The tendons of the gamma+freeze-thaw group showed a significant decrease in ultimate load, ultimate stress and stiffness compared with the other three groups. Gamma irradiation and repeated freezing-thawing (4 cycles) can change the biomechanical properties. However, no significant difference was found between these two processes on the effect of biomechanical properties. It is recommended that gamma irradiation (25. kGy) and repetitive freeze-thaw cycles (4 cycles) should not be adopted in the processing of the allograft tendons. © 2011 Elsevier Ltd.

Zhang Z.,Shanghai Institute of Endocrine and Metabolic Diseases | Zhang H.,Shanghai Institute of Endocrine and Metabolic Diseases | Li B.,Shanghai Institute of Endocrine and Metabolic Diseases | Meng X.,Shanghai Institute of Endocrine and Metabolic Diseases | And 9 more authors.
Nature Communications | Year: 2014

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity. © 2014 Macmillan Publishers Limited. All rights reserved.

PubMed | Shanghai Institute of Endocrine and Metabolic Diseases
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2011

To investigate the change points of HbA(1C) for detection of retinopathy in Chinese type 2 diabetic patients.This cross-sectional investigation included 992 diagnosed type 2 diabetic patients, who received non-mydriatic digital fundus photography examination. Joinpoint regression software was adopted to identify the change points of HbA(1C) in association with retinopathy prevalence.The mean age of all patients was 59.1 8.4 years and the duration of diabetes was 5.5 (95% CI: 5.2-5.9) years. The prevalence of retinopathy was 10.3% in total, and 4.1%, 7.4% and 19.6% in patients with different diabetes duration of 5 years, 5-10 years and >10 years, respectively. The change point of HbA(1C) was 6.5% (95%CI 5.8-7.5%), at which retinopathy prevalence began to rise sharply. Furthermore, in subjects with diabetes duration 5 years, 5-10 years and >10 years, the change points of HbA(1C) were 8.1% (95%CI 7.9-8.3%), 6.1% (95%CI 5.7-6.8%), 5.6% (95%CI 5.1-8.1%) for detection of retinopathy, respectively.The steepest increase in retinopathy prevalence occurred when HbA(1C) reached 6.5%. However, the duration of diabetes should be taken into concern, when using the change points of HbA(1C) for detection of retinopathy in diabetic patients.

PubMed | Shanghai Institute of Endocrine and Metabolic Diseases
Type: Journal Article | Journal: Endocrinology | Year: 2013

Chemerin is an adipokine involved in obesity, inflammation, and innate immune system that is highly expressed in the liver. In the present study, we find that chemerin mRNA expression is decreased in the livers of rodents with nonalcoholic fatty liver disease as well as in HepG2 cells after lipid overloading. Moreover, we report that chemerin expression and secretion are induced in HepG2 cells and primary hepatocytes from wild-type mice, but not farnesoid X receptor (FXR)-/- mice, in response to the synthetic FXR ligand GW4064. Hepatic chemerin expression is decreased in FXR-/- mice but up-regulated by GW4064 administration in wild-type mice. Dual-luciferase reporter assay and chromatin immunoprecipitation analyses further identified a functional FXR response element located in the -258-bp /+121-bp region of the chemerin gene. These data demonstrate that chemerin, a novel target gene of FXR, is related to nonalcoholic steatohepatitis.

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