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Weng J.,Guangdong Provincial Key Laboratory of Diabetology | Weng J.,Sun Yat Sen University | Soegondo S.,University of Indonesia | Schnell O.,Helmholtz Center Munich | And 5 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2015

Background: Alpha-glucosidase inhibitors are recommended in some international guidelines as first-line, second-line and third-line treatment options but are not used worldwide due to perceived greater effectiveness in Asians than Caucasians. Methods: Data from ten post-marketing non-interventional studies using acarbose, the most widely used alpha-glucosidase inhibitor, from 21 countries, provinces and country groups were pooled. Effects on glycated hemoglobin (HbA1c) were analysed for four major ethnicity/region groups (European Caucasians and Asians from East, Southeast and South Asia) to identify differences in the response to acarbose. Results: The safety and efficacy populations included 67 682 and 62 905 patients, respectively. Mean HbA1c in the total population decreased by 1.12±1.31% at the 3-month visit from 8.4% at baseline (p<0.0001). Reductions in HbA1c, fasting plasma glucose and post-prandial plasma glucose were greater in patients with higher baseline values. Acarbose was well tolerated, with few episodes of hypoglycemia (0.03%) and gastrointestinal adverse events (2.76%). Data from 30 730 Caucasians from Europe and Asians from three major regions of Asia with non-missing gender/age information and baseline/3-month HbA1c data were analysed by multivariable analyses of covariance. After adjustment for relevant baseline confounding factors, Southeast and East Asians had slightly better responses to acarbose than South Asians and European Caucasians; however, the differences were small. Conclusions: Acarbose was effective in both European Caucasians and Asians; however, after adjustment for baseline confounding factors, significant small differences in response favoured Southeast and East Asians. © 2014 The Authors. Source


Liu L.,Sun Yat Sen University | Liu L.,Guangdong Provincial Key Laboratory of Diabetology | Yang D.,Sun Yat Sen University | Yang D.,Guangdong Provincial Key Laboratory of Diabetology | And 17 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2015

Background: Glycaemic control is a great challenge in the management of type 1 diabetes mellitus (T1DM). There is limited data concerning glycaemic control among adults with T1DM. We used data from the Guangdong T1DM Translational Medicine Study to evaluate glycaemic control and its associated factors in Chinese adults with T1DM. Methods: This cross-sectional analysis included 827 participants who were 18 years of age or older and had been living with T1DM for at least 1 year. Participants with HbA1c levels <7% were compared against those with HbA1c levels≥7%. A multivariate logistic regression model was used to examine factors associated with glycaemic control. Results: Among the 827 participants, the mean age was 34.2±12.1 years and the median (interquartile range) duration of diabetes was 6.1 (3.4, 10.4) years. The median HbA1c level was 8.5% (7.5%, 10.2%). Only one-fifth of participants had HbA1c levels <7%. Insufficient glycaemic control (HbA1c≥7%) was strongly associated with infrequent self-monitoring of blood glucose (OR=1.21, 95% CI 1.14~1.29, p=0.000), high insulin dose (OR=1.27, 95% CI 1.07~1.52, p=0.006), smoking (OR=3.11, 95% CI 1.44~6.72, p=0.004), low-frequency clinical visits (OR=2.74, 95% CI 1.47~5.10, p=0.001), the presence of diabetic autoantibodies (OR=1.63, 95% CI 1.07~2.48, p=0.022) and low fasting C-peptide (FCP) levels (OR=1.21, 95% CI 1.01~1.46, p=0.049) after adjustment for age at disease onset, education level, household income and diet control. Conclusions: Most adult patients with T1DM did not achieve the HbA1c target. Identifying determinants for glycaemic control provides us valuable information to improve glycaemic control in these patients. © 2015 John Wiley & Sons, Ltd. Source


Xu F.,Sun Yat Sen University | Xu F.,Guangdong Provincial Key Laboratory of Diabetology | Zheng X.,Sun Yat Sen University | Zheng X.,Guangdong Provincial Key Laboratory of Diabetology | And 11 more authors.
Obesity | Year: 2016

Objective Recent studies have revealed that SIRT1 gain-of-function could promote adipose tissue browning for the adaptive thermogenesis under normal diet. This study investigated the role of SIRT1 loss-of-function in diet-induced obesity and insulin resistance and the mechanism involved in adipose tissue thermogenesis. Methods Male SIRT1+/- and wild-type (WT) mice were fed with a high-fat diet (HFD) for 16 weeks to induce obesity and insulin resistance, while mice on a chow diet were used as lean controls. The phenotype data were collected, and different adipose tissue depots were used for mechanism research. Results Compared with WT mice, SIRT1+/- mice exhibited increased adiposity and more severe insulin resistance with less thermogenesis under HFD challenge. Strikingly, SIRT1+/- mice displayed an exacerbated brown adipose tissue (BAT) degeneration phenotype, which was characterized by lower thermogenic activity, aggravated mitochondrial dysfunction, and more mitochondrial loss. In addition, SIRT1+/- mice showed aggravated inflammation and dysfunction in epididymal adipose tissue after HFD intervention, which also contributed to the systemic insulin resistance. Conclusions Diet-induced obesity and insulin resistance are associated with BAT degeneration in SIRT1-deficient mice, which further underlined the beneficial role of SIRT1 in obesity-associated metabolic disorders. © 2016 The Obesity Society. Source


Xu F.,Sun Yat Sen University | Xu F.,Guangdong Provincial Key Laboratory of Diabetology | Lin B.,Sun Yat Sen University | Lin B.,Guangdong Provincial Key Laboratory of Diabetology | And 12 more authors.
Diabetologia | Year: 2016

Aims/hypothesis: Accumulating evidence has revealed the significant role of glucagon-like peptide-1 (GLP-1) in weight loss. Sirtuin 1 (SIRT1) plays a vital role in the regulation of lipid metabolism. Here, we investigated the contribution of lipolytic and oxidative changes in white adipose tissue (WAT) to the weight-lowering effect induced by the GLP-1 receptor (GLP-1R) agonist exenatide (exendin-4) in mice. We also looked at the role of SIRT1 in this process. Methods: C57BL/6J mice and Sirt1+/− mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i.p. for 8 weeks while receiving a high-fat diet (HFD) after a 12 week HFD challenge. Systemic phenotypic evaluations were carried out during and after the intervention. A lentivirus-mediated short hairpin (sh)RNA vector of the Sirt1 gene was transfected into differentiated 3T3-L1 adipocytes. An in vitro model system used adipocytes induced from Sirt1-null mouse embryonic fibroblasts (MEFs). Results: Exenatide reduced fat mass and enhanced the lipolytic and oxidative capacity of WAT in diet-induced obese C57BL/6J mice. However, these effects were significantly impaired in Sirt1+/− mice compared with wild-type controls. In vitro, exendin-4 increased lipolysis and fatty acid oxidation by upregulating SIRT1 expression and activity in differentiated 3T3-L1 adipocytes. Conversely, RNA interference (i)-induced knockdown of SIRT1 attenuated the lipolytic and oxidative responses to exendin-4 in differentiated 3T3-L1 adipocytes. Again, these responses were entirely abolished in Sirt1-null MEFs after induction into adipocytes. Conclusions/interpretation: These data highlight that a GLP-1R agonist promotes brown remodelling of WAT in a SIRT1-dependent manner; this might be one of the mechanisms underlying its effect on weight loss. © 2016 Springer-Verlag Berlin Heidelberg Source

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