National Clinical Research Center for Metabolic Diseases
National Clinical Research Center for Metabolic Diseases
You S.,Emory University |
You S.,Central South University |
You S.,National Clinical Research Center for Metabolic Diseases |
Anitha M.,Emory University |
And 7 more authors.
Molecular Therapy - Methods and Clinical Development | Year: 2015
Depending on the population examined, from 6 to 83% of people with diabetes mellitus exhibit symptoms of altered gut motility, manifesting as dysphagia, reflux, early satiety, nausea, abdominal pain, diarrhea, or constipation. Hyperglycemia-induced cell loss within the enteric nervous system has been demonstrated in both diabetic rodents and patients with diabetes. Glycemic control is recommended to prevent diabetic gastroenteropathy but is often difficult to achieve with current treatment modalities. We asked if hepatic insulin gene therapy (HIGT) could inhibit the development of diabetic gastroenteropathy in mice. Bowel length, bowel transit, colonic muscle relaxation, and the numbers of both stimulatory and inhibitory neurons in the colonic myenteric plexus were compared in groups of diabetic mice (DM), control nondiabetic mice (Con), and diabetic mice treated with HIGT (HIGT). Delivery of a metabolically responsive insulin transgene to the liver of STZ-diabetic mice with an adeno-associated virus, sero-type 8 (AAV8) produced near-normal blood sugars for over 1 month and prevented anatomic, functional, and neurohistologic changes observed in diabetic mice. We conclude that in addition to normalizing oxidative metabolism in diabetic rodents, HIGT is sufficient to prevent the development of diabetic gastroenteropathy. © 2015 Official journal of the American Society of Gene & Cell Therapy
Ding L.,National Clinical Research Center for Metabolic Diseases |
Peng K.,National Clinical Research Center for Metabolic Diseases |
Lin L.,National Clinical Research Center for Metabolic Diseases |
Li M.,National Clinical Research Center for Metabolic Diseases |
And 10 more authors.
International Journal of Cardiology | Year: 2017
Background The relationship between obesity and cardiovascular disease (CVD) depends not only on the amount of body fat but also on its distribution, which has not been fully investigated in Chinese populations. We aimed to compare measures of fat accumulation in associations with subclinical coronary atherosclerosis in middle-aged Chinese adults. Methods A total of 548 participants aged 40–60 years without previous history or clinical symptoms of CVD were randomly selected to undergo abdominal computed tomography (CT) scanning and coronary CT angiography for the evaluation of subcutaneous and visceral fat accumulation and coronary atherosclerosis, respectively. γ-glutamyltranspeptidase (GGT) was used as a surrogate indicator of liver fat accumulation. Results Measures of obesity such as body-mass index (BMI), waist circumference, visceral fat areas, and GGT levels, but not subcutaneous fat areas increased substantially across groups of participants without coronary stenosis, with < 50% stenosis, and with significant (≥ 50%) stenosis after adjustment for age and sex. The multivariable multinomial logistic regression analysis showed that most obesity indicators such as BMI, waist circumference, visceral fat areas, and GGT levels were significantly associated with risks of having < 50% coronary stenosis after adjustment for conventional cardiovascular risk factors. However, only GGT levels were significantly associated with risks of having significant (≥ 50%) coronary stenosis after adjustment. In addition, no significant associations were found between measures of fat accumulation and coronary calcification. Conclusions Liver fat accumulation might be more important in the association with subclinical coronary atherosclerosis compared with general and abdominal fat accumulation. © 2017 Elsevier B.V.
DENG X.R.,National Clinical Research Center for Metabolic Diseases |
DENG X.R.,Shanghai JiaoTong University |
DING L.,National Clinical Research Center for Metabolic Diseases |
DING L.,Shanghai JiaoTong University |
And 17 more authors.
Biomedical and Environmental Sciences | Year: 2017
Serum fetuin-A levels are reportedly elevated in hyperthyroidism. However, there are few relevant epidemiologic studies. We conducted a cross-sectional study in Songnan community, China in 2009 to investigate the association between serum fetuin-A concentrations and thyroid function. A total of 2,984 participants aged 40 years and older were analyzed. Multivariable linear regression analysis revealed that serum fetuin-A concentrations were positively associated with log (free triiodothyronine) and were inversely associated with log (thyroid peroxidase antibody) after adjustment (both P < 0.05). Compared with the participants in the lowest tertile of free triiodo- thyronine and free thyroxine level, those in the highest tertile had higher fetuin-A concentrations. Additionally, high serum fetuin-A concentrations were related to high thyroid function (odds ratio 1.27, 95% confidence interval 1.01–1.61), after adjustment for conventional risk factors. © 2017 The Editorial Board of Biomedical and Environmental Sciences
Huang X.,National Clinical Research Center for Metabolic Diseases |
Huang X.,Shanghai JiaoTong University |
Xu M.,National Clinical Research Center for Metabolic Diseases |
Xu M.,Shanghai JiaoTong University |
And 22 more authors.
Medicine (United States) | Year: 2015
The fatty liver index (FLI), which is an algorithm based on waist circumference, body mass index (BMI), triglyceride, and gammaglutamyl-transferase (GGT), was initially developed to detect fatty liver in Western countries. Our study aimed to evaluate the accuracy and optimal cut-off point of the FLI for predicting nonalcoholic fatty liver disease (NAFLD) in middle-aged and elderly Chinese. This cross-sectional study included 8626 Chinese adults aged 40 years or above recruited from Jiading District, Shanghai, China. Anthropometric and biochemical features were collected by a standard protocol. NAFLD was diagnosed by hepatic ultrasonography. The accuracy and cut-off point of the FLI to detect NAFLD were evaluated by area under the receiver operator characteristic curve (AUROC) and the maximum Youden index analysis, respectively. The AUROC of the FLI for NAFLD was 0.834 (95% confidence interval: 0.825-0.842), and larger than that of its each individual component [0.786 (0.776-0.796), 0.783 (0.773-0.793), 0.727 (0.716-0.739), and 0.707 (0.695-0.719) for waist circumference, BMI, triglyceride, and GGT, respectively] (all P<0.001). The optimal cut-off point of the FLI for diagnosing NAFLD was 30 with the maximum Youden Index of 0.51, achieving a high sensitivity of 79.89% and a specificity of 71.51%. The FLI-diagnosed NAFLD individuals were in worse metabolic characteristics (waist circumference, BMI, blood pressure, serum lipids, and aminotransferases) than ultrasonography-diagnosed NAFLD patients (all P<0.05). The FLI could accurately identify NAFLD and the optimal cut-off point was 30 in middle-aged and elderly Chinese. As FLI-diagnosed NAFLD patients were in worse metabolism, much attention should be paid to the metabolic controls and managements of NAFLD. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Wang T.,National Clinical Research Center for Metabolic Diseases |
Wang T.,Shanghai JiaoTong University |
Lu J.,National Clinical Research Center for Metabolic Diseases |
Lu J.,Shanghai JiaoTong University |
And 41 more authors.
Diabetic Medicine | Year: 2015
Aims: Few studies have analysed the effect of sleep duration and snoring on hypertension and glycaemic control in patients with diabetes. This study aims to investigate the relationship of sleep duration and snoring on prevalent hypertension and glycaemic control in people with diabetes. Methods: In the baseline survey of the REACTION study, 56 032 patients with diabetes were categorized into four groups according to self-reported sleep duration: < 6, 6-7.9, 8-8.9 and ≥ 9 h. Snoring frequency was evaluated as 'usually', 'occasionally' or 'never'. Hypertension was assessed by systolic blood pressure, diastolic blood pressure, self-reported previous diagnosis and antihypertensive medications. 'Good' glycaemic control was defined as HbA1c < 53 mmol/mol (7.0%) and 'poor' glycaemic control as HbA1c ≥ 53 mmol/mol (7.0%). Results: Controlling for potential confounders and intermediates, sleep ≥ 9 h relative to intermediate sleep (6-7.9 h) was significantly associated with prevalent hypertension (OR: 1.25, 95% CI: 1.18-1.32) and poor glycaemic control (OR: 1.11, 95% CI: 1.05-1.18), and a U-shaped association was found between sleep duration and prevalent hypertension (P for quadratic trend = 0.019). Usually snoring was positively associated with prevalent hypertension (OR: 1.30, 95% CI: 1.23-1.37), whereas the association between snoring and poor glycaemic control was only on the borderline of statistical significance. Conclusions: Compared with a sleep duration of 6-7.9 h, longer sleep duration was associated with a higher prevalence of hypertension and poor glycaemic control in people with diabetes. Moreover, the relationship between sleep duration and prevalent hypertension was U-shaped. These findings may propose important public health implications for diabetes management. What's new?: Longer sleep duration (≥ 8 h) was positively associated with prevalent hypertension and poor glycaemic control in patients with diabetes, and the association between sleep duration and prevalent hypertension was U-shaped. The findings may have implications for diabetes management. © 2015 Diabetes UK.
Chen M.,Central South University |
Chen M.,National Clinical Research Center for Metabolic Diseases |
Zhang J.,Central South University |
Hu F.,Central South University |
And 4 more authors.
Diabetes/Metabolism Research and Reviews | Year: 2015
Objective: Accumulating evidence suggests an association between diabetes and cancer. Inflammation is a key event that underlies the pathological processes of the two diseases. Metformin displays anti-cancer effects, but the mechanism is not completely clear. This study investigated whether metformin regulated the microenvironment of macrophage polarization to affect the characteristics of HepG2 cells and the possible role of the Notch-signalling pathway. Methods: RAW264.7 macrophages were cultured alone or co-cultured with HepG2 cells and treated with metformin. We analysed classical (M1) and alternative (M2) gene expression in RAW264.7 cells using quantitative real-time polymerase chain reaction. Changes in mRNA and protein expressions of Notch signalling in both cell types were also detected using quantitative real-time polymerase chain reaction and Western-blotting analyses. The proliferation, apoptosis and migration of HepG2 cells were detected using Cell Titer 96 AQueous One Solution Cell Proliferation Assay (MTS) (Promega Corporation, Fitchburg, WI, USA), Annexin V-FITC/PI (7SeaPharmTech, Shanghai, China) and the cell scratch assay, respectively. Results: Metformin induced single-cultured RAW264.7 macrophages with an M2 phenotype but attenuated the M2 macrophage differentiation and inhibited monocyte chemoattractant protein-1 (MCP-1) secretion in a co-culture system. The co-cultured group of metformin pretreatment activated Notch signalling in macrophages but repressed it inHepG2 cells. Co-culture also promoted the proliferation and migration of HepG2 cells. However, along with the enhanced apoptosis, the proliferation and the migration of HepG2 cells were remarkably inhibited in another co-culture system with metformin pretreatment. Conclusions: Metformin can skew RAW264.7 macrophages toward different phenotypes according to changes in the microenvironment, which may affect the inflammatory conditions mediated by macrophages, induce apoptosis and inhibit the proliferation and migration of HepG2 cells. Notch signalling pathway is a potentially important mechanism in the regulation of metformin on macrophage polarization and the subsequent change of hepatoma cells. © 2015 John Wiley & Sons, Ltd.