Rongping Chen

Effect of Probiotics on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized, Controlled Trials

Background Previous clinical trials indicate that probiotic consumption may improve blood glucose control, however, results from randomized trials on glycemic control have been inconsistent. Objective To investigate the effects of probiotics on glycemic control in a systematic review and meta-analysis of randomized controlled trials. Data Sources PubMed, Embase, Cochrane Library, and Clinicaltrial.gov through October 2014. Data Extraction and Synthesis Two independent reviewers extracted relevant data and assessed study quality and risk of bias. Data were pooled using a random-effects model and expressed as mean differences (MD) with 95% CI. Heterogeneity was assessed (Cochran Q-statistic) and quantified (I 2). Results Seventeen randomized controlled trials were included, in which 17 fasting blood glucose (n = 1105), 11 fasting plasma insulin (n = 788), 8 homeostasis model assessment of insulin resistance (n = 635) comparisons were reported. Probiotic consumption, compared with placebo, significantly reduced fasting glucose (MD = -0.31 mmol/L; 95% CI 0.56, 0.06; p = 0.02), fasting plasma insulin (MD = -1.29 μU/mL; 95% CI -2.17, -0.41; p = 0.004), and HOMA-IR (MD = 0.48; 95% CI -0.83, -0.13; p = 0.007). Conclusions Probiotic consumption may improve glycemic control modestly. Modification of gut microbiota by probiotic supplementation may be a method for preventing and control hyperglycemia in clinical practice.

The Cytotoxic Role of Intermittent High Glucose on Apoptosis and Cell Viability in Pancreatic Beta Cells

Objectives. Glucose fluctuations are both strong predictor of diabetic complications and crucial factor for beta cell damages. Here we investigated the effect of intermittent high glucose (IHG) on both cell apoptosis and proliferation activity in INS-1 cells and the potential mechanisms. Methods. Cells were treated with normal glucose (5.5 mmol/L), constant high glucose (CHG) (25 mmol/L), and IHG (rotation per 24 h in 11.1 or 25 mmol/L) for 7 days. Reactive oxygen species (ROS), xanthine oxidase (XOD) level, apoptosis, cell viability, cell cycle, and expression of cyclinD1, p21, p27, and Skp2 were determined. Results. We found that IHG induced more significant apoptosis than CHG and normal glucose; intracellular ROS and XOD levels were more markedly increased in cells exposed to IHG. Cells treated with IHG showed significant decreased cell viability and increased cell proportion in G0/G1 phase. Cell cycle related proteins such as cyclinD1 and Skp2 were decreased significantly, but expressions of p27 and p21 were increased markedly. Conclusions. This study suggested that IHG plays a more toxic effect including both apoptosis-inducing and antiproliferative effects on INS-1 cells. Excessive activation of cellular stress and regulation of cyclins might be potential mechanism of impairment in INS-1 cells induced by IHG.

Prevalence and risk factors for diabetic retinopathy in a high-risk Chinese population.

BackgroundLifestyle plays an important role in the development of diabetic retinopathy. The lifestyle in Guangzhou is different from other cities in China as the Cantonese prefer eating rice porridge, but not spicy foods. The objectives of this study were to investigate the prevalence and determinants of diabetic retinopathy in a high-risk population of Guangzhou.MethodsSubjects (619 totals) aged over 45 years old, without known diabetes were recruited from five randomly selected Guangzhou communities in 2009–2010. All participants were invited to complete the Finnish Diabetes Risk Score (FINDRISC) questionnaire. Subjects with FINDRISC score ≥ 9 were included in the study, and underwent an investigation of demographic data, a standardized physical examination, ocular fundus examination, and laboratory analyses. The minimum criterion for diagnosis of diabetic retinopathy was the presence of at least one microaneurysm.ResultsOf 619 subjects, 208 eligible subjects (122 women) with FINDRISC score ≥ 9 were included in the study. The mean age was 69.2 ± 8.5 years. Diabetic retinopathy was detected in 31 subjects, and the prevalence of diabetic retinopathy in subjects with high risk for diabetes was 14.9%. In binary logistic regression analysis, risk factors associated with diabetic retinopathy were history of impaired glucose regulation [odds ratio (OR), 7.194; 95% confidence interval (CI): 1.083, 47.810], higher hemoglobin A1c (HbA1c; OR, 2.912; 95% CI: 1.009, 8.402), higher two-hour postprandial plasma glucose level (OR, 1.014; 95% CI: 1.003, 1.025), and presence of microalbuminuria (OR, 5.387; 95% CI: 1.255, 23.129).ConclusionsDiabetic retinopathy was prevalent in a high-risk Chinese population from Guangzhou. Histories of impaired glucose regulation and microalbuminuria were strong risk factors for diabetic retinopathy.

Prevalence and determinants of hyperuricemia in type 2 diabetes mellitus patients with central obesity in Guangdong Province in China

This study investigated the prevalence and determinants of hyperuricemia in Chinese type 2 diabetes mellitus (T2DM) patients with central obesity. A multicentric hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. At each hospital, Chinese T2DM patients with central obesity who were aged over 20 years, whose serum uric acid levels were measured, and who had lived in Guangdong Province for >=1 year, were recruited. Hyperuricemia was defined as serum uric acid >420 μmol/L in men and >360 μmol/L in women. Binary logistic regression was used to assess associated risk factors for hyperu-ricemia. A total of 2,917 T2DM patients with central obesity took part. The overall prevalence of hyperuricemia was 32.6% (36.1% for women, 28.4% for men). Binary logistic regression analyses demonstrated that women (OR: 1.576; 95% confidence interval (CI): 1.231, 2.018), high BMI (OR: 1.228; 95% CI: 1.094, 1.379), waist cir-cumference (OR: 1.135; 95% CI: 1.009, 1.276), hypertension (OR: 1.603; 95% CI: 1.263, 2.035), high total cho-lesterol (OR: 1.133; 95% CI: 1.002, 1.281), triglycerides (OR: 1.134; 95% CI: 1.069, 1.203), low HDL-cholesterol (OR: 0.820; 95% CI: 0.677, 0.995) and low estimated glomerular filtration rate (OR: 0.840; 95% CI: 0.815, 0.866) were risk factors associated with hyperuricemia. Hyperuricemia is prevalent in Chinese T2DM patients with central obesity and is significantly positively associated with women, cardiovascular risk factors such as obesity, hypertension and dyslipidemia, and low eGFR.

Betatrophin Acts as a Diagnostic Biomarker in Type 2 Diabetes Mellitus and Is Negatively Associated with HDL-Cholesterol

Objective. By assessing its circulating concentrations in type 2 diabetes mellitus (T2DM) patients, we aimed to explore the associations of betatrophin with various metabolic parameters and evaluate its diagnostic value in T2DM. Methods. A total of 58 non-diabetes-mellitus (NDM) subjects and 73 age- and sex-matched newly diagnosed T2DM patients were enrolled. Correlation analyses between circulating betatrophin levels and multiple metabolic parameters were performed. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic value of betatrophin concentration in T2DM. Results. Circulating betatrophin levels were approximately 1.8 times higher in T2DM patients than in NDM individuals (median 747.12 versus 407.41 pg/mL, P < 0.001). Correlation analysis showed that betatrophin was negatively associated with high-density lipoprotein cholesterol (HDL-C) levels in all subjects. ROC curve analysis identified betatrophin as a potent diagnostic biomarker for T2DM. The optimal cut-off point of betatrophin concentration for predicting T2DM was 501.23 pg/mL. Conclusions. Serum betatrophin levels were markedly increased in newly diagnosed T2DM patients and further elevated in obese T2DM subjects. Betatrophin was negatively correlated with HDL-C levels. Our findings indicate that betatrophin could be a potent diagnostic biomarker for T2DM.

Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor-γ2 gene on metabolic syndrome risk: A meta-analysis

BACKGROUND Associations between peroxisome proliferator-activated receptor γ2 (PPARγ2) gene polymorphism and metabolic syndrome risk remained controversial and ambiguous. Thus, we performed a meta-analysis to assess the association between Pro12Ala polymorphism in PPARγ2 gene and metabolic syndrome susceptibility. METHODS An electronic literature search was conducted on Medline, OVID, Cochrane Library database, and the China National Knowledge Internet up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the fixed or random effects model. RESULTS Ten studies involving a total of 4456 cases and 10343 controls were included in this meta-analysis. No statistical evidence of association was found between Pro12Ala polymorphism and metabolic syndrome risk in all genetic models (homozygote model: OR=0.83, 95% CI=0.62-1.12; heterozygote model: OR=1.04, 95% CI=0.94-1.14; dominant model: OR=1.02, 95% CI=0.93-1.12; recessive model: OR=0.83, 95% CI=0.62-1.11). No statistical evidence of significant association was observed when stratified by ethnicity, definition of metabolic syndrome, source of control groups and quality score of the selected articles. All in all, the results did not support a major role of the Pro12Ala variant of the PPARγ2 gene in metabolic syndrome risk. CONCLUSIONS This meta-analysis suggested that the effect of Pro12Ala polymorphism in PPARγ2 gene may not be related to metabolic syndrome as an entity. However, Pro12Ala may affect the single component of metabolic syndrome. A large, well designed study is required to more adequately assess the role for Pro12Ala polymorphism on metabolic syndrome.

Reprogramming of Mice Primary Hepatocytes into Insulin-Producing Cells by Transfection with Multicistronic Vectors

The neogenesis of insulin-producing cells (IPCs) from non-beta-cells has emerged as a potential method for treating diabetes mellitus (DM). Many groups have documented that activation of pancreatic transcription factor(s) in hepatocytes can improve the hyperglycemia in diabetic mice. In the present study, we explored a novel protocol that reprogrammed primary hepatocytes into functional IPCs by using multicistronic vectors carrying pancreatic and duodenal homeobox-1 (Pdx1), neurogenin 3 (Ngn3), and v-musculoaponeurotic fibrosarcoma oncogene homolog A (MafA). These triple-transfected cells activated multiple beta-cell genes, synthesized and stored considerable amounts of insulin, and released the hormone in a glucose-regulated manner in vitro. Furthermore, when transplanted into streptozotocin-induced diabetic mice, the cells markedly ameliorated glucose tolerance. Our results indicated that ectopic expression of Pdx1, Ngn3, and MafA facilitated hepatocytes-to-IPCs reprogramming. This approach may offer opportunities for treatment of DM.

Differentially expressed circulating LncRNAs and mRNA identified by microarray analysis in obese patients

Circulating long non-coding RNAs (lncRNAs) serve as valuable biomarkers in a number of human diseases. However, lncRNA biomarkers have yet to be identified in obesity. We aim to characterize circulating lncRNA expression in obese and non-obese human subjects. First, we assessed the genome-wide circulating lncRNA expression profiles in blood from 3 obese and 3 non-obese human subjects. We found a significant decrease in circulating levels of three lncRNAs (lncRNA-p5549, lncRNA-p21015 and lncRNA-p19461) in obese human subjects only. Next, using RT-PCR we measured the expression levels of these three lncRNAs in 33 obese and 33 non-obese human subjects and found similar differences. Moreover, we found a negative correlation between circulating levels of these three lncRNAs and body mass index (BMI), waist circumference, waist to hip ratio and fasting insulin. There was also a significant negative correlation between expression of lncRNA-p19461 and homeostasis model assessment-estimated insulin resistance. Finally, we tested the circulating levels of these three lncRNAs in 8 obese human subjects after a 12-week diet-induced weight loss program. We found that only lncRNA-p19461 expression level significantly increased. In summary, circulating lncRNAs are deregulated in obesity. Weight loss–induced changes in this profile support this observation and suggest a potential mechanistic relevance.

Cardiometabolic risk profiles associated with chronic complications in overweight and obese type 2 diabetes patients in South China.

Background Type 2 diabetes is often accompanied by altered cardiometabolic risk profiles, including abdominal obesity, hypertension, and dyslipidaemia. The association of altered cardiometabolic risk profiles with chronic complications of diabetes is not well investigated. Methods We recruited 2954 type 2 diabetes patients with a body mass index ≥25 kg/m2 who visited the diabetes clinics of 62 hospitals in 21 cities in Guangdong province of China from August 2011 to March 2012. Demographic characteristics, personal and family medical histories, and data on chronic complications of diabetes were collected. Clinical examinations and laboratory assessment were conducted. Results Abdominal obesity was found in 91.6% of the study population, elevated blood pressure in 78.3%; elevated serum triacylglycerols in 57.8%, and reduced serum HDL-C in 55.9%. Among the cardiometabolic risk factors, elevated blood pressure was significantly associated with almost all the chronic complications of diabetes. After adjusting for age, gender, duration of diabetes, and HbA1c, elevated blood pressure was significantly associated with diabetic retinopathy (OR 1.63, 95% CI: 1.22–2.19), diabetic nephropathy (OR 3.16, 95% CI: 2.25–4.46), cardiovascular disease (OR 2.71, 95% CI: 1.70–4.32), and stroke (OR 1.90, 95% CI: 1.15–3.12). Abdominal adiposity was significantly associated with diabetic nephropathy (OR 1.39, 95% CI: 1.11–1.74). Elevated triacylglycerols was significantly associated with diabetic retinopathy (OR 1.29, 95% CI: 1.05–1.58) and diabetic nephropathy (OR 1.30, 95% CI: 1.05–1.58). Reduced HDL-C was significantly associated with stroke (OR 1.41, 95% CI: 1.05–1.88). Conclusions Altered cardiometabolic risk profiles, and elevated blood pressure in particular, were significantly associated with chronic complications in overweight and obese patients with type 2 diabetes. Future studies on the prevention of chronic complications of diabetes might make lowering blood pressure a primary target.

The performance of a diabetic retinopathy risk score for screening for diabetic retinopathy in Chinese overweight/obese patients with type 2 diabetes mellitus.

Abstract Introduction. Diabetic retinopathy (DR) is a common chronic microvascular diabetic complication. The presence of DR may indicate microcirculatory dysfunction in other organ systems besides visual morbidity. The objective of this study was to develop a simple diabetic retinopathy risk score to identify DR in Chinese overweight/obese patients with type 2 diabetes mellitus (T2DM). Patients and methods. A multicentre hospital-based cross-sectional study was carried out in Guangdong Province between August 2011 and March 2012. The evaluated 2699 patients included 1263 males and 1436 females, with an average age of 59.4 ± 13.0 years. Results. The diabetic retinopathy risk score was conducted by age, duration of DM, history of antihypertensive drug treatment, and waist circumference. The area under the receiver operating characteristics curve for DR was 0.700 (95% CI 0.671–0.729). Comparing Youdens index of different values, the optimal cut-off point was 20 to predict DR. The odds ratio for one unit increase in the diabetic retinopathy risk score associated with the risk of DR was 1.104 (95% CI 1.089–1.120). Conclusions. Our data suggest that the diabetic retinopathy risk score could be a reliable primary screening tool for the presence of DR in Chinese overweight/obese patients with T2DM.