Sheyu Li

Dipeptidyl peptidase-4 inhibitors and risk of heart failure in type 2 diabetes: systematic review and meta-analysis of randomised and observational studies.

Objectives To examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of heart failure or hospital admission for heart failure in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised and observational studies. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov searched up to 25 June 2015, and communication with experts. Eligibility criteria Randomised controlled trials, non-randomised controlled trials, cohort studies, and case-control studies that compared DPP-4 inhibitors against placebo, lifestyle modification, or active antidiabetic drugs in adults with type 2 diabetes, and explicitly reported the outcome of heart failure or hospital admission for heart failure. Data collection and analysis Teams of paired reviewers independently screened for eligible studies, assessed risk of bias, and extracted data using standardised, pilot tested forms. Data from trials and observational studies were pooled separately; quality of evidence was assessed by the GRADE approach. Results Eligible studies included 43 trials (n=68 775) and 12 observational studies (nine cohort studies, three nested case-control studies; n=1 777 358). Pooling of 38 trials reporting heart failure provided low quality evidence for a possible similar risk of heart failure between DPP-4 inhibitor use versus control (42/15 701 v 33/12 591; odds ratio 0.97 (95% confidence interval 0.61 to 1.56); risk difference 2 fewer (19 fewer to 28 more) events per 1000 patients with type 2 diabetes over five years). The observational studies provided effect estimates generally consistent with trial findings, but with very low quality evidence. Pooling of the five trials reporting admission for heart failure provided moderate quality evidence for an increased risk in patients treated with DPP-4 inhibitors versus control (622/18 554 v 552/18 474; 1.13 (1.00 to 1.26); 8 more (0 more to 16 more)). The pooling of adjusted estimates from observational studies similarly suggested (with very low quality evidence) a possible increased risk of admission for heart failure (adjusted odds ratio 1.41, 95% confidence interval 0.95 to 2.09) in patients treated with DPP-4 inhibitors (exclusively sitagliptin) versus no use. Conclusions The relative effect of DPP-4 inhibitors on the risk of heart failure in patients with type 2 diabetes is uncertain, given the relatively short follow-up and low quality of evidence. Both randomised controlled trials and observational studies, however, suggest that these drugs may increase the risk of hospital admission for heart failure in those patients with existing cardiovascular diseases or multiple risk factors for vascular diseases, compared with no use.

Body Iron Stores and Heme-Iron Intake in Relation to Risk of Type 2 Diabetes: A Systematic Review and Meta-Analysis

Background and Objective Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies. Research Design and Methods Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I2 and Q statistic. Results The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15–2.39) for prospective studies, 2.29 (95% CI: 1.48–3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I2 = 66.3%; Q = 44.16, p<0.001, I2 = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21–1.43) with heterogeneity (Q = 1.39, p = 0.71, I2 = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review. Conclusions The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy

Background Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. Objective The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. Methods We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A1c (HbA1c) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. Results Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA1c (MD 0.48%, 95% CI 0.19%-0.78%) without excess adverse events. Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.37%, 95% CI –0.12%-0.86%). Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.69%, 95% CI –0.18%-0.53%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA1c reduction (with clinical decision making: MD 0.19%, 95% CI –0.24%-0.63% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.14). Conclusions The use of mobile app-based interventions yields a clinically significant HbA1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps.

Vitamin B12 status in metformin treated patients: systematic review.

Objective Randomized controlled trials and observational studies have yielded inconsistent results on the effects of metformin on vitamin B12 reduction. We therefore performed a systematic review to analyze the effects of metformin on vitamin B12 concentration. Methods PubMed, Medline, Embase, and the Cochrane central registry of controlled trials were searched to identify randomized controlled trials and observational studies exploring the association between metformin and vitamin B12 concentration in patients with type 2 diabetes mellitus or polycystic ovary syndrome. The main outcome measure was changes in serum vitamin B12 concentration after 6–208 weeks of treatment with metformin, as compared with placebo or other anti-hyperglycemic therapy. Results Six randomized controlled trials met the inclusion criteria. Serum vitamin B12 concentrations were significantly lower in patients treated with metformin than in those who received placebo or rosiglitazone (mean difference [MD], −53.93 pmol/L; 95% confidence interval [CI], −81.44 to −26.42 pmol/L, P = 0.0001). Subgroup analysis identified four trials in which patients received a lower dose of metformin (<2000 mg/d) and two in which they received a higher dose (≥2000 mg/d), with MDs in vitamin B12 concentration after metformin treatment of −37.99 pmol/L (95% CI, −57.44 to −18.54 pmol/L, P = 0.0001) and −78.62 pmol/L (95% CI, −106.37 to −50.86 pmol/L, P<0.00001), respectively. Conclusions The reduction of vitamin B12 may be induced by metformin in a dose dependent manner.

Bariatric Surgery for Type 2 Diabetes Mellitus in Patients with BMI <30 kg/m2: A Systematic Review and Meta-Analysis.

Background and Objective The role of bariatric surgery in non-obese patients with type 2 diabetes (T2DM) remains unclear, and its use in clinical practice is controversial. We conducted a systemic review and meta-analysis to investigate the metabolic changes after surgical treatment in diabetic patients with body mass index (BMI) <30 kg/m2. Methods We conducted a comprehensive search in MEDLINE (PubMed), EMBASE and the Cochrane Library of published articles from January 2000 to April 2013 reporting the clinical outcome changes in various metabolic outcomes in diabetic patients with BMI <30 kg/m2. Results Ten prospective studies including 290 patients were included in the meta-analysis. Bariatric surgery led to an overall 2.79 kg/m2 [95%CI 2.05~3.53, P<0.00001] reduction in BMI, a 1.88%[95%CI 1.32~2.43, P<0.00001] reduction in glycosylated hemoglobin, a 3.70 mmol/L [95%CI, 1.93~5.47, P<0.00001] reduction in fasting blood glucose, a 6.69 mmol/L [95%CI, 2.29~11.08, P=0.003] reduction in postprandial glucose, anda 3.37 [95%CI 0.55~6.18, P=0.02] reduction in homeostasis model assessment of insulin resistance (HOMA-IR). After surgical treatment, 76.2% of the patients were insulin free, and 61.8% patients were off medication. In total, 90(42.4%), 10(37%) and 34(37.2%) patients had post-surgical HbA1c levels of <6%,<6.5% and<7%, respectively. No deaths were observed in the included studies, and the major complication rate was 6.2%. Conclusions Based on the currently available data, bariatric surgery might improve glycemic control and weight loss in a very limited range with a doubled surgical complication rate in drug-refractory T2DM patients with BMI <30 kg/m2. It remains too premature to suggest bariatric surgery for non-obese T2DM patients.

Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case–Control Studies

Abstract Statin-related myopathy is an important adverse effect of statin which is classically unpredictable. The evidence of association between solute carrier organic anion transporter 1B1 (SLCO1B1) gene T521C polymorphism and statin-related myopathy risk remained controversial. This study aimed to investigate this genetic association. Databases of PubMed, EMBASE, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database, and Wanfang Data were searched till June 17, 2015. Case-control studies investigating the association between SLCO1B1 gene T521C polymorphism and statin-related myopathy risk were included. The Newcastle–Ottawa Scale (NOS) was used for assessing the quality of included studies. Data were pooled by odds ratios (ORs) and their 95% confidence intervals (CIs). Nine studies with 1360 cases and 3082 controls were included. Cases of statin-related myopathy were found to be significantly associated with the variant C allele (TC + CC vs TT: OR = 2.09, 95% CI = 1.27–3.43, P = 0.003; C vs T: OR = 2.10, 95% CI = 1.43–3.09, P < 0.001), especially when statin-related myopathy was defined as an elevation of creatine kinase (CK) >10 times the upper limit of normal (ULN) or rhabdomyolysis (TC + CC vs TT: OR = 3.83, 95% CI = 1.41–10.39, P = 0.008; C vs T: OR = 2.94, 95% CI = 1.47–5.89, P = 0.002). When stratified by statin type, the association was significant in individuals receiving simvastatin (TC + CC vs TT: OR = 3.09, 95% CI = 1.64–5.85, P = 0.001; C vs T: OR = 3.00, 95% CI = 1.38–6.49, P = 0.005), but not in those receiving atorvastatin (TC + CC vs TT: OR = 1.31, 95% CI = 0.74–2.30, P = 0.35; C vs T: OR = 1.33, 95% CI = 0.57–3.12, P = 0.52). The available evidence suggests that SLCO1B1 gene T521C polymorphism is associated with an increased risk of statin-related myopathy, especially in individuals receiving simvastatin. Thus, a genetic test before initiation of statins may be meaningful for personalizing the treatment.

Triclosan-loaded poly(amido amine) dendrimer for simultaneous treatment and remineralization of human dentine

In order to treat dental caries of damaged dentine, triclosan-loaded carboxyl-terminated poly(amido amine) dendrimer (PAMAM-COOH) is prepared and characterized. While being incubated in artificial saliva, triclosan-loaded PAMAM-COOH formulation can induce in situ remineralization of hydroxyapatite (HA) on etched dentine, and the regenerated HA has a similar crystal structure with natural dentine. It can also release the encapsulated triclosan for a long period. The interesting drug release profiles are controlled by both dendrimer encapsulation capability and the mineralization degree, which are ideal to obtain multifunctional properties of long-term release of anti-bacterial drug for local treatment during the remineralization process. The triclosan-loaded G4-COOH provides a general strategy to cure dental caries and repair damaged dentine at the same time, which forms a potential restorative material for dental repair.

RP105 Protects Against Apoptosis in Ischemia/Reperfusion-Induced Myocardial Damage in Rats by Suppressing TLR4- Mediated Signaling Pathways

Background: Myocardial apoptosis is heavily implicated in the myocardial damage caused by ischemia-reperfusion (I/R). Toll-like receptor 4 (TLR4) is a potent inducer of these apoptotic cascades. In contrast, the radioprotective 105 kDa protein (RP105) is a specific negative regulator of TLR4 signaling pathways. However, the precise mechanisms by which RP105 inhibits myocardium apoptosis via TLR4-associated pathways during I/R is not fully understood. Methods: We utilized a rat model of myocardial ischemic reperfusion injury (MIRI). Animals were pre-treated with Ad-EGFP adenovirus, Ad-EGFP-RP105 adenovirus, saline, or nothing (sham). After three days, rats underwent a 30min left anterior descending coronary artery occlusion and a 4h reperfusion. Mycardial tissue was assessed by immunohistochemistry, TUNEL-staining, Western blot, quantitative RT-PCR, and a morphometric assay. Results: RP105 overexpression resulted in a reduction in infarct size, fewer TUNEL-positive cardiomyocytes, and a reduction in mitochondrial-associated apoptosis cascade activity. Further, RP105 overexpression repressed I/R-induced myocardial injury by attenuating myocardial apoptosis. This was mediated by inhibiting TLR4 activation and the phosphorylation of P38MAPK and the downstream transcription factor AP-1. Conclusion: RP105 overexpression leads to the de-activation of TLR4, P38MAPK, and AP-1 signaling pathways, and subsequently represses apoptotic cascades and ensuing damage of myocardial ischemic reperfusion. These findings may become the basis of a novel therapeutic approach for reducing of cardiac damage caused by MIRI.

The Metabolic Effects of Oats Intake in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

The present study aimed to comprehensively assess if oats intake is beneficial for diabetic patients. The literature search was conducted in PubMed database up to 23 August 2015. Fourteen controlled trials and two uncontrolled observational studies were included. Compared with the controls, oats intake significantly reduced the concentrations of glycosylated hemoglobin A1c (HbA1c) (MD, −0.42%; 95% CI, −0.61% to −0.23%), fasting blood glucose (FBG) (MD, −0.39 mmol/L; 95% CI, −0.58 to −0.19 mmol/L), total cholesterol (TC) (MD, −0.49 mmol/L; 95% CI, −0.86 to −0.12 mmol/L), low-density lipoprotein cholesterol (LDL-C) (MD, −0.29 mmol/L; 95% CI, −0.48 to −0.09 mmol/L). Oatmeal significantly reduced the acute postprandial glucose and insulin responses compared with the control meal. The present study has revealed a beneficial effect of oats intake on glucose control and lipid profiles in type 2 diabetic patients. Further investigations of oats intake in patients with type 1 diabetes and the safety of oats consumption are required.

Cell-Derived Microparticles in Patients with Type 2 Diabetes Mellitus: a Systematic Review and Meta-Analysis

Background/Aims: The aim of this study was to assess the association between circulating cell-derived microparticles (MPs) and type 2 diabetes mellitus (T2DM). Methods: A literature search was performed systematically in PubMed and Embase to identify available case-control or cross-sectional studies that compared different types of cell-derived MPs in patients with T2DM and non-diabetic controls. Pooled standardized mean differences (SMDs) of each MP type were pooled using meta-analysis. Results: Forty-eight studies involving 2,460 patients with T2DM and 1,880 non-diabetic controls were included for systematic review and 34 of which were included for quantitative study by meta-analysis. In the overall analysis, the levels of circulating total MPs (TMPs), platelet-derived MPs (PMPs), monocyte-derived MPs (MMPs) and endothelium-derived MPs (EMPs) were significantly higher in T2DM patients than those in controls (TMPs: SMD, 0.64; 95%CI, 0.12∼1.15; P=0.02; PMPs: SMD, 1.19; 95%CI, 0.88∼1.50; P <0.00001; MMPs: SMD, 0.92; 95%CI, 0.66∼1.17; P <0.00001; EMPs: SMD, 0.73; 95%CI, 0.50∼0.96; P <0.00001). Meanwhile, no significant difference was shown in leukocyte-derived MPs (LMPs) level between diabetic and non-diabetic groups (SMD, 0.37; 95%CI, -0.15∼0.89; P=0.17). Conclusions: The counts of TMPs, PMPs, MMPs and EMPs elevated in patients with T2DM. And cell-derived MPs may play a role in the pathogenesis of T2DM.