ObjeCtivesTo 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. DesignSystematic review and meta-analysis of randomised and observational studies. Data sOurCes

BackgroundThe effect of glucagon-like peptide-1(GLP-1) receptor agonists on heart failure remains uncertain. We therefore conducted a systematic review to assess the possible impact of GLP-1 agonists on heart failure or hospitalization for heart failure in patients with type 2 diabetes.MethodsWe searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov to identify randomized controlled trials (RCTs) and observational studies that addressed the effect of GLP-1 receptor agonists in adults with type 2 diabetes, and explicitly reported heart failure or hospitalization for heart failure. Two paired reviewers screened reports, collected data, and assessed the risk of bias. We pooled data from RCTs and observational studies separately, and used the GRADE approach to rate the quality of evidence.ResultsWe identified 25 studies that were eligible for our review; 21 RCTs (n = 18,270) and 4 observational studies (n = 111,029). Low quality evidence from 20 RCTs suggested, if anything, a lower incidence of heart failure between GLP-1 agonists versus control (17/7,441 vs. 19/4,317; odds ratio (OR) 0.62, 95 % confidence interval (CI) 0.31 to 1.22; risk difference (RD) 19 fewer, 95 % CI 34 fewer to 11 more per 1000 over 5 years). Three cohort studies comparing GLP-1 agonists to alternative agents provided very low quality evidence that GLP-1 agonists do not increase the incidence of heart failure. One RCT provided moderate quality evidence that GLP-1 agonists were not associated with hospitalization for heart failure (lixisenatide vs placebo: 122/3,034 vs. 127/3,034; adjusted hazard ratio 0.96, 95 % CI 0.75 to 1.23; RD 4 fewer, 95 % CI 25 fewer to 23 more per 1000 over 5 years) and a case–control study provided very low quality evidence also suggesting no association (GLP-1 agonists vs. other anti-hyperglycemic drugs: 1118 cases and 17,626 controls, adjusted OR 0.67, 95 % CI 0.32 to 1.42).ConclusionsThe current evidence suggests that GLP-1 agonists do not increase the risk of heart failure or hospitalization for heart failure among patients with type 2 diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0260-0) contains supplementary material, which is available to authorized users.

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The prevalence of metabolic syndrome (MS) has been on the rise over the past few decades, and this is associated with an increased incidence of target organ damage such as left ventricular hypertrophy (LVH). This meta-analysis aims to evaluate the features of LVH in MS patients with or without high blood pressure (BP). PubMed, Cochrane Library, Embase, Science Citation Index, and China Biology Medicine Disc, WanFang data, China National Knowledge Infrastructure database, and VIP were searched. Cross-sectional studies which directly compared LVH in hypertensive patients with MS and those with hypertension alone were identified. The following parameters were analyzed: systolic blood pressure (SBP), diastolic blood pressure (DBP), left ventricular mass (LVM), left ventricular mass index (LVMI), left ventricular mass/height(2.7) (LVM/h(2.7)), interventricular septum thickness (IVSt), left ventricular end-diastolic diameter (LVEDd), left ventricular posterior wall (LVPW), ratio of early to late diastolic peak flow velocity (E/A), and relative wall thickness (RWT). Data were extracted and analyzed by Cochrane Collaboration's RevMan 5.0 software. 14 studies involving 5,994 patients were included. In four studies, MS patients with comparable level of BP had higher SBP (mmHg) [Mean Difference (MD) = 2.28, 95 % confidence intervals (CI): -0.58 to 5.13], DBP (mmHg) (MD = 1.32, 95 % CI: -0.23 to 2.87), LVM (g) (MD = 42.10, 95 % CI: 6.92-77.28), LVMI (g/m(2)) (MD = 8.93, 95 % CI: 5.29-12.57), LVM/h(2.7) (g/m(2.7)) (MD = 5.40, 95 % CI: 2.51-8.29), IVSt (mm) (MD = 0.49, 95 % CI: 0.28-0.71), LVEDd (mm) (MD = 1.04, 95 % CI: -1.10 to 3.18), LVPW (mm) (MD = 0.75, 95 % CI: 0.13-1.37), RWT (MD = 0.06, 95 % CI: -0.00 to 0.12), and lower E/A (MD = -0.08, 95 % CI: -0.18 to 0.02) when compared to the patients with hypertension alone. In other ten studies, the hypertensive patients with MS exhibited higher levels of SBP (mmHg) (MD = 4.67, 95 % CI: 2.72-6.62), DBP (mmHg) (MD = 2.03,95 % CI: 1.40-2.65), LVM (g) (MD = 24.79, 95 % CI: 20.21-29.36), LVMI(g/m(2)) (MD = 9.22, 95 % CI: 2.81-15.64), LVM/h(2.7) (g/m(2.7)) (MD = 5.97, 95 % CI: 4.14-7.80), IVSt (mm) (MD = 0.63, 95 % CI: 0.58-0.69), LVEDd (mm) (MD = 1.11, 95 % CI: 0.42-1.80), LVPW (mm) (MD = 0.63, 95 % CI: 0.31-0.94), RWT (MD = 0.02, 95 % CI: 0.01-0.03), as compared to patients with hypertension alone (P < 0.05). In addition, the MS patients combining with hypertension showed a lower E/A (MD = -0.07, 95 % CI: -0.10 to -0.04) when compared to those with hypertension alone. This study suggests that MS plays an important role in the development of LVH. MS seems to amplify hypertension-related cardiac changes. Furthermore, MS combining with higher level of BP will aggravate LVH and damage the diastolic function of left ventricle.

Epigenetic analysis of the association between the methylation status of the promoter region of the MTRR (5-methyltetrahydrofolate-homocysteine methyltransferase reductase) gene and the risk of acute lymphoblastic leukemia (ALL) in children plays an important role in the early diagnosis, assessment of the malignant degree, treatment and evaluation of the risk of relapse and prognosis of the disease. In the present study, RT-qPCR was used to detect the mRNA levels of the MTRR and MTHFR (methylenetetrahydrofolate reductase) genes in the bone marrow of 20 ALL patients and 20 age-and sex-matched controls with normal bone marrow. The methylation pattern of the MTRR promoter region in eligible DNA samples was quantitatively analyzed using MALDI-TOF MS. The results indicated that the mRNA expression level of MTRR in the bone marrow from children with ALL was lower than that in the control samples (P<0.05), but no significant difference was detected in the MTHFR gene between the two groups (P>0.05). According to the risk classification of ALL in children with high, medium and low risk, the low-risk group had a higher methylation rate of CpG_6 compared to the medium-risk group. However, the medium-risk group had a higher CpG_46.47 methylation rate compared to the low-risk group. The methylation rates of CpG_26 and CpG_46.47 in the high-risk group were higher than these rates in the low-risk group, while the CpG_42.23.44 methylation rate was lower in the high-risk group than in the low-risk group (P<0.05). The methylation rates at CpG_1, CpG_10, CpG_48 sites, score and the average methylation rate in the ALL-H (high) group (≥50x10 9 /l) were lower than these in the ALL-NH (not high) group (<50x10 9 /l) and the control group (P<0.05). We conclude that abnormal MTRR mRNA expression and the methylation of the MTRR promoter can be used to classify the risk of ALL in children.