-
1.
Effects of SGLT2 inhibitors on fractures and bone mineral density in type 2 diabetes: An updated meta-analysis.
Li, X, Li, T, Cheng, Y, Lu, Y, Xue, M, Xu, L, Liu, X, Yu, X, Sun, B, Chen, L
Diabetes/metabolism research and reviews. 2019;(7):e3170
Abstract
BACKGROUND The aim of the study is to update and determine the effects of sodium glucose cotransporter 2 (SGLT2) inhibitor therapy on fracture and bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM). METHODS We identified 27 eligible randomized controlled trials (RCTs) that compared the efficacy and safety of SGLT2 inhibitors to a placebo in 20 895 T2DM participants, with an average duration of 64.22 weeks. The relative risk (RR) of bone fracture and weighted mean difference (WMD) of changes in the BMD from baseline were determined to evaluate the risk of fracture. The degree of heterogeneity was evaluated by the I2 statistic, and publication bias was estimated using a funnel plot and Egger test. RESULTS The pooled RR was 1.02 (95% CI [0.81, 1.28]) with low heterogeneity, indicating that SGLT2 inhibitor treatment was not correlated with a higher risk of fracture. Additionally, no increased risk was found for patients with different ages, sexes, and levels of HbA1c and some biochemical indicators. Three trials with 1303 patients reported a change in the BMD from baseline. SGLT2 inhibitor treatment did not decrease the BMD at four skeletal sites (lumbar spine, femoral neck, total hip, and distal forearm), and the overall WMD was 0.08 (95% CI [-0.09, 0.26]). No significant publication bias was detected. CONCLUSIONS No increased risk for bone fracture was detected in patients with T2DM treated with SGLT2 inhibitors in this meta-analysis. SGLT2 inhibitor therapy did not appear to affect bone health, but more long-term detailed data are needed to validate this conclusion.
-
2.
Comparative Efficacy and Safety of Antihypertensive Agents for Adult Diabetic Patients with Microalbuminuric Kidney Disease: A Network Meta-Analysis.
Huang, R, Feng, Y, Wang, Y, Qin, X, Melgiri, ND, Sun, Y, Li, X
PloS one. 2017;(1):e0168582
Abstract
BACKGROUND Antihypertensive treatment mitigates the progression of chronic kidney disease. Here, we comparatively assessed the effects of antihypertensive agents in normotensive and hypertensive diabetic patients with microalbuminuric kidney disease. METHODS MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) comparing oral antihypertensive agents in adult diabetic patients with microalbuminuria. The primary efficacy outcome was reduction in albuminuria, and the primary safety outcomes were dry cough, presyncope, and edema. Random-effects pairwise and Bayesian network meta-analyses were performed to produce outcome estimates for all RCTs, only hypertensive RCTs, or only normotensive RCTs. Surface under the cumulative ranking (SUCRA) probability rankings were calculated for all outcomes. Sensitivity analyses on type 2 diabetes status, age, or follow-up duration were also performed. RESULTS A total of 38 RCTs were included in the meta-analyses. The angiotensin-converting enzyme inhibitor-calcium channel blocker (ACEI-CCB) combination therapy of captopril+diltiazem was most efficacious in reducing albuminuria irrespective of blood pressure status. However, the ACEI-angiotensin receptor blocker (ACEI-ARB) combination therapy of trandolapril+candesartan was the most efficacious in reducing albuminuria for normotensive patients, while the ACEI-CCB combination therapy of fosinopril+amlodipine was the most efficacious in reducing albuminuria for hypertensive patients. The foregoing combination therapies displayed inferior safety profiles relative to ACEI monotherapy with respect to dry cough, presyncope, and edema. With respect to type 2 diabetic patients with microalbuminuria, the Chinese herbal medicine Tangshen formula followed by the ACEI ramipril were the most efficacious in reducing albuminuria. CONCLUSIONS Trandolapril+candesartan appears to be the most efficacious intervention for reducing albuminuria for normotensive patients, while fosinopril+amlodipine appears to be the most efficacious intervention for reducing albuminuria for hypertensive patients. For practitioners opting for monotherapy, our SUCRA analysis supports the use of trandolapril and fosinopril in normotensive and hypertensive adult diabetic patients with microalbuminuria, respectively.
-
3.
Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.
Liu, CT, Raghavan, S, Maruthur, N, Kabagambe, EK, Hong, J, Ng, MC, Hivert, MF, Lu, Y, An, P, Bentley, AR, et al
American journal of human genetics. 2016;(1):56-75
Abstract
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
-
4.
The genetic polymorphisms in vitamin D receptor and the risk of type 2 diabetes mellitus: an updated meta-analysis.
Yu, F, Cui, LL, Li, X, Wang, CJ, Ba, Y, Wang, L, Li, J, Li, C, Dai, LP, Li, WJ
Asia Pacific journal of clinical nutrition. 2016;(3):614-24
Abstract
BACKGROUND AND OBJECTIVES Vitamin D receptor (VDR) genetic polymorphisms are considered to be associated with type 2 diabetes mellitus (T2DM), but this is inconclusive. The aim of this study is to quantify the association between polymorphisms of BsmI and FokI in the VDR gene and T2DM risk through literature review. METHODS AND STUDY DESIGN Original articles published from 1999 to June 2014 were discovered through PubMed, ISI Web of Science, China National Knowledge Infrastructure, Chinese Wanfang Database, and the Chinese Biomedical Literature Database. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with software STATA version 12.0. RESULTS Twenty-three articles containing 30 case-control studies were included. The association between the BsmI polymorphism and T2DM was weak in two genetic models (Bb vs bb and BB+Bb vs bb). The subgroup analysis showed that this association was only found in the studies with a small sample size (<200). A strong association between FokI polymorphism and T2DM indicated that this gene polymorphism was possibly a risk factor for T2DM (ff vs FF: OR=1.57, 95% CI: 1.28-1.93, p<0.001; Ff vs FF: OR=1.54, 95% CI: 1.31-1.81, p<0.001; ff+Ff vs FF: OR=1.57, 95% CI: 1.35-1.83, p<0.001), especially in Chinese populations. CONCLUSION More reliable conclusions about associations between VDR genetic polymorphisms and T2DM will depend on studies with larger sample size and by ethnicity.
-
5.
Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
Dastani, Z, Hivert, MF, Timpson, N, Perry, JR, Yuan, X, Scott, RA, Henneman, P, Heid, IM, Kizer, JR, Lyytikäinen, LP, et al
PLoS genetics. 2012;(3):e1002607
Abstract
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
-
6.
Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes mellitus: a HuGE review and meta-analysis.
Bao, W, Song, F, Li, X, Rong, S, Yang, W, Wang, D, Xu, J, Fu, J, Zhao, Y, Liu, L
American journal of epidemiology. 2010;(6):631-6
Abstract
Several studies have recently focused on the association between heme oxygenase-1 (HMOX1) gene promoter polymorphisms and susceptibility to type 2 diabetes mellitus; however, results have been conflicting. This systematic Human Genome Epidemiology review and meta-analysis was undertaken to integrate previous findings and summarize the effect size of the association of HMOX1 gene promoter polymorphisms with susceptibility to type 2 diabetes. The authors retrieved all studies matched to search terms from the PubMed/MEDLINE, EMBASE, and ISI Web of Science databases that had been published through December 31, 2009. The articles were then checked independently by 2 investigators according to the eligibility and exclusion criteria. For all alleles and genotypes, odds ratios were pooled using either fixed-effects or random-effects models. An increased odds ratio for type 2 diabetes was observed in persons with the (GT)(n) L (long) allele as compared with those with the (GT)(n) S (short) allele (odds ratio = 1.12, 95% confidence interval: 1.02, 1.24; P = 0.02). Furthermore, the diabetes odds ratio for persons with the LL genotype, versus those with the SS genotype, was significantly increased (odds ratio = 1.25, 95% confidence interval: 1.04, 1.50; P = 0.02). Persons carrying longer (GT)(n) repeats in the HMOX1 gene promoter may have a higher risk of type 2 diabetes.