0
selected
-
1.
Effect of DPP-IV Inhibitors on Glycemic Variability in Patients with T2DM: A Systematic Review and Meta-Analysis.
Lee, S, Lee, H, Kim, Y, Kim, E
Scientific reports. 2019;(1):13296
Abstract
Glycemic variability (GV) has been an emerging target for preventing complications related to type 2 diabetes. For reducing GV, DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs (OADs), but systematic evaluation has yet to be existed. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to evaluate the effect of DPP-IV inhibitors compared with other OADs, on GV as measured by mean amplitude of glycemic excursions (MAGE). Searches were conducted using Pubmed, EMBASE, and the Cochrane Library, from which eligible studies were retrieved; seven RCTs were included in the analysis. DPP-IV inhibitors were found to significantly reduce MAGE compared to other OADs (mean difference = -14.61; 95% CI = -19.00 to -10.21; p < 0.0001) without significant heterogeneity among sulfonylureas (mean difference = -14.93; 95% CI = -21.60 to -8.26; p < 0.0001). Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies (p = 0.006), although no differences in MAGE were found based on HbA1c values. These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients. However, further studies utilizing larger numbers of patients and longer-term follow-ups are needed.
-
2.
Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.
Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, et al
Scientific data. 2017;:170179
Abstract
To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
-
3.
The genetic architecture of type 2 diabetes.
Fuchsberger, C, Flannick, J, Teslovich, TM, Mahajan, A, Agarwala, V, Gaulton, KJ, Ma, C, Fontanillas, P, Moutsianas, L, McCarthy, DJ, et al
Nature. 2016;(7614):41-47
-
-
Free full text
-
Abstract
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
-
4.
Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.
Li, H, Kilpeläinen, TO, Liu, C, Zhu, J, Liu, Y, Hu, C, Yang, Z, Zhang, W, Bao, W, Cha, S, et al
Diabetologia. 2012;(4):981-95
-
-
Free full text
-
Abstract
AIMS/HYPOTHESIS FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.