0
selected
-
1.
Identification of type 2 diabetes loci in 433,540 East Asian individuals.
Spracklen, CN, Horikoshi, M, Kim, YJ, Lin, K, Bragg, F, Moon, S, Suzuki, K, Tam, CHT, Tabara, Y, Kwak, SH, et al
Nature. 2020;(7811):240-245
-
-
Free full text
-
Abstract
Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
-
2.
Effects of sodium-glucose cotransporter 2 inhibitors in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients: A meta-analysis of randomized controlled trials.
Wu, B, Zheng, H, Gu, J, Guo, Y, Liu, Y, Wang, Y, Chen, F, Yang, A, Wang, J, Wang, H, et al
Journal of diabetes investigation. 2019;(2):446-457
Abstract
AIMS/INTRODUCTION In the present meta-analysis, we aimed to determine the effects of sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in addition to insulin therapy on cardiovascular risk factors in type 2 diabetes patients. MATERIALS AND METHODS Randomized controlled trials were identified by searching the PubMed, Embase and Cochrane Library databases published before September 2017. The intervention group received SGLT-2i as add-on treatment to insulin therapy, and the control group received placebos in addition to insulin. We assessed pooled data, including weighted mean differences and 95% confidence intervals (CIs) using a random-effects model. RESULTS A total of 10 randomized controlled trials (n = 5,159) were eligible. The weighted mean differences for systolic blood pressure and diastolic blood pressure were -3.17 mmHg (95% CI -4.53, -1.80, I2 = 0%) and -1.60 mmHg (95% CI -2.52, -0.69, I2 = 0%) in the intervention groups. Glycosylated hemoglobin, fasting plasma glucose, postprandial glucose and daily insulin were also lower in the intervention groups, with relative weighted mean differences of -0.49% (95% CI -0.71, -0.28%, I2 = 92%), -1.10 mmol/L (95% CI -1.69, -0.51 mmol/L, I2 = 84%), -3.63 mmol/L (95% CI -4.36, -2.89, I2 = 0%) and -5.42 IU/day (95% CI -8.12, -2.72, I2 = 93%). The transformations of uric acid and bodyweight were -26.16 μmol/L (95% CI -42.14, -10.17, I2 = 80%) and -2.13 kg (95% CI -2.66, -1.60, I2 = 83%). The relative risk of hypoglycemia was 1.09 (95% CI 1.02, 1.17, P < 0.01). The relative risks of urinary tract and genital infection were 1.29 (95% CI 1.03, 1.62, P = 0.03) and 5.25 (95% CI 3.55, 7.74, P < 0.01). CONCLUSIONS The results showed that in the intervention group, greater reductions were achieved for blood pressure, glucose control, uric acid and bodyweight. This treatment regimen might therefore provide beneficial effects on the occurrence and development of cardiovascular events.
-
3.
The effect of metabolic surgery on nonobese patients (BMI<30 kg/m2) with type 2 diabetes: a systematic review.
Huang, ZP, Guo, Y, Liu, CQ, Qi, L, Zou, DJ, Zhou, WP
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2018;(6):810-820
Abstract
BACKGROUND The influence of metabolic surgery on the glucose and lipid profiles of nonobese body mass index<30 kg/m2 patients with type 2 diabetes, particularly the effect ≥1 year, remains unknown. METHODS PubMed and Ovid Embase were used. SETTING University hospitals. RESULTS In total, 21 studies including 921 patients were examined in this systematic review, the results of which revealed decrease in body mass index, waist circumference, fasting plasma glucose, glycosylated hemoglobin A1C, fasting C-peptide, fasting insulin, homeostasis model of assessment for insulin resistance index, triglycerides, total cholesterol, and low-density lipoprotein cholesterol. An increase in high-density lipoprotein cholesterol was also observed. The diabetes remission rates ranged from 13.3% to 90.2% according to 20 studies. The incidence of gastrointestinal bleeding ranged from 1% to 10% according to 9 studies. Four studies reported anemia after Roux-en-Y gastric bypass or one-anastomosis gastric bypass, with the incidence ranging from 8% to 33%. CONCLUSIONS Nonobese patients can achieve improvements in weight-related indices and glucose and lipid profiles in the short and medium term after metabolic surgery; however, the complications of metabolic surgery warrant further attention.
-
4.
HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.
Swerdlow, DI, Preiss, D, Kuchenbaecker, KB, Holmes, MV, Engmann, JE, Shah, T, Sofat, R, Stender, S, Johnson, PC, Scott, RA, et al
Lancet (London, England). 2015;(9965):351-61
Abstract
BACKGROUND Statins increase the risk of new-onset type 2 diabetes mellitus. We aimed to assess whether this increase in risk is a consequence of inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the intended drug target. METHODS We used single nucleotide polymorphisms in the HMGCR gene, rs17238484 (for the main analysis) and rs12916 (for a subsidiary analysis) as proxies for HMGCR inhibition by statins. We examined associations of these variants with plasma lipid, glucose, and insulin concentrations; bodyweight; waist circumference; and prevalent and incident type 2 diabetes. Study-specific effect estimates per copy of each LDL-lowering allele were pooled by meta-analysis. These findings were compared with a meta-analysis of new-onset type 2 diabetes and bodyweight change data from randomised trials of statin drugs. The effects of statins in each randomised trial were assessed using meta-analysis. FINDINGS Data were available for up to 223 463 individuals from 43 genetic studies. Each additional rs17238484-G allele was associated with a mean 0·06 mmol/L (95% CI 0·05-0·07) lower LDL cholesterol and higher body weight (0·30 kg, 0·18-0·43), waist circumference (0·32 cm, 0·16-0·47), plasma insulin concentration (1·62%, 0·53-2·72), and plasma glucose concentration (0·23%, 0·02-0·44). The rs12916 SNP had similar effects on LDL cholesterol, bodyweight, and waist circumference. The rs17238484-G allele seemed to be associated with higher risk of type 2 diabetes (odds ratio [OR] per allele 1·02, 95% CI 1·00-1·05); the rs12916-T allele association was consistent (1·06, 1·03-1·09). In 129 170 individuals in randomised trials, statins lowered LDL cholesterol by 0·92 mmol/L (95% CI 0·18-1·67) at 1-year of follow-up, increased bodyweight by 0·24 kg (95% CI 0·10-0·38 in all trials; 0·33 kg, 95% CI 0·24-0·42 in placebo or standard care controlled trials and -0·15 kg, 95% CI -0·39 to 0·08 in intensive-dose vs moderate-dose trials) at a mean of 4·2 years (range 1·9-6·7) of follow-up, and increased the odds of new-onset type 2 diabetes (OR 1·12, 95% CI 1·06-1·18 in all trials; 1·11, 95% CI 1·03-1·20 in placebo or standard care controlled trials and 1·12, 95% CI 1·04-1·22 in intensive-dose vs moderate dose trials). INTERPRETATION The increased risk of type 2 diabetes noted with statins is at least partially explained by HMGCR inhibition. FUNDING The funding sources are cited at the end of the paper.