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The trans-ancestral genomic architecture of glycemic traits.
Chen, J, Spracklen, CN, Marenne, G, Varshney, A, Corbin, LJ, Luan, J, Willems, SM, Wu, Y, Zhang, X, Horikoshi, M, et al
Nature genetics. 2021;(6):840-860
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Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
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A comparison between whole grain and pearled oats: acute postprandial glycaemic responses and in vitro carbohydrate digestion in healthy subjects.
Zhu, R, Fan, Z, Li, G, Wu, Y, Zhao, W, Ye, T, Wang, L
European journal of nutrition. 2020;(6):2345-2355
Abstract
PURPOSE To compare the glycaemic response of whole grain oat kernels and pearled oats cooked under normal pressure or higher pressure and examine whether replacing half of the rice in a given meal with either of the two oat grains could make a difference in acute glycaemic responses. METHODS In a randomised crossover trial, ten healthy subjects consumed two groups of test meals: (1) oat grain-only, including whole grain oats cooked under normal pressure (WONP) and higher pressure (WOHP) as well as their pearled oat counterparts, PONP and POHP; and (2) mixed meals of aforementioned oat grains and cooked rice (OG + R), including WONP + R, WOHP + R, PONP + R and POHP + R. A postprandial blood glucose test, texture profile analysis and in vitro carbohydrate digestion assay were carried out for each test meal. RESULTS Compared with the rice reference, oat grain-only meals induced lower glucose levels at all time points, lower peak values and smaller glucose excursions at 120 min (P < 0.05), but OG + Rs did not have the abovementioned effects. The oat grain-only meals had glycaemic indexes (GIs) ranging from 51 to 58, while those of OG + Rs ranged from 59 to 70. WONP + R had a 21% lower iAUC0-60 and a 40% lower iAUC60-120 value than those of rice (P < 0.05). Oat-rice mixed meals had lower iAUC0-60 values compared with that of the rice control (P < 0.05), except for POHP + R. Excellent consistency between the hydrolysis index and the GI was observed (r = 0.969, P < 0.001) in oat grain-only meals. CONCLUSIONS All oat grain-only meals could be included in the glycaemic management diet, regardless of the oat grain type or cooking treatment. In oat-rice mixed meals, whole grain oats and normal pressure cooking ensured a favourable glycaemic effect.
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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.
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Fasting capillary blood glucose: an appropriate measurement in screening for diabetes and pre-diabetes in low-resource rural settings.
Zhao, X, Zhao, W, Zhang, H, Li, J, Shu, Y, Li, S, Cai, L, Zhou, J, Li, Y, Hu, R
Journal of endocrinological investigation. 2013;(1):33-7
Abstract
OBJECTIVE To evaluate the efficiency of fasting capillary blood glucose (FCG) measurement as compared with fasting venous plasma glucose (FPG) measurement in screening diabetes and pre-diabetes in low-resource rural settings. SUBJECTS AND METHODS In 2010, 993 participants were randomly selected from 9 villages in Yunnan province using cluster sampling method. Samples for FCG and FPG test were obtained after demographics and physical examination. The oral glucose tolerance test was performed in parallel as gold standard for diagnosis. Diagnostic capacities of the FCG measurement in predicting undiagnosed diabetes and pre-diabetes were assessed. The performance of FCG and FPG tests was compared. RESULTS Fifty-seven individuals with undiagnosed diabetes and 145 subjects with pre-diabetes were detected. The concordance between FCG and FPG levels was high (r = 0.75, p < 0.001). The area under the curve (AUC) for FCG test in predicting diabetes was 0.88 [95% confidence interval (CI) 0.82-0.93] with the optimal cutoff value of 5.65 mmol/l, sensitivity of 84.2%, and specificity of 79.3%. The corresponding values in FPG tests were 0.92 (95% CI 0.88-0.97) (AUC), 6.51 mmol/l (optimal cutoff point), 82.5% (sensitivity) and 98.3% (specificity), respectively. No significant difference was found in the AUC for the two screening strategies. CONCLUSION FCG measurement is considered to be a convenient, practicable screening method in low-resource rural communities with acceptable test properties.
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Metabolic effects of bariatric surgery in type 2 diabetic patients with body mass index < 35 kg/m2.
Li, Q, Chen, L, Yang, Z, Ye, Z, Huang, Y, He, M, Zhang, S, Feng, X, Gong, W, Zhang, Z, et al
Diabetes, obesity & metabolism. 2012;(3):262-70
Abstract
AIM: The aim of this meta-analysis is to assess the metabolic effects of bariatric surgery in type 2 diabetes mellitus (T2DM) patients with body mass index (BMI) < 35 kg/m(2) . METHODS We performed an electronic literature search of published articles to identify relevant evidence since inception to June 2011. Primary outcome measures were metabolic improvement and resolution diabetes after bariatric surgery. The weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1) was applied for meta-analysis. RESULTS Thirteen trials involving 357 patients were included in the meta-analysis. The follow-up interval ranged from 6 months to 18 years. According to WMD calculation, bariatric surgery led to 5.18 kg/m(2) of BMI lowering (95% CI, 3.79-6.57, p < 0.00001), 4.8 mmol/l of fasting plasma glucose (FPG) decrement (95% CI, 3.88-5.71 mmol/l, p < 0.00001), 2.59% of HbA1c decreasing (95% CI, 2.12-3.07%, p < 0.00001), 56.67 mg/dl of triglyceride decrement (95% CI 11.53-101.82, p = 0.01) and 48.38 mg/dl of total cholesterol reduction (95% CI 21.08-75.68, p = 0.0005). Moreover, the procedures produced an increased high-density lipoprotein cholesterol by 5.37 mg/dl (95% CI -11.37-0.63, p = 0.08). However, this effect was not statistically significant. Overall, 80.0% of the patients achieved adequate glycaemic control (HbA1c < 7%) without antidiabetic medication. The surgeries produced a low incidence of major complications (3.2%) with no mortality. CONCLUSIONS Bariatric surgery is effectual and safe in the treatment of non-severely obese (BMI < 35 kg/m(2) ) T2DM patients. Moreover, the metabolic benefits acquired from the procedures can be long sustained after the surgery.