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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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C-R Relationship between Fasting Plasma Glucose and Unfavorable Outcomes in Patients of Ischemic Stroke withoutDiabetes.
Xing, L, Liu, S, Tian, Y, Yan, H, Jing, L, Chen, K, Yan, F, Li, Y, Lv, J, Sun, Y
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association. 2019;(5):1400-1408
Abstract
BACKGROUND Limited data are available on the impact of fasting plasma glucose (FPG) on outcomes in nondiabetic acute ischemic stroke patients. METHODS The prospective, multi-center, and observational study was performed at 8 hospitals in the Liaoning Province between 2015-2016, sought to elucidate the relationship between FPG and the 6-month functional outcomes in nondiabetic acute ischemic stroke patients. The primary effect measure was the adjusted odds ratio for a shift in the direction of unfavorable outcome on the modified Rankin Scale (mRS) score at 6 months, estimated with an ordinal logistic regression, and adjusted for common prognostic factors. Finally, we employed a restricted cubic spline function of linear model to characterize concentration-response (C-R) relationships between FPG and outcomes. RESULTS A total of 1260 consecutive patients were enrolled, 48.9% of patients had FPG levels >6.1mmol/L. A total of 282 (22.4%) patients achieved an unfavorable neurologic outcome. Patients achieving an unfavorable neurologic outcome had significantly higher levels of FPG than those achieving a favorable neurologic outcome (6.47mmol/L versus 7.02 mmol/L). FPG was significantly related to an unfavorable neurologic outcome in nondiabetic acute ischemic stroke patients. The C-R curve showed a nonlinear relation between FPG and 6-month mRS with the nadir at 5.9mmol/L. Moreover, the likelihood of unfavorable outcome increased by 8.5% for each 1mmol/L increase in FPG. CONCLUSIONS Early identification and prompt hyperglycemia management should be considered to improve the functional outcomes during the early poststroke stage.
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Elevated fasting serum glucose levels increase the risk of hepatocellular carcinoma: A prospective cohort study.
Liu, T, Wang, W, Cui, H, Sun, M, Wang, Y, Liu, X, Cao, L, Liu, H, Liu, S
Medicine. 2019;(30):e16369
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Abstract
Previous studies have demonstrated a positive relationship between liver cancer and diabetes mellitus. However, elevated fasting blood glucose (FBG) itself may be a risk factor for the development of hepatocellular carcinoma (HCC) rather than diabetes, and during the follow-up period, death is an event that may occur before the occurrence of HCC, which should be dealt with competing risk models. Our study aims to investigate the relationship between FBG and new-onset HCC by using competing risk regression models.We prospectively studied the relationship between FBG concentrations and risk of HCC in a cohort of 93,447 participants who were free of prior HCC, and whose demographic characteristics and biochemical parameters were recorded. Cox proportional hazards regression models and competing risk regression models were used to evaluate the association between FBG concentrations and risk of incident HCC.A total of 302 participants were diagnosed with HCC among 93,447 subjects during 810,499 person-years of follow-up. The multivariable hazard ratios (HRs) [95% confidence interval (95% CI)] for the association of FBG and log(FBG) with HCC were 1.07 (1.01∼1.12), 1.84 (1.23∼2.74) in an analysis adjusted for other potential variables. In the multivariable adjusted analysis, participants who were in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group would have increased the risk of HCC by 47% and 69%, respectively. In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of FBG with HCC were 1.46 (1.09∼1.98), 1.69 (1.27∼2.27) in the multivariable adjusted analysis. Similar results were also observed in sub-distribution hazard function model (SD model) with corresponding multivariate HRs (95% CI) of 1.46 (1.09∼2.00), 1.69 (1.25∼2.27) in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group, respectively.Higher FBG concentrations itself were positively associated with new-onset HCC in the Cox proportional hazards regression models and competing risk models. FBG concentrations can be used as a scientific and important way to identify individuals with a higher risk of HCC and control of FBG concentrations might serve as a possible way to decrease the risk of HCC among Chinese population.Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered).
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Dietary Glycemic Index and Load and the Risk of Type 2 Diabetes: A Systematic Review and Updated Meta-Analyses of Prospective Cohort Studies.
Livesey, G, Taylor, R, Livesey, HF, Buyken, AE, Jenkins, DJA, Augustin, LSA, Sievenpiper, JL, Barclay, AW, Liu, S, Wolever, TMS, et al
Nutrients. 2019;(6)
Abstract
Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dose-response meta-analysis(DRM) while withdrawing spurious results (p < 0.05), we ascertained whether these relationswould support nutrition guidance, specifically for an RR > 1.20 with a lower 95% confidence limit>1.10 across typical intakes (approximately 10th to 90th percentiles of population intakes). Thecombined T2D-GI RR was 1.27 (1.15-1.40) (p < 0.001, n = 10 studies) per 10 units GI, while that forthe T2D-GL RR was 1.26 (1.15-1.37) (p < 0.001, n = 15) per 80 g/d GL in a 2000 kcal (8400 kJ) diet.The corresponding global DRM using restricted cubic splines were 1.87 (1.56-2.25) (p < 0.001, n =10) and 1.89 (1.66-2.16) (p < 0.001, n = 15) from 47.6 to 76.1 units GI and 73 to 257 g/d GL in a 2000kcal diet, respectively. In conclusion, among adults initially in good health, diets higher in GI or GLwere robustly associated with incident T2D. Together with mechanistic and other data, thissupports that consideration should be given to these dietary risk factors in nutrition advice.Concerning the public health relevance at the global level, our evidence indicates that GI and GLare substantial food markers predicting the development of T2D worldwide, for persons ofEuropean ancestry and of East Asian ancestry.