1.
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.
2.
Trans-ethnic Meta-analysis and Functional Annotation Illuminates theĀ 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.