Diabetic Complications and Genetic Variants in the Million Veterans Program

点击翻译按钮获取中文摘要

We propose to undertake analyses within the Million Veterans Program (MVP) database to Assess Associations between Diabetic Complications and Genetic Variants. Aim 1 involves Database Development that will create a virtual baseline examination linking MVP data to VAMC outpatient visits, and, when appropriate, VAMC hospitalizations, using the electronic health record. We will conduct cutting edge Genome Wide Association Studies (GWAS) of common (CVAS) and rare (RVAS) variants. The outcomes investigated are diabetic eye, kidney, and cardiovascular complications, and hypoglycemia. Aim 2 is Diabetes Complications Analyses concerning outcome risks using time-integrated longitudinal measures of risk factors (RFs) to include both genetic variants and traditional RFs considering both single and multiple assessments of outcomes with cross-sectional and period prevalence estimates. We will analyze organ-specific and metabolic complications according to type 1 and type 2 diabetes status using EHR data in VA records. Specific outcomes investigated: Ocular (retinal disease, glaucoma), Renal (micro- and macro-albuminuria, and decreased eGFR [CKD stages and ESRD), Cardiovascular (cardiac failure), and Hypoglycemia (emergency department visits and hospitalizations, adjusted for HbA1c and glucose levels, and use of glycemic medications [from the EHR]). Aim 3 will develop Diabetic Complications Risk Scores. Both traditional RF and separate genetic prediction models will be compared using logistic regression for each outcome. Models will evaluate the role of RFs and pharmacologic therapy for abnormal blood pressure, lipids, and glucose. We will use an outcome-specific genetic score as a potential reclassification variable.