HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States Veterans

RESEARCH ARTICLE HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States Veterans P. Jordan Davis1, Mengling Liu1, Scott Sherman1,2, Sundar Natarajan1,2, Farrokh Alemi3, Ashley Jensen2, Sanja Avramovic3, Mark D. Schwartz1,2, Richard B. Hayes1* 1 Department of Population Health, NYU School of Medicine, New York, NY, United States of America, 2 VA New York Harbor Healthcare System, New York, NY, United States of America, 3 George Mason University, Fairfax, VA, United States of America a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Davis PJ, Liu M, Sherman S, Natarajan S, Alemi F, Jensen A, et al. (2018) HbA1c, lipid profiles and risk of incident type 2 Diabetes in United States Veterans. PLoS ONE 13(9): e0203484. https://doi.org/10.1371/journal. pone.0203484 Editor: Alberto G. Passi, University of Insubria, ITALY Received: April 27, 2018 Accepted: August 21, 2018 Published: September 13, 2018 Copyright: © 2018 Davis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data for this study were obtained via access to the national Corporate Data Warehouse (CDW) of the Department of Veterans Affairs (VA) Office of Information and Technology (Washington D.C.). VA patient medical and administrative data are accessible from the VINCI Workspace (Veterans Affairs Informatics and Computing Infrastructure), a VA-hosted computing environment, through a secure gateway (firewall) using a Remote Desktop Connection (RDC). VINCI provides a centralized, secure development and research platform for conducting VA studies and * Abstract United States Veterans are at excess risk for type 2 diabetes, but population differentials in risk have not been characterized. We determined risk of type 2 diabetes in relation to prediabetes and dyslipidemic profiles in Veterans at the VA New York Harbor (VA NYHHS) during 2004–2014. Prediabetes was based on American Diabetes Association hemoglobin A1c (HbA1c) testing cut-points, one of several possible criteria used to define prediabetes. We evaluated transition to type 2 diabetes in 4,297 normoglycemic Veterans and 7,060 Veterans with prediabetes. Cox proportional hazards regression was used to relate HbA1c levels, lipid profiles, demographic, anthropometric and comorbid cardiovascular factors to incident diabetes (Hazard Ratio [HR] and 95% confidence intervals). Compared to normoglycemic Veterans (HbA1c: 5.0–5.6%; 31–38 mmol/mol), risks for diabetes were >2-fold in the moderate prediabetes risk group (HbA1c: 5.7–5.9%; 39–41 mmol/mol) (HR 2.37 [1.98–2.85]) and >5-fold in the high risk prediabetes group (HbA1c: 6.0–6.4%; 42–46 mmol/mol) (HR 5.59 [4.75–6.58]). Risks for diabetes were increased with elevated VLDL (40mg/dl; HR 1.31 [1.09–1.58]) and TG/HDL (1.5mg/dl; HR 1.34 [1.12–1.59]), and decreased with elevated HDL (35mg/dl; HR 0.80 [0.67–0.96]). Transition to diabetes in Veterans was related in age-stratified risk score analyses to HbA1c, VLDL, HDL and TG/HDL, BMI, hypertension and race, with 5-year risk differentials of 62% for the lowest (5-year risk, 13.5%) vs. the highest quartile (5-year risk, 21.9%) of the risk score. This investigation identified substantial differentials in risk of diabetes in Veterans, based on a readily-derived risk score suitable for risk stratification for type 2 diabetes prevention. Introduction Type 2 diabetes is a chronic metabolic disorder defined by persistent hyperglycemia due to increased insulin resistance and/or impaired insulin secretion [1–2]. In the United States, more than 30 million people (9.4% of the population) had type 2 diabetes in 2015 [3]. With aging and increasing rates of obesity, prevalence of type 2 diabetes is also rising and is currently the seventh leading cause of death [3]. Furthermore, type 2 diabetes leads to greater risk PLOS ONE | https://doi.org/10.1371/journal.pone.0203484 September 13, 2018 1 / 12 Risk of type 2 diabetes in U.S. Veterans allows for data storage, extraction, processing and analysis. Access to linked patient level data was obtained through the Veterans Health Administration (VHA), National Data Services (NDS) and the VA Information Resource Center (VIReC), one of three Health Services Research and Development Service (HSR&D) resource centers that authorize and maintain research access to patient data and resources for research conducted within the VA. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. for cardiovascular disease and other conditions, such as blindness, kidney failure, and lower limb amputations, and is associated with greatly reduced overall life expectancy [1–4]. Nearly a quarter of U.S. Veterans have type 2 diabetes, more than double the prevalence of the general population [3,5–6]. Prediabetes describes individuals at increased risk for future development of type 2 diabetes [5,7]. Those with prediabetes have higher than normal blood glucose concentrations, but lower than diabetic diagnostic criteria [1,5,7–8]. Since the early 2000s, the American Diabetes Association has recommended assessment of glycated hemoglobin (HbA1c), a type of hemoglobin that indicates an individual’s three-month average plasma glucose concentration [9], as an alternative to glucose tolerance testing for diagnostic surveillance of diabetes and prediabetes. Despite the higher prevalence of type 2 diabetes among Veterans, little is known about the prevalence of prediabetes among Veterans and its impact on their development of type 2 diabetes [10]. Epidemiologic studies have shown that dyslipidemic profiles are independent risk factors for type 2 diabetes and can manifest prior to development of the disease [11–12]. Furthermore, dyslipidemia can cause decreased pancreatic beta cell function and survival particularly among diabetic patients [11,13–14]. Additional research is needed to examine the effects of lipid patterns in prediabetic and nondiabetic individuals on risk for incident type 2 diabetes. The relationship of HbA1c, dyslipidemias and other risk factors to type 2 diabetes occurrence in Veterans is incompletely understood. Therefore, we investigated the association of HbA1c levels and associated lipid profiles with development of incident type 2 diabetes among Veterans at the Veterans Affairs New York Harbor Healthcare System (VA NYHHS). Materials and methods Data sources Data for this study were obtained via access to the national Corporate Data Warehouse (CDW) of the Department of Veterans Affairs (VA) Office of Information and Technology (Washington D.C.). VA patient medical and administrative data are accessible from the VINCI Workspace (Veterans Affairs Informatics and Computing Infrastructu (...truncated)