Prediction of incident Type 2 diabetes: modifiable and non-modifiable risk factors among high-risk populations and diverse racial/ethnic groups

Abstract

Nearly ten percent of adults in the U.S. aged twenty years and older live with type 2 diabetes. Improving risk stratification and prediction facilitates the identification of those most likely to develop diabetes and informs prevention efforts. The aim of this dissertation was to evaluate the predictive validity of established definitions of high risk across population subgroups, and to examine the impact of modifiable and non-modifiable factors that predict type 2 diabetes risk, presented in three related manuscripts. In the first manuscript, the predictive validity of fasting glucose and glycated hemoglobin A1c (HbA1c) measures were evaluated in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based observational cohort study that enrolled 6,814 Caucasian Americans, Chinese Americans, African Americans, and Hispanic Americans aged 45-84 years. The association between fasting glucose levels at baseline and cumulative incidence of diabetes did not differ by self-reported ethnic group. However, the strength of association between HbA1c and diabetes incidence differed significantly by ethnicity. The second manuscript examined predictors of incident diabetes among individuals with pre-diabetes in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based longitudinal observational study of 5,115 African Americans and Caucasian Americans aged 18-30 years at baseline. Body mass index was the strongest predictor of diabetes; other predictors included race/ethnicity, diastolic blood pressure, and HDL-cholesterol. A final manuscript explored interactions between single nucleotide polymorphisms (SNPs), the trait of cardiorespiratory fitness, and diabetes-related outcomes in the CARDIA cohort. SNPs of rs8050136 of the fat mass and obesity associated (FTO) gene and rs3856806 of the peroxisome proliferator-activated receptor gamma (PPARG) gene were associated with HbA1c levels; the association between cardiorespiratory fitness level and HbA1c differed by genotype of rs8050136 in Caucasians and rs3856806 in African Americans. This dissertation evaluated the predictive value of current screening tools and markers of risk for type 2 diabetes. Improving diabetes prevention in population subgroups that are disproportionately affected -- particularly those with pre-diabetes and in certain race/ethnic groups -- is dependent upon effective screening tools validated across populations, and a more comprehensive understanding of the role of modifiable and non-modifiable risk factors in influencing one's diabetes risk profile.