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

Diabetes mellitus refers to a class of disorders resulting from defects in insulin secretion and/or insulin action. Nearly ten percent of adults in the United States aged twenty years and older live with type 2 diabetes, which accounts for approximately 90% to 95% of all diagnosed diabetes mellitus cases in adults. Improving risk stratification and risk 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 currently established definitions of high risk across ethnically diverse 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 across population subgroups in the Multi-Ethnic Study of Atherosclerosis (MESA), a community-based observational longitudinal cohort study that enrolled 6,814 Caucasian Americans, Chinese Americans, African Americans, and Hispanic Americans aged 45-84 years and free of clinical cardiovascular disease (CVD). Over five years, 692 incident diabetes cases occurred 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. In multivariable models, the c-statistics (markers of goodness-of-fit) from logistic regression models ranged from 0.75 in African Americans to 0.87 in Caucasians.The second manuscript examined predictors of incident diabetes among high-risk individuals with pre-diabetes in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a community-based longitudinal observational study that enrolled 5,115 African Americans and Caucasian Americans aged 18-30 years and free of clinical CVD. In the CARDIA cohort, body mass index (BMI) was the strongest predictor of diabetes among individuals with pre-diabetes other predictors included race/ethnicity, diastolic blood pressure, HDL-cholesterol, and alcohol consumption.A final manuscript explored genetic predisposition to diabetes in addition to potential 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 significantly 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 served to evaluate the predictive value of current screening tools and markers of risk for type 2 diabetes, and supported previous findings that modifiable risk factors significantly contribute to diabetes risk prediction. 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.