The Epidemiology of Severe Hypoglycemia in Type 2 Diabetes
Lee, Alexandra Kathryn
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The purpose of this dissertation is to explore the epidemiology of severe hypoglycemia in type 2 diabetes by examining risk factors and health outcomes associated with severe hypoglycemia. Severe hypoglycemia is more common with older age and reduced kidney function, but few studies have examined other factors contributing to hypoglycemia risk. Additionally, prior research has demonstrated associations of severe hypoglycemia with cardiovascular disease and dementia, but it is unclear whether such associations are causal. The first aim of this dissertation evaluates risk factors for severe hypoglycemia among community-dwelling adults with diabetes in the Atherosclerosis Risk in Communities (ARIC) Study. In this prospective analysis, we show that poor glycemic control, older age, black race, macroalbuminuria, disability, and worse cognition are independently associated with severe hypoglycemia. The second aim, addressed in a cross-sectional analysis, shows that the prevalence of elevated high-sensitivity cardiac troponin T (a biomarker of subclinical myocardial damage) is higher in those with a history of severe hypoglycemia as compared to those without. After adjustment for demographic variables, glycated hemoglobin (HbA1c), and diabetes duration, the association is attenuated and not statistically significant, suggesting that diabetes severity may partially explain this association. The third aim examines the association of severe hypoglycemia with individual cardiovascular outcomes and cause-specific mortality. This prospective analysis in the ARIC Study finds that hypoglycemia is associated with coronary heart disease (HR 2.02, 95%CI 1.27-3.20) and is suggestive of an association with peripheral artery disease. We find no association of hypoglycemia with other types of cardiovascular events, indicating hypoglycemia may contribute specifically to atherosclerotic disease. The fourth aim investigates cognitive outcomes in older adults in the ARIC study. In a cross-sectional analysis, we show that persons with a history of severe hypoglycemia have smaller total and frontal brain volumes compared to persons without hypoglycemia. In a prospective analysis, we find that severe hypoglycemia is associated with substantially increased risk of dementia (HR 2.44, 95% CI 1.70-3.49). Overall, this dissertation provides essential information on risk factors for severe hypoglycemia as well as the associated health risks, enabling providers to better weigh the pros and cons of glucose-lowering treatment in type 2 diabetes.