Peripheral Arterial Disease: Incidence, Risk Factors, and Diagnosis

This dissertation includes three manuscripts related to peripheral arterial disease. The first examines the effects of assigned glycemic control strategy on the incidence of peripheral arterial disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. The BARI 2D results show that patients assigned to control their type 2 diabetes with a strategy that primarily used insulin sensitizing agents (metformin and/or thiazolidinediones) experienced fewer incident cases of peripheral arterial disease than patients assigned to a glycemic control strategy that primarily used insulin providing agents.\ud \ud The second manuscript extends this work by examining risk factors for peripheral arterial disease in the BARI 2D trial. The analyses included traditional cardiovascular risk factors as well as biomarkers indicative of inflammation, coagulation, and fibrinolysis. In patients treated with insulin sensitizing medications, biomarkers of inflammation and related processes were associated with lower extremity outcomes while this was not the case for patients treated with insulin providing medications, a useful mechanistic insight into how the different types of diabetes drugs may affect the progression of atherosclerosis.\ud \ud The third manuscript reports the results of a data collection project evaluating the reproducibility and reliability of two methods for measuring the ankle-brachial index. Reproducibility was excellent for Doppler-measured ABI, while the Colin oscillometric device showed moderate reproducibility. Agreement between Colin and Doppler was somewhat poor; therefore, we would not recommend the Colin device for measuring ABI in clinical settings.\ud \ud Each manuscript contributes uniquely to public health significance. The first suggests that a glycemic treatment strategy based on insulin sensitizers may reduce the progression of atherosclerosis in patients with type 2 diabetes. The second demonstrated that biomarkers of inflammation and fibrinolysis offer additional predictive value over traditional cardiovascular risk factors for incidence of PAD in type 2 diabetes patients treated with insulin sensitizing medications, implying that different types of glycemic control medications may have different mechanistic effects on the progression of atherosclerosis. The third reinforces current guidelines that Doppler ABI should remain the primary diagnostic for PAD in clinical and research settings.\u