Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes

Objectives We sought to determine the differences in coronary microvascular function between patients with type 1 (insulin-deficient) and type 2 (insulin-resistant) diabetes mellitus (DM). Background Coronary vascular function is impaired in patients with DM. However, it is unclear whether the type and/or severity of this vascular dysfunction are similar in patients with type 1 and type 2 DM. Methods We studied 35 young subjects with DM (18 with type 1 and 17 with type 2), who were free of overt cardiovascular complications, and 11 age-matched healthy controls. Positron emission tomography imaging was used to measure myocardial blood flow (MBF) at rest, during adenosine-induced hyperemia (reflecting primarily endothelium-independent vasodilation), and in response to cold pressor test (CPT) (reflecting primarily endothelium-dependent vasodilation). Results The two groups of diabetics were similar with respect to age and glycemic control. The duration of diabetes was longer and high-density lipoprotein cholesterol levels were higher in type 1 than in type 2 diabetics. Basal MBF was similar in the three groups studied. The increase (from baseline) in MBF with adenosine was similar in the subjects with type 1 (161 ± 18%) and type 2 (185 ± 19%) DM, but lower than in the controls (351 ± 43%) (p < 0.001 for the comparison with both groups of diabetics). Similarly, the increase in MBF during the CPT was comparable in the subjects with type 1 (23 ± 4%) and type 2 (19 ± 3%) DM, but lower compared with the controls (66 ± 12%) (p < 0.0001 for the comparison with both groups of diabetics). These differences persisted after adjusting for the duration of diabetes, insulin treatment, metabolic abnormalities, and autonomic neuropathy. Conclusions These results demonstrate markedly reduced and similar endothelium-dependent and -independent coronary vasodilator function in subjects with both type 1 and type 2 DM. These results suggest a key role of chronic hyperglycemia in the pathogenesis of vascular dysfunction in diabetes.