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

J Am Coll Cardiol. 2003 Apr 16;41(8):1387-93. doi: 10.1016/s0735-1097(03)00166-9.


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.

MeSH terms

  • Adult
  • Analysis of Variance
  • Case-Control Studies
  • Chronic Disease
  • Coronary Circulation*
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / etiology*
  • Coronary Disease / physiopathology
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / physiopathology*
  • Female
  • Hemodynamics
  • Humans
  • Hyperglycemia / complications*
  • Hyperglycemia / etiology
  • Hyperglycemia / physiopathology
  • Male
  • Microcirculation
  • Middle Aged
  • Tomography, Emission-Computed