CLINICAL STUDY: DIABETES AND CARDIOVASCULAR DISEASE
Role of chronic hyperglycemia in the pathogenesis of coronary microvascular dysfunction in diabetes
Marcelo F. Di Carli, MD*,*  ,
James Janisse, PhD ,
George Grunberger, MD* and
Joel Ager, PhD
* Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan, USA
Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan, USA
Center for Healthcare Effectiveness Research, Wayne State University School of Medicine, Detroit, Michigan, USA
Positron Emission Tomography Center , Children’s Hospital of Michigan, Detroit, Michigan, USA
Manuscript received July 3, 2002;
revised manuscript received October 3, 2002,
accepted November 27, 2002.
* Reprint requests and correspondence: Dr. Marcelo F. Di Carli, Brigham and Women’s Hospital, Division of Nuclear Medicine, 75 Francis Street, Boston, Massachusetts, USA 02115.
mdicarli{at}bics.bwh.harvard.edu
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.
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Abbreviations and Acronyms
| | ANOVA | | analysis of variance | | BMI | | body mass index | | BP | | blood pressure | | CAD | | coronary artery disease | | CPT | | cold pressor test | | DM | | diabetes mellitus | | ECG | | electrocardiogram | | HDL | | high-density lipoprotein | | HED | | [11C]hydroxyephedrine | | MBF | | myocardial blood flow | | PET | | positron emission tomography | | ROI | | regions of interest | | vWF | | von Willebrand factor |
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