Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus.
BACKGROUND
Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance.


RESULTS
Myocardial blood flow (MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium-dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (-17%) and hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (-56%), as well as in IGT and normotensive and hypertensive diabetic patients (-85%, -91%, and -120%, respectively).


CONCLUSIONS
Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.
Prior
John O
JO
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, Calif 90095-6948, USA.
Quiñones
Manuel J
MJ
Hernandez-Pampaloni
Miguel
M
Facta
Alvaro D
AD
Schindler
Thomas H
TH
Sayre
James W
JW
Hsueh
Willa A
WA
Schelbert
Heinrich R
HR
D000328:Adult; D001783:Blood Flow Velocity; D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003925:Diabetic Angiopathies; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension; D007333:Insulin Resistance; D008297:Male; D017058:Mexican Americans; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D009569:Nitric Oxide