Coronary vasomotor abnormalities in insulin-resistant individuals.
BACKGROUND
Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects.


OBJECTIVE
To evaluate the association of insulin resistance with the presence and reversibility of coronary vasomotor abnormalities in young adults at low cardiovascular risk.


METHODS
Cross-sectional study followed by prospective, open-label treatment study.


METHODS
University hospital.


METHODS
50 insulin-resistant and 22 insulin-sensitive, age-matched Mexican-American participants without glucose intolerance or traditional risk factors for or evidence of coronary artery disease.


METHODS
3 months of thiazolidinedione therapy for 25 insulin-resistant patients.


METHODS
Glucose infusion rate in response to insulin infusion was used to define insulin resistance (glucose infusion rate < or = 4.00 mg/kg of body weight per minute [range, 0.90 to 3.96 mg/kg per minute]) and insulin sensitivity (glucose infusion rate > or = 7.50 mg/kg per minute [range, 7.52 to 13.92 mg/kg per minute]). Myocardial blood flow was measured by using positron emission tomography at rest, during cold pressor test (largely endothelium-dependent), and after dipyridamole administration (largely vascular smooth muscle-dependent).


RESULTS
Myocardial blood flow responses to dipyridamole were similar in the insulin-sensitive and insulin-resistant groups. However, myocardial blood flow response to cold pressor test increased by 47.6% from resting values in insulin-sensitive patients and by 14.4% in insulin-resistant patients. During thiazolidinedione therapy in a subgroup of insulin-resistant patients, insulin sensitivity improved, fasting plasma insulin levels decreased, and myocardial blood flow responses to cold pressor test normalized.


CONCLUSIONS
The study was not randomized, and it included only 1 ethnic group.


CONCLUSIONS
Insulin-resistant patients who do not have hypercholesterolemia or hypertension and do not smoke manifest coronary vasomotor abnormalities. Insulin-sensitizing thiazolidinedione therapy normalized these abnormalities. These results suggest an association between insulin resistance and abnormal coronary vasomotor function, a relationship that requires confirmation in larger studies.
Quiñones
Manuel J
MJ
Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California 90095, USA.
Hernandez-Pampaloni
Miguel
M
Schelbert
Heinrich
H
Bulnes-Enriquez
Isabel
I
Jimenez
Xochitl
X
Hernandez
Gustavo
G
De La Rosa
Roxana
R
Chon
Yun
Y
Yang
Huiying
H
Nicholas
Susanne B
SB
Modilevsky
Tamara
T
Yu
Katherine
K
Van Herle
Katja
K
Castellani
Lawrence W
LW
Elashoff
Robert
R
Hsueh
Willa A
WA
D000328:Adult; D015992:Body Mass Index; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D017058:Mexican Americans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D011446:Prospective Studies; D045162:Thiazolidinediones / Q000627:therapeutic use; D014055:Tomography, Emission-Computed; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione