Effect of a peroxisome proliferator-activated receptor-gamma agonist on myocardial blood flow in type 2 diabetes.
OBJECTIVE
The relationship between coronary endothelial function and insulin resistance remains speculative. We sought to determine whether pioglitazone, an insulin-sensitizing peroxisome proliferator-activated receptor (PPAR)-gamma agonist, improves cardiac endothelial function in individuals with type 2 diabetes.


METHODS
Sixteen subjects with insulin-treated type 2 diabetes and without overt cardiovascular disease were randomly assigned to receive either 45 mg of pioglitazone or matching placebo for 3 months. Rest and adenosine-stimulated myocardial blood flow (MBF) were quantified with [(13)N]ammonia and positron emission tomography at baseline and study conclusion.


RESULTS
After 3 months, HbA(1c) levels dropped by 0.68% in the pioglitazone group and increased by 0.17% in the placebo group (P = 0.009 for difference between groups). Triglyceride (-93 vs. -39 mg/dl, P = 0.026) and HDL concentrations (+4.8 vs. -6.0 mg/dl, P = 0.014) improved significantly in the pioglitazone group compared with placebo. Despite these favorable changes, there was no demonstrable change in baseline MBF (-0.05 +/- 0.24 vs. -0.09 +/- 0.24 ml . min(-1) . g(-1), P = 0.45), adenosine-stimulated MBF (0.10 +/- 0.75 vs. 0.14 +/- 0.31 ml . min(-1) . g(-1), P = 0.25), or coronary flow reserve (0.45 +/- 1.22 vs. 0.35 +/- 0.72 ml . min(-1) . g(-1), P = 0.64) after 12 weeks of exposure to pioglitazone or placebo, respectively. Regression analysis revealed that lower glucose concentration at the time of the study was associated with higher coronary flow reserve (P = 0.012).


CONCLUSIONS
Pioglitazone treatment for 12 weeks in subjects with insulin-requiring type 2 diabetes had no demonstrable effect on coronary flow reserve despite metabolic improvements. Higher ambient glucose levels contribute to impaired vascular reactivity in individuals with diabetes.
McMahon
Graham T
GT
Brigham and Women's Hospital, Division of Nuclear Medicine, 75 Francis Street, Boston, MA 02115, USA.
Plutzky
Jorge
J
Daher
Edouard
E
Bhattacharyya
Tammy
T
Grunberger
George
G
DiCarli
Marcelo F
MF
D000241:Adenosine / Q000008:administration & dosage; D000368:Aged; D003326:Coronary Circulation / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D010865:Pilot Projects; D000077205:Pioglitazone; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects
D000241:Adenosine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D000077205:Pioglitazone; D045162:Thiazolidinediones