Insulin action enhancement normalizes brachial artery vasoactivity in patients with peripheral vascular disease and occult diabetes.
OBJECTIVE
Brachial artery vasoactivity (BAVA) evaluation is a reliable, noninvasive method of assessing arterial endothelial function in vivo. We previously have shown that patients with peripheral vascular disease (PVD) and occult diabetes have abnormal BAVA results when fasting and after oral glucose intake during oral glucose tolerance test (OGTT). Troglitazone is an oral hypoglycemic agent that enhances the action of insulin. The effect of troglitazone on BAVA in patients with occult diabetes and PVD is not known.


METHODS
Patients with PVD, normal fasting glucose levels, and abnormal OGTT results were identified. With a duplex ultrasound scan, BAVA was evaluated by measuring the brachial artery (BA) flow (in millimeters per minute) before and after 5 minutes of BA occlusion during fasting and at 30 minutes, 1 hour, and 2 hours after the administration of 75 g of glucose during OGTT. Troglitazone therapy (400 mg/day) was begun, and the BAVA evaluation was repeated after 2 and 4 months. These results were compared with the results of the control group who had normal fasting glucose levels, normal OGTT results, and no evidence of PVD. A paired t test was used to compare the BA flow before and after BA occlusion, with a P value of less than.05 considered significant.


RESULTS
The control group had a normal hyperemic response with a significantly increased BA flow after 5 minutes of BA occlusion during fasting and at all stages of the OGTT. The occult diabetic group had an abnormal response to hyperemia before the treatment with troglitazone and showed little change in flow after BA occlusion. After 2 months of troglitazone therapy, BAVA results improved after oral glucose intake but not during fasting. After 4 months, BAVA results normalized both while fasting and after oral glucose intake during the OGTT.


CONCLUSIONS
Patients with occult diabetes and PVD have impaired BAVA, which normalizes after treatment with troglitazone. Insulin-action enhancers may slow the progression of PVD in patients with diabetes by improving endothelial cell function. Agents that are aimed at enhancing the action of insulin may have an advantage over the other traditional therapies for diabetes.
Avena
R
R
Departments of Surgery and Endocrinology, Veterans Affairs Medical Center, George Washington and Georgetown University Medical Centers, Washington, DC, USA.
Mitchell
M E
ME
Nylen
E S
ES
Curry
K M
KM
Sidawy
A N
AN
D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology*; D002839:Chromans / Q000494:pharmacology; D005215:Fasting; D018149:Glucose Intolerance / Q000150:complications / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006801:Humans; D006940:Hyperemia; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000150:complications / Q000503:physiopathology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone