Pioglitazone-induced insulin sensitization improves vascular endothelial function in nondiabetic patients with essential hypertension.
BACKGROUND
It has been suggested that insulin resistance is involved in the impaired vascular endothelial function not only in diabetic patients but also in hypertensive patients. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse endothelial dysfunction in hypertensive subjects.


METHODS
Fifteen nondiabetic patients with essential hypertension were enrolled in this study. An oral glucose tolerance test (OGTT) and insulin sensitivity test were performed. Insulin sensitivity was determined with the steady-state plasma glucose (SSPG) method. Only subjects with insulin resistance (SSPG > or =8.3 mmol/L) were included. Endothelium-dependent vasodilation during reactive hyperemia (flow-mediated dilation) was evaluated using ultrasonography. Six months after treatment with the insulin-sensitizing agent pioglitazone (30 mg/day), these examinations were repeated in all subjects.


RESULTS
Pioglitazone did not decrease fasting plasma glucose and hemoglobin A1c (HbA1c) in the nondiabetic subjects, although the area under the curve for glucose and insulin on OGTT significantly decreased. A marked decrease in SSPG was observed after pioglitazone treatment (10.7 +/- 1.4 to 7.9 +/- 2.1 mmol/L, P < .001). Endothelium-dependent vasodilation evaluated by flow-mediated dilation was also improved by pioglitazone (5.0% +/- 2.2% to 6.3% +/- 2.4%, P = .023). Furthermore, the increase in flow-mediated dilation was closely correlated with the decrease in SSPG (r = 0.72, P = .002) but not with the decrease in area under the curve for glucose or insulin on OGTT. Endothelium-independent dilation induced by glyceryl trinitrate was not altered by pioglitazone.


CONCLUSIONS
The present findings demonstrate that pioglitazone improves endothelial function in nondiabetic hypertensive individuals with insulin resistance, and that the improvement is associated with the amelioration of insulin resistance itself rather than that of hyperglycemia or hyperinsulinemia.
Horio
Takeshi
T
Division of Hypertension and Nephrology, Department of Medicine, National Cardiovascular Center, Suita, Japan. thorio@ri.ncvc.go.jp
Suzuki
Masaaki
M
Takamisawa
Itaru
I
Suzuki
Kazutaka
K
Hiuge
Aki
A
Yoshimasa
Yasunao
Y
Kawano
Yuhei
Y
D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001916:Brachial Artery / Q000000981:diagnostic imaging; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007564:Japan; D008297:Male; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D045162:Thiazolidinediones; D000077205:Pioglitazone