ARBs Improve Endothelial Function, Findings Show : For patients with impaired glucose intolerance, angiotensin II receptor-1 blockade helps significantly.

TORONTO — Endothelial function improves significantly with angiotensin II receptor-1 blockade in patients with impaired glucose tolerance, and quickly reverts to baseline after discontinuation of therapy, Thomas H. Schindler, M.D., reported at the annual meeting of the Society of Nuclear Medicine.

He and his colleagues at the University of California, Los Angeles, also saw a parallel and significant decrease in insulin resistance during 24 weeks of treatment.

The findings suggest that improved insulin sensitivity and the pleiotropic effects of renin-angiotensin-aldosterone system blockade may account for the reduction in new-onset type 2 diabetes that has been associated with the use of ACE inhibitors and angiotensin receptor blockers (ARBs).

The researchers set out to determine whether the insulin-sensitizing effects of ARB therapy with valsartan would improve endothelial-dependent vasomotion in 30 patients with IGT, defined as fasting glucose below 126 mg/dL and a 2-hour oral glucose tolerance test between 140 and 200 mg/dL.

“None of them had any other traditional coronary risk factors,” Dr. Schindler said. Another 20 healthy volunteers were also studied at baseline and compared with the IGT patients; they received no medication during the study.

The patients with IGT received valsartan, 160 mg a day for 12 weeks, after which the dose was doubled to 320 mg a day and continued for another 12 weeks. Treatment was discontinued at 24 weeks, and the patients were followed to 32 weeks.

“Body mass index was significantly higher in IGT patients than in controls, but both total cholesterol and low-density lipoprotein cholesterol were within the normal range and did not differ significantly between the two groups,” Dr. Schindler said.

Not unexpectedly, myocardial blood flow responses from rest to cold pressor testing were significantly lower at baseline in the IGT patients than in the controls. In contrast, endothelial-independent stimulation of myocardial blood flow did not differ between the two groups.

After 12 weeks of valsartan at 160 mg a day, myocardial blood flow response to cold pressor testing significantly improved in the IGT patients, from 0.75 mL/g per minute at baseline to 0.89 mL/g per minute at 12 weeks.

After 12 more weeks of valsartan at 320 mg, myocardial blood flow response to cold pressor testing again improved significantly, from 0.89 mL/g per minute at 12 weeks to 0.94 mL/g per minute at 24 weeks. Valsartan was discontinued for 8 weeks; the observed reaction to cold pressor testing disappeared.

In parallel fashion, insulin sensitivity—expressed as the glucose infusion rate during hyperinsulinemia euglycemic clamp—increased steadily in the IGT patients, from a baseline value of 3.2 mg/kg per minute (a clear sign that patients were insulin resistant) to 3.7 mg/kg per minute at 12 weeks and to 4.2 mg/kg per minute at 24 weeks.

At 32 weeks, the improvement in insulin sensitivity in the IGT patients had returned to baseline. In a later interview, Dr. Schindler speculated that the pleiotropic effects of the ARB—including potential anti-inflammatory, antioxidative, and antithrombotic properties—may have all helped to improve insulin sensitivity.

“We conclude that IGT in patients without other coronary risk factors is associated with coronary endothelial dysfunction and that angiotensin II receptor-1 blockade with valsartan restores endothelial function. This effect was independent of the plasma lipid profile and C-reactive protein, an inflammatory plasma marker, suggesting that these beneficial effects on the coronary endothelium may be related to an increase in insulin sensitivity and the pleiotropic effects of ARB blockade,” Dr. Schindler said.

TORONTO — Endothelial function improves significantly with angiotensin II receptor-1 blockade in patients with impaired glucose tolerance, and quickly reverts to baseline after discontinuation of therapy, Thomas H. Schindler, M.D., reported at the annual meeting of the Society of Nuclear Medicine.

He and his colleagues at the University of California, Los Angeles, also saw a parallel and significant decrease in insulin resistance during 24 weeks of treatment.

The findings suggest that improved insulin sensitivity and the pleiotropic effects of renin-angiotensin-aldosterone system blockade may account for the reduction in new-onset type 2 diabetes that has been associated with the use of ACE inhibitors and angiotensin receptor blockers (ARBs).

The researchers set out to determine whether the insulin-sensitizing effects of ARB therapy with valsartan would improve endothelial-dependent vasomotion in 30 patients with IGT, defined as fasting glucose below 126 mg/dL and a 2-hour oral glucose tolerance test between 140 and 200 mg/dL.

“None of them had any other traditional coronary risk factors,” Dr. Schindler said. Another 20 healthy volunteers were also studied at baseline and compared with the IGT patients; they received no medication during the study.

The patients with IGT received valsartan, 160 mg a day for 12 weeks, after which the dose was doubled to 320 mg a day and continued for another 12 weeks. Treatment was discontinued at 24 weeks, and the patients were followed to 32 weeks.

“Body mass index was significantly higher in IGT patients than in controls, but both total cholesterol and low-density lipoprotein cholesterol were within the normal range and did not differ significantly between the two groups,” Dr. Schindler said.

Not unexpectedly, myocardial blood flow responses from rest to cold pressor testing were significantly lower at baseline in the IGT patients than in the controls. In contrast, endothelial-independent stimulation of myocardial blood flow did not differ between the two groups.

After 12 weeks of valsartan at 160 mg a day, myocardial blood flow response to cold pressor testing significantly improved in the IGT patients, from 0.75 mL/g per minute at baseline to 0.89 mL/g per minute at 12 weeks.

After 12 more weeks of valsartan at 320 mg, myocardial blood flow response to cold pressor testing again improved significantly, from 0.89 mL/g per minute at 12 weeks to 0.94 mL/g per minute at 24 weeks. Valsartan was discontinued for 8 weeks; the observed reaction to cold pressor testing disappeared.

In parallel fashion, insulin sensitivity—expressed as the glucose infusion rate during hyperinsulinemia euglycemic clamp—increased steadily in the IGT patients, from a baseline value of 3.2 mg/kg per minute (a clear sign that patients were insulin resistant) to 3.7 mg/kg per minute at 12 weeks and to 4.2 mg/kg per minute at 24 weeks.

At 32 weeks, the improvement in insulin sensitivity in the IGT patients had returned to baseline. In a later interview, Dr. Schindler speculated that the pleiotropic effects of the ARB—including potential anti-inflammatory, antioxidative, and antithrombotic properties—may have all helped to improve insulin sensitivity.

“We conclude that IGT in patients without other coronary risk factors is associated with coronary endothelial dysfunction and that angiotensin II receptor-1 blockade with valsartan restores endothelial function. This effect was independent of the plasma lipid profile and C-reactive protein, an inflammatory plasma marker, suggesting that these beneficial effects on the coronary endothelium may be related to an increase in insulin sensitivity and the pleiotropic effects of ARB blockade,” Dr. Schindler said.

TORONTO — Endothelial function improves significantly with angiotensin II receptor-1 blockade in patients with impaired glucose tolerance, and quickly reverts to baseline after discontinuation of therapy, Thomas H. Schindler, M.D., reported at the annual meeting of the Society of Nuclear Medicine.

He and his colleagues at the University of California, Los Angeles, also saw a parallel and significant decrease in insulin resistance during 24 weeks of treatment.

The findings suggest that improved insulin sensitivity and the pleiotropic effects of renin-angiotensin-aldosterone system blockade may account for the reduction in new-onset type 2 diabetes that has been associated with the use of ACE inhibitors and angiotensin receptor blockers (ARBs).

The researchers set out to determine whether the insulin-sensitizing effects of ARB therapy with valsartan would improve endothelial-dependent vasomotion in 30 patients with IGT, defined as fasting glucose below 126 mg/dL and a 2-hour oral glucose tolerance test between 140 and 200 mg/dL.

“None of them had any other traditional coronary risk factors,” Dr. Schindler said. Another 20 healthy volunteers were also studied at baseline and compared with the IGT patients; they received no medication during the study.

The patients with IGT received valsartan, 160 mg a day for 12 weeks, after which the dose was doubled to 320 mg a day and continued for another 12 weeks. Treatment was discontinued at 24 weeks, and the patients were followed to 32 weeks.

“Body mass index was significantly higher in IGT patients than in controls, but both total cholesterol and low-density lipoprotein cholesterol were within the normal range and did not differ significantly between the two groups,” Dr. Schindler said.

Not unexpectedly, myocardial blood flow responses from rest to cold pressor testing were significantly lower at baseline in the IGT patients than in the controls. In contrast, endothelial-independent stimulation of myocardial blood flow did not differ between the two groups.

After 12 weeks of valsartan at 160 mg a day, myocardial blood flow response to cold pressor testing significantly improved in the IGT patients, from 0.75 mL/g per minute at baseline to 0.89 mL/g per minute at 12 weeks.

After 12 more weeks of valsartan at 320 mg, myocardial blood flow response to cold pressor testing again improved significantly, from 0.89 mL/g per minute at 12 weeks to 0.94 mL/g per minute at 24 weeks. Valsartan was discontinued for 8 weeks; the observed reaction to cold pressor testing disappeared.

In parallel fashion, insulin sensitivity—expressed as the glucose infusion rate during hyperinsulinemia euglycemic clamp—increased steadily in the IGT patients, from a baseline value of 3.2 mg/kg per minute (a clear sign that patients were insulin resistant) to 3.7 mg/kg per minute at 12 weeks and to 4.2 mg/kg per minute at 24 weeks.

At 32 weeks, the improvement in insulin sensitivity in the IGT patients had returned to baseline. In a later interview, Dr. Schindler speculated that the pleiotropic effects of the ARB—including potential anti-inflammatory, antioxidative, and antithrombotic properties—may have all helped to improve insulin sensitivity.

“We conclude that IGT in patients without other coronary risk factors is associated with coronary endothelial dysfunction and that angiotensin II receptor-1 blockade with valsartan restores endothelial function. This effect was independent of the plasma lipid profile and C-reactive protein, an inflammatory plasma marker, suggesting that these beneficial effects on the coronary endothelium may be related to an increase in insulin sensitivity and the pleiotropic effects of ARB blockade,” Dr. Schindler said.