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Quinapril Treatment Increases Insulin-Stimulated Endothelial Function and Adiponectin Gene Expression in Patients with Type 2 Diabetes

Department of Cardiology Y, Bispebjerg Hospital (T.S.H., H.D., N.I., A.M.-P., D.B.N., C.T.-P.), 2400 Copenhagen, Denmark; Division of Endocrinology and Diabetes Research and Training Center, Albert Einstein College of Medicine (W.L., M.H.), Bronx, New York 10461; Section on Vascular Cell Biology and Complications, Joslin Diabetes Center (C.R.-M.), Boston, Massachusetts 02215; Department of Clinical Biochemistry, Gentofte University Hospital (K.W.H.), DK-2900 Gentofte, Denmark; and Department of Cardiology B, Rigshospitalet Heart Center (L.K.), DK-2100 Copenhagen, Denmark

Address all correspondence and requests for reprints to: Dr. Thomas S. Hermann, Bispebjerg University Hospital, Y-forskning, bygning 40, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark. E-mail: th{at}heart.dk.

Objective: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism.

Methods: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study. Endothelium-dependent and -independent vasodilation was studied during serotonin or sodium nitroprusside infusion in the diabetic patients and in 15 healthy subjects. Endothelial function, insulin-stimulated endothelial function, and insulin-stimulated glucose uptake were measured before and after quinapril treatment. Blood flow was measured by venous occlusion plethysmography. Gene expression was measured by real-time PCR.

Results: Quinapril treatment increased insulin-stimulated endothelial function in the type 2 diabetic subjects (P = 0.005), whereas forearm glucose uptake was unchanged. Endothelial function was also increased by quinapril (P = 0.001). Systolic and diastolic blood pressures were reduced by quinapril (P < 0.001). Quinapril increased adiponectin gene expression in vascular tissue obtained from sc adipose biopsies.

Conclusions: Quinapril treatment increases insulin-stimulated endothelial function in patients with type 2 diabetes. Increased vascular adiponectin gene expression may contribute to this beneficial effect.

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