Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15O]CO, and positron emission tomography.

Abstract

Exaggerated vasoconstriction and blunted vasodilation of peripheral resistance arteries to various vasoactive agents characterize patients with IDDM. We characterized the hemodynamic effects of insulin in skeletal muscle in patients with IDDM. Muscle blood flow and blood volume were measured basally and during a high-dose insulin infusion (5 mU x kg(-1) x min[-1]) in seven normotensive patients with IDDM (age, 30 +/- 6 years; BMI, 24.5 +/- 2.0 kg/m2; blood pressure, 124 +/- 12/78 +/- 11 mmHg) and nine matched normal subjects, using [15O]H2O, [15O]CO, and positron emission tomography (PET). Whole-body insulin sensitivity was determined using the euglycemic insulin clamp technique. Insulin-stimulated whole-body glucose uptake was significantly lower in the patients with IDDM (45 +/- 15 micromol x kg(-1) x min[-1]) than in the normal subjects (62 +/- 14 micromol x kg(-1) x min[-1]) (P < 0.05). Insulin increased muscle blood flow by 111 +/- 69% above basal from 3.0 +/- 2.0 to 5.8 +/- 3.0 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in the normal subjects, but only by 42 +/- 30% from 2.0 +/- 0.9 to 2.9 +/- 1.4 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in patients with IDDM (P < 0.05 for change in flow in IDDM vs. normal subjects). The calculated muscle vascular resistances were comparable basally, but higher during hyperinsulinemia in the patients with IDDM (37 +/- 17 mmHg x 100 g x min x ml[-1]) than in the normal subjects (16 +/- 7 mmHg x 100 g x min x ml[-l]) (P < 0.05). Muscle blood volume increased significantly by insulin in both groups without any difference between the groups. We conclude that the ability of supraphysiological concentrations of insulin to stimulate muscle blood flow is blunted in patients with IDDM, because of the inability of insulin to stimulate linear flow velocity rather than blood volume in skeletal muscle. This defect adds yet another defect to the list of abnormalities in vascular function in IDDM, which might predispose these patients to develop hypertension.