Insulin-Induced Vasoconstriction in Muscle Microvasculature of Otherwise Healthy Persons with Type 1 Diabetes.

BACKGROUND AND OBJECTIVE: Insulin's microvascular actions and their relationship to insulin's metabolic actions have not been well-studied in adults with type 1 diabetes mellitus (T1DM). We compared metabolic and selected micro- and macro-vascular responses to insulin by healthy adult control (n=16) and T1DM (n=15) subjects without clinical microvascular disease.

DESIGN AND METHODS: We measured insulin's effect on: a) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU); b) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA); and c) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp.

RESULTS: T1DM subjects were metabolically insulin resistant (GIR = 5.2±0.7 vs 6.6±0.6 mg/min/kg, p<0.001). Insulin increased muscle microvascular blood volume and flow in control (p<0.001, for each) but not T1DM subjects. Metabolic insulin sensitivity correlated with increases of muscle microvascular perfused volume (p<0.05). Baseline measures of vascular stiffness did not differ between groups. However, during hyperinsulinemia, cfPWV was greater (p<0.02) in the T1DM group and the backward pulse wave pressure declined with insulin only in controls (p<0.03), both indices indicating that insulin induced vascular relaxation in controls only.

CONCLUSIONS: T1DM subjects have muscle microvascular insulin resistance that may precede clinical microvascular disease.