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

L. Jahn,L. Hartline,Amanda J Kleiner,W. Horton,Farhad Hasan,Alvin Wai Kit Tan,Zhenqi Liu,E. Barrett

Published 2023 in American Journal of Physiology. Endocrinology and Metabolism

ABSTRACT

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.

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