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  • Jahn, Linda A; Hartline, Lee M; Kleiner, Amanda J; Horton, William B; Hasan, Farhad; Wai Kit Tan, Alvin; Liu, Zhenqi; Barrett, Eugene J

    American journal of physiology: endocrinology and metabolism, 05/2023, Volume: 324, Issue: 5
    Journal Article

    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 the metabolic and selected micro- and macrovascular responses to insulin by healthy adult control ( = 16) and subjects with T1DM ( = 15) without clinical microvascular disease. We measured insulin's effect on ) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), ) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and ) metabolic insulin sensitivity by the glucose infusion rate (GIR) during a 2-h, 1 mU/min/kg euglycemic-insulin clamp. Subjects with T1DM were metabolically insulin resistant (GIR = 5.2 ± 0.7 vs. 6.6 ± 0.6 mg/min/kg, < 0.001). Insulin increased muscle microvascular blood volume and flow in control ( < 0.001, for each) but not in subjects with T1DM. Metabolic insulin sensitivity correlated with increases of muscle microvascular perfused volume ( < 0.05). Baseline measures of vascular stiffness did not differ between groups. However, during hyperinsulinemia, cfPWV was greater ( < 0.02) in the T1DM group and the backward pulse wave pressure declined with insulin only in controls ( < 0.03), both indices indicating that insulin-induced vascular relaxation in controls only. Subjects with T1DM have muscle microvascular insulin resistance that may precede clinical microvascular disease. Using contrast ultrasound and measures of vascular stiffness, we compared vascular and metabolic responses to insulin in patients with type 1 diabetes with age-matched controls. The patients with type 1 diabetes demonstrated both vascular and metabolic insulin resistance with more than half of the patients with diabetes having a paradoxical vasoconstrictive vascular response to insulin.