ABSTRACT
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 (n = 16) and subjects with T1DM (n = 15) without clinical microvascular disease. We measured insulin's effect on 1) skeletal muscle microvascular perfusion using contrast-enhanced ultrasound (CEU), 2) arterial stiffness using carotid-femoral pulse-wave velocity (cfPWV) and radial artery pulse wave analysis (PWA), and 3) 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, P < 0.001). Insulin increased muscle microvascular blood volume and flow in control (P < 0.001, for each) but not in subjects with T1DM. 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. Subjects with T1DM have muscle microvascular insulin resistance that may precede clinical microvascular disease.NEW & NOTEWORTHY 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.
Subject(s)
Diabetes Mellitus, Type 1 , Insulin Resistance , Adult , Humans , Insulin/metabolism , Diabetes Mellitus, Type 1/metabolism , Insulin Resistance/physiology , Vasoconstriction , Microvessels/metabolism , Muscle, Skeletal/metabolism , Glucose/metabolism , Blood Glucose/metabolismABSTRACT
DKD is a complex and multifaceted disease. A substantial portion of patients remain unable to attain clinical targets for glycosylated hemoglobin, lipids, and blood pressure. Improving outcomes requires multifactorial interventions that are best delivered through collaborative care. Targets for improvement should include screening, diagnosis, and early referral. Following referral, the patient should be cared for in an integrated framework using the 4 elements of an effective DKD care delivery model: clear roles and responsibilities, integrated QI programs, MDT approach, and effective communication facilitated through access to a shared EMR. Given the differences in the pathophysiology of DM in the renal population, a nephrologist and endocrinologist can be invaluable in improving care for this population. Large-scale trials are needed to validate the cost and usefulness of collaborative care as current data are insufficient. Based on available data, models such as the one proposed here should serve to maximize the strengths of individual providers and provide improved quality of care to patients.