Division of Endocrinology, Department of Medicine, University of Virginia, School of Medicine, Charlottesville, Virginia, United States.
Department of Pharmacology, University of Virginia, School of Medicine, Charlottesville, Virginia, United States.
Am J Physiol Endocrinol Metab. 2023 May 1;324(5):E402-E408. doi: 10.1152/ajpendo.00242.2022. Epub 2023 Mar 15.
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.
在患有 1 型糖尿病(T1DM)的成年人中,胰岛素的微血管作用及其与胰岛素代谢作用的关系尚未得到很好的研究。我们比较了健康成年对照组(= 16)和无临床微血管疾病的 T1DM 受试者(= 15)对胰岛素的代谢和选定的微血管和大血管反应。我们使用对比增强超声(CEU)测量胰岛素对骨骼肌微血管灌注的影响,使用颈动脉-股动脉脉搏波速度(cfPWV)和桡动脉脉搏波分析(PWA)测量动脉僵硬,以及在 2 小时、1 mU/min/kg 正常血糖胰岛素钳夹期间通过葡萄糖输注率(GIR)测量代谢胰岛素敏感性。T1DM 受试者存在代谢性胰岛素抵抗(GIR = 5.2 ± 0.7 对 6.6 ± 0.6 mg/min/kg,<0.001)。胰岛素增加了对照组的肌肉微血管血容量和流量(<0.001,每次),但在 T1DM 受试者中没有增加。代谢胰岛素敏感性与肌肉微血管灌注量的增加相关(<0.05)。两组之间的血管僵硬基线测量值没有差异。然而,在高胰岛素血症期间,T1DM 组的 cfPWV 更高(<0.02),并且只有对照组的反向脉搏波压力随胰岛素下降(<0.03),这两个指标均表明仅在对照组中胰岛素诱导血管舒张。T1DM 受试者存在肌肉微血管胰岛素抵抗,这可能先于临床微血管疾病。我们使用对比超声和血管僵硬测量值,比较了 1 型糖尿病患者与年龄匹配的对照组的血管和代谢对胰岛素的反应。1 型糖尿病患者表现出血管和代谢性胰岛素抵抗,超过一半的糖尿病患者对胰岛素表现出矛盾的血管收缩反应。