Caprio S, Amiel S, Tamborlane W V, Gelfand R A, Sherwin R S
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Diabetes. 1990 Feb;39(2):134-41. doi: 10.2337/diab.39.2.134.
To examine the impact of diabetes and its treatment on plasma free-fatty acid (FFA) and oxidative fuel metabolism during hypoglycemia, we combined indirect calorimetry with [3-3H]glucose during a 4-h low-dose insulin infusion (plasma insulin approximately 2-fold above basal) in six poorly controlled and nine well-controlled insulin-dependent diabetes mellitus (IDDM) patients and in six healthy subjects. Diabetic subjects received insulin overnight to maintain euglycemia before study. Although free-insulin levels and counterregulatory hormone responses were similar, the plasma glucose fall was more pronounced in well-controlled diabetic subjects. In well-controlled diabetic and healthy subjects, the small increment in insulin rapidly suppressed plasma FFA and fat oxidation by approximately 50% and stimulated carbohydrate oxidation by approximately 80%. In contrast, plasma FFA levels did not fall in poorly controlled diabetic subjects, and glucose oxidation was not stimulated. To determine whether this resistance to the antilipolytic effect of insulin occurs in the absence of hypoglycemic counterregulation, we used a sequential low-dose euglycemic insulin clamp (0.2, 0.3, and 0.5 mU.kg-1.min-1). In healthy subjects, plasma FFA was nearly maximally suppressed at the lowest insulin dose. In contrast, plasma FFA remained persistently elevated in poorly controlled diabetic subjects at each insulin dose. However, the insulin dose-response curve for suppression of plasma FFA was near normal in well-controlled subjects. We conclude that poorly controlled IDDM diabetic patients are resistant to the antilipolytic effects of insulin and show impaired stimulation of glucose oxidation during insulin-induced hypoglycemia. Amelioration of these defects in well-controlled patients may be another factor contributing to the higher risk of hypoglycemia during intensified insulin therapy.
为研究糖尿病及其治疗对低血糖期间血浆游离脂肪酸（FFA）和氧化燃料代谢的影响，我们在6例控制不佳和9例控制良好的胰岛素依赖型糖尿病（IDDM）患者以及6名健康受试者中，于4小时低剂量胰岛素输注（血浆胰岛素水平约为基础值的2倍）期间，将间接测热法与[3-³H]葡萄糖相结合。糖尿病受试者在研究前接受过夜胰岛素治疗以维持血糖正常。尽管游离胰岛素水平和反调节激素反应相似，但控制良好的糖尿病受试者血浆葡萄糖下降更为明显。在控制良好的糖尿病患者和健康受试者中，胰岛素的小幅增加迅速将血浆FFA和脂肪氧化抑制了约50%，并将碳水化合物氧化刺激了约80%。相比之下，控制不佳的糖尿病受试者血浆FFA水平并未下降，葡萄糖氧化也未受到刺激。为确定这种对胰岛素抗脂解作用的抵抗是否在无低血糖反调节的情况下发生，我们使用了连续低剂量正常血糖胰岛素钳夹技术（0.2、0.3和0.5 mU·kg⁻¹·min⁻¹）。在健康受试者中，最低胰岛素剂量时血浆FFA几乎被最大程度抑制。相比之下，在每个胰岛素剂量下，控制不佳的糖尿病受试者血浆FFA持续升高。然而，在控制良好的受试者中，抑制血浆FFA的胰岛素剂量反应曲线接近正常。我们得出结论，控制不佳的IDDM糖尿病患者对胰岛素的抗脂解作用具有抵抗性，并且在胰岛素诱导的低血糖期间葡萄糖氧化刺激受损。控制良好的患者中这些缺陷的改善可能是强化胰岛素治疗期间低血糖风险较高的另一个因素。
