Gumbiner B, Thorburn A W, Henry R R
Department of Medicine, University of California, San Diego.
J Clin Endocrinol Metab. 1991 Apr;72(4):801-7. doi: 10.1210/jcem-72-4-801.
Decreased glucose-induced thermogenesis has been observed in all forms of obesity. However, some studies implicate insulin resistance rather than obesity per se as the mechanism by which glucose-induced thermogenesis is reduced. To establish the role of insulin resistance in reduced thermogenesis independent of obesity, we compared energy expenditure in 9 nonobese individuals with noninsulin-dependent diabetes mellitus (NIDDM) to 16 nonobese control subjects using indirect calorimetry and the hyperinsulinemic clamp technique. To document the presence of insulin resistance and reduced glucose-induced thermogenesis in nonobese NIDDM, 6 individuals from each group were studied under identical conditions of hyperinsulinemia (120 mU/m2.min) and euglycemia (approximately 5 mmol/l). Both glucose uptake (0.482 +/- 0.042 vs. 0.737 +/- 0.040 g/min) and energy expenditure above basal (0.04 +/- 0.02 vs. 0.10 +/- 0.02 kcal/min) were decreased in nonobese NIDDM compared to control subjects (both P less than 0.05). To determine whether decreased glucose-induced thermogenesis could be overcome by correcting for reduced glucose uptake, the 9 nonobese NIDDM individuals were age and weight-matched to 9 control subjects and clamps were performed at matched rates of glucose uptake. During a 40 mU/m2.min insulin infusion, the nonobese NIDDM individuals were studied at hyperglycemia (17.5 +/- 1.9 mmol/L) and compared to the control subjects at euglycemia (5.1 +/- 0.1 mmol/L; P less than 0.05). Under these conditions, both groups achieved similar rates of glucose uptake (0.698 +/- 0.040 vs. 0.688 +/- 0.038 g/min, NIDDM and control subjects, respectively) and similar rates of energy expenditure above basal (0.08 +/- 0.03 vs. 0.06 +/- 0.02 kcal/min, P = NS). During 600 mU/m2.min clamps performed at hyperglycemia (19.0 +/- 1.2 vs. 14.5 +/- 1.1 mmol/L, NIDDM vs. control subjects, respectively; P less than 0.05), rates of maximal glucose uptake (1.538 +/- 0.093 vs. 1.518 +/- 0.047 g/min) and energy expenditure above basal (0.34 +/- 0.03 vs. 0.31 +/- 0.03 kcal/min) were also similar (P = NS). In conclusion nonobese NIDDM is associated with both decreased rates of glucose uptake and decreased glucose-induced thermogenesis. Decreased glucose substrate availability, due to impaired insulin action, appears to be the critical determinant of glucose-induced thermogenesis in nonobese NIDDM. These data indicate that decreased thermogenesis in NIDDM is a consequence of insulin resistance and can occur independent of obesity.
在所有类型的肥胖中均观察到葡萄糖诱导的产热减少。然而,一些研究认为是胰岛素抵抗而非肥胖本身导致了葡萄糖诱导产热的减少。为了确定胰岛素抵抗在不依赖肥胖的产热减少中所起的作用,我们使用间接测热法和高胰岛素钳夹技术,比较了9名非肥胖的非胰岛素依赖型糖尿病(NIDDM)患者与16名非肥胖对照受试者的能量消耗。为了证实非肥胖NIDDM患者存在胰岛素抵抗和葡萄糖诱导产热减少,每组6名受试者在相同的高胰岛素血症(120 mU/m²·min)和血糖正常(约5 mmol/L)条件下进行研究。与对照受试者相比,非肥胖NIDDM患者的葡萄糖摄取量(0.482±0.042 vs. 0.737±0.040 g/min)和基础能量消耗以上的能量消耗(0.04±0.02 vs. 0.10±0.02 kcal/min)均降低(P均小于0.05)。为了确定通过纠正葡萄糖摄取减少是否可以克服葡萄糖诱导产热的减少,将9名非肥胖NIDDM患者按年龄和体重与9名对照受试者匹配,并以匹配的葡萄糖摄取率进行钳夹实验。在40 mU/m²·min胰岛素输注期间,非肥胖NIDDM患者在高血糖(17.5±1.9 mmol/L)状态下进行研究,并与血糖正常(5.1±0.1 mmol/L)的对照受试者进行比较(P小于0.05)。在这些条件下,两组的葡萄糖摄取率相似(分别为0.698±0.040 vs. 0.688±0.038 g/min,NIDDM患者和对照受试者),基础能量消耗以上的能量消耗率也相似(0.08±0.03 vs. 0.06±0.02 kcal/min,P = 无显著性差异)。在高血糖(分别为19.0±1.2 vs. 14.5±1.1 mmol/L,NIDDM患者与对照受试者;P小于0.05)状态下进行600 mU/m²·min钳夹实验时,最大葡萄糖摄取率(1.538±0.093 vs. 1.518±0.047 g/min)和基础能量消耗以上的能量消耗率(0.34±0.03 vs. 0.31±0.03 kcal/min)也相似(P = 无显著性差异)。总之,非肥胖NIDDM患者与葡萄糖摄取率降低和葡萄糖诱导产热减少均相关。由于胰岛素作用受损导致的葡萄糖底物可用性降低,似乎是非肥胖NIDDM患者葡萄糖诱导产热的关键决定因素。这些数据表明,NIDDM患者产热减少是胰岛素抵抗的结果,且可独立于肥胖而发生。