Felber J P, Ferrannini E, Golay A, Meyer H U, Theibaud D, Curchod B, Maeder E, Jequier E, DeFronzo R A
Institute of Clinical Physiology, University of Pisa, Italy.
Diabetes. 1987 Nov;36(11):1341-50. doi: 10.2337/diab.36.11.1341.
Increased lipid oxidation is generally observed in subjects with obesity and diabetes and has been suggested to be responsible for the insulin resistance associated with these conditions. We measured, by continuous indirect calorimetry, lipid and glucose oxidation and nonoxidative glucose disposal in 82 obese subjects during a 100-g oral glucose tolerance test (OGTT) and in 26 during a euglycemic insulin (40 mU.min-1.m-2) clamp. The obese subjects were subdivided into those with normal glucose tolerance (group A), those with impaired glucose tolerance (group B), and those with overt diabetes (group C). Forty-five healthy nonobese subjects were subdivided into a young and an older control group, which were age-matched to the nondiabetic obese (groups A and B) and diabetic obese (group C) subjects, respectively. In the postabsorptive state, as well as in response to insulin stimulation (both OGTT and insulin clamp), lipid oxidation was significantly increased in all three obese groups in comparison with either young or older controls. Basal glucose oxidation was significantly decreased in obese nondiabetic and obese glucose--intolerant subjects (groups A and B) compared with age-matched controls. During the OGTT and during the insulin clamp, insulin-stimulated glucose oxidation was decreased in all three obese groups. In contrast, nonoxidative glucose disposal was markedly inhibited in nondiabetic and diabetic obese patients during the euglycemic insulin clamp but not during the OGTT. After glucose ingestion, nonoxidative glucose uptake was normal in nondiabetic obese and glucose-intolerant obese subjects and decreased in diabetic obese subjects. Statistical analysis revealed that lipid and glucose oxidation were strongly and inversely related in the basal state, during euglycemic insulin clamp, and during OGTT. The negative correlation between lipid oxidation and nonoxidative glucose uptake, although significant, was much weaker. Fasting and post-OGTT hyperglycemia were the strongest (negative) correlates of nonoxidative glucose disposal in both single and multiple regression models. We conclude that 1) reduced glucose oxidation and reduced nonoxidative glucose disposal partake of the insulin resistance of nondiabetic obese and diabetic obese individuals; 2) hyperglycemia provides a compensatory mechanism for the defect in nonoxidative glucose disposal in nondiabetic obese subjects; however, this compensation is characteristically lost when overt diabetes ensues; and 3) increased lipid oxidation may contribute, in part, to the defects in glucose oxidation and nonoxidative glucose uptake in obesity.
在肥胖和糖尿病患者中，通常会观察到脂质氧化增加，并且有人认为这与这些疾病相关的胰岛素抵抗有关。我们通过连续间接测热法，在82名肥胖受试者进行100克口服葡萄糖耐量试验（OGTT）期间以及26名受试者进行正常血糖胰岛素（40 mU·min⁻¹·m⁻²）钳夹期间，测量了脂质和葡萄糖氧化以及非氧化葡萄糖处置情况。肥胖受试者被分为糖耐量正常组（A组）、糖耐量受损组（B组）和显性糖尿病组（C组）。45名健康非肥胖受试者被分为年轻对照组和老年对照组，分别与非糖尿病肥胖（A组和B组）和糖尿病肥胖（C组）受试者年龄匹配。在吸收后状态以及对胰岛素刺激（OGTT和胰岛素钳夹）的反应中，与年轻或老年对照组相比，所有三个肥胖组的脂质氧化均显著增加。与年龄匹配的对照组相比，肥胖非糖尿病和肥胖糖耐量受损受试者（A组和B组）的基础葡萄糖氧化显著降低。在OGTT和胰岛素钳夹期间，所有三个肥胖组的胰岛素刺激的葡萄糖氧化均降低。相反，在正常血糖胰岛素钳夹期间，非糖尿病和糖尿病肥胖患者的非氧化葡萄糖处置受到明显抑制，但在OGTT期间未受抑制。摄入葡萄糖后，非糖尿病肥胖和糖耐量受损肥胖受试者的非氧化葡萄糖摄取正常，而糖尿病肥胖受试者的非氧化葡萄糖摄取减少。统计分析表明，在基础状态、正常血糖胰岛素钳夹期间和OGTT期间，脂质和葡萄糖氧化呈强烈负相关。脂质氧化与非氧化葡萄糖摄取之间的负相关虽然显著，但要弱得多。在单因素和多因素回归模型中，空腹和OGTT后高血糖是与非氧化葡萄糖处置最强的（负）相关因素。我们得出结论：1）葡萄糖氧化减少和非氧化葡萄糖处置减少是肥胖非糖尿病和糖尿病肥胖个体胰岛素抵抗的一部分；2）高血糖为肥胖非糖尿病受试者非氧化葡萄糖处置缺陷提供了一种代偿机制；然而，当发生显性糖尿病时，这种代偿作用通常会丧失；3）脂质氧化增加可能部分导致肥胖患者葡萄糖氧化和非氧化葡萄糖摄取缺陷。
