Taskinen M R, Bogardus C, Kennedy A, Howard B V
J Clin Invest. 1985 Aug;76(2):637-44. doi: 10.1172/JCI112016.
To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.
为评估非胰岛素依赖型糖尿病患者游离脂肪酸升高的机制，对14名肥胖的皮马族印第安糖尿病患者以及13名年龄、性别和体重匹配的非糖尿病患者的游离脂肪酸代谢、脂质和碳水化合物氧化情况进行了比较。10名糖尿病患者在接受1个月的口服降糖治疗后重复进行了这些研究。糖尿病患者的空腹血浆葡萄糖浓度升高（242±14 vs. 97±3mg/dl，P<0.01），治疗后降至142±12（P<0.01）。糖尿病患者的空腹游离脂肪酸浓度升高（477±26 vs. 390±39μmol/升，P<0.01），治疗后降至正常水平（336±32，P<0.01）。虽然游离脂肪酸转运速率与肥胖相关（r = 0.75，P<0.001），但糖尿病患者的游离脂肪酸转运并不高于非糖尿病患者，且治疗后无变化。另一方面，未经治疗的糖尿病患者游离脂肪酸的分解代谢率显著降低（0.55±0.04 vs. 0.71±0.06分钟-1，P<0.05）；治疗后升至0.80±0.09分钟-1，P<0.05，且与空腹血糖呈负相关（r = -0.52，P<0.01）。治疗后的糖尿病患者，脂质氧化率显著下降（从1.35±0.06降至1.05±0.01mg/分钟每千克去脂体重，P<0.01），而碳水化合物氧化增加（从1.21±0.10升至1.73±0.13mg/分钟每千克去脂体重，P<0.01）；脂质和碳水化合物氧化的变化相关（r = 0.72，P<0.02），在所有受试者中，脂质氧化仅占游离脂肪酸转运的约40%。数据表明，在非胰岛素依赖型糖尿病患者中，虽然由于肥胖可能导致游离脂肪酸生成增加，但血浆游离脂肪酸浓度升高也是清除减少的结果，游离脂肪酸的部分清除率似乎与糖尿病控制密切相关。此外，尽管脂质氧化显著下降，但部分清除率增加，这表明糖尿病患者的清除缺陷是由于再酯化受损，治疗后得以恢复。
