Gan Seng Khee, Samaras Katherine, Thompson Campbell H, Kraegen Edward W, Carr Andrew, Cooper David A, Chisholm Donald J
Metabolism and Diabetes Research Program, Garvan Institute of Medical Research, Sydney, Australia.
Diabetes. 2002 Nov;51(11):3163-9. doi: 10.2337/diabetes.51.11.3163.
HIV protease inhibitor-related lipodystrophy is characterized by peripheral fat loss, hyperlipidemia, and insulin resistance. Increased availability of lipid to muscle may be one of the mechanisms that induce insulin resistance. Regional fat, intramyocellular lipid (by (1)H-magnetic resonance spectroscopy), serum lipids, and insulin-stimulated glucose disposal (by hyperinsulinemic-euglycemic clamp) were quantified in 10 men who had HIV-1 infection with moderate to severe lipodystrophy and a control group of 10 nonlipodystrophic men who had HIV-1 infection and were naïve to protease inhibitors to examine the effects of lipodystrophy on glucose and lipid metabolism. Lipodystrophic subjects showed lower insulin-stimulated glucose disposal than control subjects (P = 0.001) and had increased serum triglycerides (P = 0.03), less limb fat (P = 0.02), increased visceral fat as a proportion of total abdominal fat (P = 0.003), and increased intramyocellular lipid (1.90 +/- 0.15 vs. 1.23 +/- 0.16% of water resonance peak area; P = 0.007). In both groups combined, visceral fat related strongly to intramyocellular lipid (r = 0.83, P < 0.0001) and intramyocellular lipid related negatively to insulin-stimulated glucose disposal (r = -0.71, P = 0.0005). Fasting serum cholesterol and triglycerides related positively to intramyocellular lipid and visceral fat in lipodystrophic subjects only. The data indicate that lipodystrophy is associated with increased lipid content in muscle accompanying impaired insulin action. The results do not establish causation but emphasize the interrelationships among visceral fat, myocyte lipid, and insulin action.
与HIV蛋白酶抑制剂相关的脂肪代谢障碍的特征为外周脂肪减少、高脂血症和胰岛素抵抗。脂质向肌肉的供应增加可能是诱导胰岛素抵抗的机制之一。对10名患有中度至重度脂肪代谢障碍的HIV-1感染男性以及10名未患脂肪代谢障碍、感染HIV-1且未使用过蛋白酶抑制剂的男性对照组进行了区域脂肪、肌内脂质（通过氢磁共振波谱法）、血脂以及胰岛素刺激的葡萄糖处置（通过高胰岛素-正血糖钳夹法）的定量分析，以研究脂肪代谢障碍对葡萄糖和脂质代谢的影响。脂肪代谢障碍患者的胰岛素刺激的葡萄糖处置低于对照组（P = 0.001），血清甘油三酯升高（P = 0.03），肢体脂肪减少（P = 0.02），内脏脂肪占腹部总脂肪的比例增加（P = 0.003），肌内脂质增加（水共振峰面积的1.90±0.15%对1.23±0.16%；P = 0.007）。在两组合并分析中，内脏脂肪与肌内脂质密切相关（r = 0.83，P < 0.0001），肌内脂质与胰岛素刺激的葡萄糖处置呈负相关（r = -0.71，P = 0.0005）。仅在脂肪代谢障碍患者中，空腹血清胆固醇和甘油三酯与肌内脂质和内脏脂肪呈正相关。数据表明，脂肪代谢障碍与胰岛素作用受损伴肌肉脂质含量增加有关。这些结果并未确立因果关系，但强调了内脏脂肪、肌细胞脂质和胰岛素作用之间的相互关系。
