Robert J J, Rakotoambinina B, Cochet I, Foussier V, Magre J, Darmaun D, Chevenne D, Capeau J
Unit of Pediatric Endocrinology and Diabetology, INSERM U 30, Necker-Enfants Malades Hospital, Paris, France.
Diabetologia. 1993 Dec;36(12):1288-92. doi: 10.1007/BF00400807.
Insulin resistance is present in patients suffering from lipoatrophic syndromes long before the onset of diabetes mellitus. Thus, the decreased peripheral glucose disposal may not be the only mechanism of hyperglycaemia. The kinetic parameters of glucose homeostasis were evaluated in six young females aged 15, 16, 18, 19 and 24 years with generalized lipoatrophy; one patient was studied both at 12 and 15 years. Insulin resistance was evaluated in vivo by the hyperinsulinaemic euglycaemic clamp (3-4 insulin infusion rates from 1 to 100 mU/kg.min). All patients showed a rightward shift of the dose-response curve, indicating decreased insulin sensitivity. In two patients, maximal glucose disposal was moderately decreased, while in five patients it was dramatically reduced (3.6-6.9 mg/kg.min). Fasting plasma glucose was variable (4.3-18.3 mmol/l) and did not correlate with peripheral glucose disposal rates. Hepatic glucose production, measured by infusion of [6,6-2H] glucose, varied from 1.7 to 8.3 mg/kg.min and was significantly correlated with fasting plasma glucose. The overproduction of glucose despite basal hyperinsulinism suggested hepatic insulin resistance, which was confirmed by the abnormal response to constant unlabelled glucose infusion (2 mg/kg.min) in five patients. In conclusion, impaired glucose tolerance seems to develop in generalized lipoatrophy with aggravated peripheral insulin resistance. The present data show that fasting hyperglycaemia is mainly the consequence of increased hepatic glucose production.
在患有脂肪萎缩综合征的患者中，早在糖尿病发病之前就存在胰岛素抵抗。因此，外周葡萄糖处理能力下降可能不是高血糖的唯一机制。对6名年龄分别为15岁、16岁、18岁、19岁和24岁的患有全身性脂肪萎缩的年轻女性的葡萄糖稳态动力学参数进行了评估；其中一名患者在12岁和15岁时均接受了研究。通过高胰岛素正常血糖钳夹技术（胰岛素输注速率为1至100 mU/kg·min，共3 - 4个速率）在体内评估胰岛素抵抗。所有患者的剂量 - 反应曲线均向右移动，表明胰岛素敏感性降低。在两名患者中，最大葡萄糖处理能力中度下降，而在五名患者中则显著降低（3.6 - 6.9 mg/kg·min）。空腹血糖各不相同（4.3 - 18.3 mmol/l），且与外周葡萄糖处理速率无关。通过输注[6,6 - 2H]葡萄糖测量的肝脏葡萄糖生成量在1.7至8.3 mg/kg·min之间变化，并且与空腹血糖显著相关。尽管基础胰岛素水平升高，但葡萄糖仍过度生成，提示存在肝脏胰岛素抵抗，这在五名患者对持续未标记葡萄糖输注（2 mg/kg·min）的异常反应中得到证实。总之，在全身性脂肪萎缩伴外周胰岛素抵抗加重的情况下，葡萄糖耐量似乎会受损。目前的数据表明，空腹高血糖主要是肝脏葡萄糖生成增加的结果。
