Kollind M
Department of Medicine, Danderyd Hospital, Stockholm, Sweden.
Acta Med Scand Suppl. 1988;727:1-56.
Altogether 54 male patients with insulin-dependent diabetes mellitus participated in the studies. The impact of insulin-induced hypoglycemia on posthypoglycemic insulin sensitivity was evaluated for up to 12 hours following nadir hypoglycemia. The effect on glucose homeostasis following transient elevation of counterregulatory hormones was studied by exogenous administration of adrenaline, adreno-corticotropic hormone and growth hormone and by suppression of the endogenous release of growth hormone in connection with hypoglycemia. The studies were performed in the fasting state preceded by a 24 hour intravenous insulin infusion in order to avoid interference of subcutaneous insulin. Insulin resistance was determined by a constant rate intravenous infusion of somatostatin, insulin and glucose. This test seemed appropriate for the evaluation of total insulin resistance, and its reproducibility was acceptable. By using this method it was demonstrated that insulin resistance occurred for at least 12 hours after a hypoglycemic event in patients with IDDM, and that adrenaline caused immediate insulin resistance which, however, faded out within four to six hours, while GH exerted no immediate effect on insulin sensitivity but caused marked and sustained insulin resistance after a lag period of about four hours. Cortisol had no apparent effect within six hours but enhanced the effect of GH. The magnitude of these diabetogenic effects of hypoglycemia and GH was less pronounced in patients who already were more insulin resistant. These results are compatible with the idea that adrenaline is of major importance for the counterregulation and restoration of blood glucose during the first few hours following hypoglycemia, while GH is responsible for the induction of a long-lasting state of insulin resistance. It is possible that such prolonged insulin resistance may cause posthypoglycemic hyperglycemia in patients with IDDM. These studies therefore indicate that the GH suppressing hormone somatostatin may be of clinical value as an adjunct to insulin in the treatment of patients with insulin-dependent diabetes mellitus and labile blood glucose control.
共有54名胰岛素依赖型糖尿病男性患者参与了这些研究。在低血糖最低点后长达12小时内，评估胰岛素诱导的低血糖对低血糖后胰岛素敏感性的影响。通过外源性给予肾上腺素、促肾上腺皮质激素和生长激素，以及在低血糖情况下抑制生长激素的内源性释放，研究了反调节激素短暂升高后对葡萄糖稳态的影响。研究在空腹状态下进行，之前进行24小时静脉输注胰岛素，以避免皮下胰岛素的干扰。通过持续静脉输注生长抑素、胰岛素和葡萄糖来测定胰岛素抵抗。该试验似乎适合评估总胰岛素抵抗，其可重复性是可以接受的。通过使用这种方法证明，胰岛素依赖型糖尿病患者在低血糖事件后至少12小时会出现胰岛素抵抗，肾上腺素会立即引起胰岛素抵抗，但在4至6小时内消退，而生长激素对胰岛素敏感性没有立即影响，但在约4小时的延迟期后会引起明显且持续的胰岛素抵抗。皮质醇在6小时内没有明显作用，但会增强生长激素的作用。低血糖和生长激素的这些致糖尿病作用在已经更具胰岛素抵抗的患者中不太明显。这些结果与以下观点一致，即肾上腺素在低血糖后的最初几个小时内对血糖的反调节和恢复至关重要，而生长激素则负责诱导长期的胰岛素抵抗状态。胰岛素依赖型糖尿病患者的这种长期胰岛素抵抗可能导致低血糖后高血糖。因此，这些研究表明，生长抑素这种生长激素抑制激素作为胰岛素的辅助药物，在治疗胰岛素依赖型糖尿病和血糖控制不稳定的患者中可能具有临床价值。
