Burcelin R G, Eddouks M, Beylot M, Normand S, Boitard C, Feutren G, Landais P, Riou J P, Girard J R, Bach J F
Department of Diabetes, Hopital Bichat, Paris, France.
Diabetes Care. 1993 Jun;16(6):881-8. doi: 10.2337/diacare.16.6.881.
To test the sensitivity to insulin in recent-onset IDDM patients, its course according to treatment, and the advent of remissions.
The euglycemic hyperinsulinemic clamp was used in 54 recent-onset IDDM patients and 14 healthy control subjects. Patients were tested after 1,2, and 4 wk of treatment with either insulin or insulin plus cyclosporin A, during cyclosporin A-associated long-lasting remissions, and during relapses.
Insulin sensitivity was markedly decreased in all patients at onset. It was rapidly restored by insulin therapy, whether immunosuppression was associated with it or not. Insulin sensitivity was even higher than normal in the remission patients, who also were characterized by the reappearance of some endogenous insulin secretion and the sustained normalization of blood glucose profiles. During relapses, the deterioration of the blood glucose profiles was associated with some loss of insulin sensitivity.
Cyclosporin A-associated remissions represent an original situation that associates euglycemia with the persistence of low endogenous insulin secretion. Cyclosporin A by itself had no influence on sensitivity to insulin, but allowed the reappearance of some insulin secretory capacity that contributed, with the improvement of insulin sensitivity, to the development of the diabetes honeymoon. The secretion of endogenous insulin, although lower than normal, was sufficient to secure a high sensitivity to insulin and the maintenance of normal blood glucose profiles, presumably because of the fact that insulin was released directly into the portal vein in these conditions. This metabolic state was precarious: the optimal sensitivity to insulin disappeared in patients who relapsed. These results have important clinical consequences: the preservation of islet residual secretory capacity by the use of newer nontoxic immunosuppressive protocols, combined with a minimal supportive insulin therapy in remission patients, may prolong remissions and maintain an optimal insulin sensitivity.
检测近期发病的胰岛素依赖型糖尿病（IDDM）患者对胰岛素的敏感性、其治疗过程及缓解情况。
对54例近期发病的IDDM患者和14名健康对照者采用正常血糖高胰岛素钳夹技术。患者在接受胰岛素或胰岛素加环孢素A治疗1、2和4周后、环孢素A相关的长期缓解期以及复发期进行检测。
所有患者发病时胰岛素敏感性均显著降低。无论是否联合免疫抑制治疗，胰岛素治疗均可迅速恢复胰岛素敏感性。缓解期患者的胰岛素敏感性甚至高于正常水平，其特征还包括内源性胰岛素分泌重新出现以及血糖水平持续正常。复发期间，血糖水平恶化与胰岛素敏感性部分丧失有关。
环孢素A相关的缓解代表了一种独特的情况，即血糖正常与内源性胰岛素低分泌持续存在相关。环孢素A本身对胰岛素敏感性无影响，但可使部分胰岛素分泌能力重新出现，这与胰岛素敏感性的改善共同促成了糖尿病蜜月期的出现。内源性胰岛素分泌虽低于正常水平，但足以确保对胰岛素的高敏感性和血糖水平的正常维持，推测是因为在这些情况下胰岛素直接释放到门静脉中。这种代谢状态不稳定：复发患者对胰岛素的最佳敏感性消失。这些结果具有重要的临床意义：采用更新的无毒免疫抑制方案保留胰岛残余分泌能力，同时对缓解期患者给予最低限度的支持性胰岛素治疗，可能延长缓解期并维持最佳胰岛素敏感性。
