Nosadini R, Noy G A, Nattrass M, Alberti K G, Johnston D G, Home P D, Orskov H
Diabetologia. 1982 Sep;23(3):220-8. doi: 10.1007/BF00252845.
Twelve insulin deficient Type 1 (insulin-dependent) diabetic subjects were studied over an 11 1/2 h period during both subcutaneous insulin therapy and closed loop insulin delivery, using a glucose controlled insulin system (Biostator) programmed to maintain normoglycaemia. Results were compared with those from 21 age and weight-matched normal subjects. Using the Biostator, normoglycaemia was achieved in all diabetic subjects within 3.5 h and normal profiles maintained thereafter. Blood metabolite and hormone values were evaluated during the subsequent 8 h normoglycaemic period. Subcutaneous therapy resulted in abnormal glucose levels throughout the study period (mean 8 h value 8.3 +/- 0.7 compared with 5.6 +/- 0.3 mmol/l on feedback control and 5.5 +/- 0.1 mmol/l in normal subjects). The mean value of lactate and pyruvate over the final 8 h period was 25% higher in diabetic patients than in normal subjects with no difference between the two insulin treatments (blood lactate: 0.94 +/- 0.04 on subcutaneous insulin, 0.91 +/- 0.04 on feedback control and 0.74 +/- 0.03 mmol/l in control subjects). The pre-prandial peaks of blood glycerol and plasma non-esterified fatty acids were significantly decreased or absent during both feedback control and subcutaneous therapy in comparison with the normal subjects, whereas after the midday and evening meals, total ketone body levels were significantly higher in the diabetic patients. Peripheral serum free insulin levels were two-to fourfold greater in the diabetic than in the normal subjects. There were no significant differences between levels in diabetic patients receiving subcutaneous insulin or on the Biostator. Glucose turnover (1600-1800 h) was normal on feedback control (1.41 +/- 0.20 versus 1.55 +/- 0.18 mg X kg-1 X min-1 in the normal subjects) but was significantly decreased during subcutaneous insulin (1.04 +/- 0.09 mg X kg-1 X min-1). There was, in addition, a decrease in glucose recycling during both subcutaneous insulin therapy and feedback control in the diabetic subjects. These data suggest that although fine control of glucose metabolism both in terms of circulating concentrations and rates of production can be achieved by feedback-control, insulin infusion by the peripheral route is associated with significant metabolic abnormalities, at least in the short term. Longer term studies and examination of portal insulin delivery seem warranted.
对12名胰岛素缺乏的1型（胰岛素依赖型）糖尿病患者进行了研究，研究时长为11.5小时，期间分别采用皮下胰岛素治疗和闭环胰岛素输注，使用一种经编程以维持正常血糖水平的葡萄糖控制胰岛素系统（生物人工胰腺）。将结果与21名年龄和体重匹配的正常受试者的结果进行比较。使用生物人工胰腺，所有糖尿病患者在3.5小时内实现了正常血糖水平，并在此后维持正常血糖曲线。在随后8小时的正常血糖期内评估血液代谢物和激素值。在整个研究期间，皮下治疗导致血糖水平异常（平均8小时值为8.3±0.7，而反馈控制时为5.6±0.3 mmol/L，正常受试者为5.5±0.1 mmol/L）。糖尿病患者在最后8小时内乳酸和丙酮酸的平均值比正常受试者高25%，两种胰岛素治疗之间无差异（皮下胰岛素治疗时血乳酸为0.94±0.04，反馈控制时为0.91±0.04，对照受试者为0.74±0.03 mmol/L）。与正常受试者相比，在反馈控制和皮下治疗期间，餐前血甘油和血浆非酯化脂肪酸的峰值均显著降低或消失，而在午餐和晚餐后，糖尿病患者的总酮体水平显著更高。糖尿病患者外周血清游离胰岛素水平比正常受试者高两到四倍。接受皮下胰岛素治疗的糖尿病患者与使用生物人工胰腺的患者之间的水平无显著差异。反馈控制时葡萄糖周转率（1600 - 1800小时）正常（1.41±0.20对比正常受试者的1.55±0.18 mg·kg⁻¹·min⁻¹），但皮下胰岛素治疗期间显著降低（1.04±0.09 mg·kg⁻¹·min⁻¹）。此外，糖尿病患者在皮下胰岛素治疗和反馈控制期间葡萄糖再循环均减少。这些数据表明，尽管通过反馈控制可以在循环浓度和产生速率方面实现对葡萄糖代谢的精细控制，但外周途径输注胰岛素至少在短期内与显著的代谢异常有关。似乎有必要进行长期研究并检查门静脉胰岛素输注情况。
