The metabolic and hormonal response to acute normoglycaemia in type 1 (insulin-dependent) diabetes: Studies with a glucose controlled insulin infusion system (artificial endocrine pancreas)

Abstract

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.

Diurnal Pattern of Insulin Action in Type 1 Diabetes

“…However, multiple investigators have reported correlations among the total amount of carbohydrate ingested, postprandial glucose excursions, and insulin administered when using the Biostator (21–23). Furthermore and not surprisingly, other reports confirmed that glycemic excursions, both fasting and postprandial, were tighter with the Biostator, where insulin was administered intravenously, than with subcutaneous delivery of insulin (24–26). …”

“…Although some (20,24,27) but not all (21–23,26) studies that used the Biostator controlled for physical activity levels, meal sizes, composition, and calorie content varied from meal to meal in all but one (27). Furthermore, all these studies used the Biostator system with intravenous insulin delivery and did not apply specific methods to measure postprandial SI.…”

Effects of Portal and Peripheral Venous Insulin Infusion on Glucose Production and Utilization in Depancreatized, Conscious Dogs

“…The superiority of intraportal insulin delivery over the peripheral i.v. route in diabetic animals has been emphasized by othe r s 10,11,[13][14][15]17,18 Brown et al 11 demonstrated the complete reversal of diabetes when the venous drainage from fetal pancreatic transplants was diverted to the portal circulation, but not when the venous drainage was into the systemic circulation. Goriya et al, 1314 using an open-loop insulin infusion device in pancreatectomized dogs, observed that less insulin was necessary to maintain a normal fasting blood glucose when it was infused into the portal system compared with a peripheral vein.…”

Changes in Plasma Solutes after Food

“…Thus, there was no significant rise in BG and plasma NEFA was suppressed after food (Figure 2). Both happenings presumably resulted from normal postprandial insulin secretion (Nosadini et al 1982). Serum TAA rose significantly after food, but only by a mean 79 umol/l alanine equivalents -an amount which would have been osmotically insignificant.…”