We compared the ability of closed-loop intravenous insulin infusion (i.e., an artificial "pancreas"), open-loop continuous subcutaneous insulin infusion, and intensified conventional insulin therapy (preprandial injections of regular insulin, with injection of long-acting zinc-suspension insulin before breakfast) to bring the hyperglycemia of insulin-dependent diabetic subjects to a level comparable to that of normal, nondiabetic subjects. The mean circadian levels of plasma glucose, mean amplitude of glycemic excursions, and M values (defined in Methods) did not significantly differ among the three regimens. Although these levels in the diabetic subjects approximated those in the normal subjects, the levels of plasma insulin, mean amplitude of glycemic excursions, and M values were significantly higher than those in normal subjects (P < 0.01). Therefore, at least on a short-term basis, all three regimens can produce comparable, nearly normal levels of blood sugar in such patients; moreover, closed-loop devices can be used to determine insulin requirements for conventional therapy.

No abstract

Summary. The effects of size, time of day and sequence of meal ingestion were determined in healthy subjects using a Latin square design. Plasma glucose, insulin and gastric inhibitory polypeptide, but not glucagon, were correlated with meal size. Plasma glucose, but not insulin, gastric inhibitory polypeptide or glucagon, were greater later in the day. The progressive decline in carbohydrate tolerance from 08.00 to 18.00h was associated with impaired insulin secretion estimated by C-peptide, and with impaired insulin action.

To assess the effects of size, time of day, and sequence of meals on insulin requirements determined by an artificial endocrine pancreas, eight insulin-dependent diabetics ate meals of 12.5%, 25%, and 50% of total calories (30 Kcal/kg) at 0800, 1300, and 1800 on each of 3 separate days in a randomized order in one of two sequences in a three by three Latin square design. Plasma glucose and free insulin concentrations and amounts of insulin infused by the artificial endocrine pancreas were associated with meal size (P less than 0.001) but not with time of day of meal ingestion (analysis of variance). The sequence of meal ingestion did not alter integrated plasma glucose responses, but did influence the meal-related amounts of insulin infused. Thus, consideration should be given to meal size and sequence of meal ingestion but not time of day of meal ingestion when determining prandial iv insulin requirements.