Bernard Zinman

Comparison of Algorithms for the Closed-Loop Control of Blood Glucose Using the Artificial Beta Cell

Over the past 15 years, several algorithms have been proposed and used for closed-loop blood glucose regulation. Their intent is to artificially replace the normal responses of the pancreatic beta cell absent in insulin-dependent diabetes. All of these algorithms calculate insulin infusion rates on the basis of minute-by-minute measurements of whole blood glucose concentration and its calculated rate of rise or fall. In addition, various techniques are employed to compensate for measurement delay time and the presence of noise in the measured signals. The goal of these feedback systems is to normalize blood glucose in diabetes mellitus. Interestingly, some recently optimized versions provide only a near normalization of glycemia in patients with insulin-dependent diabetes, a degree ofglycemic control which is not significantly different from intensified conventional insulin therapy.

ROLE OF CONTINUOUS COMPONENT IN SUBCUTANEOUS "OPEN-LOOP" INSULIN DELIVERY

Abstract To determine the role of the continuous component in open-loop subcutaneous insulin-infusion systems plasma-glucose and free immunoreactive insulin (IRI) levels were compared in nine lean insulin-dependent diabetics receiving insulin via a subcutaneous catheter either as premeal boluses plus a continuous infusion (SCI) or as boluses alone before meals and at bedtime (SCB). Subjects were first placed on the intravenous closed-loop system to determine insulin requirements (42±2·5 U/day) for ideal plasma-glucose control. With diet and total insulin kept constant, identical and nearly normal plasma-glucose profiles were obtained with both SCB and SCI systems during meals. The mean plasma-glucose excursions with meals were 68±10 mg/dl at breakfast, 28±14 at lunch, and 32±10 at dinner. Plasma-glucose levels remained normal after dinner until 3 A.M. (93±8 mg/dl), but by 7A.M. the level achieved with SCB was 284±18, while that with SCI remained at 96±11 mg/dl (p

The metabolic and hormonal responses to a mixed meal in umestrained pancreatectomised dogs chronically treated by portal or peripheral insulin infusion

SummaryThe metabolic and hormonal consequences of long term intravenous insulin replacement were studied in 11 pancreatectomised dogs. Insulin was delivered into the portal circulation of six animals for 164-224 days and into the peripheral circulation of the remainder for 123–365 days. Infusion rates were initially adjusted to achieve normoglycaemia in the fasting (0.37 ± 0.01 mUkg−1 min−1 portal; 0.45 ± 0.03 mU kg−1 min−1 peripheral) and post-prandial states (2.57 ± 0.07 mUkg−1 min−1 for 71/2 h portal; 3.16 ± 0.18 mUkg−1 min−1 for 7 h peripheral). Animals were fed their usual mixed diet and blood samples were drawn from indwelling catheters at regular intervals for 24 h. A matched group of six normal dogs was similarly studied. Significantly less insulin was needed for glycaemic normalisation with portal (1.05 ± 0.03 U kg−1 day−1) compared with peripheral (1.27 ± 0.08 U kg−1 day−1) infusions, but post-prandial insuhn levels were not normahsed. Glucagon levels were normal and unaffected by the route of insulin infusion. Lactate and pyruvate responses were exaggerated post-prandially in the diabetic compared with the normal dogs. Fasting non-esterified fatty acid levels were suppressed with peripheral but normal with portal insulin infusion. There were only minor differences in the branched chain, essential and other non-essential amino acids except for alanine which was significantly above normal in the diabetic animals. Fasting levels of insulin, lactate, pyruvate and non-esterified fatty acids were normahsed only with portal infusion while glucose, glucagon, 3-hydroxybutyrate and most amino acids were normalised regardless of the route of infusion. We conclude that the metabolic regulation achieved with portal insulin replacement is closer to normal than that achieved with peripheral infusion.