Hyperinsulinism Complicating Control of Diabetes Mellitus by an Artificial Beta-Cell

Abstract

Serum free insulin concentrations were measured in diabetic subjects given insulin intravenously by a glucose-controlled insulin infusion system (“closed-loop” artificial beta-cell) in two experimental situations: hourly during the day while given their usual diet and at short intervals after administration of a standardized test meal. Three of four subjects showed sustained hyperinsulinism when compared with matched controls during a day on their usual diet. In two of the subjects, the insulin levels also exceeded those seen in those subjects on their usual dose of subcutaneous insulin. The glucose levels were not completely normalized in the three hyperinsulinemic subjects, and the insulin levels were significantly correlated with plasma glucose levels. After the test meal, all six diabetic subjects studied showed a delayed rise in insulin levels, when compared with six normal subjects, followed by an abrupt rise in insulin levels to peak levels more than seven times those seen in normal subjects. We conclude that significant hyperinsulinism may accompany feedback-controlled intravenous insulin administration. This should be considered in interpreting studies done with such systems, and in design of control algorithms for future systems.