INSULIN KINETICS AND GLUCOSE-INDUCED INSULIN DELIVERY IN CHRONICALLY DIALYZED SUBJECTS - ACUTE EFFECTS OF DIALYSIS

Disordered insulin metabolism and production are known features of uremia, but their relation to the glucose intolerance and insulin resistance associated with this condition has been the subject of controversy. We investigated the kinetics of plasma insulin in eight subjects on maintenance hemodialysis for 10 ± 4 (mean ± SEM) months, using [125I]insulin as a tracer for the native hormone and noncompartmental analysis of the isotopic data. A standard glucose challenge (iv glucose tolerance test) was then given, and insulin response was quantified by deconvolution. To assess the acute effects of dialysis, each uremic subject was studied first 65-109 and then 7-22 h from the last dialysis. Insulin MCR was slightly depressed before dialysis (365 ± 48 ml/min • m2) compared with a control group of 17 healthy subjects (465 ± 22) and rose significantly (P < 0.05) after dialysis (462 ± 60). Mean residence time (69.4 ± 11.7 min) and total distribution volume (21.9 ± 2.1 liters/m2) were both much greater (P < 0.001) than normal (18.4 ± 1.2 and 8.2 ± 0.6, respectively) and were only marginally reduced by dialysis. The insulin delivery rate to the systemic circulation was 3.03 ± 0.70 mU/min-m2 before and 3.32 ± 0.77 after dialysis (vs. the rate of 2.64 ± 0.28 in the controls); in the 60 min after iv glucose, 1040 ± 278 mU/m2 (predialysis) and 1134 ± 250 (postdialysis) reached the periphery compared to 769 ± 99 of normals. Though these differences are not statistically significant, a supernormal response was evident in 3 uremic patients. Furthermore, the first peak of insulin release was greater than normal both before (P < 0.05) and after dialysis (P < 0.01). In spite of this, the plasma glucose disappearance rate was less than normal (P < 0.05) before dialysis (1.06 ± 0.14%/min vs. 1.56 ± 0.13%/min in the controls) and little improved (1.25 ± 0.13) by one dialysis. Chronically dialyzed patients show depressed insulin degradation, expanded body pool of insulin, primary (glucose-independent) enhancement of the early insulin response, and peripheral resistance to insulin action. Altogether, a single dialysis has little effect on these abnormalities. © 1979 by The Endocrine Society.