Insulin Clearance Contributes to the Variability of Nocturnal Insulin Requirement in Insulin-dependent Diabetes Mellitus

Abstract

We have previously described, in insulin-dependent diabetic subjects (IDDM), a small, but significant, increase in the insulin clearance rate (ICR) during 0600–0800 h as compared with 0100–0300 h. To determine whether this increase was also seen at more physiologic levels of insulin replacement, we calculated ICR during euglycemic clamp studies in 13 patients with IDDM with a constant infusion of insulin at 20 mU/min/ m2 and during insulin replacement from the Biostator GCIIS without exogenous glucose. During the euglycemic clamp study with constant insulin infusion at 20 mU/min/m2, the ICR was 16% higher at 0600–0800 h than at 0100–0300 h (264 ± 50 ml/min/m2 versus 228 ± 51 ml/min/m2; P < 0.005). During insulin replacement by the Biostator, the mean insulin infusion rate increased by 92 ± 27% (7.5 ±1.1 to 13.5 ±1.2 mU/min/m2; P < 0.001) and ICR increased by 123 ± 30% (130 ± 24 to 268 ± 51 ml/min/m2; P < 0.01) during the prebreakfast period when compared with 0100–0300 h. There was a highly significant correlation (r = 0.97) between the increment in insulin infusion rate and the increment in ICR. Measurement of insulin concentration in saline solutions, delivered by the Biostator at a same rate and under similar conditions to those in this study, showed that insulin delivery was stable for the 8-h period of this study. We conclude that, at levels of insulin replacement that maintain blood glucose between 90 and 100 mg/dl, variation in the ICR is an important contributor to the “dawn phenomenon” of increasing early morning blood glucose concentration and insulin requirements in diabetic subjects.