During continuous subcutaneous or intravenous insulin infusion therapy, many patients with insulin-dependent diabetes (IDD) require more insulin in the prebreakfast period (0600–0800 h) than earlier in the morning (0100–0300 h). This study was designed to assess whether variations in insulin clearance or insulin sensitivity might contribute to overnight variations in insulin requirements. Euglycemic insulin clamp studies were performed in random sequence from 2400 to 0300 h and from 0500 to 0800 h on successive nights in 10 subjects with IDD. Insulin was infused at a rate of 40 mU/min/m2 and plasma glucose concentration was maintained at 100 mg/dl by a variable rate glucose infusion from a Biostator GCIIS (Miles Laboratories, Elkhart, Indiana). Insulin clearance was (mean ± SEM) 277 ± 41 ml/min/m2 between 0700 and 0800 h compared with 256 ± 41 ml/min/m2 between 0200 and 0300 h (P < 0.05), while glucose infusion rates were the same [3.86 ± 0.52 mg/kg/min from 0730 to 0800 h versus 3.99 ± 0.51 mg/kg/min from 0230 to 0300 h (P = NS)]. All eight patients with a previously documented prebreakfast increase in insulin requirements had higher insulin clearance at this time. These results indicate that differences in insulin clearance between the prebreakfast period and the early morning may account partially for the higher prebreakfast insulin requirements in some subjects with IDD, and the variations in insulin requirements during the night are not due to variations in insulin sensitivity.

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