Clinical factors which might influence the absorption of subcutaneously injected 125I-NPH insulin were studied in 101 diabetics. The disappearance curve was monoexponential after a delay period of 1.5 +/- 0.8 h (mean +/- SD). Lipohypertrophy significantly prolonged insulin absorption (half life (T1/2) = 11.2 +/- 3.1 h, p = 0.0001). Low bicarbonate levels increased the absorption (T1/2 3.9 +/- 2.3 h, p less than 0.05). Lean diabetics had a faster absorption (6.2 +/- 1.9 h) than normal weight diabetics (7.5 +/- 2.0 h, p less than 0.02). Sex, age, diabetes duration and injection depth did not influence T1/2. The half life was significantly inversely correlated to the resting subcutaneous blood flow (r = 0.882, p less than 0.01). The overall interindividual coefficient of variation for insulin absorption in nonketotic diabetics was 27.4%. Also considerable intra-patient day-to-day variation was found (24.5%), and between different injection sites (30.2%). These variations emphasize the drawbacks of conventional insulin therapy in the management of insulin-requiring diabetics.
The disappearance rate of labeled insulin from subcutaneous tissue has shown wide variation, even using labeled insulin with biological properties identical to that of the unlabeled insulin.
GentoJte, Copenhagen, and Herlev, DenmarkPrevious investigations with iodine-labeled insulin have shown that the disappearance rate of radioactivity from subcutaneous depots provides reliable measurements of insulin absorption. 2 , 15 It is important that the labeled insulin possesses biological properties identical to those of the unlabeled. Even under these circumstances the disappearance of labeled insulin from subcutaneous tissue has wide variations in rate. 15 The absorption of insulin is determined by the factors that influence diffusive transport, e.g., the insulin concentration gradient, the total area and permeability of the absorbing capillary membrane, the diffusion coefficient, and the distance of diffusion.
5Received for publication Nov. 1, 1978. Accepted for publication Dec. 5, 1978. Reprint requests to: Klaus K¢lendorf, Steno Memorial Hospital, DK-2820 Gentofte, Denmark.The absorption rate of insulin might be enhanced when the blood flow is increased, due to recruitment of capillary surface area and reduction in distance of diffusion, or by an increase in
5980009-9236/79/050598+07$00.70/0
The absorption and miscibility of subcutaneously injected 125I-regular porcine insulin was examined in 20 insulin-treated diabetic patients. The disappearance half-life (t1/2) was 2.1 +/- 0.8 h (SD) after injection of regular insulin (40 U/ml) and 2.3 +/- 0.7 h when mixed with porcine NPH insulin (NS). A significant inverse relation was demonstrated between insulin concentration and absorption, as t1/2 was 1.8 +/- 0.7 h (P less than 0.05) when using 20 U/ml. The interindividual coefficients of variation for absorption of regular insulin were 30.9-41.6% and independent of the presence of NPH insulin. The intrapatient variability, however, was much smaller, 14.5-23.6%.
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