The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the raXe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125l-insulin increased during exercise from 0.46 ± 0.08 to 1.17 ± 0.14%/min after intramuscular injection (P < 0.001) and from 0.31 ± 0.05 to 0.45 ± 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was ∼80% greater, and the decrease in plasma glucose was ∼2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose. Because accidental intramuscular injection of insulin may occur frequently, these findings highlight a previously unobserved risk for an unexpected decrease in plasma glucose levels in connection with leg exercise in IDDM patients. This risk could be minimized by injection into a skin fold or by use of shorter needles for thigh injection.

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