The effect of exercise on the absorption of inhaled human insulin in healthy volunteers

Abstract

What is already known about this subject: Exercise is known to affect absorption of other inhaled substances, but so far there are no reports on the effect of exercise on the absorption of inhaled insulin in humans.

What this paper adds: This report is the first to investigate the effect of exercise on the absorption of inhaled insulin. In this study in healthy volunteers we found that exercise early after dosing increased absorption (15-20%) of inhaled insulin over the first 2 h after start of exercise, with an approximately 30% increase in maximal insulin concentration, and unchanged overall absorption.

Aims: To investigate the effect of moderate exercise on the absorption of inhaled insulin.

Methods: A single-centre, randomized, open-label, three-period cross-over trial was carried out in 12 nonsmoking healthy subjects. A dose of 3.5 mg inhaled human insulin was administered via a nebulizer and followed in random order by either 1) no exercise (NOEX), 2) 30 min exercise starting immediately after dosing (EX0), or 3) 30 min exercise starting 30 min after dosing (EX30). The study was carried out as a 10 h euglycaemic glucose clamp (90 mg dl(-1) (5.0 mmol l(-1))).

Results: The absorption of insulin over the first 2 h after start of exercise was 16% increased for EX0 (ratio (95%CI) 1.16 (1.04, 1.30), P = 0.01) and 20% increased for EX30 (1.20 (1.05, 1.36), P < 0.01), both compared with NOEX; the overall insulin absorption during 6 h and 10 h after dosing was not influenced by exercise. The maximum insulin concentration (C(max)) increased by 32% for EX0 and 35% for EX30 (both P < 0.01) compared with NOEX, while the time to C(max) was 31 min faster for EX0 (P < 0.01), but not significantly different after EX30, compared with NOEX.

Conclusions: A significant and clinically relevant increase of insulin absorption over the first 2 h after the beginning of exercise was observed. Until data from studies using the specific insulin inhalers exists, patients using inhaled insulin should be made aware of a potential increased absorption and higher concentration of insulin in connection with exercise.

Figure 1

Mean serum insulin concentration curves (mean ± SEM). Straight line, no exercise (NOEX); Dotted line, exercise starting immediately after dosing (EX0); Dashed line, exercise starting 30 min after dosing (EX30)

Figure 2

Mean glucose infusion rate curves (smoothed means). Straight line, no exercise (NOEX); Dotted line, exercise starting immediately after dosing (EX0); Dashed line, exercise starting 30 min after dosing (EX30)