To Örebro University

OBJECTIVES: To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.

DESIGN: A double-blind, randomized, controlled intervention study.

SETTING: The department of Internal Medicine, University Hospital, Linköping, Sweden.

SUBJECTS: Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.

INTERVENTIONS: Regular human insulin 100 U mL-1 (Actrapid) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.

MAIN OUTCOME MEASURES: Blood glucose, serum insulin, and serum C-peptide.

RESULTS: After the 160 U insulin dose the blood glucose concentration (mean +/- SE) fell from 4.3 +/- 0.2 to 2.8 +/- 0.2 mmol L-1 (P < 0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5 +/- 1.5 to 26.1 +/- 2.5 mU L-1 (P < 0.001). Serum C-peptide concentrations simultaneously decreased from 0.48 +/- 0.03 to 0.12 +/- 0.02 mmol L-1 (P < 0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.

CONCLUSIONS: Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.