The Impact of Smoking on Inhaled Insulin

Abstract

OBJECTIVE -This study, one of the first to address issues of pulmonary insulin delivery in smokers, compared pharmacokinetics of inhaled insulin delivered via the AERx insulin Diabetes Management System (iDMS) in nondiabetic cigarette smokers and nonsmokers.RESEARCH DESIGN AND METHODS -In this randomized two-period crossover efficacy and safety trial in 27 nondiabetic smokers and 16 nonsmokers (18 men/25 women, mean age 28 years, mean BMI 23.0 kg/m 2 ), subjects received single doses of inhaled insulin (33.8 IU) following overnight fasting on consecutive dosing days. On one dosing day, smokers smoked three cigarettes immediately before insulin administration ("acute smoking"); on the other dosing day, smokers had not smoked since midnight ("nonacute smoking"). After inhalation, 6-h serum insulin and serum glucose profiles were determined.RESULTS -Pharmacokinetic results for evaluable subjects were derived from serum insulin profiles. The amount of insulin absorbed during the first 6 h after dosing (area under the exogenous serum insulin curve from 0 to 6 h [AUC (0 -6 h) ]) was significantly greater in smokers (63.2 vs. 40.0 mU ⅐ l Ϫ1 ⅐ h Ϫ1 , P ϭ 0.0017); peak concentration was both higher and earlier in the smokers (maximal serum concentration of insulin [C max ] 42.0 vs. 13.9 mU/l, P Ͻ 0.0001; time to maximal serum concentration of insulin [t max ] 31.5 vs. 53.9 min, P ϭ 0.0003). The estimated intrasubject variability of AUC (0 -6 h) was 13.7 and 16.5% for nonsmokers and smokers, respectively. No safety issues arose.CONCLUSIONS -Absorption of inhaled insulin via the AERx iDMS was significantly greater in smokers, with a higher AUC (0 -6 h) and C max and a shorter t max . Intrasubject variability of AUC (0 -6 h) was low and similar in nonsmokers and smokers. These data prompt more extensive investigation of inhaled insulin in diabetic smokers. Diabetes Care 26:677-682, 2003

The Effect of Smoking Cessation and Subsequent Resumption on Absorption of Inhaled Insulin

“…The study by Himmelman et al (16) used a different insulin inhalation system that utilizes a liquid aerosol formulation, as opposed to the dry-powder formulation in the present study, and also showed a higher AUC-Insulin 0 -360 and C max and a shorter t max for inhaled insulin in smoking subjects. Thus, the effects of smoking on inhaled insulin absorption are not formulation specific.…”

“…Accordingly, smoking has been shown specifically to increase inhaled insulin absorption in healthy volunteers (13)(14)(15)(16). Therefore, the nicotine-independent effects of tobacco smoke on the lung may have implications for inhaled insulin therapy.…”

The clinical effectiveness and cost-effectiveness of inhaled insulin in diabetes mellitus: a systematic review and economic evaluation

“…Himmelmann and colleagues 71 reported that absorption was faster and peak plasma insulin concentration was greater in smokers, although immediately after smoking, absorption was slower. This study was done in non-diabetic subjects and used low doses of insulin, but it does imply that smoking could affect absorption.…”

Inhaled insulin: the solution for suboptimal diabetes control?

“…Active smoking contraindicates its use because of increased bioavailabilty of inhaled insulin, 18,19 while absorption may be retarded in non-smokers exposed to smoke. 20 In patients with type 1 diabetes, there may be problems of dose flexibility: in the present formulation, the minimum unit for dose change is 1 mg, equivalent to 3 units of injected insulin (the 3 mg blister being equivalent to around 8 units).…”