Background and aims: Smoking has repeatedly been associated with alterations in both insulin sensitivity and insulin absorption in type 2 diabetes, which should lead to differences in the pharmacokinetic (PK) and pharmacodynamic (PD) properties of regular insulin (RI). However, a direct comparison of the PK/PD-effects of RI has never been performed in these patients. Therefore, the aim of this exploratory study was to investigate the time-action profile of RI in a small group of smoking and matching non-smoking patients with type 2 diabetes using the euglycemic glucose clamp technique, which is seen as the gold standard for PD/PK investigations.
Material and methods: Nine smokers (more than 10 cigarettes per day) and nine non-smokers matched for gender, age, and BMI (without significant differences in HbA (1c), diabetes duration or blood pressure) were enrolled in the study. Patients' blood glucose was stabilized overnight at 7.2 mmol/l using a Biostator. Smokers were required to smoke one cigarette within ninety minutes prior to injection of 18 U RI s. c. in the morning. Glucose infusion rates (GIR) were registered for the subsequent 480 min.
Results: Injection of 18 U of RI resulted in significantly higher insulin concentrations in smokers compared to non-smokers, in particular in the later part of the experiment (Insulin-AUC (240-480) 10.5 +/- 2.3 (mean +/- SD) vs. 7.8 +/- 1.6 microU/ml/min, p < 0.05). This was also reflected in the PD results with a higher metabolic effect in smokers in the last four hours of the experiment (GIR-AUC (240-480) 0.9 +/- 0.4 vs. 0.6 +/- 0.3 g/kg, p < 0.05). Pharmacokinetic analyses revealed a trend towards a lower insulin clearance in smokers (1.1 +/- 0.2 vs. 1.4 +/- 0.4 l/min, p = 0.08).
Conclusions: This pilot study conducted in a small group of patients with type 2 diabetes shows that regular insulin exhibits a longer-lasting rise in insulin concentrations and a higher metabolic effect four to eight hours after injection in smokers compared to non-smokers. This suggests that hyperinsulinemia in smoking type 2 diabetic patients is at least partly caused by a deterioration in insulin clearance.