Nicotine Metabolism in Adults with Type 2 Diabetes.

Introduction: Metabolism of nicotine has implications for addiction and may be altered in people with type 2 diabetes. Thus, our objective was to analyze nicotine metabolism in adults with and without type 2 diabetes who smoke.

Methods: From an existing cross-sectional study, we analyzed nicotine metabolism in urine of 148 smokers, 36 type 2 diabetics (insulin or antidiabetic medication use and/or fasting glucose >126 mg/dL), and 112 non-diabetics. Nicotine metabolism was quantified as the nicotine metabolite ratio (NMR) = trans-3'-hydroxycotinine (3HC) divided by COT. COT and 3HC were measured in the participant urine by ultra-performance liquid chromatography tandem mass spectrometry (UPLC MS-MS). Generalized linear models were used to assess whether NMR was associated with diabetic status (yes/no).

Results: Participants categorized as high NMR smoked more cigarettes per day (p=0.002) and were more likely to be diabetic (p=0.022) compared to low NMR. We found no significant difference in total nicotine equivalents (TNE) defined as the sum of the nicotine, COT and 3HC (p>0.05). In unadjusted models, NMR was 42.5% higher in diabetics versus non-diabetics (95% CI: 12.9, 79.8; p=0.003). In models adjusted for factors significantly different between low versus high NMR participants, mean NMR was 36.5% higher in the diabetics versus non-diabetics (95% CI: 7.8, 72.8; p=0.010). Additionally, in models adjusted for known confounders of NMR, NMR was 40.6% higher in diabetics versus non-diabetics (95% CI: 9.9, 80.0; p=0.007).

Conclusions: From these data, we infer that type 2 diabetics metabolize nicotine faster, which may increase the potential for nicotine addiction.

IMPLICATIONS: Smoking is addictive and this addiction may be related to tobacco metabolism. Individuals with faster metabolism of nicotine tend to smoke more cigarettes for longer periods of time. People with type 2 diabetes may metabolize nicotine faster, which could lead to higher lifetime tobacco burden, increasing the adverse health outcomes associated with increased exposure to tobacco.