Exposure Pattern Dictates Nicotine’s Metabolic Impact in Mice: Frequency-Driven Hyperglycemia Versus Dose-Independent Dyslipidemia

Nicotine's metabolic safety profile is governed more by how often it is used than by the nominal dose. High-frequency exposure drives hyperglycaemia, whereas dyslipidaemia-lower HDL-C, higher LDL-C, and a reduced HDL-C/LDL-C ratio-emerges across all doses and schedules. These findings indicate that regulatory guidance, clinical counselling, and product-design standards for nicotine-replacement therapies and e-cigarettes must account for dosing pattern, not merely total nicotine intake. Routine metabolic monitoring may be warranted in individuals who use nicotine products frequently, even at low doses, to mitigate potential cardiometabolic risk.