Mediation of Smoking and Cardiometabolic Factors on Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes, yet the combined roles of smoking behavior and cardiometabolic factors in shaping neuropathy risks remain insufficiently understood.

To examine the associations of smoking behavior and cardiometabolic factors with DPN risk and evaluate their independent, combined, and mediating effects.

This cross-sectional study included 905 adults with type 2 diabetes attending primary care services in Indonesia. DPN risk was assessed using the Michigan Neuropathy Screening Instrument. Tobacco smoking behavior was assessed using a structured questionnaire, while cardiometabolic factors were obtained from clinical examinations and laboratory measurements. Associations were analyzed using multinomial logistic regression, and mediation pathways were examined using partial least squares-structural equation modeling.

Both active smoking and secondhand smoke exposure were associated with an increased DPN risk, particularly among active smokers also exposed to secondhand smoke. Cardiometabolic factors, including elevated glycated hemoglobin, high fasting blood glucose, and an abnormal ankle-brachial index, showed independent associations with neuropathy risks. Combined exposure analyses demonstrated a cumulative pattern, with increasing numbers of abnormal risk factors associated with progressively higher odds of neuropathy. A pathway analysis indicated that the association between smoking behaviors and DPN was primarily mediated through metabolic dysfunction and impaired peripheral perfusion, whereas the mediating role of blood pressure was limited.

These findings support the multifactorial nature of DPN and suggest that behavioral and cardiometabolic factors interact in shaping neuropathy risks. Integrating smoking exposure assessments with glycemic and vascular risk management may strengthen prevention strategies in primary care populations with type 2 diabetes.