**Background:** Diabetic peripheral neuropathy (DPN) is a common and disabling complication of type 2 diabetes (T2D), with a lifetime prevalence up to 50%. While glycemic control reduces DPN risk in type 1 diabetes by 60–70%, it only yields a 5–7% reduction in T2D, suggesting other factors are involved. Dyslipidemia has been proposed as a risk factor, but previous studies show conflicting results regarding the roles of total cholesterol (TC), LDL-C, triglycerides (TG), and HDL-C, as well as the effects of lipid-lowering therapy (LLT). Most prior research comes from Western and Australian populations, with limited data from Asian cohorts. This study aimed to investigate whether hyperlipidemia or LLT is associated with DPN in Taiwanese adults with T2D.
**Methods:** This was a retrospective, cross-sectional, hospital-based observational study conducted from January to October 2013 at a Taiwanese tertiary medical center. Eligible participants were adults >20 years with prevalent or newly diagnosed T2D, excluding those with type 1 diabetes, gestational diabetes, missing lipid measurements, or history of chemotherapy, alcohol abuse, or hereditary neuropathy. A total of 2,448 patients were included. DPN was assessed using the second component of the Michigan Neuropathy Screening Instrument (MNSI), with a score >2 indicating DPN. Anthropometric measurements, laboratory data (fasting glucose, HbA1c, lipid profiles), medication use (including statins and fibrates), and comorbidities were recorded. Hyperlipidemia was defined as TC >200 mg/dL, LDL-C >130 mg/dL, or TG >200 mg/dL. Patients were categorized into three groups: normolipidemic non-LLT users, normolipidemic LLT users, and hyperlipidemic LLT users. Multivariate logistic regression adjusted for age, waist circumference, smoking, diabetes duration, diabetes treatment type, eGFR, heart disease, and gender.
**Key Results:** Among 2,448 participants, 524 (21.4%) had DPN. Patients with DPN were older (71.1±12.4 vs 62.1±12.4 years), had larger waist circumference (92.6±10.4 vs 90.4±10.4 cm), longer diabetes duration (13.9±9.4 vs 9.3±7.9 years), lower eGFR (65.1±31.6 vs 81.5±29.8 mL/min/1.73m²), and higher prevalence of heart disease (35.3% vs 15.4%). They also had significantly lower baseline TC (185.6±38.6 vs 193.4±42.3 mg/dL) and LDL-C (114.6±32.7 vs 119±30.8 mg/dL), and lower follow-up TC (155.7±28.2 vs 162.4±28.1 mg/dL) and LDL-C (89.7±23.1 vs 94.8±23.7 mg/dL). No differences were found in TG or HDL-C. Multivariate analysis showed no significant association between DPN and hyperlipidemia (adjusted OR [aOR] 0.81, 95% CI 0.49–1.34) or LLT (aOR 1.10, 95% CI 0.58–2.09). Subgroup analyses by TC, LDL-C, statin, and fibrate use also found no significant associations: for example, follow-up hyper-TC LLT users vs normal TC non-LLT users (aOR 0.72, 95% CI 0.2–2.62), follow-up hyper-LDL-C LLT users (aOR 0.75, 95% CI 0.2–2.79), normolipidemic statin users (aOR 1.09, 95% CI 0.59–2.03), and hyperlipidemic fibrate users (aOR 0.50, 95% CI 0.16–1.6).
**Clinical Implications:** This large cross-sectional study in a Taiwanese T2D population found no independent association between hyperlipidemia or lipid-lowering drugs and DPN. Despite lower TC and LDL-C levels in DPN patients, these differences did not persist after adjustment for confounders. The findings suggest that lipid metabolism may play a minor role in DPN pathogenesis compared to other factors such as age, diabetes duration, and renal function. Clinically, this implies that while LLT is important for cardiovascular risk reduction, it may not directly influence DPN risk. The study highlights the multifactorial nature of DPN and the need for longitudinal studies to clarify causality. Limitations include the cross-sectional design, lack of nerve conduction studies, and focus on statins and fibrates only. Nonetheless, the use of a validated screening tool (MNSI) and adjustment for multiple confounders strengthens the reliability of the results.