Angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism and diabetic peripheral neuropathy: A multi-center cross-sectional study

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of type 2 diabetes mellitus (T2DM), leading to sensory, motor, and autonomic dysfunction. Its prevalence varies globally, with Indonesian cases projected to rise significantly. The aim of this study was to determine the relationship between the insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene and the prevalence of DPN in T2DM patients. The secondary objective was to investigate the association of DPN severity with several other major risk factors. This cross‑sectional observational study recruited 152 patients with T2DM from primary health centers in North Jakarta between August 2024 and March 2025. Participants underwent clinical, biochemical, electrophysiological, and genetic assessments. Diabetic peripheral neuropathy was diagnosed using diabetic neuropathy symptom (DNS) and diabetic neuropathy examination (DNE) scores and/or nerve conduction study (NCS). Genotyping employed PCR amplification of ACE I/D polymorphisms. Statistical analyses included chi‑square, Fisher's exact test, Independent-samples t-test, Pearson correlation, and odds ratios, with significance set at p<0.05. Among 152 patients with T2DM, 95 (62.5%) had DPN, with affected patients significantly older than non‑DPN cases. ACE I/D polymorphism frequencies showed no significant differences and were consistent with Hardy–Weinberg equilibrium. No significant association was observed between ACE gene I/D polymorphism and DPN among T2DM patients in the Indonesian population under any of the tested genetic models, including dominant, recessive, homozygous, heterozygous, and allelic models. Higher DNE scores were associated with higher HbA1c, blood glucose, and HDL values. This study underscores the importance of ethnicity in shaping neuropathy risk.