Identifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment.

(i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment.

Longitudinal study with annual follow-up for 3 years involving a group of T2DM (N = 283) randomly selected. ACE gene polymorphism distribution (I = insertion; D = deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation.

Baseline DPN prevalence was 28.97% (95% CI, 23.65–34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05–66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30–0.86). DPN correlated with age (P < 0.001) but not with gender (P = 0.466) or time of evolution of T2DM (P = 0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76–42.04), and accumulated incidence was 10.4% 3 years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53–0.96). DPN presence remained correlated with age (P = 0.002), but not with gender (P = 0.490) or time of evolution (P = 0.630).

In our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.