In a post-hoc analysis of the NATHAN 1 trial, the use of ALA (vs. placebo) was associated with better outcome in terms of NIS-LL following 4-year treatment in patients with mild-to-moderate DPN, which was predicted by higher age, lower BMI, male sex, normal blood pressure, history of cardiovascular disease (CVD), insulin treatment, longer duration of diabetes and neuropathy, and higher neuropathy stage (144). This evidence concerns the gene INS and cardiovascular disorder.