Association between alpha-lipoic acid use and macrovascular complications in patients with diabetic neuropathy

Abstract

Purpose : Alpha-lipoic acid (ALA) is an antioxidant used for the treatment of diabetic neuropathy in some countries. However, its potential impact on macrovascular complications remains unclear. This study examined the association between ALA use and cardiovascular (CV) outcomes and mortality in individuals with diabetes. Methods : A retrospective cohort study was conducted using the Korean National Health Insurance Service Health Screening Cohort data. Participants aged 40-79 years diagnosed with diabetic neuropathy between 2011 and 2015 were followed until December 2019. ALA users were defined as those prescribed ALA for >= 6 months. Propensity score matching balanced baseline characteristics, and Cox proportional hazards models evaluated the associations between ALA use and myocardial infarction (MI), stroke, diabetic foot ulcer, amputation, CV mortality, and all-cause mortality. Results : A total of 8,740 participants (4,370 ALA users, 4,370 non-users) were included after matching. Over a median follow-up of 8.0 years, ALA use was associated with a lower risk of MI (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74-0.98), CV mortality (HR 0.73, 95% CI 0.55-0.96), and all-cause mortality (HR 0.82, 95% CI 0.72-0.93), while no significant associations were observed for stroke, diabetic foot ulcer, or amputation. MI risk reduction was more pronounced in those with a high Charlson comorbidity index. In a dose-response analysis of ALA users, a higher cumulative defined daily dose within the first year was significantly associated with a greater reduction in the risks of MI, CV mortality, and all-cause mortality (P for trend = 0.004, 0.011, and < 0.001, respectively). Conclusion : ALA use was associated with a reduced risk of MI and mortality in a dose-dependent manner. This suggests a potential protective role of ALA against macrovascular complications in patients with diabetic neuropathy.