Association of new subtypes of diabetes with cardiovascular disease: Insights from Mendelian randomization

Purpose: Globally, the incidence of cardiovascular disease-related mortality has gradually increased, with higher cardiovascular morbidity in individuals with diabetes. In 2018, researchers stratified new diabetes subgroups using cluster analyses; however, it is still unclear whether a causal relationship exists between these diabetes subtypes and cardiovascular disease. Thus, in this study, we aimed to assess the potential causal relationship between the subtypes of diabetes mellitus and cardiovascular disease using two-sample Mendelian randomization analysis. Methods: Two-sample Mendelian randomization was used to analyze causal associations between the diabetes subtype and cardiovascular disease using inverse variance-weighted analysis, which was the primary analytical method. Results Severe insulin-deficient diabetes (SIDD) was found to be a potential risk factor for peripheral arterial disease (odds ratio [OR] = 1.03; 95% confidence interval [Cl]=1.00–1.06; P=0.048). Severe autoimmune diabetes (SAID) was a risk factor for peripheral arterial disease (OR=1.03; 95% Cl=1.01–1.05; P=0.004), and a potential protective factor against atrial fibrillation (OR=0.99; 95% Cl=0.98–1.00; P=0.049). Conclusion: SAID bears a positive causal association with peripheral arterial disease, with evidence suggesting a negative association with atrial fibrillation. SIDD bears a positive causal association with peripheral arterial disease. This study facilitates further enhancement of cardiovascular disease management by clarifying the subtype of diabetes and cardiovascular interrelationships.