Diabetes Tied to More Limb Events and Deaths in Premature PAD

Among patients diagnosed with peripheral artery disease (PAD) at ages 35 to 50 years, diabetes was associated with higher risks of major adverse limb events (MALE) and all-cause mortality, according to a retrospective population-based cohort study published as an accepted manuscript in the Journal of the Endocrine Society. The mortality association was stronger than among patients diagnosed after age 50.

Investigators used electronic health records from the central district of Clalit Health Services in Israel to identify patients diagnosed with PAD from January 2000 through April 2026. Of 4,538 patients diagnosed at ages 35 to 50 years, the study’s definition of premature PAD, 1,902 (42%) had diabetes.

Over a median follow-up of 12.0 years, MALE, defined as lower-extremity revascularization or major amputation, occurred in 11.4% of patients with diabetes vs 3.7% of those without. All-cause mortality, assessed over a median of 10.8 years, was 27.9% vs 9.1%. After multivariable adjustment, diabetes remained associated with higher risks of MALE (adjusted hazard ratio [aHR], 1.44; 95% CI, 1.03-2.01) and mortality (aHR, 1.41; 95% CI, 1.18-1.70).

In age-stratified analyses, the association between diabetes and MALE did not differ significantly by age (P for interaction = 0.498). Excess mortality associated with diabetes emerged only after 5 years of follow-up (hazard ratio beyond 5 years, 1.80; 95% CI, 1.45-2.23).

The associations were directionally consistent but not statistically significant in a complete-case sensitivity analysis that also adjusted for body mass index and smoking status, both of which had substantial missing data. The authors also cited the retrospective design, reliance on ICD-10 coding, inability to distinguish type 1 from type 2 diabetes, and data from a single Israeli health system as limitations. They concluded that diabetes identifies patients with premature PAD at particularly high risk.

Source: Kirzhner A, Abu Khadija H, Alnees M, et al. Age-dependent impact of diabetes on limb events and mortality in patients with peripheral artery disease. J Endocr Soc. Published online October 15, 2026. doi:10.1210/jendso/bvag237