Determinants of time to severe in-stent restenosis in patients with diabetes mellitus after drug-eluting coronary stenting

BACKGROUND: Despite advances in drug-eluting stents (DES), patients with diabetes mellitus (DM) remain at 1.5-2 times higher risk of in-stent restenosis (ISR) than non-diabetics. However, the temporal progression and predictors of severe ISR in this population are not well defined. METHODS: A retrospective cohort analysis was conducted on 323 diabetic patients who underwent follow-up angiography after everolimus-eluting coronary stenting at a single center between May 2017 to December 2024. The primary outcome was the time to severe ISR (defined as ≥ 70% luminal narrowing). Demographic, clinical, metabolic (including METS-IR), and procedural (Gensini score, lesion characteristics) variables were analyzed. Cox regression identified predictors of accelerated restenosis, and a risk-stratification model was developed and validated internally. RESULTS: The median time to severe ISR was 7 months. Independent predictors included elevated D-dimer (HR = 1.001, p = 0.0004), BNP (HR = 1.001, p = 0.0001), METS-IR (HR = 1.378, p = 0.012), Gensini score (HR = 1.004, p = 0.032), and bilateral lesions (HR = 1.242, p = 0.03). Older age was identified as a protective factor, as was higher hemoglobin too. The risk model showed moderate discrimination (AUC = 0.702; sensitivity 68%; specificity 67%) and clinical utility on decision-curve analysis. CONCLUSION: Severe ISR manifests early in diabetics, driven by metabolic dysregulation, thrombotic activity, and procedural complexity. The validated risk-stratification model facilitates personalized surveillance and targeted interventions to mitigate the ISR burden on this vulnerable population.