Association between prediabetes, frailty, and cardiovascular outcomes in the oldest old: A retrospective nationwide cohort study

Aims: To investigate the association between prediabetes, frailty, and the risk of myocardial infarction (MI), stroke, heart failure (HF), and all-cause mortality in the oldest old. Methods: A nationwide retrospective cohort study of individuals aged 80+ classified as prediabetic (HbA1c 5.7%–6.4% or impaired fasting glucose 100–125 mg/dL) or normoglycemic during two baseline periods (2005–2006 and 2014–2015) and follow-up (2007–2013 and 2016–2022). Frailty was assessed using the cumulative deficit method. Results: Among 126,323 participants (61.4% females, mean age 84.1 ± 3.7 years), 34,151 (27.0%) were classified as persons with prediabetes and 92,172 (73.0%) as normoglycemic at baseline. Over seven years, 13.5% progressed to diabetes, 47.4% regressed to normoglycemia, and 39.1% remained with prediabetes. Non-frail individuals were more likely to progress to diabetes than the severely frail (15.0% vs. 9.3%). Prediabetes was associated with lower all-cause mortality (HR 0.86, 95% CI 0.85–0.88) but not MI (HR 0.98, 95% CI 0.94–1.02), while it was associated with increased risks of HF (HR 1.06, 95% CI 1.03–1.09) and stroke (HR 1.06, 95% CI 1.02–1.10). Conclusions: In the oldest old (aged 80+), prediabetes is associated with reduced all-cause mortality but slightly increased risks of HF and stroke. Frailty modulates prediabetes progression, with non-frail individuals more likely to develop diabetes.