Patients with type 2 diabetes exhibit impaired exercise capacity and altered fuel metabolism in heart failure with preserved ejection fraction (HFpEF). The findings were presented at the European Association for the Study of Diabetes Congress 2025.

HFpEF patients often experience exercise intolerance, but the impact of type 2 diabetes on oxygen uptake and substrate utilization remained unclear. This case-control study evaluated 112 patients with HFpEF, including 56 with type 2 diabetes and 56 matched controls with normal glucose tolerance, using maximal cardiopulmonary exercise testing combined with cardiac ultrasound and breath-by-breath indirect calorimetry.

Patients with type 2 diabetes demonstrated 9% lower peak oxygen uptake (VO2peak 12.5±2.9 vs 13.8±3.5 mL•min⁻¹•kg⁻¹; p=0.031) despite similar breathing and hemodynamic responses. Maximal fat oxidation was reduced (0.16±0.07 vs 0.19±0.08 g•min⁻¹; p=0.040), with an earlier shift to carbohydrate metabolism (47±12 vs 52±12 %VO2max; p=0.020). Maximal fat oxidation and the exercise intensity triggering carbohydrate crossover were strongly correlated with VO2peak (p<0.0001 and p=0.0011, respectively).

These results indicate that metabolic inflexibility, characterized by low fat oxidation and early reliance on carbohydrates, contributes to reduced exercise capacity in HFpEF patients with type 2 diabetes, highlighting a potential role of mitochondrial dysfunction in functional impairment.