In individuals with T2DM, peak VO2 and ventilatory efficiency were significantly reduced in very high-risk CKD, while ventilatory threshold was assessable in 97-98% of participants across all stages.
Observational (n=461)
Does cardiopulmonary exercise response vary by chronic kidney disease stage in non-dialysis individuals with type 2 diabetes?
In non-dialysis patients with type 2 diabetes, advanced chronic kidney disease is associated with reduced peak VO₂ and ventilatory efficiency, suggesting impaired renal buffering capacity limits functional capacity.
Abstract Background Comorbid diabetes and chronic kidney disease (CKD) are associated with markedly elevated cardiovascular morbidity and mortality. Although exercise is recommended to mitigate cardiovascular risk in individuals with diabetes or CKD, no established guidelines exist for those with both conditions. A major barrier to developing safe and effective exercise training strategies is the lack of research on exercise responses in this population. Purpose This study aimed to: (1) characterise cardiopulmonary exercise testing (CPX) profiles by CKD stage in individuals with type 2 diabetes (T2DM); and (2) investigate the pathophysiology of exercise intolerance in individuals with comorbid T2DM and CKD. Methods This retrospective study analysed CPX records from non-dialysis-requiring individuals with T2DM (2005–2023). Exclusion criteria included known cardiovascular disease, other systemic diseases, and beta-blocker use. Symptom-limited CPX was conducted using a cycle ergometer with a ramp protocol and an optimised work rate (WR). CPX parameters included peak oxygen uptake (VO₂), ventilatory threshold (VT), mechanical efficiency (ΔVO₂/ΔWR), peak O₂ pulse (VO₂/HR), and ventilatory efficiency (VE/VCO₂ slope, VE/VCO₂ at VT). Participants were stratified by CKD stage according to the 2024 Kidney Disease: Improving Global Outcomes guideline into low-, moderate-, high-, and very high-risk groups. Planned contrasts compared parameters between the low-risk group and others using accelerated bias-corrected bootstrapping. Hypotheses tested were: (1) peak VO₂, VT, ΔVO₂/ΔWR, and VO₂/HR would be lower in each of the higher-risk groups compared to the low-risk group; and (2) ventilatory efficiency would be reduced (higher VE/VCO₂ values) in each of the higher-risk groups. P-values were corrected via the Benjamini-Hochberg procedure (false discovery rate, 0.05). The study was approved by the Research Ethics Committee of our hospital. Results A total of 461 CPX datasets from individuals with T2DM (male: 300; age: 60±13 years; BMI: 25.9±4.8 kg/m²) were analysed. No cardiovascular events occurred during CPX (Table 1). Peak VO₂ and ventilatory efficiency were preserved in the moderate- and high-risk CKD groups but were significantly reduced in the very high-risk group (Table 2). In contrast, endurance work tolerance (VT) and mechanical efficiency remained unchanged across CKD stages. VT was assessable in nearly all participants, regardless of CKD stage (98, 98, 97, and 97%, respectively). Conclusions Exercise tolerance varies by CKD stage in individuals with T2DM. The reduction in ventilatory efficiency in advanced CKD suggests impaired renal buffering capacity for exercise-induced metabolic acidosis, necessitating greater respiratory effort during intensive exercise. This may be a key limiting factor in functional capacity. Individualised exercise training based on CKD stage is recommended, with VT-guided training feasible for very high-risk individuals.Table 1 Table 2
Kinoshita et al. (Sat,) conducted a observational in Comorbid type 2 diabetes and chronic kidney disease (n=461). Very high-risk CKD stage vs. Low-, moderate-, and high-risk CKD stages was evaluated on Cardiopulmonary exercise testing parameters including peak VO2, ventilatory threshold, mechanical efficiency, peak O2 pulse, and ventilatory efficiency. In individuals with T2DM, peak VO2 and ventilatory efficiency were significantly reduced in very high-risk CKD, while ventilatory threshold was assessable in 97-98% of participants across all stages.