Hyperlactatemia and pulmonary gas exchange at rest and during exercise: lessons from patients on metformin

What effect does elevated resting hyperlactatemia have on the response to a moderate level of exercise and on the determination of the gas-exchange threshold (GET)? We first identified 163 diabetic patients treated with metformin, a medication that has been shown to produce, in a significant proportion of patients, an innocuous high resting hyperlactatemia and who underwent cardio-pulmonary exercise testing at the Cleveland Clinic. We found that 102 patients had resting La 3. 5 mM (Group 3). We examined relationships between resting La, minute ventilation, pulmonary gas exchange, pH, and arterial blood gases at rest and during exercise (Welch’s test, and Cohen’s d to estimate effect size). None of the baseline data exhibited an effect size consistent with a clinically meaningful confounder. Group 3 had significantly lower HCO₃⁻ (22. 5 ± 2. 3 mM) than Group 0 (24. 2 ± 2. 4 mM, p < 0. 01). {V̇} E was also significantly higher in Group 3. Despite elevated lactate in Group 3 at rest, the respiratory exchange ratio (RER) averaged 0. 85 ± 0. 12 and did not differ from the other groups. GET could be identified based on the {V̇} O₂/ {V̇} CO₂ relationship in all groups. Finally, the ventilatory and gas exchange responses to exercise showed no differences between groups. An elevated blood lactate concentration is insufficient, by itself, to reproduce the gas-exchange signature of supra-threshold exercise or to disrupt GET determination.