229-LB: Plasma Lactate and Muscle Aerobic Substrate Oxidation: Does Elevated Lactate Precede Obesity?

Background: The incidence of metabolic diseases is rising and there is a dire need for early detection of risk in order to implement prevention. Fasting plasma lactate concentrations have been shown to be elevated in individuals with obesity and predictive of the development of T2D. An elevated lactate concentration is the product of a shift to glycolysis and a possible reduction in oxidative capacity. However, it is unknown if there are associations between lactate and oxidative capacity in healthy individuals that may predispose them to metabolic disease. Aim: The aim of this study was to determine if fasting lactate concentrations were linked with a reduction in skeletal muscle oxidative capacity in a young healthy population. Methods: Young (age 22 ± 0.5; N=30) lean (BMI (22.4 ± 0.4 kg/m2) women were screened for fasting plasma lactate. Subjects underwent assessments of body composition, aerobic capacity (VO2 peak), skeletal muscle oxidative capacity via near infrared spectroscopy (NIRS) and fasting glucose and insulin were measured for calculating HOMA-IR. Fatty acid oxidation rate was also determined in a subset of samples from skeletal muscle biopsies (vastus lateralis). Results: The women were insulin sensitive (HOMA-IR 1.1 ± 0.1) and had a mean fasting lactate of 0.9 ± 0.1 mmol/L. Time till exhaustion on the VO2 peak test was inversely associated with lactate (R2 = 0.20, p=0.05). Likewise, the rate of deoxygenated hemoglobin (NIRS) (R2 = 0.23, p=0.03) and skeletal muscle fatty acid oxidation (R2 = 0.72, p=0.004) were also inversely associated with fasting lactate. Lactate was inversely correlated with HDL:LDL (R2 = 0.57, p=0.02) and positively correlated with waist:hip (R2 = 0.52, p=0.02). Conclusion: Plasma lactate was inversely related to skeletal muscle oxidative capacity and with metabolic parameters that are risk factors for obesity and T2D. Fasting plasma lactate may thus be a biomarker for identifying healthy individuals at risk for metabolic diseases.