Effect of Progressive Weight Loss on Lactate Metabolism: a Randomized Controlled Trial

OBJECTIVE: Lactate is an intermediate of glucose metabolism that has been implicated in the pathogenesis of insulin resistance. This study evaluated the relationship between glucose kinetics and plasma lactate concentration ([LAC]) before and after manipulating insulin sensitivity by progressive weight loss. METHODS: Forty people with obesity (BMI=37.9±4.3 kg/m(2)) were randomized to weight maintenance (n=14) or weight loss (n=19). Subjects were studied before and after 6 months of weight maintenance and before and after 5%, 11% and 16% weight loss. A hyperinsulinemic-euglycemic clamp procedure in conjunction with [6,6-(2)H(2)]glucose tracer infusion was used to assess glucose kinetics. RESULTS: At baseline, fasting [LAC] correlated positively with endogenous glucose production rate (r=0.532, p=0.001) and negatively with insulin sensitivity, assessed as the insulin-stimulated glucose disposal (r=−0.361, p=0.04). Progressive (5% through 16%) weight loss caused a progressive decrease in fasting [LAC], and the decrease in fasting [LAC] after 5% weight loss was correlated with the decrease in endogenous glucose production (r=0.654, p=0.002) and the increase in insulin sensitivity (r=−0.595, p=0.007). CONCLUSION: This study demonstrates the inter-relationships among weight loss, hepatic and muscle glucose kinetics, insulin sensitivity, and [LAC], and suggests that [LAC] can serve as an additional biomarker of glucose-related insulin resistance.