3038-LB: Associations between Fasting Lactate, Beta-Cell Function, and Diet Are Differentially Impacted by Race

Introduction and Objective: Fasting lactate is elevated in type 2 diabetes (T2D). Racial differences in beta-cell function following diet therapy have been observed, but it is not known whether race modifies the effect of diet on lactate handling and its association with beta-cell responsiveness. This study was designed to examine the effect of two different diets on fasting lactate and the acute C-peptide (ACP) response to glucose in individuals with T2D. Methods: African American (AA) and European American (EA) adults with T2D were randomized to either a ketogenic diet (KD) or low-fat diet (LFD) for 12 weeks. Serum fasting lactate was measured at weeks 0 and 12. ACP was determined by a hyperglycemic clamp. Analysis of covariance was used to test the race x diet interaction on change in lactate, adjusting for sex and baseline values for lactate, fasting glucose, and insulin sensitivity. Partial correlations within each race group were used to examine associations between change in lactate and change in ACP, adjusting for baseline values, diet group, sex, and change in weight. Results: Lactate did not differ by race or diet group at baseline, but decreased across all participants from weeks 0 to 12 (P<0.05). There was a significant race × diet interaction (P=0.001) on change in lactate, where an effect of diet was observed in EA (~6-fold greater decrease on the KD, P<0.01), but not in AA. Change in lactate was inversely associated with change in ACP within AA (r=-0.45, P<0.05), but not in EA. Conclusion: Both diets reduced lactate, but only EA experienced greater reductions in response to the KD, and only AA showed an association with improvement in beta-cell function. The race differences in the lactate response to the intervention suggest the existence of distinct metabolic phenotypes, and that chronic elevated lactate in AA may reflect accelerated beta-cell failure that leads to earlier T2D onset. Further research is needed to define race-specific metabolic pathways related to loss of beta-cell responsiveness.