A New Oral Model to Assess Postprandial Lactate Production Rate

Objective: Pediatric obesity predisposes children and adolescents to early onset insulin resistance and dysglycemia. In the last 20 years this has led to a rise in the prevalence of prediabetes, diabetes and fatty liver in youngsters, due to the high degree of insulin resistance experienced by these patients and the consequent high availability of glucose. As glucose accesses the liver, it is partly metabolized through glycolysis, whose main product is pyruvate that is then converted into Acetyl CoA and lactate. Therefore, lactate production rate (LPR) represents the best proxy for the assessment of glycolysis. Since to date there are not methods to estimate postprandial LPR, here we proposed a novel oral glucose-lactate model to estimate LPR during an oral glucose tolerance test and tested it in 24 youth with and without obesity. Methods: The model is based on the oral glucose minimal model and assumes that LPR is a fraction (fr) of glucose disposal rate, proportional to glucose concentration and controlled by insulin action. Results: The model well fitted the glucose and lactate data, and provided both precise parameter estimates (e.g., fr = 22.5 [12.6-54.1]%, median [IQR]), CV = 18 [13-25]%) and LPR time course. Conclusions: The proposed model is a valid tool to assess LPR, and thus glycolysis, during OGTT in nondiabetic subjects. Significance: The proposed methodology will allow to assess postprandial LPR in simple and cost-effective way.