A New Model to Assess Lactate Synthetic Rate during an Oral Glucose Tolerance Test

Pediatric obesity is fueling an unprecedented 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 synthetic rate (LSR) represents the best proxy for the assessment of glycolysis. Since to date there are not techniques to estimate postprandial LSR, we propose a novel method to estimate LSR during an oral glucose tolerance test (OGTT). We developed a oral glucose-lactate model and tested it in 25 youth (9M; age =16[2] yrs, median[IQR], BMI =27.6[8.5] kg/m2) who underwent a 3-hour (OGTT). The model is based on the oral glucose minimal model and assumes that LSR is a fraction (F) of glucose disposal rate, proportional to glucose concentration and controlled by insulin action. The model well fitted the glucose and lactate data (Figure 1 A-B), and provided both precise parameter estimates (e.g., F=20 [30] %, CV=18 [11]%) and LSR time course (Figure 1 C). In conclusion, the proposed model is a valid tool to assess LSR, and thus glycolysis, during OGTT in different pathophysiological states.