Abstract
Assessment of insulin secretion is key to diagnose postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized complication following bariatric surgery. To this end, the Oral C-peptide Minimal Model (OCMM) can be used. This usually requires fixing C-peptide (CP) kinetics to the ones derived from the Van Cauter population model (VCPM), which has never been validated in PHH individuals. The objective of this work was to test the validity of the OCMM coupled with the VCPM in PHH subjects and propose a method to overcome the observed limitations. Two cohorts of adults with PHH after gastric bypass (GB) underwent either a 75 g oral glucose (9F/3M; age=42±9 y; BMI=28.3±6.9 kg/m2) or a 60 g mixed-meal (7F/3M; age = 43 ± 11 y; BMI=27.5±4.2 kg/m2) tolerance test. The OCMM was identified on CP concentration data with CP kinetics fixed to VCPM (VC approach). In both groups, the VC approach underestimated CP-peak and overestimated CP-tail suggesting CP kinetics predicted by VCPM to be inaccurate in this population. Thus, the OCMM was identified using CP kinetics estimated from the data (DB approach) using a Bayesian Maximum a Posteriori estimator. CP data were well predicted in all the subjects using the DB approach, highlighting a significantly faster CP kinetics in patients with PHH compared to the one predicted by VCPM. Finally, a simulation study was used to validate the proposed approach. The present findings question the applicability of the VCPM in patients with PHH after GB and call for CP bolus experiments to develop a reliable CP kinetic model in this population.
Highlights
Postprandial hyperinsulinemic hypoglycemia is an increasingly recognized metabolic complication affecting up to a third of patients following gastric bypass surgery (1, 2)
Since inaccuracy in C-peptide kinetics may negatively affect the estimation of insulin secretion, the applicability of the Van Cauter population model to predict C-peptide kinetics in patients suffering from postprandial hyperinsulinemic hypoglycemia must be investigated
We tested the validity of the Oral C-peptide Minimal Model (OCMM) (11, 18) coupled with the Van Cauter population model for C-peptide kinetics in post-gastric bypass surgery individuals suffering from postprandial hyperinsulinemic hypoglycemia
Summary
Postprandial hyperinsulinemic hypoglycemia is an increasingly recognized metabolic complication affecting up to a third of patients following gastric bypass surgery (1, 2). The Van Cauter population model was originally validated in normal, obese, and non-insulin-dependent diabetic individuals and its use within approaches to estimate insulin secretion was shown to yield similar average estimates in the target population as when individual estimates from C-peptide bolus data are used (15, 16). This might not hold true when the Van Cauter population model is applied to different populations, such as patients having undergone bariatric surgery, procedures that substantially alter glucose kinetics and secretion of gluco-regulatory hormones (17). Since inaccuracy in C-peptide kinetics may negatively affect the estimation of insulin secretion, the applicability of the Van Cauter population model to predict C-peptide kinetics in patients suffering from postprandial hyperinsulinemic hypoglycemia must be investigated
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