Can indirect calorimetry combined to analysis of expired 13CO2 predict insulin resistance ? A preliminary study in healthy children

Abstract

Introduction: Insulin resistance is increasingly found in the paediatric age group, resulting from elevated endogenous glucose production (hepatic glycogenolysis and gluconeogenesis) and/or altered glucose utilization (glucose oxidation and glycogen synthesis). These variables can be computed from the simultaneous use of indirect calorimetry and breath 13CO2 measurement, both non invasive methods. Objective: Predicting insulin resistance in targeted subjects requires to establish first the normal developmental pattern of glucose oxidation and glycogen turnover in school-aged children. Patients/Material and Methods: A beverage containing naturally enriched 13C maize glucose was given every hour during four hours, at a rate of 3 mg/kg/min, to 47 lean healthy subjects of both sexes, aged 12.4 ± 2.6 yrs (mean ± SD) of whom 11 aged 7-9 yrs (group 1, G1), 20 aged 10-13 yrs (G2) and 16 aged 14-17 yrs (G3). Energy expenditure (EE) and total glucose oxidation (TGO) were measured during the last two hours by indirect calorimetry. Exogenous glucose oxidation (EGO) was determined by the analysis of 13CO2 production in expired air. Glycogen degradation (GD) (mostly hepatic in resting conditions) was calculated as [TGO - EGO], and total glycogen synthesis (TGS) (liver and skeletal muscle) was calculated as [glucose intake - EGO]. Results: EE correlated negatively with age (r = -0.76, p < 0.001) as well as TGO (r = -0.66, p < 0.001) and GD (r = -0.59, p < 0.001), whereas EGO and TGS did not change signficantly. When expressed as age groups, EE decreased from 0.025 (G1) to 0.017 kcal/kg/min (G3) (p < 0.001). TGO fell from 4.61 (G1) to 4.25 (G2) and 2.93 mg/kg/min (G3) (p < 0.001 vs G1 and G2). Values for GD was 2.58, 2.30 and 1.23 mg/kg/min respectively (p = 0.004 for G3 vs G1 and p = 0.003 for G3 vs G2). Conclusions: 1) Indirect calorimetry coupled with breath 13CO2 measurement after oral glucose intake can easily be used in school-aged children. 2) This original non invasive procedure allows to assess glycogen degradation and synthesis simultaneously and, consequently, to describe the developmental pattern of whole body glycogen turnover in health and disease. 3) This pilot study shows significant changes in EE, TGO and GD with age in healthy subjects. These new data provide standardized values to be used in the evaluation of subjects at risk to develop anomalies of glucose metabolism