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Elevated hepatic glucose production in children with cystic fibrosis
C L Kien1, C A Horswill, W B Zipf
1Department of Pediatrics, Ohio State University College of Medicine, Columbia 43205, USA.
Insights
Children with cystic fibrosis (CF) show elevated hepatic glucose output (HGO) despite normal insulin levels. Tolbutamide therapy did not correct this early metabolic defect in CF patients.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Cystic Fibrosis Research
Background:
- Cystic Fibrosis (CF) is a genetic disorder affecting multiple organs, including the pancreas.
- Early detection of metabolic disturbances in CF is crucial for timely intervention.
- Hepatic glucose output (HGO) regulation may be altered in children with CF.
Purpose of the Study:
- To investigate potential early signs of impaired insulin secretion in glucose-tolerant children with CF.
- To determine if elevated hepatic glucose output (HGO) is present in these children.
- To assess the efficacy of tolbutamide therapy in correcting potential metabolic defects.
Main Methods:
- Studied eight glucose-tolerant pediatric CF patients and five healthy controls.
- Assessed fasting and post-meal glucose and insulin levels.
- Measured hepatic glucose output (HGO) using isotope dilution and indirect calorimetry, both in fasting state and during glucose infusion.
- Evaluated the effect of 2 weeks of oral tolbutamide therapy on HGO.
Main Results:
- Fasting glucose, insulin, and insulin-connecting peptide levels were comparable between CF patients and controls.
- Meal stimulation tests suggested defective insulin secretion in the fed state for CF patients.
- Fasting HGO was significantly higher in CF patients when normalized to body weight or fat-free mass, but not when normalized to resting energy expenditure.
- HGO was suppressed during glucose infusion in CF patients.
- Tolbutamide therapy did not alter fasting or glucose-infused HGO in CF patients.
Conclusions:
- Fasting hepatic glucose output (HGO) is elevated in children with cystic fibrosis (CF) relative to energy expenditure.
- This elevation may represent an early metabolic alteration in CF, independent of overt diabetes.
- Tolbutamide therapy did not demonstrate efficacy in normalizing HGO in this pediatric CF cohort.
Abstract:
We hypothesized that elevated hepatic glucose output (HGO) may occur in children with cystic fibrosis (CF) as an early sign of declining insulin secretion and that tolbutamide therapy would correct the defect. We studied eight glucose-tolerant CF patients (mean +/- SD, 9.1 +/- 1.9 y) and five healthy controls (9.0 +/- 1.6 y). Fasting glucose, insulin, and insulin-connecting peptide concentrations were not different in the CF and control subjects; however, meal stimulation tests in the CF patients suggested that insulin secretion was defective in the fed state. HGO (mg.kg-1 body weight.min-1) was 26% higher in the CF patients (4.2 +/- 0.7 versus 3.1 +/- 0.6 in HC) (p = 0.016). When normalized for fat-free mass (mg.kg fat-free mass-1.min-1), HGO was 27% higher in CF (4.9 +/- 0.8 versus 3.8 +/- 0.5) (p = 0.015). However, when expressed as a function of resting energy expenditure (mg.kcal-1), HGO was not significantly different in CF (121 +/- 22) versus healthy controls (116 +/- 30). In seven of the CF group, HGO was re-assessed after a 2-h glucose infusion at a rate of 0.90 +/- 0.02 mg.kg-1.min-1. HGO was suppressed (p < 0.05) by an amount equal to 103 +/- 18% of the glucose infusion rate. Finally, in five CF patients, HGO was re-measured after 2 wk of oral therapy with tolbutamide (750 mg/d). Tolbutamide did not affect HGO (fasting or during the glucose infusion). In conclusion, fasting HGO was elevated in the CF patients in proportion to energy expenditure.