Glucose Tolerance, Insulin Secretion, and Insulin Sensitivity in Children and Adolescents with Cystic Fibrosis and No Prior History of Diabetes

Objective

To determine the prevalence of abnormalities of glucose metabolism in pediatric outpatients with cystic fibrosis (CF).

Study design

Children and adolescents (n = 73, mean age 15.0 ± 3.7 years) with CF not previously diagnosed with diabetes underwent 3-hour oral glucose tolerance testing. All subjects with CF were clinically stable and were not being treated for active infection. A reference group of young lean adults was used for comparison. Subjects were classified as having normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM), including impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or diabetes, by standard criteria. The insulinogenic index was calculated as a measure of β-cell function, and insulin resistance was estimated with the homeostatic model assessment.

Results

The reference group was significantly older than the patients with CF, but in the control subjects, the AGM and NGT were comparable in body mass index z-scores (−0.8 ± 1.3, −0.6 ± 1.1, −0.21 ± 0.9 kg/m²). Thirty-eight percent of subjects with CF had AGM: 43% IGT, 29% IFG, 14% IGT/IFG, and 14% diabetes. In spite of distinct differences in glycemic response, the subjects with NGT and AGM had marked abnormalities of insulin secretion relative to the control subjects (Insulinogenic index 5.8 ± 1.0, 5.3 ± 0.8, and 53.5 ± 10.0 uU/mL/mmol/L, respectively; P < .0001). Insulin sensitivity did not differ among the 3 groups, although there was a trend toward greater insulin resistance in the subjects with AGM (homeostatic model assessment: CF-NGT 1.5 ± 0.2, CF-AGM 1.9 ± 0.3, REF 1.3 ± 0.1, P = NS).

Conclusion

Abnormalities in glucose metabolism are frequent in young patients with CF without a prior diagnosis of diabetes and are associated with marked defects in insulin secretion. Given the poor β-cell function in patients with CF, even small reductions in insulin sensitivity may be an important determinant of AGM.

Abbreviations: AGM, Abnormal glucose metabolism, AUC, Area under the curve, BMI, Body mass index, CF, Cystic fibrosis, CFRD, Cystic fibrosis–related diabetes, FEV1%, Forced expiratory volume in 1 second, HOMA, Homeostatic model assessment, IFG, Impaired fasting glucose, IGT, Impaired glucose tolerance, IR, Insulin resistance, NGT, Normal glucose tolerance, OGTT, Oral glucose tolerance test