Insulin-secretion abnormalities and clinical deterioration related to impaired glucose tolerance in cystic fibrosis.
OBJECTIVE
To evaluate insulin-secretion kinetics and insulin sensitivity in cystic fibrosis (CF) patients with normal glucose tolerance (CF-NGT), impaired glucose tolerance (CF-IGT) or CF-related diabetes (CFRD), and the potential effects of moderate hyperglycemia on clinical and nutritional status.


METHODS
Cross-sectional study including 50 outpatients with CF. Patients underwent both oral (OGGT) and intravenous (IVGTT) glucose tolerance tests in order to assess insulin secretion and peripheral insulin sensitivity. Homeostasis assessment model and OGGT were used to investigate insulin sensitivity. Forced expiratory volume in the first second (FEV(1)) and forced vital capacity (FVC) were measured to evaluate pulmonary function. Body mass index (BMI) was determined to assess nutritional status.


RESULTS
Insulin secretion was significantly decreased (and delayed at OGTT) in the CFRD group (n = 9) versus the CF-IGT group (n = 10) and the CF-IGT versus the CF-NGT group (n = 31). Insulin sensitivity was significantly different in the CF-IGT and CFRD groups versus the CF-NGT group. FEV(1), FVC and BMI presented a significant linear correlation with plasma glucose value at 120 min at OGTT and were significantly lower in both CF-IGT and CFRD versus the CF-NGT group, whereas no differences were found between the CF-IGT and CFRD groups.


CONCLUSIONS
CF patients with IGT present diminished insulin secretion and increased peripheral insulin resistance, correlating with a worse clinical status, undernutrition and impaired pulmonary function. These findings open the question of whether early treatment of mild alterations of glucose metabolism with insulin secretagogues or short-action insulin may lead to improvement of clinical status in CF patients.
Tofé
Santiago
S
Pediatric Diabetes Unit, Department of Pediatrics, Hospital Ramón y Cajal, University of Alcalá, Crta. de Colmenar Km 9.1, 28 034 Madrid, Spain.
Moreno
José C
JC
Máiz
Luis
L
Alonso
Milagros
M
Escobar
Héctor
H
Barrio
Raquel
R
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D005838:Genotype; D018149:Glucose Intolerance / Q000150:complications* / Q000235:genetics / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male
C505032:CFTR protein, human; D007328:Insulin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator