Glucose tolerance and insulin secretion, morbidity, and death in patients with cystic fibrosis.
OBJECTIVE
To describe the history, mechanisms, and consequences of cystic fibrosis (CF)-related diabetes, from childhood to early adulthood.


METHODS
Pancreatic beta-cell function was estimated from the plasma insulin/glucose ratios during oral glucose tolerance test (total area under the curve and deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls). Progression of glucose metabolism abnormalities was evaluated by analysis for interval censored data; rates of pulmonary transplantation and death by Kaplan-Meier analysis.


RESULTS
Impaired glucose tolerance was found in 20% of patients at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes, >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at 20 years, 40% at 30 years. Early impairment was associated with lower survival rates and higher rates of lung transplantation. The area under the curve(glucose) correlated with decreased body mass index and height. Decrease in early insulin secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not differ between the groups. Increased inflammation correlated with insulin resistance and impaired glucose tolerance.


CONCLUSIONS
CF-related diabetes, mainly because of beta-cell deficiency, is frequent early in life and associated with impaired nutritional state and growth, increased rates of terminal respiratory failure, and death.
Bismuth
Elise
E
Department of Pediatric Diabetology, Bichat Hospital, Paris, France.
Laborde
Kathleen
K
Taupin
Pierre
P
Velho
Gilberto
G
Ribault
Virginie
V
Jennane
Farida
F
Grasset
Etienne
E
Sermet
Isabelle
I
de Blic
Jacques
J
Lenoir
Gérard
G
Robert
Jean-Jacques
JJ
D000293:Adolescent; D000328:Adult; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000453:epidemiology / Q000209:etiology*; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016040:Lung Transplantation / Q000706:statistics & numerical data; D008297:Male; D017678:Sex Distribution; D015996:Survival Rate
D007328:Insulin