Endogenous and Exogenous Insulin Responses in Patients With Cystic Fibrosis

Abstract

Eight male patients with cystic fibrosis, normal nutrition, normal physical activity, relatively mild pulmonary disease, no evidence of liver disease and no family history of diabetes mellitus underwent a series of carbohydrate tolerance tests in comparison with a group of 18 normal male subjects matched for age and body weight. Compared with the normal group, the patients with cystic fibrosis had significantly impaired glucose tolerance and significantly lower serum immunoreactive insulin levels during oral and intravenous glucose tolerance tests; serum insulin levels were also significantly lower after intravenous administration of tolbutamide in the patients with cystic fibrosis, but the reduction in blood glucose concentration in each group was not significantly different. During an intravenous insulin test, the decrease in blood glucose concentration was the same for both groups, in spite of significantly lower serum insulin levels in the patients with cystic fibrosis. The percentage fall in plasma free fatty acids was at least as great in the patients with cystic fibrosis as in normals during the test procedures, while a significant decrease in plasma alpha-amino nitrogen after intravenously administered insulin was seen only in the patients with cystic fibrosis. These studies suggest that the carbohydrate intolerance of cystic fibrosis is consequent upon an impaired insulin response to glucose, but that this insulin deficiency is partly compensated for by increased peripheral tissue sensitivity to insulin.

Cystic Fibrosis and Diabetes Mellitus

“…Th e production of insulin by non be ta cells ma y be sufficient to limit the progression from glucos e intolera nce to frank DM a nd pot entiall y for the a bse nce of ketoacidosis in CF/DM . Addition all y, we ha ve suggested that the peripher al tissue in C F ma y show increased insulin se ns itivity (100). Thi s ha s been extended by the ob ser vati on that monoc yte s from CF pati ents ha ve increased insulin binding because of an increased number of ce llular insulin receptor s (104,105).…”