PROINSULIN, PROINSULIN INTERMEDIATE AND INSULIN IN CYSTIC-FIBROSIS

OBJECTIVE We determined the changes in insulin, intact proinsulin and 32-33 split proinsulin as markers of beta cell damage in assessing the state of carbohydrate intolerance in patients with cystic fibrosis. D ESIGN Measurements of insulin, proinsulin and 32-33 proinsulin concent rations in cystic fibrosis following oral glucose tolerance test (OGTT ). SUBJECTS Sixteen cystic fibrosis patients attending the chest outpa tient clinic for follow-up, age range 14-42 years, and 14 healthy cont rols matched for age and body mass index. MEASUREMENTS Insulin, intact proinsulin and 32-33 split proinsulin were measured immunoradiometric ally at 0, 30, 60, 90 and 120 minutes after an OGTT. Glucose and HbA1 were also measured. RESULTS Cystic fibrosis patients were divided into two groups according to their OGTT results: those with diabetes melli tus or impaired glucose tolerance and those with normal glucose tolera nce. Insulin concentrations and insulin/glucose ratios at 30 minutes w ere lower in both cystic fibrosis groups in comparison with the contro l. There was also a significant increase in the lime to reach peak ins ulin levels in both cystic fibrosis groups. Fasting intact proinsulin concentrations and the proportion of proinsulin-like molecules were si gnificantly higher in cystic fibrosis with diabetes mellitus or impair ed glucose tolerance than in the control group, but not in the normal glucose tolerance cystic fibrosis group. There was no significant diff erence in the plasma concentrations of 32-33 split proinsulin amongst the three groups. CONCLUSIONS Abnormal beta cell function in cystic fi brosis patients was reflected initially in a diminished 30-minute insu lin response to oral glucose. A significant rise in fasting intact pro insulin and the proportion of proinsulin-like molecules was seen only in cystic fibrosis patients who had progressed to impaired glucose tol erance or diabetes mellitus. Cystic fibrosis patients with normal gluc ose tolerance showed changes intermediate between the control and the other group.