TOLBUTAMIDE CAUSES A MODEST INCREASE IN INSULIN-SECRETION IN CYSTIC-FIBROSIS PATIENTS WITH IMPAIRED GLUCOSE-TOLERANCE

We examined the effect of intravenous (IV) tolbutamide administration on glucose and hormone levels in cystic fibrosis (CF) patients with im paired first-phase insulin secretion and oral glucose tolerance (oral glucose tolerance test [OGTT]) and compared them with CF patients with only an impaired first-phase insulin secretion and healthy control su bjects. Five CF patients with an impaired OGTT, ie, a serum glucose va lue of 7.8 mmol/L or greater 120 minutes after an oral glucose load (g roup I), five CF patients with a normal OGTT, ie, a serum glucose not exceeding 7.8 mmol/L 120 minutes after oral glucose (group II), and fi ve healthy control (CON) subjects underwent IV glucose tolerance tests with glucose alone (IVGTT) and glucose administered in conjunction wi th tolbutamide ([IVTTT] 25 mg/kg; maximum dose, 1 g). Serum glucose le vels were measured using the glucose oxidase method; insulin, C peptid e, and glucagon levels were measured by the double-antibody radioimmun oassay (RIA) technique. Serum immunoreactive trypsin (IRT) and hemoglo bin A(1) (HbA(1)) levels and height and weight were measured for each subject, and in addition, pulmonary function was assessed in those wit h CF. There were no significant differences in the area under the curv e (AUG) for glucose or glucagon levels or the serum glucose disappeara nce rate (k value) between group I, group II, or CON subjects during t he IVGTT. First-phase insulin and C-peptide secretion was abnormal dur ing IVGTT and IVTTT in the CF groups: in group I it was severely impai red, whereas in group II it was between group I and CON values. During the IVTTT serum glucose levels and glucose k values were not signific antly altered in any of the three groups as compared with the IVGTT. T olbutamide administration significantly increased the AUC for serum in sulin in group II and CON subjects as compared with IVGTT values (67% and 135%, respectively, P < .05), with a modest (P > .05) increase in group I levels (28%). Likewise, there were significant increases in th e AUC for C-peptide with IVTTT in group II (49%, P <.05) and CON subje cts (58%, P < .01), with a lesser increase in group I (21%). The gluca gon AUC was not significantly altered in IVTTT as compared with IVGTT in any group. These observations suggest that endocrine function in CF subjects is a continuous spectrum from those with diabetes mellitus t o normals. Only long term studies will determine if the residual secre tion of insulin in response to oral sulfonylurea is of clinical import ance. Copyright (C) 1995 by W.B. Saunders Company