Tolbutamide causes a modest increase in insulin secretion in cystic fibrosis patients with impaired glucose tolerance

Abstract

We examined the effect of intravenous (IV) tolbutamide administration on glucose and hormone levels in cystic fibrosis (CF) patients with impaired 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 subjects. Five CF patients with an impaired OGTT, ie, a serum glucose value of 7.8 mmol/L or greater 120 minutes after an oral glucose load (group 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 five healthy control (CON) subjects underwent IV glucose tolerance tests with glucose alone (IVGTT) and glucose administered in conjunction with tolbutamide ([IVTTT] 25 mg/kg; maximum dose, 1 g). Serum glucose levels were measured using the glucose oxidase method; insulin, C-peptide, and glucagon levels were measured by the double-antibody radioimmunoassay (RIA) technique. Serum immunoreactive trypsin (IRT) and hemoglobin A 1 (HbA 1) levels and height and weight were measured for each subject, and in addition, pulmonary function was assessed in those with CF. There were no significant differences in the area under the curve (AUC) for glucose or glucagon levels or the serum glucose disappearance rate ( k value) between group I, group II, or CON subjects during the IVGTT. First-phase insulin and C-peptide secretion was abnormal during IVGTT and IVTTT in the CF groups: in group I it was severely impaired, whereas in group II it was between group I and CON values. During the IVTTT serum glucose levels and glucose k values were not significantly altered in any of the three groups as compared with the IVGTT. Tolbutamide administration significantly increased the AUC for serum insulin 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 the AUC for C-peptide with IVTTT in group II (49%, P < .05) and CON subjects (58%, P < .01), with a lesser increase in group I (21%). The glucagon 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 to normals. Only long-term studies will determine if the residual secretion of insulin in response to oral sulfonylurea is of clinical importance.