Reduced pancreatic insulin release and reduced peripheral insulin sensitivity contribute to hyperglycaemia in cystic fibrosis.
Traditional opinion holds that patients with cystic fibrosis (CF) develop impaired glucose tolerance or diabetes due to insulinopenia caused by fibrosis of the pancreas. However, studies on the dynamics of insulin secretion and peripheral insulin action have yielded conflicting results. We studied 18 patients with CF (9 male, 9 female, age 15-29 years) and 17 healthy control subjects (8 male, 9 female, 20-32 years). Oral glucose tolerance tests and combined i.v.-glucose-tolbutamide-tests were performed on separate days in fasting subjects. Bergman's "Minimal Model" was used to quantitate both peripheral insulin sensitivity (SI) and insulin-independent glucose disposal (glucose effectiveness; SG). Based on National Diabetes Data Group criteria, 4 patients were classified as diabetic (22%; CF-DM), 3 patients (17%) had impaired glucose tolerance (CF-IGT) while glucose metabolism was normal in 11 patients (61%; CF-NGT). Irrespective of the degree of glucose tolerance, the insulin response to oral glucose was not reduced but delayed, up to 60 min in the CF-IGT/DM group. First-phase insulin release (0-10 min) after i.v.-glucose was significantly lower in CF patients (29% of healthy controls; P < 0.0001), with no difference between the CF-NGT and CF-IGT/DM groups. Insulin release following tolbutamide injection was only marginally reduced in CF patients (64% of controls). In contrast, SI was significantly reduced in the subgroup of CF patients with abnormal glucose metabolism (CF-IGT/DM: 0.97 +/- 0.16 x 10(-4) l/min/pmol; control group: 1.95 +/- 0.25; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Holl
R W
RW
Department of Paediatrics I, University of Ulm, Germany.
Heinze
E
E
Wolf
A
A
Rank
M
M
Teller
W M
WM
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003550:Cystic Fibrosis / Q000150:complications*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000503:physiopathology; D011972:Receptor, Insulin; D013997:Time Factors
D007328:Insulin; D011972:Receptor, Insulin