Mechanisms of glucose intolerance in cystic fibrosis.
OBJECTIVE
Although cystic fibrosis-related diabetes (CFRD), a poor prognostic factor in cystic fibrosis (CF), is characterized by insulinopenia, the role of insulin resistance is unclear. Using a prospective study design, we measured insulin resistance, pancreatic beta-cell function and correlated glycaemic status with clinical parameters.


METHODS
Oral glucose tolerance test was performed in 60 stable adult CF patients. Insulin sensitivity and beta-cell function were measured using the homeostatic model assessment (HOMA2), Stumvoll and oral glucose insulin sensitivity (OGIS) indices.


RESULTS
Forty-two (70%) had normal glucose tolerance (NGT), 10 (17%) impaired glucose tolerance (IGT) and eight (13%) CFRD. There was no difference in insulin sensitivity among the three groups (HOMA2: NGT 280, IGT 250, CFRD 339, P = 0.42; Stumvoll: NGT 0.128, IGT 0.126, CFRD 0.129, P = 0.76; and OGIS: NGT 515, IGT 472, CFRD 472, P = 0.12). Pancreatic beta-cell function (CFRD 50% vs. NGT 67%; P < 0.05) and first-phase insulin secretion were reduced in CFRD (250 vs. NGT 509; P = 0.004). First-phase insulin secretion was inversely correlated with 1-h (r = -0.74; P < 0.0001) and 2-h glucose levels (r = -0.34; P < 0.05). There was no difference in body mass index or poor lung function (forced expiratory volume in 1 s: CFRD 54% vs. NGT 65%; P = 0.43). However, there were more hospital admissions in the CFRD group (three vs. NGT one per patient per year; P < 0.05).


CONCLUSIONS
CFRD is characterized by qualitative and quantitative defects in insulin secretion, but not insulin resistance, and is associated with increased hospital admissions for pulmonary exacerbations.
Mohan
K
K
The Adult Cystic Fibrosis Unit, The Cardiothoracic Centre NHS Trust, Liverpool L143PE, UK.
Miller
H
H
Dyce
P
P
Grainger
R
R
Hughes
R
R
Vora
J
J
Ledson
M
M
Walshaw
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000097:blood / Q000150:complications*; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology*; D004812:Epidemiologic Methods; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000209:etiology*; D005951:Glucose Tolerance Test; D038321:Glycemic Index; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin