Mechanisms of glucose intolerance in cystic fibrosis

K Mohan, H Miller, P Dyce, R Grainger… - Diabetic …, 2009 - Wiley Online Library
K Mohan, H Miller, P Dyce, R Grainger, R Hughes, J Vora, M Ledson, M Walshaw
Diabetic medicine, 2009Wiley Online Library
Aims 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 β‐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 β‐cell
function were measured using the homeostatic model assessment (HOMA2), Stumvoll and …
Abstract
Aims  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 β‐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 β‐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 β‐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.
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