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P53 MECHANISMS OF GLUCOSE INTOLERANCE IN CYSTIC FIBROSIS
K. Mohan, H. Miller, P. Dyce, R. Grainger, R. Hughes, M. J. Ledson, M. J. Walshaw. The Liverpool Heart and Chest Hospital, Liverpool, UK
Introduction: The pathogenesis of cystic fibrosis-related diabetes (CFRD), a poor prognostic factor in cystic fibrosis (CF), is poorly understood. To look at this further we studied the role of insulin secretion and resistance in adult CF patients and correlated glycaemic parameters with clinical status.
Methods: A standard 2-h oral glucose tolerance test was performed in 60 stable adult CF patients not known to have CFRD. Blood samples for plasma glucose and insulin were collected before and at 30, 60, 90 and 120 minutes after glucose ingestion. Insulin secretion and sensitivity were determined by homeostatic model assessment (HOMA 2), Stumvoll and oral glucose insulin sensitivity (OGIS) indices.
Results: 42 (70%) had a normal glucose tolerance (NGT), 10 (17%) impaired glucose tolerance (IGT) and eight (13%) diabetes mellitus (CFRD). Fasting plasma glucose and insulin levels were similar among the CF subgroups. Beta cell function (HOMA 2: CFRD 50% + 14 vs NGT 67% + 20; p<0.05) and first phase insulin secretion were reduced in CFRD (250 + 116 vs NGT 509 + 292; p = 0.004). First phase insulin secretion was inversely correlated with 1 and 2-h glucose levels (r = −0.74, p<0.001 and r = −0.34, p<0.05, respectively). The time to reach peak insulin was delayed in both IGT and CFRD (99 and 101 minutes; both p<0.01 vs NGT 75). There was no difference in insulin sensitivity among the three groups (HOMA 2: NGT 280 + 130, IGT 250 + 107, CFRD 339 + 160; p = 0.42; Stumvoll: NGT 0.128 + 0.017, IGT 0.126 + 0.016, CFRD 0.129 + 0.012; p = 0.76; OGIS: NGT 515 + 68, IGT 472 + 62, CFRD 472 + 52; p = 0.12). Although there was no difference …