Ventilation inhomogeneity is associated with OGTT-derived insulin secretory defects in cystic fibrosis

Progressive deterioration of β-cell function is the main mechanism underlying diabetes in cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patients years before its onset. We aimed to evaluate if OGTT-derived indices of β-cell function are associated with early markers of lung disease. We carried out a cross-sectional study on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiple breath washout test. β-cell glucose sensitivity and the insulinogenic indices were used as markers of β-cell function and first-phase insulin response to glucose stimulus. We used sex- and age-adjusted multiple linear regression models to estimate the association between OGTT-derived indices and lung function measures. An increment of β-cell glucose sensitivity equal to its interquartile range was associated with an increase in ppFEV1 of 7.6 points (95%CI: 0.8; 14.4) as well as with a decrease in LCI of -1.96 units (95%CI: -3.40; -0.51) and in Scond of -0.016 L-1 (95%CI: -0.026; -0.007). The corresponding figures for insulinogenic index were: 8.6 (95%CI: 3.4; 13.9) for ppFEV1 , -2.03 (95%CI: -3.13; -0.94) for LCI, and -0.014 L-1 (95%CI: -0.021; -0.071) for Scond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with Scond . Deterioration of β-cell function is related to early lung disease in young patients with mild to normal pulmonary function. This relationship is independent from hyperglycemia and mainly involves conductive airways.