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

Progressive deteriorationof?-cell function is the main mechanismunderlying diabetesin cystic fibrosis (CF). Diabetes negatively impacts the clinical status of CF patientsyears before its onset.We aimed toevaluate ifOGTT-derived indices of?-cell functionare associated with early markers of lung disease. We carried out a cross-sectionalstudy on 80 CF patients who performed OGTT, spirometry, and nitrogen-multiplebreath washout test.?-cell glucose sensitivity and the insulinogenic indices were usedas markers of?-cell function and first-phase insulin response to glucose stimulus. Weused sex- and age-adjusted multiple linear regression models to estimate theassociation between OGTT-derived indices and lung function measures. An incrementof?-cell glucose sensitivity equal to its interquartile range was associated with anincrease in ppFEV1of 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 inScondof-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) forppFEV1,-2.03 (95%CI:-3.13;-0.94) for LCI, and-0.014 L-1(95%CI:-0.021;-0.071)forScond. When adjusting also for 2-h plasma glucose, both?-cell glucose sensitivityand insulinogenic index remained inversely associated withScond. Deterioration of?-cell function is related to early lung disease in young patients with mild to normalpulmonary function. This relationship is independent from hyperglycemia and mainlyinvolves conductive airways.