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

Abstract

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 ppFEV 1 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 S cond 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 ppFEV 1 , −2.03 (95%CI: −3.13; −0.94) for LCI, and −0.014 L −1 (95%CI: −0.021; −0.071) for S cond . When adjusting also for 2-h plasma glucose, both β-cell glucose sensitivity and insulinogenic index remained inversely associated with S cond . Deterioration of βcell 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.

Lumacaftor/ivacaftor in cystic fibrosis: effects on glucose metabolism and insulin secretion

“…In fact, although the etiology of CFRD is not completely understood, the current view is that it is a multifactorial condition resulting from a combination of insulin deficiency and resistance. We used a model [ 19 ] previously adopted to quantify the insulin secretory and sensitivity defects inherent to CF compared to healthy controls [ 23 ], their dependence on sex and age [ 16 ] and their relationship to respiratory defects [ 24 ].…”

Polymorphism of clinical manifestations of cystic fibrosis-related diabetes

“…В то же время гетерогенность фенотипических проявлений МВ среди людей с одинаковым генотипом гена CFTR позволяет предполагать, что существуют другие факторы, влияющие на тяжесть заболевания. Так, гены-модификаторы могут модулировать фенотипические проявления МВ и его осложнений [11,12]. Показана связь полиморфизмов в гене TCF7L2 (transcription factor 7-like 2) у взрослых больных МВ с нарушениями углеводного обмена и с развитием СД 2 типа у людей без МВ [13,14].…”

Cystic fibrosis related diabetes: Medical management

“…Although abnormalities on this test predict long term outcomes in CF, the diagnostic endpoints we currently use are based on data from adults with type 2 diabetes and are not specific to CF. There is evidence that CF patients who do not meet formal criteria for glucose abnormalities by OGTT are still experiencing clinical decline [21,49]. However, at this point, there have been no large systematic trials to determine what cut points would be best for determining risk for adverse clinical outcomes in cystic fibrosis.…”