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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 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., (© 2018 Wiley Periodicals, Inc.)

In vivo studies have investigated the role of β-cell dysfunction in type 2 diabetes (T2D), whereas in vitro research on islets has elucidated key mechanisms that control the insulin secretion rate. However, the relevance of the cellular mechanisms identified in vitro (i.e., the triggering and amplifying pathways) has not been established in vivo. Furthermore, the mechanisms underpinning β-cell dysfunction in T2D remain undetermined. We propose a unifying explanation of several characteristic features of insulin secretion both in vitro and in vivo by using a mathematical model. The model describes the triggering and amplifying pathways and reproduces a variety of in vitro and in vivo tests in subjects with and without T2D, identifies the mechanisms modulating first-phase insulin secretion rate in response to basal hyperglycemia or insulin resistance, and shows that β-cell dysfunction in T2D can be explained by an impaired amplifying pathway with no need to postulate defects in intracellular calcium handling., (© 2017 by the American Diabetes Association.)