Glucose tolerance stages in Cystic Fibrosis are idenfied by a unique pattern of defects of Beta-cell function

Aim To assess the order of severity of the defects of three direct determinants of glucose regulation, i.e., beta-cell function, insulin clearance and insulin sensitivity, in patients with CF categorized according their glucose tolerance status, including early elevation of mid-OGTT glucose values (>140 and < 200 mg/dL), named AGT140. Methods Two hundred and thirty-two CF patients aged 10-25 underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modelling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between five glucose tolerance stages [NGT, AGT140, Indeterminate glucose Tolerance (INDET), impaired glucose tolerance (IGT), Cystic fibrosis related diabetes (CFRD)] and glucometabolic variables was assessed with general linear model. Results Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (p<0.001) with AGT140 patients significantly differing from NGT (all p<0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all p<0.01). Insulin clearance was not significantly associated with glucose tolerance stages (p=0.162). Each class of glucose tolerance was uniquely identified by a specific combination of defects of the direct determinants of glucose regulation. Conclusions In CF patients each of the five glucose tolerance stages shows a unique pattern of defects of the direct determinants of glucose regulation, with AGT140 patients significantly differing from NGT and being similar to IGT. These findings suggest to recognize AGT 140 as a distinct glucose tolerance class and to reconsider the grade of glucometabolic deterioration across glucose tolerance stages in CF.