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Objective We aimed to assess the order of severity of the defects of 3 direct determinants of glucose regulation—beta-cell function, insulin clearance, and insulin sensitivity—in patients with cystic fibrosis (CF), categorized according their glucose tolerance status, including early elevation of mid-level oral glucose tolerance test (OGTT) glucose values (&amp;gt;140 and &amp;lt;200 mg/dL), referred to as AGT140. Methods A total of 232 CF patients aged 10 to 25 years underwent OGTT. Beta-cell function and insulin clearance were estimated by OGTT mathematical modeling and OGTT-derived biomarkers of insulin secretion and sensitivity were calculated. The association between glucometabolic variables and 5 glucose tolerance stages (normal glucose tolerance [NGT], AGT140, indeterminate glucose tolerance [INDET], impaired glucose tolerance [IGT], cystic fibrosis–related diabetes CFRD]) was assessed with a general linear model. Results Beta-cell function and insulin sensitivity progressively worsened across glucose tolerance stages (P &amp;lt; 0.001), with AGT140 patients significantly differing from NGT (all P &amp;lt; 0.01). AGT140 and INDET showed a degree of beta-cell dysfunction similar to IGT and CFRD, respectively (all P &amp;lt; 0.01). Insulin clearance was not significantly associated with glucose tolerance stages (P = 0.162). Each stage 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 5 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 that AGT140 should be recognized as a distinct glucose tolerance stage and that reconsideration of the grade of glucometabolic deterioration across glucose tolerance stages in CF is warranted.

Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function