223-LB: Beta-Cell Function but Not Insulin Sensitivity Is Impaired in Nondiabetic Cystic Fibrosis Adults Assessed with the Oral Minimal Model Method

Abstract

Insulin deficiency in cystic fibrosis (CF) is the primary cause of impaired glucose tolerance and diabetes. However, along with insulin deficiency, insulin sensitivity may also play an important role. Herein we aimed to quantify insulin action and secretion in nondiabetic CF adults in comparison with healthy controls after an oral glucose tolerance test (OGTT) with the oral minimal model method. Sixteen nondiabetic CF (7F; age=22±2 y; BMI=22±2 kg/m2; BW=66±10 kg) and seven healthy adults (3F; age=22±2 y; BMI=22±2 kg/m2; BW=66±9 kg) underwent an OGTT. Plasma glucose, insulin and C-peptide were measured for 5 h. The oral glucose and C-peptide minimal models were used to quantify indices of glucose absorption, insulin sensitivity, β-cell responsiveness and disposition index. Insulin sensitivity was similar (mean±SE; p-value from two-sample t-test) in CF and healthy (23±3 and 16±3 10-4 dL/kg/min per uU/mL; NS), while percentage of glucose absorbed within the first two hours was significantly higher in CF (70±3 vs. 53±4 %; p<0.005). In contrast, β-cell responsiveness was significantly reduced in CF (42±4 vs. 118±16 10-9 min-1) due to a reduction both in the dynamic (320±45 vs. 1316±172 10-9; p<0.005) and static (42±4 vs. 118±16 10-9 min-1; p<0.005) component. The delay in the static component was also higher, but not significantly, in CF (15±4 vs. 8±3 min; NS). As a consequence, the disposition index was significantly reduced in CF (1659±423 vs. 3303±426 10-14 dL/kg/min2 per pmol/L; p<0.05). Of note, no difference in incremental Area Under Curve (0-5 h) of glucose (6186±884 vs. 3680±1113 mg/dL*min; NS), insulin (4901±559 vs. 8577±2032 uU/mL*min; NS) and C-peptide (331±33 vs. 349±82 nmol/L*min; NS) in CF vs. healthy was observed. In conclusion, the oral minimal model method showed that abnormal glucose tolerance in our cohort of CF patients is due to an impaired β-cell function, while insulin action is similar and glucose absorption is higher. Disclosure M. Schiavon: None. G.M. Toffolo: None. C. Cobelli: None. K. Nair: None. A. Moran: Other Relationship; Self; Novo Nordisk Inc. Funding National Institutes of Health (R01DK101402); National Center for Advancing Translational Sciences (UL1-TR-000114)