(DCP085) CYSTIC FIBROSIS-RELATED DIABETES DEVELOPS FROM A COMBINATION OF INSULIN SECRETORY DEFECTS AND INSULIN RESISTANCE

Background: The relative contributions of insulin secretory defects and insulin resistance to the Cystic Fibrosis-Related Diabetes (CFRD) are poorly understood. We have previously characterized a low insulinogenic index is a risk factor for the progression to CFRD. We aimed to 1) determine which indices of insulin resistance predict progression to CFRD and 2) to model the relative contributions of insulin secretory function and insulin resistance to the risk of CFRD.

METHODS AND RESULTS: 303 patients underwent a 2-hour OGTT with blood sampling every 30 minutes at 12-to-24 months intervals until they developed CFRD or until the end of the follow-up (up to 15 years). Indices of insulin resistance/sensitivity were calculated from OGTT glucose and insulin measurements. CFRD-free survival was assessed by survival analysis. Insulin sensitivity, as assessed by the Stumvoll 2001 index, decreased according to A1c (p < 0.0001). The CFRD-free survival was significantly different between quartiles of insulin sensitivity as assessed by the Stumvoll 2001 index (p < 0.0001). There was no significant difference when the same analysis was performed for the 9 other indices. When patients were subdivided according to both insulin sensitivity (Stumvoll 2001) and insulin secretion (insulinogenic index), CFRD-free survival was significantly lower in those with the lowest insulinogenic index and the lowest insulin sensitivity (OR 9.24 ; p< 0.0001).

Conclusion: The Stumvoll 2001index correlated with glucose homeostasis and risk of progression to CFRD. It is the best model that can be performed on a population level to improve understanding of the role insulin resistance plays in CFRD. Patients with combined low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period.