Cystic fibrosis-related diabetes develops from a combination of insulin secretion defects and insulin resistance.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE

Original Publication: Oxford : Wiley-Blackwell, c1999-

Cystic Fibrosis*/complications ; Cystic Fibrosis*/blood ; Insulin Resistance* ; Glucose Tolerance Test* ; Insulin Secretion* ; Insulin*/metabolism ; Insulin*/blood ; Disease Progression*; Humans ; Male ; Female ; Adult ; Adolescent ; Diabetes Mellitus/metabolism ; Blood Glucose/metabolism ; Young Adult ; Child

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD.
Materials and Methods: Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD-free survival was assessed by survival analysis.
Results: Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD-free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD-free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices.
Conclusions: Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period.
(© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

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2883 Canadian Cystic Fibrosis Foundation

Keywords: database research; insulin resistance; insulin secretion; observational study; real‐world evidence

0 (Insulin)
0 (Blood Glucose)

Date Created: 20240809 Date Completed: 20240918 Latest Revision: 20240918

20240918

10.1111/dom.15844

39118592