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Insulinogenic index and early phase insulin secretion predict increased risk of worsening glucose tolerance and of cystic fibrosis-related diabetes

Published:August 24, 2022DOI:https://doi.org/10.1016/j.jcf.2022.07.014

      Highlights

      • The standard oral glucose tolerance test (OGTT) for cystic fibrosis-related diabetes (CFRD) is limited by sensitivity, specificity, and reproducibility. We are looking for ways to improve the information we get from the OGTT to make it a more valuable test.
      • The insulinogenic index (IGI) can easily be estimated from glucose and insulin measurements collected at baseline and after 30 min during an OGTT. This measure can tell us how well a person's insulin-producing beta cells are responding to a sugar load.
      • In our prospective CF cohort (n = 189), participants with a low IGI had a higher risk of glycemic deterioration and development of CFRD over the study follow up of up to 15 years.
      • IGI is easily measured in a clinical setting and could be a way to get more information from the OGTT about patients most at risk of progressing to CFRD.

      Abstract

      Objective

      Measures of stimulated insulin secretion are emerging as important predictors of diabetes mellitus in at-risk populations. We analyzed the utility of clinical estimates of insulin secretion in a prospective cohort at risk for cystic fibrosis-related diabetes (CFRD).

      Methods

      We divided the profiles of 189 people with CF (pwCF) followed longitudinally in the Montreal CF cohort (mean follow up 6.6 ± 1.2 years) according to quartiles of the insulinogenic index (IGI; (I30-I0)/(G30-G0)); area under the curve for insulin normalized for glucose (AUCins/glu), and HOMA-B at baseline to compare clinical characteristics and risk of CFRD according to quartiles for each measure. We also compared characteristics of 40 pwCF found to have de novo CFRD at baseline.

      Results

      At baseline, IGI and AUCins/glu were lower in subjects with de novo CFRD and those who later developed CFRD than those who never developed CFRD (p < 0.0001 for each). Subjects with the lowest quartiles of IGI, AUCins/glu, and AUCins/glu 0–30 had increased risk of developing CFRD by Kaplan-Meier analysis (p = 0.0244, p = 0.0024, and p = 0.0338, respectively). There was no significant difference in risk between quartiles of HOMA-B. Subjects in the lowest quartile of IGI showed a significant increase in 2-hour OGTT glucose and AUCglu between the initial and final study visits (p = 0.0027 and p = 0.0044, respectively).

      Conclusion

      IGI is easily measured in a clinical setting and needs to be validated in prospective studies as a potential tool to improve risk stratification in CFRD with direct relevance to pathogenesis.

      Keywords

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