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

Kathryn J Potter, Valérie Boudreau, Anne Bonhoure, François Tremblay, Annick Lavoie, Maité Carricart, Peter A Senior, Rémi Rabasa-Lhoret

Journal: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 2023;22(1):50-58

PMID: 36028423

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; (I-I)/(G-G)); area under the curve for insulin normalized for glucose (AUC), 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 AUC 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, AUC and AUC 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 AUC 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.

Copyright © 2022. Published by Elsevier B.V.

Address: Montreal Clinical Research Institute (IRCM), Montréal, Québec, Canada.; Montreal Clinical Research Institute (IRCM), Montréal, Québec, Canada; Department of Nutrition, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Cystic Fibrosis Clinic, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.; Cystic Fibrosis Clinic, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada.; Division of Endocrinology, University of Alberta, Edmonton, Alberta, Canada.; Montreal Clinical Research Institute (IRCM), Montréal, Québec, Canada; Department of Nutrition, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Division of Experimental Medicine, Faculty of Medicine, McGill University, Montréal, Québec, Canada; Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada; Cystic Fibrosis Clinic, Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, Québec, Canada. Electronic address: [email protected].
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