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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Article info
Publication history
Published online: August 24, 2022
Accepted:
July 25,
2022
Received in revised form:
July 23,
2022
Received:
January 10,
2022
Identification
Copyright
© 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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- Early Glucose abnormalities in cystic fibrosis – how best to measure them, and what is to be done about them?Journal of Cystic FibrosisVol. 22Issue 1
- PreviewIn recent decades, two concepts have grown to increasing prominence in the field of cystic fibrosis related diabetes (CFRD). The first notion is that glucose abnormalities can be detected well before the diagnosis of CFRD can be made using current diagnostic criteria. The second concept is that it is biologically plausible that these glucose abnormalities may be of clinical importance to people with cystic fibrosis (via mechanisms that include increasing glucose in airway secretions [1], thereby promoting respiratory infections, as well as through catabolism from reduced secretion of insulin, a potent anabolic hormone [2].
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