Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis
© 2022 The Authors..
Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.
Methods: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and β-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI.
Results: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change.
Conclusions: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. β-cell function adjusted for insulin sensitivity (oDIcoeo) did not change.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Journal of clinical & translational endocrinology - 30(2022) vom: 06. Dez., Seite 100311 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chan, Christine L [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 28.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.jcte.2022.100311 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351318453 |
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| 100 | 1 | |a Chan, Christine L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 28.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2022 The Authors. | ||
| 520 | |a Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear | ||
| 520 | |a Methods: Twenty youth and adults with CF underwent frequently sampled oral glucose tolerance tests (fsOGTT) before and after ETI initiation. Glucose, insulin, and C-peptide were collected at 0, 10, 30, 60, 90, and 120 min after 1.75 g/kg (max 75 g) of dextrose. HbA1c and continuous glucose monitoring (CGM) were collected in a subset. Estimates of insulin secretion (C-peptide index), insulin resistance (HOMA2 IR and IS(OGTT Cpep)), and β-cell function (C-peptide oral disposition index, oDIcoeo), were compared before and after ETI | ||
| 520 | |a Results: Participants were a median (IQR) of 20.4 (14.1, 28.6) years old, 75 % male. Follow-up occurred 10.5 (10.0, 12.3) months after ETI initiation. BMI z-score increased from 0.3 (-0.3, 0.8) to 0.8 (0.4, 1.5), p = 0.013 between visits. No significant differences were observed in glucose tolerance, glucose area under the curve, nor fsOGTT glucose concentrations before and after ETI. Median (IQR) C-peptide index increased from 5.7 (4.1, 8.3) to 8.8 (5.5, 10.8) p = 0.013 and HOMA2 IR increased (p < 0.001), while oDIcoeo was unchanged (p = 0.67). HbA1c decreased from 5.5 % (5.5, 5.8) to 5.4 % (5.2, 5.6) (p = 0.003) while CGM variables did not change | ||
| 520 | |a Conclusions: BMI z-score and measures of both insulin resistance and insulin secretion increased within the first year of ETI initiation. β-cell function adjusted for insulin sensitivity (oDIcoeo) did not change | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AUC, Area under the curve | |
| 650 | 4 | |a BMI, Body mass index | |
| 650 | 4 | |a CFRD, Cystic fibrosis related diabetes | |
| 650 | 4 | |a Elexacaftor/tezacaftor/ivacaftor | |
| 650 | 4 | |a FEV1, Forced expiratory volume in 1 sec | |
| 650 | 4 | |a FVC, Forced vital capacity | |
| 650 | 4 | |a HbA1c, Hemoglobin A1c | |
| 650 | 4 | |a Hemoglobin A1c | |
| 650 | 4 | |a Insulin resistance | |
| 650 | 4 | |a Insulin secretion | |
| 650 | 4 | |a OGTT, Oral glucose tolerance testing | |
| 650 | 4 | |a Oral glucose tolerance testing | |
| 650 | 4 | |a [3–6]: Cystic fibrosis related diabetes | |
| 650 | 4 | |a fsOGTT, Frequently sampled OGTT | |
| 650 | 4 | |a oDI, Oral disposition index | |
| 700 | 1 | |a Granados, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Moheet, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Sachinkumar |e verfasserin |4 aut | |
| 700 | 1 | |a Vigers, Timothy |e verfasserin |4 aut | |
| 700 | 1 | |a Arbeláez, Ana Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Yaling |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Shanming |e verfasserin |4 aut | |
| 700 | 1 | |a Norris, Andrew W |e verfasserin |4 aut | |
| 700 | 1 | |a Ode, Katie Larson |e verfasserin |4 aut | |
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