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Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study

BACKGROUND: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in s...

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Autores principales: Åberg, N. David, Åberg, Daniel, Jood, Katarina, Nilsson, Michael, Blomstrand, Christian, Kuhn, H. Georg, Svensson, Johan, Jern, Christina, Isgaard, Jörgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091156/
https://www.ncbi.nlm.nih.gov/pubmed/30081862
http://dx.doi.org/10.1186/s12883-018-1107-3
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author Åberg, N. David
Åberg, Daniel
Jood, Katarina
Nilsson, Michael
Blomstrand, Christian
Kuhn, H. Georg
Svensson, Johan
Jern, Christina
Isgaard, Jörgen
author_facet Åberg, N. David
Åberg, Daniel
Jood, Katarina
Nilsson, Michael
Blomstrand, Christian
Kuhn, H. Georg
Svensson, Johan
Jern, Christina
Isgaard, Jörgen
author_sort Åberg, N. David
collection PubMed
description BACKGROUND: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (ΔIGF-I, further transformed into ΔIGF-I-quintiles, ΔIGF-I-q) are associated with IS severity and outcome. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. RESULTS: In general, the levels of s-IGF-I decreased (positive ΔIGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd ΔIGF-I-q showed the strongest association to mRS 0–2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18–11.9], and after 2 years, the 5th ΔIGF-I-q (OR 3.63, 95% CI 1.40–9.38) showed the strongest association to mRS 0–2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 0.31). CONCLUSIONS: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12883-018-1107-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-60911562018-08-20 Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study Åberg, N. David Åberg, Daniel Jood, Katarina Nilsson, Michael Blomstrand, Christian Kuhn, H. Georg Svensson, Johan Jern, Christina Isgaard, Jörgen BMC Neurol Research Article BACKGROUND: Insulin-like growth factor I (IGF-I) has neuroprotective effects in experimental ischemic stroke (IS). However, in patients who have suffered IS, various associations between the levels of serum IGF-I (s-IGF-I) and clinical outcome have been reported, probably reflecting differences in sampling time-points and follow-up periods. Since changes in the levels of post-stroke s-IGF-I have not been extensively explored, we investigated whether decreases in the levels of s-IGF-I between the acute time-point (median, 4 days) and 3 months (ΔIGF-I, further transformed into ΔIGF-I-quintiles, ΔIGF-I-q) are associated with IS severity and outcome. METHODS: In the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) conducted in Gothenburg, Sweden, patients with IS who had s-IGF-I measurements available were included (N = 354; 65% males; mean age, 55 years). Baseline stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) and converted into NIHSS-quintiles (NIHSS-q). Outcomes were assessed using the modified Rankin Scale (mRS) at 3 months and 2 years. RESULTS: In general, the levels of s-IGF-I decreased (positive ΔIGF-I), except for those patients with the most severe NIHSS-q. After correction for sex and age, the 3rd ΔIGF-I-q showed the strongest association to mRS 0–2 [Odds Ratio (OR) 5.11, 95% confidence interval (CI) 2.18–11.9], and after 2 years, the 5th ΔIGF-I-q (OR 3.63, 95% CI 1.40–9.38) showed the strongest association to mRS 0–2. The associations remained significant after multivariate correction for diabetes, smoking, hypertension, and hyperlipidemia after 3 months, but were not significant (p = 0.057) after 2 years. The 3-month associations withstood additional correction for baseline stroke severity (p = 0.035), whereas the 2-year associations were further attenuated (p = 0.31). CONCLUSIONS: Changes in the levels of s-IGF-I are associated primarily with temporally near 3-month outcomes, while associations with long-term 2-year outcomes are weakened and attenuated by other factors. The significance of the change in post-stroke s-IGF-I is compatible with a positive role for IGF-I in IS recovery. However, the exact mechanisms are unknown and probably reflects combinations of multiple peripheral and central actions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12883-018-1107-3) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-06 /pmc/articles/PMC6091156/ /pubmed/30081862 http://dx.doi.org/10.1186/s12883-018-1107-3 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Åberg, N. David
Åberg, Daniel
Jood, Katarina
Nilsson, Michael
Blomstrand, Christian
Kuhn, H. Georg
Svensson, Johan
Jern, Christina
Isgaard, Jörgen
Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title_full Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title_fullStr Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title_full_unstemmed Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title_short Altered levels of circulating insulin-like growth factor I (IGF-I) following ischemic stroke are associated with outcome - a prospective observational study
title_sort altered levels of circulating insulin-like growth factor i (igf-i) following ischemic stroke are associated with outcome - a prospective observational study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091156/
https://www.ncbi.nlm.nih.gov/pubmed/30081862
http://dx.doi.org/10.1186/s12883-018-1107-3
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