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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in peopl...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360755/ https://www.ncbi.nlm.nih.gov/pubmed/32665614 http://dx.doi.org/10.1038/s41598-020-68130-y |
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author | Jain, Ruchi Özgümüş, Türküler Jensen, Troels Mygind du Plessis, Elsa Keindl, Magdalena Møller, Cathrine Laustrup Falhammar, Henrik Nyström, Thomas Catrina, Sergiu-Bogdan Jörneskog, Gun Jessen, Leon Eyrich Forsblom, Carol Haukka, Jani K. Groop, Per-Henrik Rossing, Peter Groop, Leif Eliasson, Mats Eliasson, Björn Brismar, Kerstin Al-Majdoub, Mahmoud Nilsson, Peter M. Taskinen, Marja-Riitta Ferrannini, Ele Spégel, Peter Berg, Tore Julsrud Lyssenko, Valeriya |
author_facet | Jain, Ruchi Özgümüş, Türküler Jensen, Troels Mygind du Plessis, Elsa Keindl, Magdalena Møller, Cathrine Laustrup Falhammar, Henrik Nyström, Thomas Catrina, Sergiu-Bogdan Jörneskog, Gun Jessen, Leon Eyrich Forsblom, Carol Haukka, Jani K. Groop, Per-Henrik Rossing, Peter Groop, Leif Eliasson, Mats Eliasson, Björn Brismar, Kerstin Al-Majdoub, Mahmoud Nilsson, Peter M. Taskinen, Marja-Riitta Ferrannini, Ele Spégel, Peter Berg, Tore Julsrud Lyssenko, Valeriya |
author_sort | Jain, Ruchi |
collection | PubMed |
description | Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D. |
format | Online Article Text |
id | pubmed-7360755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73607552020-07-16 Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes Jain, Ruchi Özgümüş, Türküler Jensen, Troels Mygind du Plessis, Elsa Keindl, Magdalena Møller, Cathrine Laustrup Falhammar, Henrik Nyström, Thomas Catrina, Sergiu-Bogdan Jörneskog, Gun Jessen, Leon Eyrich Forsblom, Carol Haukka, Jani K. Groop, Per-Henrik Rossing, Peter Groop, Leif Eliasson, Mats Eliasson, Björn Brismar, Kerstin Al-Majdoub, Mahmoud Nilsson, Peter M. Taskinen, Marja-Riitta Ferrannini, Ele Spégel, Peter Berg, Tore Julsrud Lyssenko, Valeriya Sci Rep Article Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D. Nature Publishing Group UK 2020-07-14 /pmc/articles/PMC7360755/ /pubmed/32665614 http://dx.doi.org/10.1038/s41598-020-68130-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Jain, Ruchi Özgümüş, Türküler Jensen, Troels Mygind du Plessis, Elsa Keindl, Magdalena Møller, Cathrine Laustrup Falhammar, Henrik Nyström, Thomas Catrina, Sergiu-Bogdan Jörneskog, Gun Jessen, Leon Eyrich Forsblom, Carol Haukka, Jani K. Groop, Per-Henrik Rossing, Peter Groop, Leif Eliasson, Mats Eliasson, Björn Brismar, Kerstin Al-Majdoub, Mahmoud Nilsson, Peter M. Taskinen, Marja-Riitta Ferrannini, Ele Spégel, Peter Berg, Tore Julsrud Lyssenko, Valeriya Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title | Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title_full | Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title_fullStr | Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title_full_unstemmed | Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title_short | Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
title_sort | liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360755/ https://www.ncbi.nlm.nih.gov/pubmed/32665614 http://dx.doi.org/10.1038/s41598-020-68130-y |
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