Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
(2020) In Scientific Reports 10(1).- Abstract
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... (More)
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.
(Less)
- author
- organization
-
- EXODIAB: Excellence of Diabetes Research in Sweden
- Diabetes - Islet Patophysiology (research group)
- Translational Muscle Research (research group)
- Diabetes - Molecular Metabolism (research group)
- Internal Medicine - Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- Centre for Analysis and Synthesis
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 10
- issue
- 1
- article number
- 11561
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:32665614
- scopus:85087929026
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-020-68130-y
- language
- English
- LU publication?
- yes
- id
- d90c4873-8fd4-45ad-8588-1b2935544706
- date added to LUP
- 2020-07-27 12:47:14
- date last changed
- 2024-05-16 15:09:41
@article{d90c4873-8fd4-45ad-8588-1b2935544706,
abstract = {{<p>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.</p>}},
author = {{Jain, Ruchi and Özgümüş, Türküler and Jensen, Troels Mygind and du Plessis, Elsa and Keindl, Magdalena and Møller, Cathrine Laustrup and Falhammar, Henrik and Nyström, Thomas and Catrina, Sergiu Bogdan and Jörneskog, Gun and Jessen, Leon Eyrich and Forsblom, Carol and Haukka, Jani K. and Groop, Per Henrik and Rossing, Peter and Groop, Leif and Eliasson, Mats and Eliasson, Björn and Brismar, Kerstin and Al-Majdoub, Mahmoud and Nilsson, Peter M. and Taskinen, Marja Riitta and Ferrannini, Ele and Spégel, Peter and Berg, Tore Julsrud and Lyssenko, Valeriya}},
issn = {{2045-2322}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes}},
url = {{http://dx.doi.org/10.1038/s41598-020-68130-y}},
doi = {{10.1038/s41598-020-68130-y}},
volume = {{10}},
year = {{2020}},
}