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Peter Spégel

Principal investigator

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Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes

Author

  • Ruchi Jain
  • Türküler Özgümüş
  • Troels Mygind Jensen
  • Elsa du Plessis
  • Magdalena Keindl
  • Cathrine Laustrup Møller
  • Henrik Falhammar
  • Thomas Nyström
  • Sergiu Bogdan Catrina
  • Gun Jörneskog
  • Leon Eyrich Jessen
  • Carol Forsblom
  • Jani K. Haukka
  • Per Henrik Groop
  • Peter Rossing
  • Leif Groop
  • Mats Eliasson
  • Björn Eliasson
  • Kerstin Brismar
  • Mahmoud Al-Majdoub
  • Peter M. Nilsson
  • Marja Riitta Taskinen
  • Ele Ferrannini
  • Peter Spégel
  • Tore Julsrud Berg
  • Valeriya Lyssenko

Summary, in English

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.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Islet Patophysiology
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Molecular Metabolism
  • Internal Medicine - Epidemiology
  • EpiHealth: Epidemiology for Health
  • Centre for Analysis and Synthesis

Publishing year

2020

Language

English

Publication/Series

Scientific Reports

Volume

10

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Genomics, Diabetes and Endocrinology
  • Diabetes - Molecular Metabolism
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 2045-2322