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

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Jain , R , Ozgumus , T , Jensen , T M , du Plessis , E , Keindl , M , Moller , C L , Falhammar , H , Nystrom , T , Catrina , S-B , Jorneskog , G , Jessen , L E , Forsblom , C , Haukka , J K , Groop , P-H , Rossing , P , Groop , L , Eliasson , M , Eliasson , B , Brismar , K , Al-Majdoub , M , Nilsson , P M , Taskinen , M-R , Ferrannini , E , Spegel , P , Berg , T J & Lyssenko , V 2020 , ' Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes ' , Scientific Reports , vol. 10 , no. 1 , 11561 .

Title: Liver nucleotide biosynthesis is linked to protection from vascular complications in individuals with long-term type 1 diabetes
Author: Jain, Ruchi; Ozgumus, Turkuler; Jensen, Troels Mygind; du Plessis, Elsa; Keindl, Magdalena; Moller, Cathrine Laustrup; Falhammar, Henrik; Nystrom, Thomas; Catrina, Sergiu-Bogdan; Jorneskog, Gun; Jessen, Leon Eyrich; Forsblom, Carol; Haukka, Jani K.; Groop, Per-Henrik; Rossing, Peter; Groop, Leif; Eliasson, Mats; Eliasson, Bjorn; Brismar, Kerstin; Al-Majdoub, Mahmoud; Nilsson, Peter M.; Taskinen, Marja-Riitta; Ferrannini, Ele; Spegel, Peter; Berg, Tore Julsrud; Lyssenko, Valeriya
Contributor organization: Nefrologian yksikkö
HUS Abdominal Center
University of Helsinki
Helsinki University Hospital Area
CAMM - Research Program for Clinical and Molecular Metabolism
Faculty of Medicine
Research Programs Unit
Department of Medicine
Per Henrik Groop / Principal Investigator
Centre of Excellence in Complex Disease Genetics
Institute for Molecular Medicine Finland
HUS Heart and Lung Center
Date: 2020-07-14
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
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 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 beta-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.
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion

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