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 . https://doi.org/10.1038/s41598-020-68130-y
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 Clinicum |
Date: | 2020-07-14 |
Language: | eng |
Number of pages: | 12 |
Belongs to series: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | https://doi.org/10.1038/s41598-020-68130-y |
URI: | http://hdl.handle.net/10138/321989 |
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. |
Subject: |
CHRONIC KIDNEY-DISEASE
INSULIN-RESISTANCE ADULT PATIENTS FAT-CONTENT BENFOTIAMINE METABOLISM GLUCOSE PREVALENCE SERUM ACID 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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