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Human complement component C3 N-glycome changes in type 1 diabetes complications

AIM: Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complicati...

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Autores principales: Šoić, Dinko, Štambuk, Jerko, Tijardović, Marko, Keser, Toma, Lauc, Gordan, Bulum, Tomislav, Lovrenčić, Marijana Vučić, Rebrina, Sandra Vučković, Tomić, Martina, Novokmet, Mislav, Smirčić-Duvnjak, Lea, Gornik, Olga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244649/
https://www.ncbi.nlm.nih.gov/pubmed/37293493
http://dx.doi.org/10.3389/fendo.2023.1101154
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author Šoić, Dinko
Štambuk, Jerko
Tijardović, Marko
Keser, Toma
Lauc, Gordan
Bulum, Tomislav
Lovrenčić, Marijana Vučić
Rebrina, Sandra Vučković
Tomić, Martina
Novokmet, Mislav
Smirčić-Duvnjak, Lea
Gornik, Olga
author_facet Šoić, Dinko
Štambuk, Jerko
Tijardović, Marko
Keser, Toma
Lauc, Gordan
Bulum, Tomislav
Lovrenčić, Marijana Vučić
Rebrina, Sandra Vučković
Tomić, Martina
Novokmet, Mislav
Smirčić-Duvnjak, Lea
Gornik, Olga
author_sort Šoić, Dinko
collection PubMed
description AIM: Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. RESEARCH DESIGN AND METHODS: Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. RESULTS: Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. CONCLUSION: This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity.
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spelling pubmed-102446492023-06-08 Human complement component C3 N-glycome changes in type 1 diabetes complications Šoić, Dinko Štambuk, Jerko Tijardović, Marko Keser, Toma Lauc, Gordan Bulum, Tomislav Lovrenčić, Marijana Vučić Rebrina, Sandra Vučković Tomić, Martina Novokmet, Mislav Smirčić-Duvnjak, Lea Gornik, Olga Front Endocrinol (Lausanne) Endocrinology AIM: Changes in N-glycosylation have been described in numerous diseases and are being considered as biomarkers of ongoing pathological condition. Previous studies demonstrated the interrelation of N-glycosylation and type 1 diabetes (T1D), particularly linking serum N-glycan changes with complications accompanying the disease. Moreover, the role of complement component C3 in diabetic nephropathy and retinopathy has been implicated, and C3 N-glycome was found to be altered in young T1D patients. Therefore, we investigated associations between C3 N-glycan profiles and albuminuria and retinopathy accompanying T1D, as well as glycosylation connection with other known T1D complication risk factors. RESEARCH DESIGN AND METHODS: Complement component C3 N-glycosylation profiles have been analyzed from 189 serum samples of T1D patients (median age 46) recruited at a Croatian hospital centre. Using our recently developed high-throughput method, relative abundances of all six of the C3 glycopeptides have been determined. Assessment of C3 N-glycome interconnection with T1D complications, hypertension, smoking status, estimated glomerular filtration rate (eGFR), glycaemic control and duration of the disease was done using linear modelling. RESULTS: Significant changes of C3 N-glycome in severe albuminuria accompanying type 1 diabetes were observed, as well as in T1D subjects with hypertension. All except one of the C3 glycopeptides proved to be associated with measured HbA1c levels. One of the glycoforms was shown to be changed in non-proliferative T1D retinopathy. Smoking and eGFR showed no effect on C3 N-glycome. Furthermore, C3 N-glycosylation profile was shown to be independent of disease duration. CONCLUSION: This study empowered the role of C3 N-glycosylation in T1D, showing value in distinguishing subjects with different diabetic complications. Being independent of the disease duration, these changes may be associated with the disease onset, making C3 N-glycome a potential novel marker of the disease progression and severity. Frontiers Media S.A. 2023-05-24 /pmc/articles/PMC10244649/ /pubmed/37293493 http://dx.doi.org/10.3389/fendo.2023.1101154 Text en Copyright © 2023 Šoić, Štambuk, Tijardović, Keser, Lauc, Bulum, Lovrenčić, Rebrina, Tomić, Novokmet, Smirčić-Duvnjak and Gornik https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Šoić, Dinko
Štambuk, Jerko
Tijardović, Marko
Keser, Toma
Lauc, Gordan
Bulum, Tomislav
Lovrenčić, Marijana Vučić
Rebrina, Sandra Vučković
Tomić, Martina
Novokmet, Mislav
Smirčić-Duvnjak, Lea
Gornik, Olga
Human complement component C3 N-glycome changes in type 1 diabetes complications
title Human complement component C3 N-glycome changes in type 1 diabetes complications
title_full Human complement component C3 N-glycome changes in type 1 diabetes complications
title_fullStr Human complement component C3 N-glycome changes in type 1 diabetes complications
title_full_unstemmed Human complement component C3 N-glycome changes in type 1 diabetes complications
title_short Human complement component C3 N-glycome changes in type 1 diabetes complications
title_sort human complement component c3 n-glycome changes in type 1 diabetes complications
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244649/
https://www.ncbi.nlm.nih.gov/pubmed/37293493
http://dx.doi.org/10.3389/fendo.2023.1101154
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