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Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant

Type 1 diabetes patients carrying a ‘protective’ insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proli...

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Autores principales: van Tienhoven, René, Vu, Anh Nguyet, Kaddis, John S., Roep, Bart O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879388/
https://www.ncbi.nlm.nih.gov/pubmed/36701305
http://dx.doi.org/10.1371/journal.pone.0280872
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author van Tienhoven, René
Vu, Anh Nguyet
Kaddis, John S.
Roep, Bart O.
author_facet van Tienhoven, René
Vu, Anh Nguyet
Kaddis, John S.
Roep, Bart O.
author_sort van Tienhoven, René
collection PubMed
description Type 1 diabetes patients carrying a ‘protective’ insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term diabetic complications. Insulin gene polymorphisms were evaluated in 1,363 type 1 diabetes patients participating in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study that compared intensive versus conventional insulin therapy in relation with development of PDR and DKD with a follow-up of over two decades. PDR and DKD were absent in type 1 diabetes patients carrying the protective INS variant and receiving intensive insulin therapy (the current standard of clinical care) 1–5 years from their diagnosis (n = 67; mean post-diagnosis follow up of 20.4 ± 1.6 years), versus 11 of 258 patients (4.3%) lacking this variant (20.4 ± 1.8 years follow up). In the secondary intervention group of the intensive therapy arm (1–15 years of disease), PDR was significantly less frequent in carriers of the protective INS variant than those without it (4 of 83 [4.8%] vs. 31 of 260 [11.9%]; p = 0.032; 26.1 ± 3.9 and 26.3 ± 4.1 years follow-up, respectively), whereas DKD frequencies were no different between those with or without this variant (5 of 83 [6.0%] vs. 11 of 260 [4.2%]). Carrying a copy of this protective INS variant further reduces the risk of diabetic complications achieved by intensive insulin therapy and marks a disease endotype with superior glycemic control, increased and extended beta cell function, and prevention of DKD and PDR.
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spelling pubmed-98793882023-01-27 Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant van Tienhoven, René Vu, Anh Nguyet Kaddis, John S. Roep, Bart O. PLoS One Research Article Type 1 diabetes patients carrying a ‘protective’ insulin gene (INS) variant present a disease endotype with reduced insulin antibody titers, preserved beta cell function and improved glycemic control. We tested whether this protective INS variant associated with lowered risk for development of proliferative diabetic retinopathy (PDR) and diabetic kidney disease (DKD) as long-term diabetic complications. Insulin gene polymorphisms were evaluated in 1,363 type 1 diabetes patients participating in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study that compared intensive versus conventional insulin therapy in relation with development of PDR and DKD with a follow-up of over two decades. PDR and DKD were absent in type 1 diabetes patients carrying the protective INS variant and receiving intensive insulin therapy (the current standard of clinical care) 1–5 years from their diagnosis (n = 67; mean post-diagnosis follow up of 20.4 ± 1.6 years), versus 11 of 258 patients (4.3%) lacking this variant (20.4 ± 1.8 years follow up). In the secondary intervention group of the intensive therapy arm (1–15 years of disease), PDR was significantly less frequent in carriers of the protective INS variant than those without it (4 of 83 [4.8%] vs. 31 of 260 [11.9%]; p = 0.032; 26.1 ± 3.9 and 26.3 ± 4.1 years follow-up, respectively), whereas DKD frequencies were no different between those with or without this variant (5 of 83 [6.0%] vs. 11 of 260 [4.2%]). Carrying a copy of this protective INS variant further reduces the risk of diabetic complications achieved by intensive insulin therapy and marks a disease endotype with superior glycemic control, increased and extended beta cell function, and prevention of DKD and PDR. Public Library of Science 2023-01-26 /pmc/articles/PMC9879388/ /pubmed/36701305 http://dx.doi.org/10.1371/journal.pone.0280872 Text en © 2023 van Tienhoven et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
van Tienhoven, René
Vu, Anh Nguyet
Kaddis, John S.
Roep, Bart O.
Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title_full Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title_fullStr Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title_full_unstemmed Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title_short Low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
title_sort low risk for diabetic complications in type 1 diabetes patients carrying a protective insulin gene variant
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9879388/
https://www.ncbi.nlm.nih.gov/pubmed/36701305
http://dx.doi.org/10.1371/journal.pone.0280872
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