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Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes
Integration of genomic and other data has begun to stratify type 2 diabetes in prognostically meaningful ways, but this has yet to impact on mainstream diabetes practice. The subgroup of diabetes caused by single gene defects thus provides the best example to date of the vision of ‘precision diabete...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522735/ https://www.ncbi.nlm.nih.gov/pubmed/35618782 http://dx.doi.org/10.1007/s00125-022-05720-7 |
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author | Bonnefond, Amélie Semple, Robert K. |
author_facet | Bonnefond, Amélie Semple, Robert K. |
author_sort | Bonnefond, Amélie |
collection | PubMed |
description | Integration of genomic and other data has begun to stratify type 2 diabetes in prognostically meaningful ways, but this has yet to impact on mainstream diabetes practice. The subgroup of diabetes caused by single gene defects thus provides the best example to date of the vision of ‘precision diabetes’. Monogenic diabetes may be divided into primary pancreatic beta cell failure, and primary insulin resistance. In both groups, clear examples of genotype-selective responses to therapy have been advanced. The benign trajectory of diabetes due to pathogenic GCK mutations, and the sulfonylurea-hyperresponsiveness conferred by activating KCNJ11 or ABCC8 mutations, or loss-of-function HNF1A or HNF4A mutations, often decisively guide clinical management. In monogenic insulin-resistant diabetes, subcutaneous leptin therapy is beneficial in some severe lipodystrophy. Increasing evidence also supports use of ‘obesity therapies’ in lipodystrophic people even without obesity. In beta cell diabetes the main challenge is now implementation of the precision diabetes vision at scale. In monogenic insulin-resistant diabetes genotype-specific benefits are proven in far fewer patients to date, although further genotype-targeted therapies are being evaluated. The conceptual paradigm established by the insulin-resistant subgroup with ‘adipose failure’ may have a wider influence on precision therapy for common type 2 diabetes, however. For all forms of monogenic diabetes, population-wide genome sequencing is currently forcing reappraisal of the importance assigned to pathogenic mutations when gene sequencing is uncoupled from prior suspicion of monogenic diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00125-022-05720-7) contains a slideset of the figures for download, which is available to authorised users. |
format | Online Article Text |
id | pubmed-9522735 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-95227352022-10-01 Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes Bonnefond, Amélie Semple, Robert K. Diabetologia Review Integration of genomic and other data has begun to stratify type 2 diabetes in prognostically meaningful ways, but this has yet to impact on mainstream diabetes practice. The subgroup of diabetes caused by single gene defects thus provides the best example to date of the vision of ‘precision diabetes’. Monogenic diabetes may be divided into primary pancreatic beta cell failure, and primary insulin resistance. In both groups, clear examples of genotype-selective responses to therapy have been advanced. The benign trajectory of diabetes due to pathogenic GCK mutations, and the sulfonylurea-hyperresponsiveness conferred by activating KCNJ11 or ABCC8 mutations, or loss-of-function HNF1A or HNF4A mutations, often decisively guide clinical management. In monogenic insulin-resistant diabetes, subcutaneous leptin therapy is beneficial in some severe lipodystrophy. Increasing evidence also supports use of ‘obesity therapies’ in lipodystrophic people even without obesity. In beta cell diabetes the main challenge is now implementation of the precision diabetes vision at scale. In monogenic insulin-resistant diabetes genotype-specific benefits are proven in far fewer patients to date, although further genotype-targeted therapies are being evaluated. The conceptual paradigm established by the insulin-resistant subgroup with ‘adipose failure’ may have a wider influence on precision therapy for common type 2 diabetes, however. For all forms of monogenic diabetes, population-wide genome sequencing is currently forcing reappraisal of the importance assigned to pathogenic mutations when gene sequencing is uncoupled from prior suspicion of monogenic diabetes. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s00125-022-05720-7) contains a slideset of the figures for download, which is available to authorised users. Springer Berlin Heidelberg 2022-05-27 2022 /pmc/articles/PMC9522735/ /pubmed/35618782 http://dx.doi.org/10.1007/s00125-022-05720-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Bonnefond, Amélie Semple, Robert K. Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title | Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title_full | Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title_fullStr | Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title_full_unstemmed | Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title_short | Achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
title_sort | achievements, prospects and challenges in precision care for monogenic insulin-deficient and insulin-resistant diabetes |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9522735/ https://www.ncbi.nlm.nih.gov/pubmed/35618782 http://dx.doi.org/10.1007/s00125-022-05720-7 |
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