Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Bonnefond, Amélie, Semple, Robert K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
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
_version_ 1784800122567131136
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
work_keys_str_mv AT bonnefondamelie achievementsprospectsandchallengesinprecisioncareformonogenicinsulindeficientandinsulinresistantdiabetes
AT semplerobertk achievementsprospectsandchallengesinprecisioncareformonogenicinsulindeficientandinsulinresistantdiabetes