<b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>

<p dir="ltr">Maturity Onset Diabetes of the Young (MODY) can present after the age of 40 years, but its prevalence, clinical characteristics, and the utility of simple clinical features for selecting cases in this age group remain poorly defined. We analysed whole-exome and clinical...

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Prif Awdur: Luke N Sharp (22551717) (author)
Awduron Eraill: Uyenlinh L Mirshahi (22551718) (author), Kevin Colclough (422231) (author), Timothy S Hall (22551719) (author), Jeremy S Haley (22551721) (author), Stuart J Cannon (22551727) (author), Thomas W Laver (22551731) (author), Michael N Weedon (21698) (author), Andrew T Hattersley (21706) (author), David J Carey (22551733) (author), Kashyap A Patel (22551735) (author)
Cyhoeddwyd: 2025
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author Luke N Sharp (22551717)
author2 Uyenlinh L Mirshahi (22551718)
Kevin Colclough (422231)
Timothy S Hall (22551719)
Jeremy S Haley (22551721)
Stuart J Cannon (22551727)
Thomas W Laver (22551731)
Michael N Weedon (21698)
Andrew T Hattersley (21706)
David J Carey (22551733)
Kashyap A Patel (22551735)
author2_role author
author
author
author
author
author
author
author
author
author
author_facet Luke N Sharp (22551717)
Uyenlinh L Mirshahi (22551718)
Kevin Colclough (422231)
Timothy S Hall (22551719)
Jeremy S Haley (22551721)
Stuart J Cannon (22551727)
Thomas W Laver (22551731)
Michael N Weedon (21698)
Andrew T Hattersley (21706)
David J Carey (22551733)
Kashyap A Patel (22551735)
author_role author
dc.creator.none.fl_str_mv Luke N Sharp (22551717)
Uyenlinh L Mirshahi (22551718)
Kevin Colclough (422231)
Timothy S Hall (22551719)
Jeremy S Haley (22551721)
Stuart J Cannon (22551727)
Thomas W Laver (22551731)
Michael N Weedon (21698)
Andrew T Hattersley (21706)
David J Carey (22551733)
Kashyap A Patel (22551735)
dc.date.none.fl_str_mv 2025-11-25T15:02:22Z
dc.identifier.none.fl_str_mv 10.2337/figshare.30521159.v1
dc.relation.none.fl_str_mv https://figshare.com/articles/figure/_b_MODY_is_prevalent_in_later-onset_diabetes_has_potential_for_targeted_therapy_but_is_challenging_to_identify_b_/30521159
dc.rights.none.fl_str_mv CC BY-NC-SA 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Other biological sciences not elsewhere classified
Monogenic Diabetes
Maturity-Onset Diabetes of the Young (MODY)
Genetics & Genomics
Genetic Screening
Late Onset
dc.title.none.fl_str_mv <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
dc.type.none.fl_str_mv Image
Figure
info:eu-repo/semantics/publishedVersion
image
description <p dir="ltr">Maturity Onset Diabetes of the Young (MODY) can present after the age of 40 years, but its prevalence, clinical characteristics, and the utility of simple clinical features for selecting cases in this age group remain poorly defined. We analysed whole-exome and clinical data from 51,619 individuals with diabetes diagnosed after age 40 from one UK and one US cohort. The prevalence of MODY due to pathogenic variant in the 10 most common MODY genes was 1 in 191 (0.52%) in the UK cohort and 1 in 633 (0.16%) in the US cohort. For subtypes with treatment implications (GCK, HNF1A, HNF4A, ABCC8, KCNJ11), prevalence was 1 in 234 and 1 in 935, respectively. GCK-MODY was most common, followed by HNF4A and lower-penetrance RFX6-MODY. Clinical features of MODY largely overlapped with non-MODY either insulin-treated from diagnosis or not insulin-treated from diagnosis. Only BMI, HbA1c and HDL were statistically different in MODY from non-MODY in both cohorts (all P<0.0018). Applying strict clinical criteria (BMI<25 and noninsulin treated and parent with diabetes) only increased the MODY diagnosis to 2.64% and 0.87% but missed over 86% of cases. MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify.</p>
eu_rights_str_mv openAccess
id Manara_205753e987414d5fa4022298f0d1e631
identifier_str_mv 10.2337/figshare.30521159.v1
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/30521159
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY-NC-SA 4.0
spelling <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>Luke N Sharp (22551717)Uyenlinh L Mirshahi (22551718)Kevin Colclough (422231)Timothy S Hall (22551719)Jeremy S Haley (22551721)Stuart J Cannon (22551727)Thomas W Laver (22551731)Michael N Weedon (21698)Andrew T Hattersley (21706)David J Carey (22551733)Kashyap A Patel (22551735)Other biological sciences not elsewhere classifiedMonogenic DiabetesMaturity-Onset Diabetes of the Young (MODY)Genetics & GenomicsGenetic ScreeningLate Onset<p dir="ltr">Maturity Onset Diabetes of the Young (MODY) can present after the age of 40 years, but its prevalence, clinical characteristics, and the utility of simple clinical features for selecting cases in this age group remain poorly defined. We analysed whole-exome and clinical data from 51,619 individuals with diabetes diagnosed after age 40 from one UK and one US cohort. The prevalence of MODY due to pathogenic variant in the 10 most common MODY genes was 1 in 191 (0.52%) in the UK cohort and 1 in 633 (0.16%) in the US cohort. For subtypes with treatment implications (GCK, HNF1A, HNF4A, ABCC8, KCNJ11), prevalence was 1 in 234 and 1 in 935, respectively. GCK-MODY was most common, followed by HNF4A and lower-penetrance RFX6-MODY. Clinical features of MODY largely overlapped with non-MODY either insulin-treated from diagnosis or not insulin-treated from diagnosis. Only BMI, HbA1c and HDL were statistically different in MODY from non-MODY in both cohorts (all P<0.0018). Applying strict clinical criteria (BMI<25 and noninsulin treated and parent with diabetes) only increased the MODY diagnosis to 2.64% and 0.87% but missed over 86% of cases. MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify.</p>2025-11-25T15:02:22ZImageFigureinfo:eu-repo/semantics/publishedVersionimage10.2337/figshare.30521159.v1https://figshare.com/articles/figure/_b_MODY_is_prevalent_in_later-onset_diabetes_has_potential_for_targeted_therapy_but_is_challenging_to_identify_b_/30521159CC BY-NC-SA 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/305211592025-11-25T15:02:22Z
spellingShingle <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
Luke N Sharp (22551717)
Other biological sciences not elsewhere classified
Monogenic Diabetes
Maturity-Onset Diabetes of the Young (MODY)
Genetics & Genomics
Genetic Screening
Late Onset
status_str publishedVersion
title <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
title_full <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
title_fullStr <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
title_full_unstemmed <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
title_short <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
title_sort <b>MODY is prevalent in later-onset diabetes, has potential for targeted therapy but is challenging to identify</b>
topic Other biological sciences not elsewhere classified
Monogenic Diabetes
Maturity-Onset Diabetes of the Young (MODY)
Genetics & Genomics
Genetic Screening
Late Onset