Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI
ObjectiveThis study seeks to understand type 2 diabetes (T2D) heterogeneity through detailed phenotypic characterization of various T2D genetic subtypes using advanced magnetic resonance imaging (MRI) techniques.Study design and methodMRI data from over 44,000 UK Biobank participants was used to cha...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2025.1605721/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849467254114091008 |
|---|---|
| author | Elena P. Sorokin Madeleine Cule Marjola Thanaj Nicolas Basty Brandon Whitcher Naveed Sattar E. Louise Thomas Jimmy D. Bell Hanieh Yaghootkar |
| author_facet | Elena P. Sorokin Madeleine Cule Marjola Thanaj Nicolas Basty Brandon Whitcher Naveed Sattar E. Louise Thomas Jimmy D. Bell Hanieh Yaghootkar |
| author_sort | Elena P. Sorokin |
| collection | DOAJ |
| description | ObjectiveThis study seeks to understand type 2 diabetes (T2D) heterogeneity through detailed phenotypic characterization of various T2D genetic subtypes using advanced magnetic resonance imaging (MRI) techniques.Study design and methodMRI data from over 44,000 UK Biobank participants was used to characterize distinct T2D genetic subtypes based on a compendium of imaging-derived phenotypes (IDPs) quantifying body fat distribution, organ volumes, and muscle quality. Partitioned polygenic risk scores (pPS) representing genetic T2D subtypes were associated with adipose tissue distribution across ten compartments, liver and pancreas volume, three muscle mass indices, and fatty acid composition in subcutaneous and visceral fat.ResultsSubtype pPS marked by insulin deficiency were associated with lower subcutaneous fat, while insulin resistance subtypes were associated with higher adiposity with evidence of fat excess in multiple organs, including the pancreas, paraspinal muscle, thigh muscle, iliopsoas muscle, and other organs not routinely quantified at scale in human cohorts. Distinct patterns of muscle mass and fatty acid composition further differentiated subtype pPS, underscoring variation in metabolic profiles linked to specific genetic pathways.ConclusionThe use of non-invasive MRI to phenotype T2D at a granular level has provided unique insights into the disease’s heterogeneity, confirming and expanding upon known genetic associations. These findings highlight the potential of using MRI for pathophysiological insights into T2D. |
| format | Article |
| id | doaj-art-54d7221c90d84df29e307cbc3f301443 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-54d7221c90d84df29e307cbc3f3014432025-08-20T03:27:43ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.16057211605721Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRIElena P. Sorokin0Madeleine Cule1Marjola Thanaj2Nicolas Basty3Brandon Whitcher4Naveed Sattar5E. Louise Thomas6Jimmy D. Bell7Hanieh Yaghootkar8Calico Life Sciences LLC, South San Francisco, CA, United StatesCalico Life Sciences LLC, South San Francisco, CA, United StatesResearch Center for Optimal Health, School of Life Sciences, University of Westminster, London, United KingdomResearch Center for Optimal Health, School of Life Sciences, University of Westminster, London, United KingdomResearch Center for Optimal Health, School of Life Sciences, University of Westminster, London, United KingdomSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United KingdomResearch Center for Optimal Health, School of Life Sciences, University of Westminster, London, United KingdomResearch Center for Optimal Health, School of Life Sciences, University of Westminster, London, United KingdomJoseph Banks Laboratories, School of Natural Science, College of Health and Science, University of Lincoln, Lincoln, United KingdomObjectiveThis study seeks to understand type 2 diabetes (T2D) heterogeneity through detailed phenotypic characterization of various T2D genetic subtypes using advanced magnetic resonance imaging (MRI) techniques.Study design and methodMRI data from over 44,000 UK Biobank participants was used to characterize distinct T2D genetic subtypes based on a compendium of imaging-derived phenotypes (IDPs) quantifying body fat distribution, organ volumes, and muscle quality. Partitioned polygenic risk scores (pPS) representing genetic T2D subtypes were associated with adipose tissue distribution across ten compartments, liver and pancreas volume, three muscle mass indices, and fatty acid composition in subcutaneous and visceral fat.ResultsSubtype pPS marked by insulin deficiency were associated with lower subcutaneous fat, while insulin resistance subtypes were associated with higher adiposity with evidence of fat excess in multiple organs, including the pancreas, paraspinal muscle, thigh muscle, iliopsoas muscle, and other organs not routinely quantified at scale in human cohorts. Distinct patterns of muscle mass and fatty acid composition further differentiated subtype pPS, underscoring variation in metabolic profiles linked to specific genetic pathways.ConclusionThe use of non-invasive MRI to phenotype T2D at a granular level has provided unique insights into the disease’s heterogeneity, confirming and expanding upon known genetic associations. These findings highlight the potential of using MRI for pathophysiological insights into T2D.https://www.frontiersin.org/articles/10.3389/fgene.2025.1605721/fulltype 2 diabetes subtypesmagnetic resonance imagingprecision medicinepolygenic risk scoreectopic fat |
| spellingShingle | Elena P. Sorokin Madeleine Cule Marjola Thanaj Nicolas Basty Brandon Whitcher Naveed Sattar E. Louise Thomas Jimmy D. Bell Hanieh Yaghootkar Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI Frontiers in Genetics type 2 diabetes subtypes magnetic resonance imaging precision medicine polygenic risk score ectopic fat |
| title | Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI |
| title_full | Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI |
| title_fullStr | Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI |
| title_full_unstemmed | Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI |
| title_short | Genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal MRI |
| title_sort | genetic subtypes of type 2 diabetes are distinguished through the lens of abdominal mri |
| topic | type 2 diabetes subtypes magnetic resonance imaging precision medicine polygenic risk score ectopic fat |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2025.1605721/full |
| work_keys_str_mv | AT elenapsorokin geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT madeleinecule geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT marjolathanaj geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT nicolasbasty geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT brandonwhitcher geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT naveedsattar geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT elouisethomas geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT jimmydbell geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri AT haniehyaghootkar geneticsubtypesoftype2diabetesaredistinguishedthroughthelensofabdominalmri |