Phenotypic and genetic classification of diabetes
Open accessAbstract
The historical subclassification of diabetes into predominantly types 1 and 2 is well appreciated to inadequately capture the heterogeneity seen in patient presentations, disease course, response to therapy and disease complications. This review summarises proposed data-driven approaches to further refine diabetes subtypes using clinical phenotypes and/or genetic information. We highlight the benefits as well as the limitations of these subclassification schemas, including practical barriers to their implementation that would need to be overcome before incorporation into clinical practice.
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Different subtypes/endotypes/clusters of T2D are associated with different risks of disease progression, with particularly high risk for MASLD/MASH progression in individuals with severe insulin resistance.
“Different subtypes/endotypes/clusters of T2D are associated with different risks of disease progression, 58,59 with particularly high risk for MASLD/MASH progression in those individuals with severe insulin resistance.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [58]
The ‘Five clinical subtypes of diabetes at time of diagnosis’ section reports different complication risks across clusters and a higher prevalence of non-alcoholic fatty liver in the severe insulin-resistant (SIRD) group. It does not report a particularly high risk of MASLD/MASH progression in that group; prevalence of fatty liver does not establish progression. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn several independent cohorts, subgroups have been identified that were either characterized by lower pancreatic β-cell function as described by lower HOMA2-B indices or distinct subgroups characterized by higher insulin resistance as described by higher HOMA2-IR indices.
“In several independent cohorts, subgroups have been identified that were either characterized by lower pancreatic β-cell function as described by lower HOMA2-B indices or distinct subgroups characterized by higher insulin resistance as described by higher HOMA2-IR indices (17-19).”
From Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2) (2024) · cites this paper as [17]
Recent epidemiologic studies have combined analyses of genetic markers, clinical traits, and circulating biomarkers to propose that people living with T2D can be stratified into consistent phenotypic subtypes or clusters.
“Recent epidemiologic studies have combined analyses of genetic markers, clinical traits, and circulating biomarkers to propose that people living with T2D can be stratified into consistent phenotypic subtypes or clusters (17).”
From Tirzepatide Improved Markers of Islet Cell Function and Insulin Sensitivity in People With T2D (SURPASS-2) (2024) · cites this paper as [17]
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References 68 · Cited by 108
Research works printed but not linked: 1
- [37]Mirshahi UL, Colclough K, Wright CF et al (2021) The penetrance of age-related monogenic disease depends on ascertainment context. medRxiv 21259641 (Preprint). 28 Jun 2021. Available from: 10.1101/2021.06.28.21259641 (accessed 9 Jun 2022) · DOI
- Authors
- Deutsch, A. J., Ahlqvist, E., & Udler, M. S.
- Affiliations
- Broad Institute (US)
- Lund University (SE)
- Corresponding author
- Ahlqvist, Emma
- Udler, Miriam S.
- Venue
- Diabetologia
- Published
- 2022-08-12
- Volume
- 65
- Issue
- 11
- Pages
- 1758-1769
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC9522707
- OpenAlex
- W4291010743
- Cited by
- 108
- References
- 68
- Citations by year
- 2026: 18 · 2025: 30 · 2024: 27 · 2023: 27 · 2022: 6
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Research Council
- Massachusetts General Hospital (Transformative Scholar Award)
- NIH/NIDDK (T32DK007028, K23DK114551)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- type 1 diabetes, type 2 diabetes, diabetes phenotypes, genetic classification, diabetes heterogeneity, clinical course, treatment response, disease complications, clinical implementation
- MeSH terms
- Diabetes Mellitus, Type 2, Humans, Phenotype, Precision Medicine
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