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Novel Subgroups of ...
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Schrader, SiljaLund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmö, Sweden.
(author)
Novel Subgroups of Type 2 Diabetes Display Different Epigenetic Patterns That Associate With Future Diabetic Complications
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-05-24
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American Diabetes Association,2022
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electronicrdacarrier
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LIBRIS-ID:oai:DiVA.org:uu-487988
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-487988URI
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https://doi.org/10.2337/dc21-2489DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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OBJECTIVE Type 2 diabetes (T2D) was recently reclassified into severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD), which have different risk of complications. We explored whether DNA methylation differs between these subgroups and whether subgroup-unique methylation risk scores (MRSs) predict diabetic complications. RESEARCH DESIGN AND METHODS Genome-wide DNA methylation was analyzed in blood from subjects with newly diagnosed T2D in discovery and replication cohorts. Subgroup-unique MRSs were built, including top subgroup-unique DNA methylation sites. Regression models examined whether MRSs associated with subgroups and future complications. RESULTS We found epigenetic differences between the T2D subgroups. Subgroup-unique MRSs were significantly different in those patients allocated to each respective subgroup compared with the combined group of all other subgroups. These associations were validated in an independent replication cohort, showing that subgroup-unique MRSs associate with individual subgroups (odds ratios 1.6-6.1 per 1-SD increase, P < 0.01). Subgroup-unique MRSs were also associated with future complications. Higher MOD-MRS was associated with lower risk of cardiovascular (hazard ratio [HR] 0.65, P = 0.001) and renal (HR 0.50, P < 0.001) disease, whereas higher SIRD-MRS and MARD-MRS were associated with an increased risk of these complications (HR 1.4-1.9 per 1-SD increase, P < 0.01). Of 95 methylation sites included in subgroup-unique MRSs, 39 were annotated to genes previously linked to diabetes-related traits, including TXNIP and ELOVL2. Methylation in the blood of 18 subgroup-unique sites mirrors epigenetic patterns in tissues relevant for T2D, muscle and adipose tissue. CONCLUSIONS We identified differential epigenetic patterns between T2D subgroups that associated with future diabetic complications. These data support a reclassification of diabetes and the need for precision medicine in T2D subgroups.
Subject headings and genre
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Perfilyev, AlexanderLund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmö, Sweden.
(author)
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Ahlqvist, EmmaLund Univ, Dept Clin Sci, Genom Diabet & Endocrinol Unit, Malmö, Sweden.
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Groop, LeifLund Univ, Dept Clin Sci, Genom Diabet & Endocrinol Unit, Malmö, Sweden.
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Vaag, AllanSteno Diabet Ctr, Type Diabet Biol Res 2, Copenhagen, Denmark.
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Martinell, Mats,1971-Uppsala universitet,Allmänmedicin och preventivmedicin,Acad Primary Care Ctr, Uppsala, Sweden.(Swepub:uu)matma554
(author)
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Garcia-Calzon, SoniaLund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmö, Sweden.;Univ Navarra, Dept Food Sci & Physiol, Pamplona, Spain.
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Ling, CharlotteLund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmö, Sweden.
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Lund Univ, Scania Univ Hosp, Diabet Ctr, Epigenet & Diabet Unit,Dept Clin Sci, Malmö, Sweden.Lund Univ, Dept Clin Sci, Genom Diabet & Endocrinol Unit, Malmö, Sweden.
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Related titles
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In:Diabetes Care: American Diabetes Association45:7, s. 1621-16300149-59921935-5548
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