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  • García-Calzón, SoniaLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital,University of Navarra (author)

Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes

  • Article/chapterEnglish2020

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  • 2020

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  • LIBRIS-ID:oai:lup.lub.lu.se:42d5c223-4095-4445-81be-709626559adb
  • https://lup.lub.lu.se/record/42d5c223-4095-4445-81be-709626559adbURI
  • https://doi.org/10.1126/SCITRANSLMED.AAZ1803DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associated with a higher risk of not responding to or not tolerating metformin with odds ratios between 1.43 and 3.09 per 1-SD methylation increase. Methylation risk scores (MRSs) of the 11 identified sites differed between glycemic responders and nonresponders with areas under the curve (AUCs) of 0.80 to 0.98. MRSs of the 4 sites associated with future metformin intolerance generated AUCs of 0.85 to 0.93. Some of these blood-based methylation markers mirrored the epigenetic pattern in adipose tissue, a key tissue in diabetes pathogenesis, and genes to which these markers were annotated to had biological functions in hepatocytes that altered metformin- related phenotypes. Overall, we could discriminate between glycemic responders/nonresponders and participants tolerant/ intolerant to metformin at diagnosis by measuring blood-based epigenetic markers in drug-naïve patients with T2D. This epigenetics-based tool may be further developed to help patients with T2D receive optimal therapy.

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  • Perfilyev, AlexanderLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)med-apy (author)
  • Martinell, MatsUppsala University (author)
  • Ustinova, MontaLatvian Biomedical Research and Study Centre (author)
  • Kalamajski, SebastianLund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)se8335ka (author)
  • Franks, Paul W.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
  • Bacos, KarlLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)medk-kb0 (author)
  • Elbere, IlzeLatvian Biomedical Research and Study Centre (author)
  • Pihlajamäki, JussiUniversity of Eastern Finland,Kuopio University Hospital (author)
  • Volkov, PetrLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Diabetes - Epigenetics,Lund University Research Groups,Diabetic Complications,Skåne University Hospital(Swepub:lu)med-pvo (author)
  • Vaag, AllanSteno Diabetes Center Copenhagen(Swepub:lu)med-ava (author)
  • Groop, LeifLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups(Swepub:lu)endo-lgr (author)
  • Maziarz, MarlenaLund University,Lunds universitet,Diabetiska komplikationer,Forskargrupper vid Lunds universitet,Diabetic Complications,Lund University Research Groups(Swepub:lu)ma4353ma (author)
  • Klovins, JanisLatvian Biomedical Research and Study Centre,University of Latvia (author)
  • Ahlqvist, EmmaLund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)infl-eah (author)
  • Ling, CharlotteLund University,Lunds universitet,Diabetes - epigenetik,Forskargrupper vid Lunds universitet,Diabetes - Epigenetics,Lund University Research Groups,Skåne University Hospital(Swepub:lu)endo-cl0 (author)
  • Diabetes - epigenetikForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Science Translational Medicine12:5611946-6234

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