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Sökning: onr:"swepub:oai:DiVA.org:uu-423368" > Epigenetic markers ...

  • Garcia-Calzon, SoniaLund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden.;Univ Navarra, Dept Nutr Food Sci & Physiol, Pamplona 31008, Spain. (författare)

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

  • Artikel/kapitelEngelska2020

Förlag, utgivningsår, omfång ...

  • AMER ASSOC ADVANCEMENT SCIENCE,2020
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-423368
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-423368URI
  • https://doi.org/10.1126/scitranslmed.aaz1803DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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-naive 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-naive patients with T2D. This epigenetics-based tool may be further developed to help patients with T2D receive optimal therapy.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Perfilyev, AlexanderLund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Martinell, Mats,1971-Uppsala universitet,Allmänmedicin och preventivmedicin(Swepub:uu)matma554 (författare)
  • Ustinova, MontaLatvian Biomed Res & Study Ctr, Ratsupites St 1,K-1, LV-1067 Riga, Latvia. (författare)
  • Kalamajski, SebastianLund Univ, Diabet Ctr, Genet & Mol Epidemiol Unit, Dept Clin Sci, S-21428 Malmö, Sweden. (författare)
  • Franks, Paul W.Lund Univ, Diabet Ctr, Genet & Mol Epidemiol Unit, Dept Clin Sci, S-21428 Malmö, Sweden. (författare)
  • Bacos, KarlLund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Elbere, IlzeLatvian Biomed Res & Study Ctr, Ratsupites St 1,K-1, LV-1067 Riga, Latvia. (författare)
  • Pihlajamaki, JussiUniv Eastern Finland, Internal Med, Inst Publ Hlth & Clin Nutr, Kuopio 70211, Finland.;Kuopio Univ Hosp, Clin Nutr & Obes Ctr, Kuopio 70210, Finland. (författare)
  • Volkov, PetrLund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Vaag, AllanSteno Diabet Ctr, Type Diabet Biol Res 2, DK-2820 Gentofte, Denmark. (författare)
  • Groop, LeifLund Univ, Scania Univ Hosp, Dept Clin Sci, Genom Diabet & Endocrinol Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Maziarz, RlenaLund Univ, Dept Clin Sci, Bioinformat Unit, Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Klovins, JanisLatvian Biomed Res & Study Ctr, Ratsupites St 1,K-1, LV-1067 Riga, Latvia.;Univ Latvia, Fac Biol, LV-1004 Riga, Latvia. (författare)
  • Ahlqvist, EmmaLund Univ, Scania Univ Hosp, Dept Clin Sci, Genom Diabet & Endocrinol Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Ling, CharlotteLund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden. (författare)
  • Lund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden.;Univ Navarra, Dept Nutr Food Sci & Physiol, Pamplona 31008, Spain.Lund Univ, Scania Univ Hosp, Dept Clin Sci, Epigenet & Diabet Unit,Diabet Ctr, S-21428 Malmö, Sweden. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Science Translational Medicine: AMER ASSOC ADVANCEMENT SCIENCE12:5611946-62341946-6242

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