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  • Slieker, Roderick CLeiden University Medical Centre (author)

Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-08-10
  • American Diabetes Association,2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:07f6d2b7-e7a4-405b-ab64-3eae227558ec
  • https://lup.lub.lu.se/record/07f6d2b7-e7a4-405b-ab64-3eae227558ecURI
  • https://doi.org/10.2337/db20-1281DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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

Notes

  • Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.

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  • Donnelly, Louise AUniversity of Dundee (author)
  • Fitipaldi, HugoLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)(Swepub:lu)hu3745fi (author)
  • Bouland, Gerard ALeiden University Medical Centre (author)
  • Giordano, Giuseppe NLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)(Swepub:lu)med-geg (author)
  • Åkerlund, MikaelLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)(Swepub:lu)medk-mak (author)
  • Gerl, Mathias JLipotype GmbH (author)
  • Ahlqvist, EmmaLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)(Swepub:lu)infl-eah (author)
  • Ali, AshfaqSteno Diabetes Center Copenhagen(Swepub:lu)cob-aaf (author)
  • Dragan, IulianSwiss Institute for Bioinformatics (SIB) (author)
  • Elders, PetraAmsterdam Public Health (author)
  • Festa, AndreasEli Lilly Regional Operations G.m.b.H. (author)
  • Hansen, Michael KJanssen Pharmaceuticals, US(Swepub:lu)mi0167ha (author)
  • van der Heijden, Amber AAmsterdam Public Health (author)
  • Aly, Dina MansourLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)(Swepub:lu)di3053ma (author)
  • Kim, MinSteno Diabetes Center Copenhagen (author)
  • Kuznetsov, DmitrySwiss Institute for Bioinformatics (SIB) (author)
  • Mehl, FlorenceSwiss Institute for Bioinformatics (SIB) (author)
  • Klose, ChristianLipotype GmbH (author)
  • Simons, KaiLipotype GmbH (author)
  • Pavo, ImreEli Lilly Regional Operations G.m.b.H. (author)
  • Pullen, Timothy JKing's College London (author)
  • Suvitaival, TommiSteno Diabetes Center Copenhagen (author)
  • Wretlind, AsgerSteno Diabetes Center Copenhagen (author)
  • Rossing, PeterSteno Diabetes Center Copenhagen (author)
  • Lyssenko, ValeriyaUniversity of Bergen(Swepub:lu)endo-vly (author)
  • Quigley, Cristina LegidoSteno Diabetes Center Copenhagen (author)
  • Groop, LeifLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö),University of Helsinki(Swepub:lu)endo-lgr (author)
  • Thorens, BernardUniversity of Lausanne (author)
  • Franks, Paul WLund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Livsmedelsteknik,Avdelningen för livsmedel och läkemedel,Institutionen för processteknik och tillämpad biovetenskap,Institutioner vid LTH,Lunds Tekniska Högskola,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Department of Food Technology, Engineering and Nutrition,Division of Food and Pharma,Department of Process and Life Science Engineering,Departments at LTH,Faculty of Engineering, LTH,Ophthalmology (Malmö),Harvard University(Swepub:lu)med-plf (author)
  • Ibberson, MarkSwiss Institute for Bioinformatics (SIB) (author)
  • Rutter, Guy AKing's College London (author)
  • Beulens, Joline WjAmsterdam Public Health (author)
  • 't Hart, Leen MLeiden University Medical Centre (author)
  • Pearson, Ewan RUniversity of Dundee(Swepub:lu)ew1481pe (author)
  • Leiden University Medical CentreUniversity of Dundee (creator_code:org_t)

Related titles

  • In:Diabetes: American Diabetes Association70:11, s. 2683-26931939-327X0012-1797

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