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

Slieker, Roderick C (author)
Leiden University Medical Centre
Donnelly, Louise A (author)
University of Dundee
Fitipaldi, Hugo (author)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)
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Bouland, Gerard A (author)
Leiden University Medical Centre
Giordano, Giuseppe N (author)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)
Åkerlund, Mikael (author)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)
Gerl, Mathias J (author)
Lipotype GmbH
Ahlqvist, Emma (author)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)
Ali, Ashfaq (author)
Steno Diabetes Center Copenhagen
Dragan, Iulian (author)
Swiss Institute for Bioinformatics (SIB)
Elders, Petra (author)
Amsterdam Public Health
Festa, Andreas (author)
Eli Lilly Regional Operations G.m.b.H.
Hansen, Michael K (author)
Janssen Pharmaceuticals, US
van der Heijden, Amber A (author)
Amsterdam Public Health
Aly, Dina Mansour (author)
Lund University,Lunds universitet,-lup-obsolete,Forskargrupper vid Lunds universitet,Oftalmologi (Malmö),LUDC (Lund University Diabetes Centre)-lup-obsolete,Lund University Research Groups,Ophthalmology (Malmö)
Kim, Min (author)
Steno Diabetes Center Copenhagen
Kuznetsov, Dmitry (author)
Swiss Institute for Bioinformatics (SIB)
Mehl, Florence (author)
Swiss Institute for Bioinformatics (SIB)
Klose, Christian (author)
Lipotype GmbH
Simons, Kai (author)
Lipotype GmbH
Pavo, Imre (author)
Eli Lilly Regional Operations G.m.b.H.
Pullen, Timothy J (author)
King's College London
Suvitaival, Tommi (author)
Steno Diabetes Center Copenhagen
Wretlind, Asger (author)
Steno Diabetes Center Copenhagen
Rossing, Peter (author)
Steno Diabetes Center Copenhagen
Lyssenko, Valeriya (author)
University of Bergen
Quigley, Cristina Legido (author)
Steno Diabetes Center Copenhagen
Groop, Leif (author)
Lund 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
Thorens, Bernard (author)
University of Lausanne
Franks, Paul W (author)
Lund 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
Ibberson, Mark (author)
Swiss Institute for Bioinformatics (SIB)
Rutter, Guy A (author)
King's College London
Beulens, Joline Wj (author)
Amsterdam Public Health
't Hart, Leen M (author)
Leiden University Medical Centre
Pearson, Ewan R (author)
University of Dundee
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 (creator_code:org_t)
2021-08-10
2021
English.
In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:11, s. 2683-2693
Related links:
http://dx.doi.org/10...
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https://lup.lub.lu.s...
https://doi.org/10.2...
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

ANDIS
diabetes
Diabetics

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