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

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Harvard

Slieker, RC, Donnelly, LA, Fitipaldi, H, Bouland, GA, Giordano, GN, Åkerlund, M, Gerl, MJ, Ahlqvist, E, Ali, A, Dragan, I, Elders, P, Festa, A, Hansen, MK, van der Heijden, AA, Aly, DM, Kim, M, Kuznetsov, D, Mehl, F, Klose, C, Simons, K, Pavo, I, Pullen, TJ, Suvitaival, T, Wretlind, A, Rossing, P, Lyssenko, V, Quigley, CL, Groop, L, Thorens, B, Franks, PW, Ibberson, M, Rutter, GA, Beulens, JW, 't Hart, LM & Pearson, ER 2021, 'Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMIRHAPSODY Study', Diabetes. https://doi.org/10.2337/db20-1281

APA

Slieker, R. C., Donnelly, L. A., Fitipaldi, H., Bouland, G. A., Giordano, G. N., Åkerlund, M., Gerl, M. J., Ahlqvist, E., Ali, A., Dragan, I., Elders, P., Festa, A., Hansen, M. K., van der Heijden, A. A., Aly, D. M., Kim, M., Kuznetsov, D., Mehl, F., Klose, C., ... Pearson, E. R. (2021). Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMIRHAPSODY Study. Diabetes. https://doi.org/10.2337/db20-1281

CBE

Slieker RC, Donnelly LA, Fitipaldi H, Bouland GA, Giordano GN, Åkerlund M, Gerl MJ, Ahlqvist E, Ali A, Dragan I, Elders P, Festa A, Hansen MK, van der Heijden AA, Aly DM, Kim M, Kuznetsov D, Mehl F, Klose C, Simons K, Pavo I, Pullen TJ, Suvitaival T, Wretlind A, Rossing P, Lyssenko V, Quigley CL, Groop L, Thorens B, Franks PW, Ibberson M, Rutter GA, Beulens JW, 't Hart LM, Pearson ER. 2021. Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMIRHAPSODY Study. Diabetes. https://doi.org/10.2337/db20-1281

MLA

Vancouver

Slieker RC, Donnelly LA, Fitipaldi H, Bouland GA, Giordano GN, Åkerlund M o.a. Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMIRHAPSODY Study. Diabetes. 2021 aug 10. https://doi.org/10.2337/db20-1281

Author

Slieker, Roderick C ; Donnelly, Louise A ; Fitipaldi, Hugo ; Bouland, Gerard A ; Giordano, Giuseppe N ; Åkerlund, Mikael ; Gerl, Mathias J ; Ahlqvist, Emma ; Ali, Ashfaq ; Dragan, Iulian ; Elders, Petra ; Festa, Andreas ; Hansen, Michael K ; van der Heijden, Amber A ; Aly, Dina Mansour ; Kim, Min ; Kuznetsov, Dmitry ; Mehl, Florence ; Klose, Christian ; Simons, Kai ; Pavo, Imre ; Pullen, Timothy J ; Suvitaival, Tommi ; Wretlind, Asger ; Rossing, Peter ; Lyssenko, Valeriya ; Quigley, Cristina Legido ; Groop, Leif ; Thorens, Bernard ; Franks, Paul W ; Ibberson, Mark ; Rutter, Guy A ; Beulens, Joline Wj ; 't Hart, Leen M ; Pearson, Ewan R. / Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study. I: Diabetes. 2021.

Bibtex

@article{7ccc1c21de0b4e13b4a8b1090865d33f,
title = "Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes: an IMIRHAPSODY Study",
abstract = "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.",
author = "Slieker, {Roderick C} and Donnelly, {Louise A} and Hugo Fitipaldi and Bouland, {Gerard A} and Giordano, {Giuseppe N} and Mikael {\AA}kerlund and Gerl, {Mathias J} and Emma Ahlqvist and Ashfaq Ali and Iulian Dragan and Petra Elders and Andreas Festa and Hansen, {Michael K} and {van der Heijden}, {Amber A} and Aly, {Dina Mansour} and Min Kim and Dmitry Kuznetsov and Florence Mehl and Christian Klose and Kai Simons and Imre Pavo and Pullen, {Timothy J} and Tommi Suvitaival and Asger Wretlind and Peter Rossing and Valeriya Lyssenko and Quigley, {Cristina Legido} and Leif Groop and Bernard Thorens and Franks, {Paul W} and Mark Ibberson and Rutter, {Guy A} and Beulens, {Joline Wj} and {'t Hart}, {Leen M} and Pearson, {Ewan R}",
note = "{\textcopyright} 2021 by the American Diabetes Association.",
year = "2021",
month = aug,
day = "10",
doi = "10.2337/db20-1281",
language = "English",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",

}

RIS

TY - JOUR

T1 - Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes

T2 - an IMIRHAPSODY Study

AU - Slieker, Roderick C

AU - Donnelly, Louise A

AU - Fitipaldi, Hugo

AU - Bouland, Gerard A

AU - Giordano, Giuseppe N

AU - Åkerlund, Mikael

AU - Gerl, Mathias J

AU - Ahlqvist, Emma

AU - Ali, Ashfaq

AU - Dragan, Iulian

AU - Elders, Petra

AU - Festa, Andreas

AU - Hansen, Michael K

AU - van der Heijden, Amber A

AU - Aly, Dina Mansour

AU - Kim, Min

AU - Kuznetsov, Dmitry

AU - Mehl, Florence

AU - Klose, Christian

AU - Simons, Kai

AU - Pavo, Imre

AU - Pullen, Timothy J

AU - Suvitaival, Tommi

AU - Wretlind, Asger

AU - Rossing, Peter

AU - Lyssenko, Valeriya

AU - Quigley, Cristina Legido

AU - Groop, Leif

AU - Thorens, Bernard

AU - Franks, Paul W

AU - Ibberson, Mark

AU - Rutter, Guy A

AU - Beulens, Joline Wj

AU - 't Hart, Leen M

AU - Pearson, Ewan R

N1 - © 2021 by the American Diabetes Association.

PY - 2021/8/10

Y1 - 2021/8/10

N2 - 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.

AB - 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.

U2 - 10.2337/db20-1281

DO - 10.2337/db20-1281

M3 - Journal article

C2 - 34376475

JO - Diabetes

JF - Diabetes

SN - 0012-1797

ER -

ID: 67592580