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Identification of biomarkers for glycaemic deterioration in type 2 diabetes
- Source :
- Slieker, R C, Donnelly, L A, Akalestou, E, Lopez-Noriega, L, Melhem, R, Güneş, A, Abou Azar, F, Efanov, A, Georgiadou, E, Muniangi-Muhitu, H, Sheikh, M, Giordano, G N, Åkerlund, M, Ahlqvist, E, Ali, A, Banasik, K, Brunak, S, Barovic, M, Bouland, G A, Burdet, F, Canouil, M, Dragan, I, Elders, P J M, Fernandez, C, Festa, A, Fitipaldi, H, Froguel, P, Gudmundsdottir, V, Gudnason, V, Gerl, M J, van der Heijden, A A, Jennings, L L, Hansen, M K, Kim, M, Leclerc, I, Klose, C, Kuznetsov, D, Mansour Aly, D, Mehl, F, Marek, D, Melander, O, Niknejad, A, Ottosson, F, Pavo, I, Duffin, K, Syed, S K, Shaw, J L, Cabrera, O, Pullen, T J, Simons, K, Solimena, M, Suvitaival, T, Wretlind, A, Rossing, P, Lyssenko, V, Legido Quigley, C, Groop, L, Thorens, B, Franks, P W, Lim, G E, Estall, J, Ibberson, M, Beulens, J W J, 't Hart, L M, Pearson, E R & Rutter, G A 2023, ' Identification of biomarkers for glycaemic deterioration in type 2 diabetes ', Nature Communications, vol. 14, 2533 . https://doi.org/10.1038/s41467-023-38148-7, Slieker, R C, Donnelly, L A, Akalestou, E, Lopez-Noriega, L, Melhem, R, Güneş, A, Abou Azar, F, Efanov, A, Georgiadou, E, Muniangi-Muhitu, H, Sheikh, M, Giordano, G N, Åkerlund, M, Ahlqvist, E, Ali, A, Banasik, K, Brunak, S R, Barovic, M, Bouland, G A, Burdet, F, Canouil, M, Dragan, I, Elders, P J M, Fernandez, C, Festa, A, Fitipaldi, H, Froguel, P, Gudmundsdottir, V, Gudnason, V, Gerl, M J, van der Heijden, A A, Jennings, L L, Hansen, M K, Kim, M, Leclerc, I, Klose, C, Kuznetsov, D, Mansour Aly, D, Mehl, F, Marek, D, Melander, O, Niknejad, A, Ottosson, F, Pavo, I, Duffin, K, Syed, S K, Shaw, J L, Cabrera, O, Pullen, T J, Simons, K, Solimena, M, Suvitaival, T, Wretlind, A, Rossing, P, Lyssenko, V, Legido Quigley, C, Groop, L, Thorens, B, Franks, P W, Lim, G E, Estall, J, Ibberson, M, Beulens, J W J, ’t Hart, L M, Pearson, E R & Rutter, G A 2023, ' Identification of biomarkers for glycaemic deterioration in type 2 diabetes ', Nature Communications, vol. 14, no. 1, 2533 . https://doi.org/10.1038/s41467-023-38148-7, Nature Communications, 14(1):2533. Nature Publishing Group UK
- Publication Year :
- 2023
-
Abstract
- We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
- Subjects :
- Male
Multidisciplinary
Blood Glucose/metabolism
Insulin/metabolism
General Physics and Astronomy
General Chemistry
Biomarkers/metabolism
Diabetes Mellitus, Type 2/metabolism
Lipids
General Biochemistry, Genetics and Molecular Biology
Extracellular Matrix Proteins/metabolism
Mice
Animals
Islets of Langerhans/metabolism
Cell Adhesion Molecules/metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Database :
- OpenAIRE
- Journal :
- Slieker, R C, Donnelly, L A, Akalestou, E, Lopez-Noriega, L, Melhem, R, Güneş, A, Abou Azar, F, Efanov, A, Georgiadou, E, Muniangi-Muhitu, H, Sheikh, M, Giordano, G N, Åkerlund, M, Ahlqvist, E, Ali, A, Banasik, K, Brunak, S, Barovic, M, Bouland, G A, Burdet, F, Canouil, M, Dragan, I, Elders, P J M, Fernandez, C, Festa, A, Fitipaldi, H, Froguel, P, Gudmundsdottir, V, Gudnason, V, Gerl, M J, van der Heijden, A A, Jennings, L L, Hansen, M K, Kim, M, Leclerc, I, Klose, C, Kuznetsov, D, Mansour Aly, D, Mehl, F, Marek, D, Melander, O, Niknejad, A, Ottosson, F, Pavo, I, Duffin, K, Syed, S K, Shaw, J L, Cabrera, O, Pullen, T J, Simons, K, Solimena, M, Suvitaival, T, Wretlind, A, Rossing, P, Lyssenko, V, Legido Quigley, C, Groop, L, Thorens, B, Franks, P W, Lim, G E, Estall, J, Ibberson, M, Beulens, J W J, 't Hart, L M, Pearson, E R & Rutter, G A 2023, ' Identification of biomarkers for glycaemic deterioration in type 2 diabetes ', Nature Communications, vol. 14, 2533 . https://doi.org/10.1038/s41467-023-38148-7, Slieker, R C, Donnelly, L A, Akalestou, E, Lopez-Noriega, L, Melhem, R, Güneş, A, Abou Azar, F, Efanov, A, Georgiadou, E, Muniangi-Muhitu, H, Sheikh, M, Giordano, G N, Åkerlund, M, Ahlqvist, E, Ali, A, Banasik, K, Brunak, S R, Barovic, M, Bouland, G A, Burdet, F, Canouil, M, Dragan, I, Elders, P J M, Fernandez, C, Festa, A, Fitipaldi, H, Froguel, P, Gudmundsdottir, V, Gudnason, V, Gerl, M J, van der Heijden, A A, Jennings, L L, Hansen, M K, Kim, M, Leclerc, I, Klose, C, Kuznetsov, D, Mansour Aly, D, Mehl, F, Marek, D, Melander, O, Niknejad, A, Ottosson, F, Pavo, I, Duffin, K, Syed, S K, Shaw, J L, Cabrera, O, Pullen, T J, Simons, K, Solimena, M, Suvitaival, T, Wretlind, A, Rossing, P, Lyssenko, V, Legido Quigley, C, Groop, L, Thorens, B, Franks, P W, Lim, G E, Estall, J, Ibberson, M, Beulens, J W J, ’t Hart, L M, Pearson, E R & Rutter, G A 2023, ' Identification of biomarkers for glycaemic deterioration in type 2 diabetes ', Nature Communications, vol. 14, no. 1, 2533 . https://doi.org/10.1038/s41467-023-38148-7, Nature Communications, 14(1):2533. Nature Publishing Group UK
- Accession number :
- edsair.doi.dedup.....fa1654ea5cf5cf5976c8684f5b8cb7ed