{"entity": "researcher", "timestamp": "2026-08-20T21:26:59.742Z", "family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "affiliations": ["Department of Clinical and Biomedical Sciences, University of Exeter College of Medicine & Health, Exeter, EX25DW, United Kingdom."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a"}}, "publications": [{"entity": "publication", "iuid": "81125aa4de9c48f19f7693e284da1de9", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/81125aa4de9c48f19f7693e284da1de9.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/81125aa4de9c48f19f7693e284da1de9"}}, "title": "A Biological-Systems-Based Analyses Using Proteomic and Metabolic Network Inference Reveals Mechanistic Insights into Hepatic Lipid Accumulation: An IMI-DIRECT Study.", "authors": [{"family": "Atabaki", "given": "Natalie N", "initials": "NN"}, {"family": "Coral", "given": "Daniel E", "initials": "DE"}, {"family": "Pomares-Millan", "given": "Hugo", "initials": "H"}, {"family": "Smith", "given": "Kieran", "initials": "K"}, {"family": "Behjat", "given": "Harry H", "initials": "HH"}, {"family": "Koivula", "given": "Robert W", "initials": "RW"}, {"family": "Tura", "given": "Andrea", "initials": "A"}, {"family": "Miller", "given": "Hamish", "initials": "H"}, {"family": "Pinnick", "given": "Katherine", "initials": "K"}, {"family": "Agudelo", "given": "Leandro", "initials": "L", "orcid": "0000-0002-3951-9956", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b70c74f201804654a6b2cc1487421f20.json"}}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Brown", "given": "Andrew A", "initials": "AA"}, {"family": "Chabanova", "given": "Elizaveta", "initials": "E"}, {"family": "Chmura", "given": "Piotr J", "initials": "PJ"}, {"family": "Jacobsen", "given": "Ulrik P", "initials": "UP"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY"}, {"family": "Elders", "given": "Petra J M", "initials": "PJM"}, {"family": "Fernandez-Tajes", "given": "Juan J", "initials": "JJ"}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Haid", "given": "Mark", "initials": "M"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Hansen", "given": "Elizaveta L", "initials": "EL"}, {"family": "Jones", "given": "Angus G", "initials": "AG"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Kalamajski", "given": "Sebastian", "initials": "S"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "Muilwijk", "given": "Mirthe", "initials": "M"}, {"family": "Tsirigos", "given": "Konstantinos D", "initials": "KD"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J"}, {"family": "van Oort", "given": "Sabine", "initials": "S"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Beulens", "given": "Joline W", "initials": "JW"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S", "orcid": "0000-0003-0316-5866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/560f89e3ea56424fb96ca55aad9b9814.json"}}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Gupta", "given": "Ramneek", "initials": "R"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hart", "given": "Leen T", "initials": "LT"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a.json"}}, {"family": "Hodson", "given": "Leanne", "initials": "L"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF"}, {"family": "Merino", "given": "Jordi", "initials": "J"}, {"family": "Ohlsson", "given": "Mattias", "initials": "M"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/022e140799b6466ea123319c3d70c76e.json"}}, {"family": "Tomlinson", "given": "Jeremy", "initials": "J"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Yaghootkar", "given": "Hanieh", "initials": "H"}, {"family": "Karpe", "given": "Fredrik", "initials": "F"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/102c7e93640c43c9bbbedd1626adfd7b.json"}}, {"family": "Thomas", "given": "Elizabeth Louise", "initials": "EL", "orcid": "0000-0003-4235-4694", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b85b142cc9748669e6b24272efb4728.json"}}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Pearson", "given": "Ewan R", "initials": "ER", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e27e9e47f1cc4a969268eb5a65b8045b.json"}}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}], "type": "journal article", "published": "2025-06-02", "journal": {"title": "medRxiv", "issn-l": null}, "abstract": "To delineate organ-specific and systemic drivers of metabolic dysfunction-associated steatotic liver disease (MASLD), we applied integrative causal inference across clinical, imaging, and proteomic domains in individuals with and without type 2 diabetes (T2D).\n\nWe used Bayesian network analyses to quantify causal pathways linking adipose distribution, glycemia, and insulin dynamics with fatty liver using data from the IMI-DIRECT prospective cohort study. Measurements were made of glucose and insulin dynamics (using frequently-sampled metabolic challenge tests), MRI-derived abdominal and liver fat content, serological biomarkers, and Olink plasma proteomics from 331 adults with new-onset T2D and 964 adults free from diabetes at enrolment. The common protocols used in these two cohorts provided the opportunity for replication analyses to be performed. When the direction of the effect could not be determined with high probability through Bayesian networks, complementary two-sample Mendelian randomization (MR) was employed.\n\nHigh basal insulin secretion rate (BasalISR) was identified as the primary causal driver of liver fat accumulation in both diabetes and non-diabetes. Excess visceral adipose tissue (VAT) was bidirectionally associated with liver fat, indicating a self-reinforcing metabolic loop. Basal insulin clearance (Clinsb) worsened as a consequence of liver fat accumulation to a greater degree before the onset of T2D. Out of 446 analysed proteins, 34 mapped to these metabolic networks and 27 were identified in the non-diabetes network, 18 in the diabetes network, and 11 were common between the two networks. Key proteins directly associated with liver fat included GUSB, ALDH1A1, LPL, IGFBP1/2, CTSD, HMOX1, FGF21, AGRP, and ACE2. Sex-stratified analyses revealed distinct proteomic drivers: GUSB and LEP were most predictive of liver fat in females and males, respectively.\n\nBasal insulin hypersecretion is a modifiable, causal driver of MASLD, particularly prior to glycaemic decompensation. Our findings highlight a multifactorial, sex- and disease-stage-specific proteo-metabolic architecture of hepatic steatosis. Proteins such as GUSB, ALDH1A1, LPL, and IGFBPs warrant further investigation as potential biomarkers or therapeutic targets for MASLD prevention and treatment.", "doi": "10.1101/2025.06.02.25328773", "pmid": "40502600", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC12155020"}, {"db": "pii", "key": "2025.06.02.25328773"}], "notes": [], "created": "2026-08-20T11:05:58.807Z", "modified": "2026-08-20T11:05:58.916Z"}, {"entity": "publication", "iuid": "97dcb877641d4da1b812ef995b72d5d3", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/97dcb877641d4da1b812ef995b72d5d3.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/97dcb877641d4da1b812ef995b72d5d3"}}, "title": "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits.", "authors": [{"family": "Brown", "given": "Andrew A", "initials": "AA", "orcid": "0000-0002-8087-3033", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b690d27df56b44dc8a070e4265afc8ca.json"}}, {"family": "Fernandez-Tajes", "given": "Juan J", "initials": "JJ"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d12504acae5c4f31b83f75c3d7786cd4.json"}}, {"family": "Brorsson", "given": "Caroline A", "initials": "CA"}, {"family": "Koivula", "given": "Robert W", "initials": "RW"}, {"family": "Davtian", "given": "David", "initials": "D"}, {"family": "Dupuis", "given": "Th\u00e9o", "initials": "T"}, {"family": "Sartori", "given": "Ambra", "initials": "A"}, {"family": "Michalettou", "given": "Theodora-Dafni", "initials": "TD", "orcid": "0000-0003-2119-1099", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f0a44cd4ea604ce4a93b16870965dcc2.json"}}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Adam", "given": "Jonathan", "initials": "J"}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Caiazzo", "given": "Robert", "initials": "R", "orcid": "0000-0001-5383-0540", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/155b9c8799064e04be5118147542a25c.json"}}, {"family": "Cederberg", "given": "Henna", "initials": "H"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Elders", "given": "Petra J M", "initials": "PJM"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN", "orcid": "0000-0002-6719-6680", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dc30138be60e49d481bfc5f03a8fe61f.json"}}, {"family": "Haid", "given": "Mark", "initials": "M", "orcid": "0000-0001-6118-1333", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4398da6ddb245bdb982ac3a0b352c40.json"}}, {"family": "Hansen", "given": "Torben", "initials": "T", "orcid": "0000-0001-8748-3831", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9e9a365eccb44b28b293c7decc6f4b9f.json"}}, {"family": "Hansen", "given": "Tue H", "initials": "TH", "orcid": "0000-0001-5948-8993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/73418e2efdc1459483138da74b0abad6.json"}}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a.json"}}, {"family": "Heggie", "given": "Alison J", "initials": "AJ"}, {"family": "Howald", "given": "C\u00e9dric", "initials": "C"}, {"family": "Jones", "given": "Angus G", "initials": "AG", "orcid": "0000-0002-0883-7599", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb98d0951469460d8e87bbd7e71741db.json"}}, {"family": "Kokkola", "given": "Tarja", "initials": "T", "orcid": "0000-0002-3303-3912", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fc389880431a46e49fcbe0eae12908ea.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M", "orcid": "0000-0002-3394-7749", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/81c631c24b2e4c479ac6976eab7b1e88.json"}}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Mari", "given": "Andrea", "initials": "A", "orcid": "0000-0002-1436-5591", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3b7dd1ab06074d1188e40713d8807c48.json"}}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "Mourby", "given": "Miranda", "initials": "M"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Nilsson", "given": "Birgitte", "initials": "B"}, {"family": "Pattou", "given": "Francois", "initials": "F", "orcid": "0000-0001-8388-3766", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0769cc7e166943cb98978c45c12d749a.json"}}, {"family": "Penet", "given": "Deborah", "initials": "D"}, {"family": "Raverdy", "given": "Violeta", "initials": "V"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Romano", "given": "Luciana", "initials": "L"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Sharma", "given": "Sapna", "initials": "S"}, {"family": "Teare", "given": "Harriet", "initials": "H"}, {"family": "'t Hart", "given": "Leen", "initials": "L", "orcid": "0000-0003-4401-2938", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c36c8ed413ed4d6f975341fe511035e3.json"}}, {"family": "Tsirigos", "given": "Konstantinos D", "initials": "KD"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3090-269X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e2fa5c4f74894d6a833afd105ec72848.json"}}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8263a26f474946de8b61a2080051d37b.json"}}, {"family": "Frost", "given": "Gary", "initials": "G", "orcid": "0000-0003-0529-6325", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/894534933d064d1f802f1690ea56f162.json"}}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Jablonka", "given": "Bernd", "initials": "B"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Pavo", "given": "Imre", "initials": "I", "orcid": "0000-0002-2016-7049", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1691b459fdb84772b1e8595e8de617f3.json"}}, {"family": "Pedersen", "given": "Oluf", "initials": "O", "orcid": "0000-0002-3321-3972", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a0ef37542aea4e67a322b0d6179cd59e.json"}}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "DIRECT Consortium", "given": "", "initials": ""}, {"family": "Adamski", "given": "Jerzy", "initials": "J", "orcid": "0000-0001-9259-0199", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6871f2a0d4414a58be2e7f26a59d3ca9.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/022e140799b6466ea123319c3d70c76e.json"}}, {"family": "Pearson", "given": "Ewan R", "initials": "ER", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e27e9e47f1cc4a969268eb5a65b8045b.json"}}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET", "orcid": "0000-0002-9302-6490", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6683f17defc34cad9389fd7fef36aca4.json"}}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02cba70871df48eb84c17e82f95baae4.json"}}], "type": "journal article", "published": "2023-08-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "5062", "issn-l": "2041-1723"}, "abstract": "We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.", "doi": "10.1038/s41467-023-40569-3", "pmid": "37604891", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10442420"}, {"db": "pii", "key": "10.1038/s41467-023-40569-3"}], "notes": [], "created": "2026-08-20T08:52:44.576Z", "modified": "2026-08-20T08:52:45.407Z"}, {"entity": "publication", "iuid": "ca320476e9aa498aaac894559da40b92", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/ca320476e9aa498aaac894559da40b92.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/ca320476e9aa498aaac894559da40b92"}}, "title": "Author Correction: Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models.", "authors": [{"family": "Alles\u00f8e", "given": "Rosa Lundbye", "initials": "RL"}, {"family": "Lundgaard", "given": "Agnete Troen", "initials": "AT", "orcid": "0000-0001-7447-6560", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e6d31459d60f4ce789790f6a6ef62328.json"}}, {"family": "Hern\u00e1ndez Medina", "given": "Ricardo", "initials": "R", "orcid": "0000-0001-6373-2362", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ca886502c85a48b88ffca91c7bfd4199.json"}}, {"family": "Aguayo-Orozco", "given": "Alejandro", "initials": "A"}, {"family": "Johansen", "given": "Joachim", "initials": "J", "orcid": "0000-0001-7052-1870", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6632c093611e4773aa14b1e81d23e32d.json"}}, {"family": "Nissen", "given": "Jakob Nybo", "initials": "JN"}, {"family": "Brorsson", "given": "Caroline", "initials": "C"}, {"family": "Mazzoni", "given": "Gianluca", "initials": "G"}, {"family": "Niu", "given": "Lili", "initials": "L", "orcid": "0000-0003-4571-4368", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0bd02c00c9ed4bf6998b7d53a4869eaa.json"}}, {"family": "Biel", "given": "Jorge Hernansanz", "initials": "JH", "orcid": "0000-0002-3125-2951", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b4f7b4e611404a14babf48998278717b.json"}}, {"family": "Leal Rodr\u00edguez", "given": "Cristina", "initials": "C", "orcid": "0000-0002-3133-0630", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/191706530d834312a25dc1135308064c.json"}}, {"family": "Brasas", "given": "Valentas", "initials": "V"}, {"family": "Webel", "given": "Henry", "initials": "H"}, {"family": "Benros", "given": "Michael Eriksen", "initials": "ME", "orcid": "0000-0003-4939-9465", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/0d2caccd100b4dbcba0be788cdcafedc.json"}}, {"family": "Pedersen", "given": "Anders Gorm", "initials": "AG", "orcid": 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"https://publications-affiliated.scilifelab.se/researcher/06b17b204aaa442293ac0b9981b84b43.json"}}, {"family": "Bell", "given": "Jimmy", "initials": "J"}, {"family": "Thomas", "given": "E Louise", "initials": "EL", "orcid": "0000-0003-4235-4694", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9b85b142cc9748669e6b24272efb4728.json"}}, {"family": "Frost", "given": "Gary", "initials": "G", "orcid": "0000-0003-0529-6325", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/894534933d064d1f802f1690ea56f162.json"}}, {"family": "Thomsen", "given": "Henrik", "initials": "H"}, {"family": "Hansen", "given": "Elizaveta", "initials": "E"}, {"family": "Hansen", "given": "Tue Haldor", "initials": "TH", "orcid": "0000-0001-5948-8993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/73418e2efdc1459483138da74b0abad6.json"}}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "Muilwijk", "given": "Mirthe", "initials": "M"}, {"family": "Blom", "given": "Marieke T", "initials": "MT"}, {"family": "'t Hart", "given": "Leen M", "initials": "LM"}, {"family": "Pattou", "given": "Francois", "initials": "F"}, {"family": "Raverdy", "given": "Violeta", "initials": "V"}, {"family": "Brage", "given": "Soren", "initials": "S"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "Mourby", "given": "Miranda", "initials": "M"}, {"family": "Kaye", "given": "Jane", "initials": "J", "orcid": "0000-0002-7311-4725", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/119626aab80347b08e5143547fc8d921.json"}}, {"family": "Hattersley", "given": "Andrew", "initials": "A", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a.json"}}, {"family": "McDonald", "given": "Timothy", "initials": "T"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M", "orcid": "0000-0002-3270-9167", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ce961d525f784428b1b6cdd4d3ed0c1a.json"}}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Forgie", "given": "Ian", "initials": "I"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Pedersen", "given": "Oluf", "initials": "O", "orcid": "0000-0002-3321-3972", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a0ef37542aea4e67a322b0d6179cd59e.json"}}, {"family": "Hansen", "given": "Torben", "initials": "T", "orcid": "0000-0001-8748-3831", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9e9a365eccb44b28b293c7decc6f4b9f.json"}}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/022e140799b6466ea123319c3d70c76e.json"}}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Pearson", "given": "Ewan", "initials": "E"}, {"family": "Banasik", "given": "Karina", "initials": "K"}, {"family": "Rasmussen", "given": "Simon", "initials": "S", "orcid": "0000-0001-6323-9041", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/65dab4aefc624749a6b8d003bcd54200.json"}}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S", "orcid": "0000-0003-0316-5866", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/560f89e3ea56424fb96ca55aad9b9814.json"}}, {"family": "IMI DIRECT Consortium", "given": "", "initials": ""}], "type": "published erratum", "published": "2023-07-00", "journal": {"title": "Nat. Biotechnol.", "issn": "1546-1696", "volume": "41", "issue": "7", "pages": "1026", "issn-l": "1087-0156"}, "abstract": null, "doi": "10.1038/s41587-023-01805-9", "pmid": "37130959", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10344774"}, {"db": "pii", "key": "10.1038/s41587-023-01805-9"}], "notes": [], "created": "2026-08-20T08:59:30.416Z", "modified": "2026-08-20T08:59:31.137Z"}, {"entity": "publication", "iuid": "77910c659eba495088c76361a47a6739", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/77910c659eba495088c76361a47a6739.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/77910c659eba495088c76361a47a6739"}}, "title": "Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study.", "authors": [{"family": "Bizzotto", "given": "Roberto", "initials": "R", "orcid": "0000-0002-8251-1730", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8e59c1b67213459d9ade9f1dc87ea865.json"}}, {"family": "Jennison", "given": "Christopher", "initials": "C"}, {"family": "Jones", "given": "Angus G", "initials": "AG", "orcid": "0000-0002-0883-7599", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/fb98d0951469460d8e87bbd7e71741db.json"}}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Tura", "given": "Andrea", "initials": "A"}, {"family": "Kennedy", "given": "Gwen", "initials": "G"}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Thomas", "given": "E Louise", "initials": "EL"}, {"family": "Frost", "given": "Gary", "initials": "G", "orcid": "0000-0003-0529-6325", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/894534933d064d1f802f1690ea56f162.json"}}, {"family": "Eriksen", "given": "Rebeca", "initials": "R"}, {"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Brage", "given": "Soren", "initials": "S"}, {"family": "Kaye", "given": "Jane", "initials": "J"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/dfbb9bb951f04ed3ac56eb4890d3186a.json"}}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "'t Hart", "given": "Leen M", "initials": "LM"}, {"family": "Beulens", "given": "Joline W", "initials": "JW", "orcid": "0000-0002-4181-0937", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/26b2b48b79a942e8ab9cb7382585ce21.json"}}, {"family": "Elders", "given": "Petra", "initials": "P"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M", "orcid": "0000-0002-3270-9167", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ce961d525f784428b1b6cdd4d3ed0c1a.json"}}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Allin", "given": "Kristine H", "initials": "KH", "orcid": "0000-0002-6880-5759", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/57d2acb6ed9146908728b751c105a37c.json"}}, {"family": "Hansen", "given": "Torben", "initials": "T", "orcid": "0000-0001-8748-3831", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/9e9a365eccb44b28b293c7decc6f4b9f.json"}}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "Lundgaard", "given": "Agnete T", "initials": "AT"}, {"family": "Thomsen", "given": "Henrik S", "initials": "HS"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Tsirigos", "given": "Konstantinos D", "initials": "KD"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A"}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41b3d44662484e0289f07fa25d045cf4.json"}}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ", "orcid": "0000-0003-3559-6660", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/11b833983c5d4416bceac079dcee38d6.json"}}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8263a26f474946de8b61a2080051d37b.json"}}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Pearson", "given": "Ewan R", "initials": "ER", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e27e9e47f1cc4a969268eb5a65b8045b.json"}}, {"family": "Mari", "given": "Andrea", "initials": "A", "orcid": "0000-0002-1436-5591", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3b7dd1ab06074d1188e40713d8807c48.json"}}, {"family": "IMI DIRECT consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "Diabetes Care", "issn": "1935-5548", "volume": "44", "issue": "2", "pages": "511-518", "issn-l": null}, "abstract": "We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).\n\nA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), \u03b2-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.\n\nFaster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R 2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.\n\nDeteriorating insulin sensitivity and \u03b2-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, \u03b2-cell function, and insulin clearance may be relevant to prevent progression.", "doi": "10.2337/dc20-1567", "pmid": "33323478", "labels": [], "xrefs": [{"db": "pii", "key": "dc20-1567"}, {"db": "figshare", "key": "10.2337/figshare.13222205"}], "notes": [], "created": "2026-08-20T13:03:02.855Z", "modified": "2026-08-20T13:03:03.150Z"}]}