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"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"}, {"entity": "publication", "iuid": "91d79151cbc04b138ee2edacd6436a8d", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/91d79151cbc04b138ee2edacd6436a8d.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/91d79151cbc04b138ee2edacd6436a8d"}}, "title": "Correction to: The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.", "authors": [{"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "White", "given": "Tom", "initials": "T"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Beulens", "given": "Joline", "initials": "J"}, {"family": "Brage", "given": "S\u00f8ren", "initials": "S"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET"}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Frost", "given": "Gary", "initials": "G"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Hattersley", "given": "Andrew", "initials": "A"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM"}, {"family": "Teare", "given": "Harriet J A", "initials": "HJA"}, {"family": "Thomas", "given": "E Louise", "initials": "EL"}, {"family": "Vinuela", "given": "Ana", "initials": "A"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Pearson", "given": "Ewan", "initials": "E"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "IMI DIRECT Consortium", "given": "", "initials": ""}], "type": "published erratum", "published": "2021-01-00", "journal": {"title": "Diabetologia", "issn": "1432-0428", "volume": "64", "issue": "1", "pages": "260-261", "issn-l": "0012-186X"}, "abstract": "Unfortunately, 'Present address' was omitted from one of the addresses provided for Mark I. McCarthy (#26).", "doi": "10.1007/s00125-020-05311-4", "pmid": "33184701", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7852866"}, {"db": "pii", "key": "10.1007/s00125-020-05311-4"}], "notes": [], "created": "2026-08-20T06:38:46.550Z", "modified": "2026-08-20T06:38:46.565Z"}, {"entity": "publication", "iuid": "b278c460903745109e2e319080ac66b2", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b278c460903745109e2e319080ac66b2.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b278c460903745109e2e319080ac66b2"}}, "title": "Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study.", "authors": [{"family": "Obura", "given": "Morgan", "initials": "M"}, {"family": "Beulens", "given": "Joline W J", "initials": "JWJ", "orcid": "0000-0002-6788-5232", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e20a7d8bc053421187c08a4aa70ab559.json"}}, {"family": "Slieker", "given": "Roderick", "initials": "R"}, {"family": "Koopman", "given": "Anitra D M", "initials": "ADM"}, {"family": "Hoekstra", "given": "Trynke", "initials": "T"}, {"family": "Nijpels", "given": "Giel", "initials": "G"}, {"family": "Elders", "given": "Petra", "initials": "P"}, {"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Pavo", "given": "Imre", "initials": "I", "orcid": "0000-0002-2016-7049", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1691b459fdb84772b1e8595e8de617f3.json"}}, {"family": "Forgie", "given": "Ian", "initials": "I"}, {"family": "Jablonka", "given": "Bernd", "initials": "B"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Perry", "given": "Mandy H", "initials": "MH"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02cba70871df48eb84c17e82f95baae4.json"}}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"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": "Jurek", "initials": "J"}, {"family": "Teare", "given": "Harriet J A", "initials": "HJA"}, {"family": "Pearson", "given": "Ewan R", "initials": "ER"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "'t Hart", "given": "Leen M", "initials": "LM"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "IMI-DIRECT Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-11-30", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "11", "pages": "e0242360", "issn-l": "1932-6203"}, "abstract": "Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.\n\nThe study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.\n\nAt baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.\n\nDifferent glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.", "doi": "10.1371/journal.pone.0242360", "pmid": "33253307", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7703960"}, {"db": "pii", "key": "PONE-D-20-16974"}], "notes": [], "created": "2026-08-20T12:44:09.441Z", "modified": "2026-08-20T12:44:09.551Z"}, {"entity": "publication", "iuid": "0b538c90f0654190887107e8427b81de", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/0b538c90f0654190887107e8427b81de.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/0b538c90f0654190887107e8427b81de"}}, "title": "The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.", "authors": [{"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "White", "given": "Tom", "initials": "T"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Beulens", "given": "Joline", "initials": "J"}, {"family": "Brage", "given": "S\u00f8ren", "initials": "S"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET"}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Frost", "given": "Gary", "initials": "G"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Hattersley", "given": "Andrew", "initials": "A"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM"}, {"family": "Teare", "given": "Harriet J A", "initials": "HJA"}, {"family": "Thomas", "given": "E Louise", "initials": "EL"}, {"family": "Vinuela", "given": "Ana", "initials": "A"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Pearson", "given": "Ewan", "initials": "E"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "IMI DIRECT Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Diabetologia", "issn": "1432-0428", "volume": "63", "issue": "4", "pages": "744-756", "issn-l": "0012-186X"}, "abstract": "It is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N \u2264 920) or with recently diagnosed type 2 diabetes (cohort 2: N \u2264 435).\n\nWe defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively.\n\nThe TC and TC-PA models showed better fit than null models (TC: \u03c72 = 242, p = 0.004 and \u03c72 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: \u03c72 = 180, p = 0.041 and \u03c72 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle.\n\nThese analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.", "doi": "10.1007/s00125-019-05083-6", "pmid": "32002573", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7054368"}, {"db": "pii", "key": "10.1007/s00125-019-05083-6"}], "notes": [], "created": "2026-08-20T06:38:42.624Z", "modified": "2026-08-20T06:38:42.706Z"}, {"entity": "publication", "iuid": "67ba27f099f64f6b931017b40921250b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/67ba27f099f64f6b931017b40921250b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/67ba27f099f64f6b931017b40921250b"}}, "title": "Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study", "authors": [{"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N", "orcid": "0000-0001-7229-1888", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6a3b275f37d948a1af96477938ddfe5b.json"}}, {"family": "Ohlsson", "given": "Mattias", "initials": "M", "orcid": "0000-0003-1145-4297", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/4fd8fb1306ae4becbb494fca9ad667aa.json"}}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02cba70871df48eb84c17e82f95baae4.json"}}, {"family": "Frau", "given": "Francesca", "initials": "F"}, {"family": "Pomares-Millan", "given": "Hugo", "initials": "H", "orcid": "0000-0001-9245-4576", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/bfc3253ee46d47d7a37a94d1275501a0.json"}}, {"family": "Haid", "given": "Mark", "initials": "M"}, {"family": "Jones", "given": "Angus G", "initials": "AG"}, {"family": "Thomas", "given": "E Louise", "initials": "EL"}, {"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Mutie", "given": "Pascal M", "initials": "PM"}, {"family": "Fitipaldi", "given": "Hugo", "initials": "H"}, {"family": "Fernandez", "given": "Juan", "initials": "J"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Cederberg", "given": "Henna", "initials": "H"}, {"family": "Chabanova", "given": "Elizaveta", "initials": "E"}, {"family": "Dale", "given": "Matilda", "initials": "M"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE"}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Hong", "given": "Mun Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d12504acae5c4f31b83f75c3d7786cd4.json"}}, {"family": "Elders", "given": "Petra JM", "initials": "PJ"}, {"family": "Kennedy", "given": "Gwen", "initials": "G"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Pedersen", "given": "Helle Krogh", "initials": "HK"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "Pattou", "given": "Francois", "initials": "F"}, {"family": "Raverdy", "given": "Violeta", "initials": "V"}, {"family": "H\u00e4ussler", "given": "Ragna S", "initials": "RS"}, {"family": "Sharma", "given": "Sapna", "initials": "S"}, {"family": "Thomsen", "given": "Henrik S", "initials": "HS"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "\u2018t Hart", "given": "Leen M", "initials": "LM"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Brage", "given": "Soren", "initials": "S"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Frost", "given": "Gary", "initials": "G"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Beulens", "given": "Joline WJ", "initials": "JW"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/022e140799b6466ea123319c3d70c76e.json"}}, {"family": "Gupta", "given": "Ramneek", "initials": "R"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Pearson", "given": "Ewan R", "initials": "ER"}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}], "type": "posted-content", "published": "2020-02-11", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2020.02.10.20021147", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T09:55:58.853Z", "modified": "2026-08-20T09:55:59.055Z"}, {"entity": "publication", "iuid": "a596c6d360494748a589a2cb0b2c5aa1", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a596c6d360494748a589a2cb0b2c5aa1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a596c6d360494748a589a2cb0b2c5aa1"}}, "title": "Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.", "authors": [{"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A"}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Hudson", "given": "Michelle", "initials": "M"}, {"family": "Koopman", "given": "Anitra D M", "initials": "ADM"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Siloaho", "given": "Maritta", "initials": "M"}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Brage", "given": "S\u00f8ren", "initials": "S"}, {"family": "Brorsson", "given": "Caroline A", "initials": "CA"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Groves", "given": "Christopher J", "initials": "CJ"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Perry", "given": "Mandy H", "initials": "MH"}, {"family": "Rauh", "given": "Simone P", "initials": "SP"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Teare", "given": "Harriet J A", "initials": "HJA"}, {"family": "Thomas", "given": "E Louise", "initials": "EL"}, {"family": "Tura", "given": "Andrea", "initials": "A"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "White", "given": "Tom", "initials": "T"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Bell", "given": "Jimmy D", "initials": "JD"}, {"family": "Beulens", "given": "Joline W", "initials": "JW"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET"}, {"family": "Froguel", "given": "Philippe", "initials": "P"}, {"family": "Frost", "given": "Gary", "initials": "G"}, {"family": "Gupta", "given": "Ramneek", "initials": "R"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hattersley", "given": "Andrew", "initials": "A"}, {"family": "Jablonka", "given": "Bernd", "initials": "B"}, {"family": "Kaye", "given": "Jane", "initials": "J"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Pearson", "given": "Ewan", "initials": "E", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/e27e9e47f1cc4a969268eb5a65b8045b.json"}}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8263a26f474946de8b61a2080051d37b.json"}}, {"family": "IMI DIRECT Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2019-09-00", "journal": {"title": "Diabetologia", "issn": "1432-0428", "volume": "62", "issue": "9", "pages": "1601-1615", "issn-l": "0012-186X"}, "abstract": "Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).\n\nFrom a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at ~18 months (both cohorts) and at ~48 months (cohort 1) or ~36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe.\n\nUsing ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean \u00b1 SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m2; fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m2; fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l.\n\nThe IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.", "doi": "10.1007/s00125-019-4906-1", "pmid": "31203377", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6677872"}, {"db": "pii", "key": "10.1007/s00125-019-4906-1"}], "notes": [], "created": "2026-08-20T06:38:44.622Z", "modified": "2026-08-20T06:38:44.724Z"}, {"entity": "publication", "iuid": "2ead5ea6b1314b0ea33828665d478edb", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2ead5ea6b1314b0ea33828665d478edb.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2ead5ea6b1314b0ea33828665d478edb"}}, "title": "Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium", "authors": [{"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2ceb821c78774b9f8931463351046f1f.json"}}, {"family": "Forgie", "given": "Ian M", "initials": "IM"}, {"family": "Kurbasic", "given": "Azra", "initials": "A"}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02cba70871df48eb84c17e82f95baae4.json"}}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Hansen", "given": "Tue H", "initials": "TH", "orcid": "0000-0001-5948-8993", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/73418e2efdc1459483138da74b0abad6.json"}}, {"family": "Hudson", "given": "Michelle", "initials": "M"}, {"family": "Koopman", "given": "Anitra", "initials": "A"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Siloaho", "given": "Maritta", "initials": "M"}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Brage", "given": "S\u00f8ren", "initials": "S"}, {"family": "Brorsson", "given": "Caroline A", "initials": "CA"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY"}, {"family": "Masi", "given": "Federico De", "initials": "FD"}, {"family": "Groves", "given": "Christopher J", "initials": "CJ"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41b3d44662484e0289f07fa25d045cf4.json"}}, {"family": "Perry", "given": "Mandy H", "initials": "MH"}, {"family": "Rauh", "given": "Simone P", "initials": "SP"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Teare", "given": "Harriet J A", "initials": "HJA"}, {"family": "Thomas", "given": "Louise", "initials": "L"}, {"family": "Tura", "given": "Andrea", "initials": "A"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "White", "given": "Tom", "initials": "T", "orcid": "0000-0001-8456-0803", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f851cbeafad2485685a5a080649b5ddc.json"}}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Bell", "given": "Jimmy", "initials": "J"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Dekker", "given": "Jacqueline", "initials": "J"}, {"family": "Dermitzakis", "given": "Emmanouil T", "initials": "ET"}, {"family": "Froguel", "given": "Philippe", "initials": "P"}, {"family": "Frost", "given": "Gary", "initials": "G"}, {"family": "Gupta", "given": "Ramneek", "initials": "R"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hattersley", "given": "Andrew", "initials": "A"}, {"family": "Jablonka", "given": "Bernd", "initials": "B"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/022e140799b6466ea123319c3d70c76e.json"}}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/102c7e93640c43c9bbbedd1626adfd7b.json"}}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Pearson", "given": "Ewan", "initials": "E"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8263a26f474946de8b61a2080051d37b.json"}}], "type": "posted-content", "published": "2018-04-16", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/300244", "pmid": null, "labels": [], "xrefs": [], "notes": [], "created": "2026-08-20T11:10:01.566Z", "modified": "2026-08-20T11:10:01.671Z"}]}