Diabetes Research on Patient Stratification

NCT03814915 | Completed

• 1 other identifier: IMIDIRECT_2012
• Study Type: observational
• Target: 3,049
• Locations: 0 countries
• Sites: N/A

Brief Summary

The overarching goal of the IMI DIRECT (Innovative Medicines Initiative Diabetes Research on Patient Stratification) Consortium is the identification of biomarkers that aid therapeutic targeting in prediabetes (Study 1) or early onset type 2 diabetes (Study 2).

Conditions

Type2 Diabetes

Keywords

Gene-environment interaction; Genome; Glycaemic control; Lifestyle; Microbiome; Prediabetes; Proteome; Type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• Glycemic deterioration

  Change in glucose (or HbA1c) over time and/or progression to anti diabetic medications/insulin

  Up to 10 years follow-up

Study Arms (2)

Study 1 - Prediabetes

The primary objective of Study 1 is to collect biosamples and information that might yield novel, predictive biomarkers for glycaemic deterioration in non-diabetic high-risk participants. Participants in Study 1 were recruited from existing prospective cohort studies in or around each of the following European cities: Malmö, Sweden (Malmö Diet and Cancer Study); Amsterdam, The Netherlands (Hoorn Study); Copenhagen, Denmark (Inter99); and Kuopio, Finland (METSIM). A clinically practicable screening tool (DIRECT-DETECT) was used to identify at-risk participants from existing cohort studies, who were then recruited into this new prospective cohort study (Study 1).

Study 2- Diabetic

The primary objective of Study 2 is to collect biosamples and information that might yield novel, predictive biomarkers for glycaemic deterioration in people who have recently been diagnosed with type 2 diabetes. Participants in Study 2 of DIRECT are recruited from or nearby each of the following European cities: Malmö, Sweden; Amsterdam, the Netherlands; Copenhagen, Denmark; Exeter, UK; Newcastle, UK; Dundee, UK. Potential participants are recruited through targeted searches of existing databases and research registers combined with person-to-person contact at educational clinics and through routine retinal screening programmes.

Eligibility Criteria

• Age: 35 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

White European (self-report of parental ethnicity), Age ≥35 and \<75 years

You may qualify if:

• No treatment with insulin-sensitising, glucose-lowering or other antidiabetic drugs
• Fasting capillary blood glucose \<10 mmol/l at baseline
• White European (self-report of parental ethnicity)
• Age ≥35 and \<75 years

You may not qualify if:

• Diagnosed diabetes of any type, HbA1c ≥6.5% (48 mmol/mol) or fasting plasma glucose ≥7.0 mmol/l or 2 h plasma glucose \>11.0 mmol/l previously
• For women, pregnancy, lactation or plans to conceive within the study period
• Use of a pacemaker
• Study 2
• Patients diagnosed with type 2 diabetes not less than 6 months and not more than 24 months before baseline examination
• Management by lifestyle with or without metformin therapy
• All HbA1c \<7.6% (\<60 mmol/mol) within previous 3 months
• White European
• Age ≥35 and \<75
• Estimated GFR \>50 ml/min'
• Type 1 diabetes
• A previous HbA1c \>9.0% (\>75 mmol/mol)
• Prior treatment with insulin or an oral hypoglycaemic agent other than metformin
• BMI \<20 or \>50 kg/m2
• Pregnancy, lactation or plans to conceive within the study period

Sponsors & Collaborators

• Lund University: lead

Related Publications (3)

• Koivula RW, Heggie A, Barnett A, Cederberg H, Hansen TH, Koopman AD, Ridderstrale M, Rutters F, Vestergaard H, Gupta R, Herrgard S, Heymans MW, Perry MH, Rauh S, Siloaho M, Teare HJ, Thorand B, Bell J, Brunak S, Frost G, Jablonka B, Mari A, McDonald TJ, Dekker JM, Hansen T, Hattersley A, Laakso M, Pedersen O, Koivisto V, Ruetten H, Walker M, Pearson E, Franks PW; DIRECT Consortium. Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia. 2014 Jun;57(6):1132-42. doi: 10.1007/s00125-014-3216-x. Epub 2014 Apr 4.

  PMID: 24695864 BACKGROUND

• Lyu L, Fan Y, Vogt JK, Clos-Garcia M, Bonnefond A, Pedersen HK, Dutta A, Koivula R, Sharma S, Allin KH, Brorsson C, Cederberg H, Chabanova E, De Masi F, Dermitzakis E, Elders PJ, Blom MT, Hollander M, Eriksen R, Forgie I, Frost G, Giordano GN, Grallert H, Haid M, Hansen TH, Jablonka B, Kokkola T, Mahajan A, Mari A, McDonald TJ, Musholt PB, Pavo I, Prehn C, Ridderstrale M, Ruetten H, Hart LM', Schwenk JM, Stankevic E, Thomsen HS, Vangipurapu J, Vestergaard H, Vinuela A, Walker M, Hansen T, Linneberg A, Nielsen HB, Brunak S, McCarthy MI, Froguel P, Adamski J, Franks PW, Laakso M, Beulens JWJ, Pearson E, Pedersen O. The dynamics of the gut microbiota in prediabetes during a four-year follow-up among European patients-an IMI-DIRECT prospective study. Genome Med. 2025 Jul 15;17(1):78. doi: 10.1186/s13073-025-01508-7.

  PMID: 40665409 DERIVED

• Atabaki-Pasdar N, Ohlsson M, Vinuela A, Frau F, Pomares-Millan H, Haid M, Jones AG, Thomas EL, Koivula RW, Kurbasic A, Mutie PM, Fitipaldi H, Fernandez J, Dawed AY, Giordano GN, Forgie IM, McDonald TJ, Rutters F, Cederberg H, Chabanova E, Dale M, Masi F, Thomas CE, Allin KH, Hansen TH, Heggie A, Hong MG, Elders PJM, Kennedy G, Kokkola T, Pedersen HK, Mahajan A, McEvoy D, Pattou F, Raverdy V, Haussler RS, Sharma S, Thomsen HS, Vangipurapu J, Vestergaard H, 't Hart LM, Adamski J, Musholt PB, Brage S, Brunak S, Dermitzakis E, Frost G, Hansen T, Laakso M, Pedersen O, Ridderstrale M, Ruetten H, Hattersley AT, Walker M, Beulens JWJ, Mari A, Schwenk JM, Gupta R, McCarthy MI, Pearson ER, Bell JD, Pavo I, Franks PW. Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts. PLoS Med. 2020 Jun 19;17(6):e1003149. doi: 10.1371/journal.pmed.1003149. eCollection 2020 Jun.

  PMID: 32559194 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood Omics: Fasting blood samples taken for genomic, transcriptomic, proteomic and metabolomic assessments. Microbiome Urine Toenail clippings

MeSH Terms

Conditions

Prediabetic State; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ewan Pearson, FRCP

  University of Dundee

  PRINCIPAL INVESTIGATOR

• Paul W Franks, PhD

  Lund University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2019
• First Posted: January 24, 2019
• Study Start: October 15, 2012
• Primary Completion: July 31, 2019
• Study Completion: July 31, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share