Diabetes Research on Patient Stratification

NCT ID: NCT03814915

Last Updated: 2020-01-18

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 3049 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-10-15
• Study Completion Date: 2019-07-31

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).

Detailed Description

There are two multicentre prospective cohort studies within the glycaemic deterioration work package of IMI DIRECT (WP2). These two cohorts are designed to address the area of glycaemic deterioration by amassing data and biomaterials that will be used to discover novel biomarkers for glycaemic deterioration in people at high risk of developing type 2 diabetes (Study 1) and in those who have recently been diagnosed with the disease (Study 2).

Conditions

Type2 Diabetes

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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).

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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

• 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'

Exclusion Criteria

• 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
• Any other significant medical reason for exclusion as determined by the investigator

Study 2

• 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
• Any other significant medical reason for exclusion as determined by the investigator

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lund University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ewan Pearson, FRCP

Role: PRINCIPAL_INVESTIGATOR

University of Dundee

Paul W Franks, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University

References

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.

Reference Type: BACKGROUND

PMID: 24695864 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40665409 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32559194 (View on PubMed)

Other Identifiers

IMIDIRECT_2012

Identifier Type: -

Identifier Source: org_study_id