Diabetes Research on Patient Stratification (DIRECT)

DIabetes REsearCh on Patient straTification

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).

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes

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).

• Study Type: Observational
• Enrollment (Actual): 3049

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

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

Description

Study 1

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

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

Inclusion Criteria:

• 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:

• 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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glycemic deterioration	Change in glucose (or HbA1c) over time and/or progression to anti diabetic medications/insulin	Up to 10 years follow-up

Collaborators and Investigators

• Sponsor: Lund University
• Investigators: Principal Investigator: Ewan Pearson, FRCP, University of Dundee; Principal Investigator: Paul W Franks, PhD, Lund University

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2012
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: January 21, 2019
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Microbiome; Prediabetes; Type 2 diabetes; Genome; Lifestyle; Glycaemic control; Proteome; Gene-environment interaction
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: IMIDIRECT_2012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No