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.
OBJECTIVE
The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.


METHODS
Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires.


CONCLUSIONS
DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.
Department of Clinical Sciences, Lund University, Genetic and Molecular Epidemiology, CRC, Skåne University Hospital Malmö, Building 91, Level 10, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.
Robert W
RW
Koivula
Alison
A
Heggie
Anna
A
Barnett
Henna
H
Cederberg
Tue H
TH
Hansen
Anitra D
AD
Koopman
Martin
M
Ridderstråle
Femke
F
Rutters
Henrik
H
Vestergaard
Ramneek
R
Gupta
Sanna
S
Herrgård
Martijn W
MW
Heymans
Mandy H
MH
Perry
Simone
S
Rauh
Maritta
M
Siloaho
Harriet J A
HJ
Teare
Barbara
B
Thorand
Jimmy
J
Bell
Søren
S
Brunak
Gary
G
Frost
Bernd
B
Jablonka
Andrea
A
Mari
Tim J
TJ
McDonald
Jacqueline M
JM
Dekker
Torben
T
Hansen
Andrew
A
Hattersley
Markku
M
Laakso
Oluf
O
Pedersen
Veikko
V
Koivisto
Hartmut
H
Ruetten
Mark
M
Walker
Ewan
E
Pearson
Paul W
PW
Franks
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011446:Prospective Studies
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents