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Diabetologia. 2019 Sep;62(9):1601-1615. doi: 10.1007/s00125-019-4906-1. Epub 2019 Jun 15.

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.

Author information

1
Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, CRC, Skåne University Hospital Malmö, Building 91, Level 10, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.
2
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
3
Population Health & Genomics, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, UK.
4
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
5
Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Geneva, Switzerland.
6
Swiss Institute of Bioinformatics, Geneva, Switzerland.
7
Institute of Cellular Medicine (Diabetes), Newcastle University, Newcastle upon Tyne, UK.
8
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.
9
NIHR Exeter Clinical Research Facility, University of Exeter Medical School, Exeter, UK.
10
Department of Epidemiology and Biostatistics, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
11
Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
12
Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospital, the Capital Region, Copenhagen, Denmark.
13
MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
14
Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
15
Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark.
16
Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
17
Department of Clinical Sciences, Clinical Obesity, Skåne University Hospital Malmö, Lund University, Malmö, Sweden.
18
Novo Nordisk A/S, Søborg, Denmark.
19
HeLEX, Nuffield Department of Population Health, University of Oxford, Old Road Campus, Headington, Oxford, UK.
20
Research Centre for Optimal Health, Department of Life Sciences, University of Westminster, London, UK.
21
Institute of Neurosciences, National Research Council, Padova, Italy.
22
Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
23
The Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark.
24
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
25
CNRS, Pasteur Institute of Lille, University of Lille, Lille, France.
26
Nutrition and Dietetics Research Group, Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, Hammersmith Campus, London, UK.
27
Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.
28
Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt am Main, Germany.
29
Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, Stockholm, Sweden.
30
Eli Lilly Regional Operations GmbH, Vienna, Austria.
31
NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, UK.
32
Population Health & Genomics, Medical Research Institute, University of Dundee, Dundee, DD1 9SY, UK. e.z.pearson@dundee.ac.uk.
33
Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, CRC, Skåne University Hospital Malmö, Building 91, Level 10, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden. paul.franks@med.lu.se.
34
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. paul.franks@med.lu.se.
35
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. paul.franks@med.lu.se.
36
Department of Public Health & Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden. paul.franks@med.lu.se.

Abstract

AIMS/HYPOTHESIS:

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).

METHODS:

From 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.

RESULTS:

Using 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 ± 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.

CONCLUSIONS/INTERPRETATION:

The 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.

KEYWORDS:

Diet; Ectopic fat; Genome; Glycaemic control; Insulin secretion; Insulin sensitivity; Personalised medicine; Physical activity; Prediabetes; Type 2 diabetes

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