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

Robert W. Koivula, Ian M. Forgie, Azra Kurbasic, Ana Viñuela, Alison Heggie, Giuseppe N. Giordano, Tue H. Hansen, Michelle Hudson, Anitra D. M. Koopman, Femke Rutters, Maritta Siloaho, Kristine H. Allin, S. ren Brage, Caroline A. Brorsson, Adem Y. Dawed, Federico de Masi, Christopher J. Groves, Tarja Kokkola, Anubha Mahajan, Mandy H. PerrySimone P. Rauh, Martin Ridderstråle, Harriet J. A. Teare, E. Louise Thomas, Andrea Tura, Henrik Vestergaard, Tom White, Jerzy Adamski, Jimmy D. Bell, Joline W. Beulens, S. ren Brunak, Emmanouil T. Dermitzakis, Philippe Froguel, Gary Frost, Ramneek Gupta, Torben Hansen, Andrew Hattersley, Bernd Jablonka, Jane Kaye, Markku Laakso, Timothy J. McDonald, Oluf Pedersen, Jochen M. Schwenk, Imre Pavo, Andrea Mari, Mark I. McCarthy, Hartmut Ruetten, Mark Walker, Ewan Pearson, Paul W. Franks, IMI DIRECT Consortium

Research output: Contribution to journalArticleAcademicpeer-review


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.
Original languageEnglish
Pages (from-to)1601-1615
Number of pages15
Issue number9
Publication statusPublished - 1 Sep 2019

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