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, Søren 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, Søren 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

*Corresponding author for this work

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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.

Original languageEnglish
JournalDiabetologia
Volume62
Issue number9
Pages (from-to)1601-1615
ISSN0012-186X
DOIs
Publication statusPublished - 2019

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