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
Creators: name: Koivula, Robert W.
name: Forgie, Ian M.
name: Kurbasic, Azra
name: Viñuela, Ana
name: Heggie, Alison
name: Giordano, Giuseppe N.
name: Hansen, Tue H.
name: Hudson, Michelle
name: Koopman, Anitra D. M.
name: Rutters, Femke
name: Siloaho, Maritta
name: Allin, Kristine H.
name: Brage, Søren
name: Brorsson, Caroline A.
name: Dawed, Adem Y.
name: De Masi, Federico
name: Groves, Christopher J.
name: Kokkola, Tarja
name: Mahajan, Anubha
name: Perry, Mandy H.
name: Rauh, Simone P.
name: Ridderstråle, Martin
name: Teare, Harriet J. A.
name: Thomas, E. Louise
name: Tura, Andrea
name: Vestergaard, Henrik
name: White, Tom
name: Adamski, Jerzy
name: Bell, Jimmy D.
name: Beulens, Joline W.
name: Brunak, Søren
name: Dermitzakis, Emmanouil T.
name: Froguel, Philippe
name: Frost, Gary
name: Gupta, Ramneek
name: Hansen, Torben
name: Hattersley, Andrew
name: Jablonka, Bernd
name: Kaye, Jane
name: Laakso, Markku
name: McDonald, Timothy J.
name: Pedersen, Oluf
name: Schwenk, Jochen M.
name: Pavo, Imre
name: Mari, Andrea
name: McCarthy, Mark I.
name: Ruetten, Hartmut
name: Walker, Mark
name: Pearson, Ewan
name: Franks, Paul W.
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: Article
Diet
Ectopic fat
Genome
Glycaemic control
Insulin secretion
Insulin sensitivity
Personalised medicine
Physical activity
Prediabetes
Type 2 diabetes

description: 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.