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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • 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 Perry
  • Simone P Rauh
  • Martin Ridderstråle
  • Harriet J A Teare
  • E Louise Thomas
  • Andrea Tura
  • drb459, drb459
  • Tom White
  • Jerzy Adamski
  • Jimmy D Bell
  • Joline W Beulens
  • Brunak, Søren
  • Emmanouil T Dermitzakis
  • Philippe Froguel
  • Gary Frost
  • Ramneek Gupta
  • Hansen, Torben
  • Andrew Hattersley
  • Bernd Jablonka
  • Jane Kaye
  • Markku Laakso
  • Timothy J McDonald
  • Pedersen, Oluf Borbye
  • Jochen M Schwenk
  • Imre Pavo
  • Andrea Mari
  • Mark I McCarthy
  • Hartmut Ruetten
  • Mark Walker
  • Ewan Pearson
  • Paul W Franks
  • IMI-DIRECT consortium

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.

Udgave nummer9
Sider (fra-til)1601-1615
StatusUdgivet - 2019

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