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.

Diabetologia 2019 Sep 15;62(9):1601-1615. Epub 2019 Jun 15.

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.

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/m; 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/m; 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.

Download full-text PDF

Source Listing
September 2019
9 Reads
6.671 Impact Factor

Publication Analysis

Top Keywords

glucose mmol/l
mmol/l 2 h
fasting glucose
type diabetes
kg/m fasting
years bmi
age years
prediabetes risk
cohort study
mmol/l final
2 h glucose
cohort prediabetes
baseline age
cohort participants
cent participants
follow-up examinations
cohort diabetes
participants cohort

Altmetric Statistics


(Supplied by CrossRef)
Article in Diabetes Res Clin Pract
NH Cho et al.
Diabetes Res Clin Pract 2018
Article in Diabetes Care
American Diabetes Association et al.
Diabetes Care 2011
Article in J Clin Invest
C Weyer et al.
J Clin Invest 1999
Article in Diabetes Metab
A Ringborg et al.
Diabetes Metab 2010
Article in Diabet Med
W Rathmann et al.
Diabet Med 2009
Article in Lancet Diabetes Endocrinol
E Ahlqvist et al.
Lancet Diabetes Endocrinol 2018
Article in Diabetologia
RW Koivula et al.
Diabetologia 2014
Article in Diabetes
A Stancakova et al.
Diabetes 2009
Article in Diabetologia
SA Hills et al.
Diabetologia 2004
Article in Int J Epidemiol
F Rutters et al.
Int J Epidemiol 2018
Article in Scand J Public Health
AI Christensen et al.
Scand J Public Health 2012

Similar Publications