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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
Lund Univ, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Dept Clin Sci,Diabet Ctr,CRC, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Sci Life Lab, Stockholm, Sweden..ORCID iD: 0000-0001-8141-8449
Lund Univ, Skane Univ Hosp Malmo, Genet & Mol Epidemiol Unit, Dept Clin Sci,Diabet Ctr,CRC, Bldg 91,Level 10,Jan Waldenstroms Gata 35, SE-20502 Malmo, Sweden.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Sect Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
2019 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, no 9, p. 1601-1615Article in journal (Refereed) Published
Abstract [en]

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 similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 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(2); 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(2); 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.

Place, publisher, year, edition, pages
SPRINGER , 2019. Vol. 62, no 9, p. 1601-1615
Keywords [en]
Diet, Ectopic fat, Genome, Glycaemic control, Insulin secretion, Insulin sensitivity, Personalised medicine, Physical activity, Prediabetes, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:kth:diva-257545DOI: 10.1007/s00125-019-4906-1ISI: 000478770300009PubMedID: 31203377Scopus ID: 2-s2.0-85067006221OAI: oai:DiVA.org:kth-257545DiVA, id: diva2:1354502
Note

QC 20190925

Available from: 2019-09-25 Created: 2019-09-25 Last updated: 2019-09-25Bibliographically approved

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Schwenk, Jochen M.

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