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

被引：20

作者：

Koivula, Robert W. ^{[1
,2
]}

Forgie, Ian M. ^{[3
]}

Kurbasic, Azra ^{[1
]}

Vinuela, Ana ^{[4
,5
,6
]}

Heggie, Alison ^{[7
]}

Giordano, Giuseppe N. ^{[1
]}

Hansen, Tue H. ^{[8
]}

Hudson, Michelle ^{[9
]}

Koopman, Anitra D. M. ^{[10
]}

Rutters, Femke ^{[10
]}

Siloaho, Maritta ^{[11
,12
]}

Allin, Kristine H. ^{[8
,13
]}

Brage, Soren ^{[14
,15
]}

Brorsson, Caroline A. ^{[16
]}

Dawed, Adem Y. ^{[3
]}

De Masi, Federico ^{[16
]}

Groves, Christopher J. ^{[2
]}

Kokkola, Tarja ^{[11
,12
]}

Mahajan, Anubha ^{[17
]}

Perry, Mandy H. ^{[9
]}

Rauh, Simone P. ^{[10
]}

Ridderstrale, Martin ^{[18
,19
]}

Teare, Harriet J. A. ^{[20
]}

Thomas, E. Louise ^{[21
]}

Tura, Andrea ^{[22
]}

Vestergaard, Henrik ^{[8
]}

White, Tom ^{[14
]}

Adamski, Jerzy ^{[23
]}

Bell, Jimmy D. ^{[21
]}

Beulens, Joline W. ^{[10
]}

Brunak, Soren ^{[16
,24
]}

Dermitzakis, Emmanouil T. ^{[4
,5
,6
]}

Froguel, Philippe ^{[25
,26
]}

Frost, Gary ^{[27
]}

Gupta, Ramneek ^{[16
]}

Hansen, Torben ^{[8
,15
]}

Hattersley, Andrew ^{[9
,28
]}

Jablonka, Bernd ^{[29
]}

Kaye, Jane ^{[20
]}

Laakso, Markku ^{[11
,12
]}

McDonald, Timothy J. ^{[9
]}

Pedersen, Oluf ^{[8
]}

Schwenk, Jochen M. ^{[30
]}

Pavo, Imre ^{[31
]}

Mari, Andrea ^{[22
]}

McCarthy, Mark I. ^{[2
,17
,32
]}

Ruetten, Hartmut ^{[29
]}

Walker, Mark ^{[7
]}

Pearson, Ewan ^{[3
]}

Franks, Paul W. ^{[1
,2
,33
,34
]}

机构：

[1] 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

[2] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

[3] Univ Dundee, Med Res Inst, Populat Hlth & Genom, Dundee DD1 9SY, Scotland

[4] Univ Geneva, Med Sch, Dept Genet Med & Dev, Geneva, Switzerland

[5] Univ Geneva, Inst Genet & Genom Geneva iGE3, Geneva, Switzerland

[6] Swiss Inst Bioinformat, Geneva, Switzerland

[7] Newcastle Univ, Inst Cellular Med Diabet, Newcastle Upon Tyne, Tyne & Wear, England

[8] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark

[9] Univ Exeter, Med Sch, NIHR Exeter Clin Res Facil, Exeter, Devon, England

[10] Vrije Univ Amsterdam, Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Epidemiol & Biostat, Amsterdam, Netherlands

[11] Univ Eastern Finland, Dept Med, Kuopio, Finland

[12] Kuopio Univ Hosp, Kuopio, Finland

[13] Bispebjerg & Frederiksberg Hosp, Dept Clin Epidemiol, Copenhagen, Denmark

[14] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England

[15] Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark

[16] Tech Univ Denmark, Dept Bio & Hlth Informat, Lyngby, Denmark

[17] Univ Oxford, Wellcome Ctr Human Genet, Oxford, England

[18] Lund Univ, Skane Univ Hosp Malmo, Clin Obes, Dept Clin Sci, Malmo, Sweden

[19] Novo Nordisk AS, Soborg, Denmark

[20] Univ Oxford, Nuffield Dept Populat Hlth, HeLEX, Old Rd Campus, Oxford, England

[21] Univ Westminster, Dept Life Sci, Res Ctr Optimal Hlth, London, England

[22] CNR, Inst Neurosci, Padua, Italy

[23] German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany

[24] Univ Copenhagen, Novo Nordisk Fdn, Ctr Prot Res, Copenhagen, Denmark

[25] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England

[26] Univ Lille, CNRS, Pasteur Inst Lille, Lille, France

[27] Imperial Coll London, Div Diabet Endocrinol & Metab, Dept Med, Nutr & Dietet Res Grp, Hammersmith Campus, London, England

[28] Univ Exeter, Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England

[29] Sanofi Aventis Deutschland GmbH R&D, Frankfurt, Germany

[30] KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Sci Life Lab, Stockholm, Sweden

[31] Eli Lilly Reg Operat GmbH, Vienna, Austria

[32] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford, England

[33] Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[34] Umea Univ, Sect Med, Dept Publ Hlth & Clin Med, Umea, Sweden

来源：

DIABETOLOGIA | 2019年 / 62卷 / 09期

基金：

瑞典研究理事会; 英国惠康基金;

关键词：

Diet; Ectopic fat; Genome; Glycaemic control; Insulin secretion; Insulin sensitivity; Personalised medicine; Physical activity; Prediabetes; Type; 2; diabetes; BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; INSULIN SENSITIVITY; COHORT PROFILE; FAT-CONTENT; DESIGN; TESTS; RESISTANCE; RELEASE; RISK;

D O I：

10.1007/s00125-019-4906-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 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.

引用

页码：1601 / 1615

页数：15

共 31 条

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