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

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; Henrik Vestergaard; Tom White; Jerzy Adamski; Jimmy D. Bell; Joline W. Beulens; Søren Brunak; Emmanouil T. Dermitzakis; Philippe Froguel; Gary Frost; Ramneek Gupta; Torben Hansen; Andrew Hattersley; Bernd Jablonka; Jane Kaye; Markku Laakso; Timothy J. McDonald; Oluf Pedersen; Jochen M. Schwenk; Imre Pavo; Andrea Mari; Mark I. McCarthy; Hartmut Ruetten; Mark Walker; Ewan Pearson; Paul W. Franks

doi:10.1007/s00125-019-4906-1

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

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. PerrySimone P. Rauh, Martin Ridderstråle, Harriet J. A. Teare, E. Louise Thomas, Andrea Tura, Henrik Vestergaard, Tom White, Jerzy Adamski, Jimmy D. Bell, Joline W. Beulens, Søren Brunak, Emmanouil T. Dermitzakis, Philippe Froguel, Gary Frost, Ramneek Gupta, Torben Hansen, Andrew Hattersley, Bernd Jablonka, Jane Kaye, Markku Laakso, Timothy J. McDonald, Oluf Pedersen, Jochen M. Schwenk, Imre Pavo, Andrea Mari, Mark I. McCarthy, Hartmut Ruetten, Mark Walker, Ewan Pearson (Lead / Corresponding author), Paul W. Franks (Lead / Corresponding author),

Population Health and Genomics

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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.

Original language	English
Pages (from-to)	1601-1615
Number of pages	15
Journal	Diabetologia
Volume	62
Issue number	9
Early online date	15 Jun 2019
DOIs	https://doi.org/10.1007/s00125-019-4906-1
Publication status	Published - 1 Sept 2019

Keywords

Diet
Ectopic fat
Genome
Glycaemic control
Insulin secretion
Insulin sensitivity
Personalised medicine
Physical activity
Prediabetes
Type 2 diabetes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Final Published VersionFinal published version, 1.22 MBLicence: CC BY

Cite this

Koivula, R. W., Forgie, I. M., Kurbasic, A., Viñuela, A., Heggie, A., Giordano, G. N., Hansen, T. H., Hudson, M., Koopman, A. D. M., Rutters, F., Siloaho, M., Allin, K. H., Brage, S., Brorsson, C. A., Dawed, A. Y., De Masi, F., Groves, C. J., Kokkola, T., Mahajan, A. (2019). 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, 62(9), 1601-1615. https://doi.org/10.1007/s00125-019-4906-1

@article{e47e3c5a102f4cec9a0e28af899af97a,

title = "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",

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{\textquoteright} 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{\textquoteright} 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.",

keywords = "Diet, Ectopic fat, Genome, Glycaemic control, Insulin secretion, Insulin sensitivity, Personalised medicine, Physical activity, Prediabetes, Type 2 diabetes",

author = "Koivula, {Robert W.} and Forgie, {Ian M.} and Azra Kurbasic and Ana Vi{\~n}uela and Alison Heggie and Giordano, {Giuseppe N.} and Hansen, {Tue H.} and Michelle Hudson and Koopman, {Anitra D. M.} and Femke Rutters and Maritta Siloaho and Allin, {Kristine H.} and S{\o}ren Brage and Brorsson, {Caroline A.} and Dawed, {Adem Y.} and {De Masi}, Federico and Groves, {Christopher J.} and Tarja Kokkola and Anubha Mahajan and Perry, {Mandy H.} and Rauh, {Simone P.} and Martin Ridderstr{\aa}le and Teare, {Harriet J. A.} and Thomas, {E. Louise} and Andrea Tura and Henrik Vestergaard and Tom White and Jerzy Adamski and Bell, {Jimmy D.} and Beulens, {Joline W.} and S{\o}ren Brunak and Dermitzakis, {Emmanouil T.} and Philippe Froguel and Gary Frost and Ramneek Gupta and Torben Hansen and Andrew Hattersley and Bernd Jablonka and Jane Kaye and Markku Laakso and McDonald, {Timothy J.} and Oluf Pedersen and Schwenk, {Jochen M.} and Imre Pavo and Andrea Mari and McCarthy, {Mark I.} and Hartmut Ruetten and Mark Walker and Ewan Pearson and Franks, {Paul W.}",

note = "This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115317 (DIRECT), resources of which are composed of financial contribution from the European Union{\textquoteright}s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. RWK was funded by a STAR Award Novo Nordisk co-financed PhD fellowship. The work undertaken by PWF was supported in part by programme grants from the ERC-2015-CoG_NASCENT_681742 and the Swedish Research Council; strategic funding for Lund University Diabetes Centre, where some of the work described herein was performed, was provided by the Swedish Research Council, Strategic Research Area Exodiab, (Dnr 2009-1039), the Swedish Foundation for Strategic Research (IRC15-0067), the Swedish Research Council, Linnaeus grant (Dnr 349-2006-237). EP holds a Wellcome Trust Investigator award (grant reference 102820/Z/13/Z). Contributions to this work by SBru. were co-financed by the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001).",

year = "2019",

month = sep,

day = "1",

doi = "10.1007/s00125-019-4906-1",

language = "English",

volume = "62",

pages = "1601--1615",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "9",

}

Koivula, RW, Forgie, IM, Kurbasic, A, Viñuela, A, Heggie, A, Giordano, GN, Hansen, TH, Hudson, M, Koopman, ADM, Rutters, F, Siloaho, M, Allin, KH, Brage, S, Brorsson, CA, Dawed, AY, De Masi, F, Groves, CJ, Kokkola, T, Mahajan, A, Perry, MH, Rauh, SP, Ridderstråle, M, Teare, HJA, Thomas, EL, Tura, A, Vestergaard, H, White, T, Adamski, J, Bell, JD, Beulens, JW, Brunak, S, Dermitzakis, ET, Froguel, P, Frost, G, Gupta, R, Hansen, T, Hattersley, A, Jablonka, B, Kaye, J, Laakso, M, McDonald, TJ, Pedersen, O, Schwenk, JM, Pavo, I, Mari, A, McCarthy, MI, Ruetten, H, Walker, M, Pearson, E, Franks, PW 2019, '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, vol. 62, no. 9, pp. 1601-1615. https://doi.org/10.1007/s00125-019-4906-1

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. / Koivula, Robert W.; Forgie, Ian M.; Kurbasic, Azra et al.
In: Diabetologia, Vol. 62, No. 9, 01.09.2019, p. 1601-1615.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes

T2 - descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium

AU - Koivula, Robert W.

AU - Forgie, Ian M.

AU - Kurbasic, Azra

AU - Viñuela, Ana

AU - Heggie, Alison

AU - Giordano, Giuseppe N.

AU - Hansen, Tue H.

AU - Hudson, Michelle

AU - Koopman, Anitra D. M.

AU - Rutters, Femke

AU - Siloaho, Maritta

AU - Allin, Kristine H.

AU - Brage, Søren

AU - Brorsson, Caroline A.

AU - Dawed, Adem Y.

AU - De Masi, Federico

AU - Groves, Christopher J.

AU - Kokkola, Tarja

AU - Mahajan, Anubha

AU - Perry, Mandy H.

AU - Rauh, Simone P.

AU - Ridderstråle, Martin

AU - Teare, Harriet J. A.

AU - Thomas, E. Louise

AU - Tura, Andrea

AU - Vestergaard, Henrik

AU - White, Tom

AU - Adamski, Jerzy

AU - Bell, Jimmy D.

AU - Beulens, Joline W.

AU - Brunak, Søren

AU - Dermitzakis, Emmanouil T.

AU - Froguel, Philippe

AU - Frost, Gary

AU - Gupta, Ramneek

AU - Hansen, Torben

AU - Hattersley, Andrew

AU - Jablonka, Bernd

AU - Kaye, Jane

AU - Laakso, Markku

AU - McDonald, Timothy J.

AU - Pedersen, Oluf

AU - Schwenk, Jochen M.

AU - Pavo, Imre

AU - Mari, Andrea

AU - McCarthy, Mark I.

AU - Ruetten, Hartmut

AU - Walker, Mark

AU - Pearson, Ewan

AU - Franks, Paul W.

N1 - This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115317 (DIRECT), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. RWK was funded by a STAR Award Novo Nordisk co-financed PhD fellowship. The work undertaken by PWF was supported in part by programme grants from the ERC-2015-CoG_NASCENT_681742 and the Swedish Research Council; strategic funding for Lund University Diabetes Centre, where some of the work described herein was performed, was provided by the Swedish Research Council, Strategic Research Area Exodiab, (Dnr 2009-1039), the Swedish Foundation for Strategic Research (IRC15-0067), the Swedish Research Council, Linnaeus grant (Dnr 349-2006-237). EP holds a Wellcome Trust Investigator award (grant reference 102820/Z/13/Z). Contributions to this work by SBru. were co-financed by the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001).

PY - 2019/9/1

Y1 - 2019/9/1

N2 - 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.

AB - 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.

KW - Diet

KW - Ectopic fat

KW - Genome

KW - Glycaemic control

KW - Insulin secretion

KW - Insulin sensitivity

KW - Personalised medicine

KW - Physical activity

KW - Prediabetes

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=85067006221&partnerID=8YFLogxK

U2 - 10.1007/s00125-019-4906-1

DO - 10.1007/s00125-019-4906-1

M3 - Article

C2 - 31203377

AN - SCOPUS:85067006221

SN - 0012-186X

VL - 62

SP - 1601

EP - 1615

JO - Diabetologia

JF - Diabetologia

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Cite this

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

Stratified Medicine in Type 2 Diabetes: Insights from the Study of Drug Response (New Investigator Award)

Research output

Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Cite this