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; IMI-DIRECT consortium

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^*, Paul W Franks, IMI-DIRECT consortium

^*Corresponding author for this work

Disease Systems Biology Program

9 Citations (Scopus)

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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
Journal	Diabetologia
Volume	62
Issue number	9
Pages (from-to)	1601-1615
ISSN	0012-186X
DOIs	https://doi.org/10.1007/s00125-019-4906-1
Publication status	Published - 1 Sept 2019

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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., ... IMI-DIRECT consortium (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

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 › Journal article › Research › peer-review

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 & IMI-DIRECT consortium 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

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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' 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.",

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} and {IMI-DIRECT consortium}",

year = "2019",

month = sep,

day = "1",

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

language = "English",

volume = "62",

pages = "1601--1615",

journal = "Diabetologia",

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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

AU - IMI-DIRECT consortium

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.

U2 - 10.1007/s00125-019-4906-1

DO - 10.1007/s00125-019-4906-1

M3 - Journal article

C2 - 31203377

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

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