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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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; Viñuela, Ana; Heggie, Alison; Giordano, Giuseppe N; Hansen, Tue H.; Hudson, Michelle; Koopman, Anitra D M; Rutters, Femke; Siloaho, Maritta; Allin, Kristine H.; Brage, Søren; Brorsson, Caroline A; Dawed, Adem Y; De Masi, Federico; Groves, Christopher J; Kokkola, Tarja; Mahajan, Anubha; Perry, Mandy H; Rauh, Simone P; Ridderstråle, Martin; Teare, Harriet J A; Thomas, E Louise; Tura, Andrea; Vestergaard, Henrik; White, Tom; Adamski, Jerzy; Bell, Jimmy D; Beulens, Joline W; Brunak, Søren; Dermitzakis, Emmanouil T; Froguel, Philippe; Frost, Gary; Gupta, Ramneek; Hansen, Torben; Hattersley, Andrew; Jablonka, Bernd; Kaye, Jane; Laakso, Markku; McDonald, Timothy J; Pedersen, Oluf; Schwenk, Jochen M; Pavo, Imre; Mari, Andrea; McCarthy, Mark I; Ruetten, Hartmut; Walker, Mark; Pearson, Ewan; Franks, Paul W; IMI-DIRECT consortium.
In: Diabetologia, Vol. 62, No. 9, 2019, p. 1601-1615.Research output: Contribution to journal › Journal article › Research › peer-review
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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
AU - IMI-DIRECT consortium
PY - 2019
Y1 - 2019
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
VL - 62
SP - 1601
EP - 1615
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 9
ER -
ID: 222712567