Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

Emilia Huvinen; Jari Lahti; Miira M. Klemetti; Paula H. Bergman; Katri Räikkönen; Marju Orho-Melander; Hannele Laivuori; Saila B. Koivusalo

doi:10.1007/s00125-022-05712-7

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

Emilia Huvinen, Jari Lahti, Miira M. Klemetti, Paula H. Bergman, Katri Räikkönen, Marju Orho-Melander, Hannele Laivuori, Saila B. Koivusalo

Tutkimustuotos: Artikkeli › Scientific › vertaisarvioitu

Abstrakti

Aims/hypothesis: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m² and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA_1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration: ClinicalTrials.gov identifier: NCT01698385 Graphical abstract: [Figure not available: see fulltext.]

Alkuperäiskieli	Englanti
Sivumäärä	11
Julkaisu	DIABETOLOGIA
Vuosikerta	65
Numero	8
DOI - pysyväislinkit	https://doi.org/10.1007/s00125-022-05712-7
Tila	Julkaistu - 2022
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

Jufo-taso 2

!!ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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10.1007/s00125-022-05712-7Lisenssi: CC BY

s00125-022-05712-7Final published version, 667 KBLisenssi: CC BY

https://urn.fi/URN:NBN:fi:tuni-202205275300Lisenssi: CC BY

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@article{03a105e9ae01421b927fe17beda1d436,

title = "Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes",

abstract = "Aims/hypothesis: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration: ClinicalTrials.gov identifier: NCT01698385 Graphical abstract: [Figure not available: see fulltext.]",

keywords = "Diet, Genetic risk, Gene–environment interaction, Gestational diabetes, Lifestyle intervention, Physical activity, Polygenic risk score, Prevention, Type 2 diabetes",

author = "Emilia Huvinen and Jari Lahti and Klemetti, {Miira M.} and Bergman, {Paula H.} and Katri R{\"a}ikk{\"o}nen and Marju Orho-Melander and Hannele Laivuori and Koivusalo, {Saila B.}",

note = "Funding Information: Open Access funding provided by University of Helsinki including Helsinki University Central Hospital. This study was funded by the Finnish Medical Foundation, the Alfred Kordelin Foundation, the Juho Vainio Foundation, the Ahokas Foundation, the Finnish Foundation for Cardiovascular Disease, the Academy of Finland, the Special State Subsidy for Health Science Research of Helsinki University Hospital, Samfundet Folkh{\"a}lsan, Finska L{\"a}kares{\"a}llskapet, the Viipuri Tuberculosis Foundation, the Finnish Diabetes Research Foundation, the State Provincial Office of Southern Finland, a health promotion grant from the Finnish Ministry of Social Affairs and Health (EU H2020-PHC-2014 DynaHealth grant number 633595) and the Social Insurance Institution of Finland. The funders did not have any role in designing or conducting the study, in the collection, management, analysis or interpretation of the data, or in the preparation, review or approval of the manuscript and the decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

doi = "10.1007/s00125-022-05712-7",

language = "English",

volume = "65",

journal = "DIABETOLOGIA",

issn = "0012-186X",

publisher = "Springer Verlag",

number = "8",

}

TY - JOUR

T1 - Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

AU - Huvinen, Emilia

AU - Lahti, Jari

AU - Klemetti, Miira M.

AU - Bergman, Paula H.

AU - Räikkönen, Katri

AU - Orho-Melander, Marju

AU - Laivuori, Hannele

AU - Koivusalo, Saila B.

N1 - Funding Information: Open Access funding provided by University of Helsinki including Helsinki University Central Hospital. This study was funded by the Finnish Medical Foundation, the Alfred Kordelin Foundation, the Juho Vainio Foundation, the Ahokas Foundation, the Finnish Foundation for Cardiovascular Disease, the Academy of Finland, the Special State Subsidy for Health Science Research of Helsinki University Hospital, Samfundet Folkhälsan, Finska Läkaresällskapet, the Viipuri Tuberculosis Foundation, the Finnish Diabetes Research Foundation, the State Provincial Office of Southern Finland, a health promotion grant from the Finnish Ministry of Social Affairs and Health (EU H2020-PHC-2014 DynaHealth grant number 633595) and the Social Insurance Institution of Finland. The funders did not have any role in designing or conducting the study, in the collection, management, analysis or interpretation of the data, or in the preparation, review or approval of the manuscript and the decision to submit the manuscript for publication. Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Aims/hypothesis: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration: ClinicalTrials.gov identifier: NCT01698385 Graphical abstract: [Figure not available: see fulltext.]

AB - Aims/hypothesis: The aim of this study was to assess the interaction between genetic risk and lifestyle intervention on the occurrence of gestational diabetes mellitus (GDM) and postpartum diabetes. Methods: The RADIEL study is an RCT aimed at prevention of GDM and postpartum diabetes through lifestyle intervention. Participants with a BMI ≥30 kg/m2 and/or prior GDM were allocated to intervention and control groups before pregnancy or in early pregnancy. The study visits took place every 3 months before pregnancy, once in each trimester, and at 6 weeks and 6 and 12 months postpartum. We calculated a polygenic risk score (PRS) based on 50 risk variants for type 2 diabetes. Results: Altogether, 516 participants provided genetic and GDM data. The PRS was associated with higher glycaemic levels (fasting glucose and/or HbA1c) and a lower insulin secretion index in the second and third trimesters and at 12 months postpartum, as well as with a higher occurrence of GDM and glycaemic abnormalities at 12 months postpartum (n = 356). There was an interaction between the PRS and lifestyle intervention (p=0.016 during pregnancy and p=0.024 postpartum) when analysing participants who did not have GDM at the first study visit during pregnancy (n = 386). When analysing women in tertiles according to the PRS, the intervention was effective in reducing the age-adjusted occurrence of GDM only among those with the highest genetic risk (OR 0.37; 95% CI 0.17, 0.82). The risk of glycaemic abnormalities at 12 months postpartum was reduced in the same group after adjusting additionally for BMI, parity, smoking and education (OR 0.35; 95% CI 0.13, 0.97). Conclusions/interpretation: Genetic predisposition to diabetes modifies the response to a lifestyle intervention aimed at prevention of GDM and postpartum diabetes. This suggests that lifestyle intervention may benefit from being tailored according to genetic risk. Clinical trial registration: ClinicalTrials.gov identifier: NCT01698385 Graphical abstract: [Figure not available: see fulltext.]

KW - Diet

KW - Genetic risk

KW - Gene–environment interaction

KW - Gestational diabetes

KW - Lifestyle intervention

KW - Physical activity

KW - Polygenic risk score

KW - Prevention

KW - Type 2 diabetes

U2 - 10.1007/s00125-022-05712-7

DO - 10.1007/s00125-022-05712-7

M3 - Article

AN - SCOPUS:85129248017

SN - 0012-186X

VL - 65

JO - DIABETOLOGIA

JF - DIABETOLOGIA

IS - 8

ER -

Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes

Abstrakti

Julkaisufoorumi-taso

!!ASJC Scopus subject areas

YK:n kestävän kehityksen tavoitteet

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