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

Huvinen, Emilia ; Lahti, Jari ; Klemetti, Miira M. ; Bergman, Paula H. ; Räikkönen, Katri ; Orho-Melander, Marju LU ; Laivuori, Hannele and Koivusalo, Saila B. (2022) In Diabetologia 65(8). p.1291-1301
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... (More)

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.]

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diet, Genetic risk, Gene–environment interaction, Gestational diabetes, Lifestyle intervention, Physical activity, Polygenic risk score, Prevention, Type 2 diabetes
in
Diabetologia
volume
65
issue
8
pages
11 pages
publisher
Springer
external identifiers
  • pmid:35501401
  • scopus:85129248017
ISSN
0012-186X
DOI
10.1007/s00125-022-05712-7
language
English
LU publication?
yes
id
8bd942d4-845f-4d12-b85b-8eb630d79091
date added to LUP
2022-08-15 11:11:13
date last changed
2025-01-25 19:35:28
@article{8bd942d4-845f-4d12-b85b-8eb630d79091,
  abstract     = {{<p>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/m<sup>2</sup> 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<sub>1c</sub>) 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.]</p>}},
  author       = {{Huvinen, Emilia and Lahti, Jari and Klemetti, Miira M. and Bergman, Paula H. and Räikkönen, Katri and Orho-Melander, Marju and Laivuori, Hannele and Koivusalo, Saila B.}},
  issn         = {{0012-186X}},
  keywords     = {{Diet; Genetic risk; Gene–environment interaction; Gestational diabetes; Lifestyle intervention; Physical activity; Polygenic risk score; Prevention; Type 2 diabetes}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1291--1301}},
  publisher    = {{Springer}},
  series       = {{Diabetologia}},
  title        = {{Genetic risk of type 2 diabetes modifies the effects of a lifestyle intervention aimed at the prevention of gestational and postpartum diabetes}},
  url          = {{http://dx.doi.org/10.1007/s00125-022-05712-7}},
  doi          = {{10.1007/s00125-022-05712-7}},
  volume       = {{65}},
  year         = {{2022}},
}