Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2022 Aug;65(8):1291-1301.
doi: 10.1007/s00125-022-05712-7. Epub 2022 Apr 30.

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

Emilia Huvinen  1 , Jari Lahti  2 , Miira M Klemetti  3 , Paula H Bergman  4 , Katri Räikkönen  2 , Marju Orho-Melander  5 , Hannele Laivuori  6   7   8   9 , Saila B Koivusalo  3   10
Affiliations
Randomized Controlled Trial

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

Emilia Huvinen et al. Diabetologia. 2022 Aug.

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.

Keywords: Diet; Genetic risk; Gene–environment interaction; Gestational diabetes; Lifestyle intervention; Physical activity; Polygenic risk score; Prevention; Type 2 diabetes.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Occurrence of GDM among women in the control and intervention groups according to their genetic risk of type 2 diabetes (tertiles of PRS), adjusted for age, smoking, years of education, parity and pre-pregnancy BMI. Error bars indicate 95% CI
Fig. 2
Fig. 2
Occurrence of glycaemic abnormalities (impaired fasting glucose, impaired glucose tolerance or type 2 diabetes) at 12 months postpartum among women in the control and intervention groups according to their genetic risk of type 2 diabetes (tertiles of PRS), adjusted for age, smoking, years of education, parity and pre-pregnancy BMI. Error bars indicate 95% CI
See this image and copyright information in PMC

References

    1. Saeedi M, Cao Y, Fadl H, Gustafson H, Simmons D. Increasing prevalence of gestational diabetes mellitus when implementing the IADPSG criteria: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2021;172:108642. doi: 10.1016/j.diabres.2020.108642. - DOI - PubMed
    1. Ornoy A, Becker M, Weinstein-Fudim L, Ergaz Z. Diabetes during pregnancy: a maternal disease complicating the course of pregnancy with long-term deleterious effects on the offspring. A clinical review. Int J Mol Sci. 2021;22(6):2965. doi: 10.3390/ijms22062965. - DOI - PMC - PubMed
    1. Lowe WL, Jr, Scholtens DM, Lowe LP, et al. Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity. J Am Med Assoc. 2018;320(10):1005–1016. doi: 10.1001/jama.2018.11628. - DOI - PMC - PubMed
    1. Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ. 2020;369:m1361. doi: 10.1136/bmj.m1361. - DOI - PMC - PubMed
    1. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343–1350. doi: 10.1056/NEJM200105033441801. - DOI - PubMed

Publication types

Associated data