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

Genetic risk of type 2 diabetes modifies the association between lifestyle and glycemic health at 5 years postpartum among high-risk women

“…Contrary to our results, many studies,29–32 including our own during pregnancy and first postpartum year,19 have shown an association between a type 2 diabetes PRS and glycemic outcomes. Similar to our study, many studies have also addressed women with a history of GDM 30–32.…”

“…After adjusting for age, HLS was associated with reduced risk of glycemic abnormalities only among women at highest genetic risk of type 2 diabetes. This is well in line with our previous findings from pregnancy and the first postpartum year 19. In the total study sample, however, the HLS associated with health benefits such as a lower BMI and body fat percentage, highlighting the importance of supporting healthy lifestyle among all postpartum women.…”

“…DNA was extracted from blood samples of 537 participants with a Maxiprep kit (Qiagen, Valencia, California, USA) and our prior publication provides detailed information on the genetic methods 19. In 2014, we genotyped 336 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes, obesity, and hyperlipidemia.…”

“…After assessing the genetic risk of type 2 diabetes with a polygenic risk score (PRS),18 we detected an interaction both during pregnancy and the first postpartum year. The RADIEL lifestyle intervention was efficient in reducing the occurrence of GDM and glycemic abnormalities 1 year postpartum but only among the women at highest genetic risk 19…”

Progression to type 2 diabetes mellitus after gestational diabetes mellitus diagnosed by IADPSG criteria: Systematic review and meta-analysis

“…Our results indicated that even the milder degrees of gestational hyperglycemia diagnosed by the more stringent IADPSG criteria still had a higher risk of subsequent progression to T2DM and pre-diabetes. Genetic predisposition might be one possible contributor to the progression to T2DM after GDM as increasing evidence have indicated that GDM may share similar genetic susceptibilities with T2DM ( 23 – 26 ). Genome wide association studies (GWAS) and other studies have reported that several genetic variants (such as MTNR1B, TCF7L2, IGF2BP2, CDKAL1, GCK ) are associated with increased risk of both GDM and T2DM, suggesting that these conditions might have a shared genetic background ( 27 , 28 ).…”