Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program

Chen, Yuhang; Liu, Huikun; Wang, Leishen; Zhou, Tao; Liang, Zhaoxia; Li, Weiqin; Shang, Xiaoyun; Leng, Junhong; Shen, Yun; Hu, Gang; Qi, Lü

doi:10.1093/ajcn/nqz121

Cited by 12 publications

(8 citation statements)

References 47 publications

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“…In one randomized study, women with prior GDM and a CDKAL1 risk variant received more benefit from the lifestyle intervention 17. Also MC4R has shown an interaction with lifestyle intervention on changes in fasting insulin and HOMA-IR 1–3 years postpartum: again, individuals with the risk allele responded to a lifestyle intervention with improvements in insulin resistance 39. In the RADIEL study, 5 years postpartum lifestyle was associated with better glycemic health only among women with prepregnancy obesity 20.…”

Section: Discussionmentioning

confidence: 99%

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

Tieu,

Koivusalo,

Lahti

et al. 2024

BMJ Open Diab Res Care

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IntroductionLifestyle interventions are effective in preventing type 2 diabetes, but genetic background may influence the individual response. In the Finnish gestational diabetes prevention study, RADIEL, lifestyle intervention during pregnancy and first postpartum year was effective in preventing gestational diabetes (GDM) and postpartum glycemic abnormalities only among women at highest genetic risk of type 2 diabetes. This study aimed to assess whether still 5 years postpartum the genetic risk modifies the association between lifestyle and glycemic health.Research design and methodsThe RADIEL study (randomized controlled trial) aimed to prevent GDM with a lifestyle intervention among high-risk women (body mass index ≥30 kg/m2and/or prior GDM). The follow-up study 5 years postpartum included anthropometric measurements, laboratory assessments, device-measured physical activity (PA), and questionnaires. A Healthy Lifestyle Score (HLS) indicated adherence to lifestyle goals (PA, diet, smoking) and a polygenic risk score (PRS) based on 50 type 2 diabetes risk alleles depicted the genetic risk.ResultsAltogether 314 women provided genetic and glycemic data 5 years postpartum. The PRS for type 2 diabetes was not associated with glycemic abnormalities, nor was HLS in the total study sample. There was, however, an interaction between HLS and type 2 diabetes PRS on glycemic abnormalities (p=0.03). When assessing the association between HLS and glycemic abnormalities in PRS tertiles, HLS was associated with reduced risk of glycemic abnormalities only among women at the highest genetic risk (p=0.008).ConclusionsThese results extend our previous findings from pregnancy and first postpartum year demonstrating that still at 5 years postpartum, healthy lifestyle is associated with a lower risk of prediabetes/diabetes only among women at the highest genetic risk of type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

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

Tieu,

Koivusalo,

Lahti

et al. 2024

BMJ Open Diab Res Care

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“…Another study showed that the relationship between MC4R 17782313rs polymorphism and type 2 diabetes depends on diet. In fact, people with a C-risk allele had a lower risk of type 2 diabetes with less adherence to the Mediterranean dietary pattern, whilst people with a high adherence to the Mediterranean dietary pattern had a lower risk of type 2 diabetes [73]. Yilmaz et al (2015) examined the association between MC4R rs17782313 polymorphism of overeating and depression, and found that BMI was associated with the rs17782313 C allele.…”

Section: Model 1 Is Considered As An Adjusted Modelmentioning

confidence: 99%

The interaction between MC4R gene variant (rs17782313) and dominant dietary patterns on depression in obese and overweight women: a cross sectional study

et al. 2023

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Background Previous studies have shown that the minor allele (C allele) for melanocortin 4 receptor (MC4R) rs17782313 may be associated with depressed mood. Moreover, dietary patterns have potentially adverse effects on depression. This study investigates the interactions between the MC4R gene variant (rs17782313) and dietary patterns on depression among Iranian obese and overweight women. Methods A total of 289 Iranian overweight and obese women, aged 18–50 years, were enrolled in this cross-sectional study. Biochemical, anthropometric, and body composition indices were assessed in all participants. Moreover, MC4R rs17782313, by the restriction fragment length polymorphism (PCR-RFLP) method, and depression, using the 21-item Depression Anxiety Stress Scales (DASS) questionnaire, were assessed. Food intakes were assessed by completing a 147-item semi-quantitative food frequency questionnaire (FFQ). Results By the use of factor analysis, 2 major dietary patterns were extracted: healthy dietary pattern (HDP) and unhealthy dietary pattern (UDP). Binary logistic analysis showed that individuals with minor allele risk (CC) with high adherence to the unhealthy pattern increased odds for depression (OR: 8.77, 95%CI: -0.86-18.40, P: 0.07), after controlling for confounders. Also, a logical inverse relationship was observed between CT genotype and HDP on depression in the crude and adjusted models (OR: -0.56, 95% CI: -3.69-2.57, P: 0.72) (OR: -4.17, 95% CI: -9.28-0.94, P: 0.11), although this interaction was not statistically significant. Conclusion According to the above findings, adherence to unhealthy food intake pattern increases odds of depression in MC4R risk allele (C allele) carriers. To confirm these findings, more studies are needed in the form of clinical trials and prospective studies with higher sample sizes.

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“…It has been demonstrated that environmental exposures such as diet and/or physical activity may modulate the effect of T2D loci (such as TCF7L2, PPARG, and CDKAL1 ) on the risk of T2D ( Dietrich et al, 2019 ). Nevertheless, only a handful of studies have investigated genetic×environmental interactions on GDM ( Chen et al, 2019 ; Grotenfelt et al, 2016 ; Popova et al, 2017 ), and to date, no study has tested the interaction between a genome-wide PRS with other GDM risk factors, on the risk of GDM.…”

Section: Introductionmentioning

confidence: 99%

The genetic risk of gestational diabetes in South Asian women

Lamri

Limbachia

Schulze

et al. 2022

eLife

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South Asian women are at increased risk of developing gestational diabetes (GDM). Few studies have investigated the genetic contributions to GDM risk. We investigated the association of a type 2 diabetes (T2D) polygenic risk score (PRS), on its own, and with GDM risk factors, on GDM-related traits using data from two birth cohorts in which South Asian women were enrolled during pregnancy. 837 and 4,372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-gram glucose tolerance test. PRSs were derived using GWAS results from an independent multi-ethnic study (~18% South Asians). Associations with fasting plasma glucose (FPG); 2h post-load glucose (2hG); area under the curve glucose; and GDM were tested using linear and logistic regressions. The population attributable fraction (PAF) of the PRS was calculated. Every 1 SD increase in the PRS was associated with a 0.085 mmol/L increase in FPG ([95%CI=0.07-0.10], P=2.85 × 10-20); 0.21 mmol/L increase in 2hG ([95%CI=0.16-0.26], P=5.49 × 10-16); and a 45% increase in the risk of GDM ([95%CI=32-60%], P=2.27 × 10-14), independent of parental history of diabetes and other GDM risk factors. PRS tertile 3 accounted for 12.5% of the population's GDM alone, and 21.7% when combined with family history. A few weak PRS and GDM risk factors interactions modulating FPG and GDM were observed. Together, these results show that a T2D PRS and family history of diabetes are strongly and independently associated with multiple GDM-related traits in women of South Asian descent, an effect that could be modulated by other environmental factors.

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Lifestyle intervention modifies the effect of the MC4R genotype on changes in insulin resistance among women with prior gestational diabetes: Tianjin Gestational Diabetes Mellitus Prevention Program

Cited by 12 publications

References 47 publications

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

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

The interaction between MC4R gene variant (rs17782313) and dominant dietary patterns on depression in obese and overweight women: a cross sectional study

The genetic risk of gestational diabetes in South Asian women

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