Obesity and diabetes genetic variants associated with gestational weight gain.
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ABSTRACT: Objective
We sought to determine whether genetic variants associated with diabetes and obesity predict gestational weight gain.Study design
A total of 960 participants in the Pregnancy, Infection, and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity.Results
Among Caucasian and African American women (n = 960), KCNQ1 risk allele carriage was directly associated with weight gain (P < .01). In Bayesian hierarchical models among Caucasian women (n = 628), we found posterior odds ratios >3 for inclusion of TCF2 and THADA SNPs in our models. Among African American women (n = 332), we found associations between risk allele carriage and weight gain for the THADA and INSIG2 SNPs. In Bayesian variable selection models, we found an interaction between the TSPAN8 risk allele and pregravid obesity, with lower weight gain among obese risk allele carriers.Conclusion
We found evidence that diabetes and obesity risk alleles interact with maternal pregravid body mass index to predict gestational weight gain.
SUBMITTER: Stuebe AM
PROVIDER: S-EPMC3222335 | biostudies-literature | 2010 Sep
REPOSITORIES: biostudies-literature
Publications
Obesity and diabetes genetic variants associated with gestational weight gain.
Stuebe Alison M AM Lyon Helen H Herring Amy H AH Ghosh Joyee J Wise Alison A North Kari E KE Siega-Riz Anna Maria AM
American journal of obstetrics and gynecology 20100901 3
<h4>Objective</h4>We sought to determine whether genetic variants associated with diabetes and obesity predict gestational weight gain.<h4>Study design</h4>A total of 960 participants in the Pregnancy, Infection, and Nutrition cohorts were genotyped for 27 single-nucleotide polymorphisms (SNPs) associated with diabetes and obesity.<h4>Results</h4>Among Caucasian and African American women (n = 960), KCNQ1 risk allele carriage was directly associated with weight gain (P < .01). In Bayesian hierar ...[more]
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Project description:IntroductionPre-pregnancy obesity, gestational diabetes mellitus (GDM), and gestational weight gain (GWG) are associated with each other. This is the first study to investigate whether genetic variants were associated with having GDM, and whether genetic variants-related GDM were associated with adiposity including pre-pregnancy obesity and excessive GWG in Turkish women.Patients and methodsWomen with GDM (n = 160) and without GDM (n = 145) were included in case-controlled study. Genotyping of the HNF1A gene (p.I27L rs1169288, p.98V rs1800574, p.S487N rs2464196), the VDR gene (p.BsmI rs1544410, p.ApaI rs7975232, p.TaqI rs731236, p.FokI rs2228570), and FTO gene (rs9939609) SNPs were performed by using RT-PCR.ResultsThe FTO AA genotype was associated with an increased risk of having GDM (AA vs. AT + TT, 24.4% vs. 12.4%, OR = 2.27, 95% CI [1.23-4.19], p = 0.007). The HNF1A p.I27L GT/TT genotype was associated with increased GDM risk (GT + TT vs. GG-wild, 79.4% vs. 65.5%, OR = 2.02, 95% CI 1.21-3.38], p = 0.007). However, all VDR gene SNPs and the HNF1A p.A98V, p.S487N were not associated with having GDM (p > 0.05). The FTO AA genotype was associated with an increased risk for pre-pregnancy overweight/obesity (OR = 1.43, 95% CI [1.25-3.4], p = 0.035), but not associated with excessive GWG after adjusting for pre-pregnancy weight (p > 0.05). Pre-pregnancy weight, weight at delivery, and GWG did not differ in both VDR and HNF1A gene carriers (p > 0.05). HOMA-IR and HbA1c were increased in both p.I27L TT and FTO AA genotype carriers (p < 0.05).ConclusionThe adiposity-related gene FTO is associated with GDM by the effect of FTO on pre-pregnancy obesity. The diabetes-related p.I27L gene is associated with GDM by increasing insulin resistance.
| S-EPMC6518700 | biostudies-literature
Project description:Background:Our objective was to examine the associations of parental body mass index (BMI) and maternal gestational weight gain with childhood-onset type 1 diabetes. Comparing the associations of maternal and paternal BMI with type 1 diabetes in the offspring will provide further insight into the role of unmeasured confounding by characteristics linked to BMI in both parents. Methods:We studied 132 331 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC) who were born between February 1998 and July 2009. Exposures of interest included parental BMI and maternal gestational weight gain obtained by maternal report. We used Cox-proportional hazards regression to examine the risk of type 1 diabetes (n=499 cases), which was ascertained by national childhood diabetes registers. Results:The incidence of type 1 diabetes was 32.7 per 100 000 person-years in MoBa and 28.5 per 100 000 person-years in DNBC. Both maternal pre-pregnancy obesity, adjusted hazard ratio (HR) 1.41 [95% confidence interval (CI): 1.06, 1.89] and paternal obesity, adjusted HR 1.51 (95% CI: 1.11, 2.04), were associated with childhood-onset type 1 diabetes. The associations were similar after mutual adjustment. In contrast, maternal total gestational weight gain was not associated with childhood-onset type 1 diabetes, adjusted HR 1.00 (95% CI: 0.99, 1.02) per kilogram increase. Conclusions:Our study suggests that the association between maternal obesity and childhood-onset type 1 diabetes is not likely explained by intrauterine mechanisms, but possibly rather by unknown environmental factors influencing BMI in the family.
| S-EPMC5913633 | biostudies-literature
Project description:Maternal nutritional and metabolic status influence fetal growth. This study investigated the contribution of gestational weight gain (GWG), gestational diabetes (GDM), and maternal obesity to birthweight and newborn body fat. It is a secondary analysis of a prospective study including 204 women with a pregestational body mass index (BMI) of 18.5-24.9 kg/m2 and 219 women with BMI ≥ 30 kg/m2. GDM was screened in the second and third trimester and was treated by dietary intervention, and insulin if required. Maternal obesity had the greatest effect on skinfolds (+1.4 mm) and cord leptin (+3.5 ng/mL), but no effect on birthweight. GWG was associated with increased birthweight and skinfolds thickness, independently from GDM and maternal obesity. There was an interaction between third trimester weight gain and GDM on birthweight and cord leptin, but not with maternal obesity. On average, +1 kg in third trimester was associated with +13 g in birthweight and with +0.64 ng/mL in cord leptin, and a further 32 g and 0.89 ng/mL increase in diabetic mothers, respectively. Maternal obesity is the main contributor to neonatal body fat. There is an independent association between third trimester weight gain, birthweight, and neonatal body fat, enhanced by GDM despite intensive treatment.
| S-EPMC7698189 | biostudies-literature
Project description:BackgroundGestational weight gain (GWG) is associated with a range of health outcomes, but little is known about the factors that influence it.ObjectiveThe objective was to test the hypothesis that maternal and fetal genetic variants that are reliably associated with adiposity are associated with GWG.DesignWe examined the association of a risk allele score by using 4 adiposity-related single nucleotide polymorphisms (SNPs; rs9939609 in FTO, rs17782313 near MC4R, rs6548238 near TMEM18, and rs10938397 near GNPDA2) with GWG in a pregnancy cohort in which women had detailed repeated assessment of GWG (median number of weight measurements: 10; interquartile range: 8, 11). The numbers included in our analyses varied between 2324 and 7563 for different variant-outcome analyses. A linear spline random-effects model was used to model weight change with gestational age and to relate genetic variants to this. This modeling confirmed 3 distinct periods of GWG: 0-18, 19-28, and ≥29 wk of gestation.ResultsMaternal risk allele score and SNPs in FTO, MC4R, and TMEM18 were positively associated with prepregnancy weight. Maternal allele score was inversely associated with GWG in the first 18 wk of pregnancy (-14.46 g/wk per allele; 95% CI: -24.75, -4.17 g/wk per allele) but was not associated with other periods of GWG. Offspring allele score and maternal and offspring individual SNPs were not associated with GWG in any period or with birth weight or postnatal weight retention.ConclusionsOur findings suggest that neither maternal nor fetal adiposity-related genetic variants are associated with greater GWG. The inverse association of maternal allele score with GWG in the first 18 wk requires replication.
| S-EPMC3127507 | biostudies-literature
Project description:OBJECTIVE:We examined the association between gestational weight gain (GWG) and offspring obesity at age 36 months. METHODS:Mother-infant dyads (n?=?609) were followed from a first study visit (mean [standard deviation]: 18.8 [2.7] weeks gestation) to 36 months postpartum. Total GWG over the entire pregnancy was defined as excessive or non-excessive according to the 2009 Institute of Medicine guidelines. Four mutually exclusive categories of excessive or non-excessive GWG across early (conception to first study visit) and late (first study visit to delivery) pregnancy defined GWG pattern. Body mass index (BMI) z-scores ?95th percentile of the 2000 Centers for Disease Control (CDC) references defined offspring obesity at 36 months. Multivariable log-binomial models adjusted for pre-pregnancy BMI and breastfeeding were used to estimate the association between GWG and childhood obesity risk. RESULTS:Nearly half of the women had total excessive GWG. Of these, 46% gained excessively during both early and late pregnancy while 22% gained excessively early and non-excessively late, and the remaining 32% gained non-excess weight early and excessively later. Thirteen per cent of all children were obese at 36 months. Excessive total GWG was associated with more than twice the risk of child obesity (adjusted risk ratio [95% confidence interval]: 2.20 [1.35, 3.61]) compared with overall non-excessive GWG. Compared with a pattern of non-excessive GWG in both early and late pregnancy, excessive GWG in both periods was associated with an increased risk of obesity (2.39 [1.13, 5.08]). CONCLUSIONS:Excessive GWG is a potentially modifiable factor that may influence obesity development in early childhood.
| S-EPMC4379119 | biostudies-literature
Project description:ObjectiveThis study aimed to compare attendance of nutritional counseling, dietary composition, exercise patterns, and socioeconomic factors among obese women with inappropriate gestational weight gain (iGWG) versus appropriate GWG (aGWG).Study designMedicaid-eligible women receiving prenatal care at a tertiary care center from January 2013 to December 2015 were offered individualized nutritional counseling by a registered dietitian encouraging well-balanced meals and 150 min/wk of exercise. We conducted a prospective case-control study of obese women (body mass index or BMI ≥30) with a singleton gestation with iGWG (<11 or >20 pounds) versus aGWG (11-20 pounds). Dietary intake, activity level, and socioeconomic factors were compared with Chi-square, Fisher's exact, Student's t-test, and Wilcoxon Rank Sum tests as indicated, and odds ratios with 95% confidence intervals were calculated. Multivariate regression analysis for significant variables was performed. A subgroup analysis of women with BMI ≥40 was planned.ResultsA total of 401 women were analyzed: 78% (n = 313) with iGWG and 22% (n = 88) with aGWG. Demographics were similar between groups. Women with iGWG less frequently reported physician reinforcement of counseling and reported more physical inactivity and unemployment; there were no differences in caloric intake or macronutrient profile between groups. Multivariate regression identified physician reinforcement and employment as independent predictors of aGWG. Among women with BMI ≥40 (n = 133), those with iGWG (78%) were less likely to attend counseling, report physician reinforcement of counseling, and have adequate caloric and protein intake when compared with those with aGWG (22%). Activity level and socioeconomic factors were not different between groups.ConclusionPhysician reinforcement of nutritional counseling, greater activity level, and employment are associated with aGWG in women with BMI ≥30, while individualized professional nutritional counseling and dietary modifications were further associated with aGWG in women with BMI ≥40. Thus, greater focus should be placed on enhancing exposure to counseling and altering nutritional and exercise choices to optimize aGWG.Key points· Physician reinforcement of nutritional counseling by a dietitian is crucial for obese women.. · Physical inactivity and unemployment are associated with inappropriate gestational weight gain.. · Nutritional counseling is associated with appropriate gestational weight gain in women with BMI ≥40..
| S-EPMC9105824 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to evaluate the independent contribution of maternal obesity and gestational weight gain (GWG) in excess of the Institute of Medicine's guidelines on levels of maternal serum inflammatory and metabolic measures.Study designBanked maternal serum samples from 120 subjects with documented prepregnancy or first trimester body mass index (BMI) were utilized for analyte analyses. Validated, BMI-specific formulas were utilized to categorize GWG as either insufficient, at goal or excess based on the Institute of Medicine guidelines with gestational age adjustments. Serum was analyzed for known inflammatory or metabolic pathway intermediates using the Luminex xMap system with the MILLIPLEX Human Metabolic Hormone Magnetic Bead Panel. Measured analytes included interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α and metabolic markers amylin, c-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, pancreatic polypeptide, and peptide YY. Kruskal-Wallis ANOVA and Pearson's correlation coefficients were calculated for each marker.ResultsC-peptide, insulin, and leptin all varied significantly with both obesity and GWG while glucagon-like peptide-1 varied by BMI but not GWG. These analytes covaried with other metabolic analytes, but not with inflammatory analytes.ConclusionMaternal metabolic biomarkers at delivery vary significantly with both obesity and GWG. Taken together, these findings suggest that GWG (with and without comorbid obesity) is an important mediator of measurable metabolites in pregnancy but is not necessarily accompanied by inflammatory measures in serum. These findings are consistent with GWG being an independent risk factor for metabolic disturbances during pregnancy.
| S-EPMC8630982 | biostudies-literature
Project description:Excessive pre-pregnancy weight is a known risk factor of pregnancy complications. The purpose of this analysis was to assess the relationship between several categories of maternal weight and the risk of developing hypertension and diabetes in pregnancy, and the relationship of these complications with the results of the newborn. It was carried out in a common cohort of pregnant women and taking into account the influence of disturbing factors. Our analysis was conducted in a prospective cohort of 912 Polish pregnant women, recruited during 2015-2016. We evaluated the women who subsequently developed diabetes with dietary modification (GDM-1) (n = 125) and with insulin therapy (GDM-2) (n = 21), as well as the women who developed gestational hypertension (GH) (n = 113) and preeclampsia (PE) (n = 24), compared to the healthy controls. Odds ratios of the complications (and confidence intervals (95%)) were calculated in the multivariate logistic regression. In the cohort, 10.8% of the women had pre-pregnancy obesity (body mass index (BMI) ? 30 kg/m2), and 36.8% had gestational weight gain (GWG) above the range of the Institute of Medicine recommendation. After correction for excessive GWG and other confounders, pre-pregnancy obesity (vs. normal BMI) was associated with a higher odds ratio of GH (AOR = 4.94; p < 0.001), PE (AOR = 8.61; p < 0.001), GDM-1 (AOR = 2.99; p < 0.001), and GDM-2 (AOR = 11.88; p <0.001). The threshold risk of development of GDM-2 occurred at lower BMI values (26.9 kg/m2), compared to GDM-1 (29.1 kg/m2). The threshold point for GH was 24.3 kg/m2, and for PE 23.1 kg/m2. For GWG above the range (vs. GWG in the range), the adjusted odds ratios of GH, PE, GDM-1, and GDM-2 were AOR = 1.71 (p = 0.045), AOR = 1.14 (p = 0.803), AOR = 0.74 (p = 0.245), and AOR = 0.76 (p = 0.672), respectively. The effect of maternal edema on all the results was negligible. In our cohort, hypertension and diabetes were associated with incorrect birth weight and gestational age at delivery. Conclusions: This study highlights the importance and influence of excessive pre-pregnancy maternal weight on the risk of pregnancy complications such as diabetes and hypertension which can impact fetal outcomes.
| S-EPMC7355601 | biostudies-literature
Project description:ObjectiveGestational weight gain (GWG) above recommendations is a risk factor for adverse maternal, perinatal, and long-term outcomes. This study hypothesized that prepregnancy weight gain may portend excess GWG.MethodsAmong 1,126 women (51% of whom were of Black race) in the Coronary Artery Risk Development in Young Adults (CARDIA) study with post-baseline births, the prepregnancy annual rate of BMI change per woman was estimated (slope; 5 years before pregnancy) and was related to the risk of GWG above Institute of Medicine recommendations using mixed-effects models (binary) and GWG z score (continuous), adjusting for confounders, and stratified by prepregnancy overweight/obesity status.ResultsA total of 626 women (56%) had excess GWG. Each standard deviation increase in prepregnancy BMI (0.16 kg/m2 per year) was associated with an 18% increased risk of excess GWG (95% CI: 1.13-1.23), adjusted for covariates. Stratified results showed an association for women without overweight or obesity (adjusted relative risk = 1.71 [95% CI: 1.38-2.13]) but not among those with overweight or obesity (adjusted relative risk = 0.98 [95% CI: 0.91-1.05]). When evaluated as a z score, prepregnancy weight gain was associated with higher GWG among women with and without overweight or obesity (mean = 0.24 [0.10] and 0.28 [0.12] z score, respectively).ConclusionsWeight gain before pregnancy is associated with higher GWG during pregnancy. Assessment of prepregnancy weight changes may identify those at risk for high GWG.
| S-EPMC9996907 | biostudies-literature
Project description:ObjectiveThis study aimed to evaluate gestational weight gain and birth weight in women with gestational diabetes mellitus of two Brazilian cohorts enrolled three decades apart.MethodsThe authors compared data of 2362 women from the Lifestyle INtervention for Diabetes Prevention After Pregnancy study (LINDA-Brasil, 2014-2017) to those of 359 women from the Estudo Brasileiro de Diabetes Gestacional study (EBDG, 1991-1995). Gestational weight gain was classified by the 2009 Institute of Medicine criteria; large and small for gestational age newborns, by the Intergrowth-21st chart. Differences in birth weight means between pregestational BMI and gestational weight gain categories were evaluated by ANOVA; the associations of gestational weight gain and birth weight, through multivariable Poisson regression.ResultsIn LINDA-Brasil, women presented higher pregestational body mass index (30.3±6.5 vs. 24.6±4.4kg/m2) and were frequently obese (46.4 vs. 11.1%) compared to those of the EBDG. In the EBDG, gestational weight gain was larger (11.3±6.1 vs. 9.2±7.6kg) and rates of small for gestational age higher (7.5 vs. 4.5%) compared to LINDA-Brasil. In LINDA-Brasil, excessive gestational weight gain was associated to macrosomia (adjusted relative risk [aRR]: 1.59, 95% CI 1.08-2.35) and large for gestational age (aRR: 1.40; 95% CI 1.05-1.86); less gain increased the risk of low birth weight (aRR: 1.66; 95% CI 1.05-2.62) and small for gestational age (aRR: 1.79; 95% CI 1.03-3.11). These associations were similar in the EBDG, although not statistically significant.ConclusionsImprovements in gestational weight gain and rates of small for gestational age occurred over time in gestational diabetes mellitus pregnancies, accompanied by a worsening in maternal weight profile. This highlights the nutritional transition during this period and the importance of avoiding excessive gestational weight gain as well as promoting adequate weight before conception.
| S-EPMC9432266 | biostudies-literature