Lipid Metabolism Is Dysregulated before, during and after Pregnancy in a Mouse Model of Gestational Diabetes.
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ABSTRACT:
SUBMITTER: Furse S
PROVIDER: S-EPMC8306994 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundGestational diabetes mellitus (GDM) is a metabolic disease that can have long-term adverse effects on the cognitive function of mothers. In our study, we explored the changes in metabolic health and cognitive function in mice of middle- and old- age after exposure to GDM, and whether metformin therapy during pregnancy provided long-term benefits.ResultsMice with GDM demonstrated significant cognitive impairment in old age, which was associated with insulin resistance. Gestational metformin therapy was shown to increase insulin sensitivity and improve cognition. The ovarian aging rate was also accelerated in mice exposed to GDM during pregnancy, which may be related to fatty acid metabolism in the ovaries.ConclusionTreatment with metformin during pregnancy was shown to improve fatty acid metabolism in ovarian tissues.MethodDuring pregnancy, mice were fed with a high-fat diet (GDM group) or a low-fat diet (Control group), and a third group received metformin while receiving a high-fat diet (Treatment group). At 12 months old, the mice completed an oral glucose tolerance test, insulin tolerance test, Morris water maze test, female sex hormones were measured, and metabolite profiles of tissue from the ovaries, hypothalamus, and pituitary glands were analysed using gas chromatography-mass spectrometry.
| S-EPMC7425475 | biostudies-literature
Project description:Purpose of reviewIn this review, we summarize studies investigating genetics of gestational diabetes mellitus (GDM) and glucose metabolism in pregnancy. We describe these studies in the context of the larger body of literature on type 2 diabetes (T2D) and glycemic trait genomics.Recent findingsWe reviewed 23 genetic association studies for GDM and performed a meta-analysis, which revealed variants at eight T2D loci significantly associated with GDM after the Bonferroni correction. These studies suggest that GDM and T2D share a number of genetic risk loci. Only two unbiased genome-wide association studies (GWASs) have successfully revealed genetic associations for GDM and related glycemic traits in pregnancy. A GWAS for GDM in Korean women identified two loci (near CDKAL1 and MTNR1B) known to be associated with T2D, though the association of the MTNR1B locus with GDM appears to be stronger than that for T2D. A multi-ethnic GWAS for glycemic traits in pregnancy identified two novel loci (near HKDC1 and BACE2) which appear to be associated with post-load glucose and fasting c-peptide specifically in pregnant women. There are ongoing efforts to use this genetic information, in the form of polygenic scores, to predict risk of GDM and postpartum T2D. The body of literature examining genetic associations with GDM is limited, especially when compared to the available literature on T2D and glycemic trait genomics. Additional genetic discovery for glucose metabolism in pregnant women will require larger pregnancy cohorts and international collaborative efforts. Studies on the clinical implications of these findings are also warranted.
| S-EPMC8132191 | biostudies-literature
Project description:Aims:The present study evaluates association between physical activity and Gestational Diabetes Mellitus (GDM), for it can be an effective intervention for its management. Though physical activity helps maintain glucose homeostasis, evidences of GDM risk are less extensive. Therefore, this study also identifies its correlation with maternal blood glucose levels. Materials and Methods:A prospective case-control study was carried out among pregnant women attending regular antenatal clinic at two private hospitals. The study comprised of 100 cases and 273 matched controls. Data was collected by personal interviews using a standard questionnaire. Physical activity was assessed using long form of International Physical Activity Questionnaire (IPAQ) reported as Metabolic Equivalent-Minutes per week (MET-Minutes/Week). Statistical Package for Social Sciences (SPSS) was used for analysis. Results:Results shows high exposure rates for low-to-moderate physical activity among cases, across all domains and sub-activities. The odds of GDM engaged in domestic and gardening activities for <2999 MET-minutes per week are 10 times higher than involved for ≥3000 MET-minutes per week (P < 0.001). The study also shows poor or no correlation between physical activity during pregnancy and maternal blood glucose levels. Conclusion:Despite existence of poor or no relationship with maternal blood glucose levels, prolonged sedentary behavior and decreased physical activities, especially domestic, are potential risk factors for GDM, a major finding of the study.
| S-EPMC6166569 | biostudies-other
Project description:Objectives: Gestational diabetes mellitus (GDM) is a common complication in pregnancy, affecting around 14% of all pregnancies each year. It will likely further increase, as obesity becomes more prevalent. The impact of GDM on cardiovascular changes in pregnant women and her child is still unclear. The aim of the study was to measure the effects of physical activity before pregnancy on the cardiovascular system in patients with GDM in pregnancy. Methods: Two hundred and six pregnant women were included in this observational study. All participants were recruited at the tertiary level teaching University Hospital "Klinikum rechts der Isar" between 28 and 32 weeks gestation. Questionnaires dealing with pre-pregnancy daily and physical activity (PA) were evaluated. The cardiovascular status of the mothers included measurements of the intima-media thickness (IMT) of the carotid arteries. PA level was performed with a standardized 6-min-walking-test. Results: Ninety-nine women with GDM with a mean age of 33.84 (± 4.7) years were examined. One hundred seven healthy pregnant women aged 32.6 (± 4.2) years served as controls. The mean weight in the study group was 73.0 (± 20.3) kg and 61.7 (± 9.5) kg in the control group. Based on the higher weight in the study group, the Body Mass Index (BMI) was also significantly higher than in the control group (26.3 ± 7.1 vs. 21.6 ± 3; p < 0.001). The frequency of PA was significantly higher in the control group (p < 0.001). The objective fitness level was worse in pregnant women with GDM compared to healthy controls (472 vs. 523 m, p < 0.001). PA before and during pregnancy was less performed in the study group (86 vs. 64.5%, p = 0.002; 69 vs. 45.7%, p = 0.003). Women who were physically inactive before pregnancy had a 3-times higher risk to develop GDM compared to active women (OR = 2.67). The IMT was significantly thicker in the study group (0.48 ± 0.042 mm vs. 0.45 ± 0.042) mm; p = 0.006). Conclusion: Physical activity before pregnancy and a lower initial weight reduces the risk of developing GDM and cardiovascular risk factors in pregnancy. The development of prevention programs is certainly necessary.
| S-EPMC7456967 | biostudies-literature
Project description:Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. While pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM. In this review, we summarize the current state of knowledge about metabolic adaptations to pregnancy and the role of adiponectin in these processes, with a focus on GDM. Recent studies from rodent model systems have clarified that adiponectin deficiency during pregnancy contributes to GDM development. The upregulation of adiponectin alleviates hyperglycemia in pregnant mice, although much remains to be understood for adiponectin to be utilized clinically for GDM.
| S-EPMC9958871 | biostudies-literature
Project description:ObjectiveTo investigate the correlation of trends in lipid profiles from first to second trimester with trends in insulin indices and gestational diabetes mellitus (GDM).MethodsSecondary analysis of an ongoing prospective cohort study was conducted on 1234 pregnant women in a single center. Lipid profiles, glucose metabolism and insulin indices were collected in the first and second trimesters. Trends in lipid profiles were divided into four subgroups: low-to-low, high-to-high, high-to-low and low-to-high group. Insulin indices including homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were calculated to evaluate insulin resistance (IR). Trends in insulin indices were described as: no IR, persistent IR, first-trimester IR alone and second-trimester IR alone. Pearson correlation analysis and multivariate logistic regression were performed to assess the associations of lipid profiles subgroups with insulin indices and GDM.ResultsFirst- and second-trimester total cholesterol (TC), triglycerides (TG) and high-density lipoprotein cholesterol were strongly correlated to first- and second-trimester insulin indices. Only TG had a sustained correlation with glucose metabolism indices. High-to-high low-density lipoprotein cholesterol (LDL-c) was an independent risk factor for GDM. High-to-high TG and high-to-low TG groups were independent risk factors for persistent IR. High-to-high TG and low-to-high TG groups were independent risk factors for second-trimester IR alone.ConclusionTG has a sustained correlation with insulin indices and glucose metabolism indices. Persistently high TG is an independent risk factor for persistent IR and second-trimester IR alone. Regardless of whether pregnant women have first-trimester IR, lower TG levels help reduce the risk for persistent IR or subsequent development of IR. These results highlight the benefit of lowering TG levels in early and middle pregnancy to prevent the development of IR.
| S-EPMC9880552 | biostudies-literature
Project description:Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11-14 weeks' gestation (first trimester) and 15-18.9 weeks' gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37-3.09] (unadjusted); and 1.89 [95% CI 1.26-2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97-2.16] (unadjusted) and 1.11 [95% CI 0.74-1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.
| S-EPMC4766100 | biostudies-literature
Project description:Aims/hypothesisAntenatal obesity and associated gestational diabetes (GDM) are increasing worldwide. While pre-existing insulin resistance is implicated in GDM in obese women, the responsible metabolic pathways remain poorly described. Our aim was to compare metabolic profiles in blood of obese pregnant women with and without GDM 10 weeks prior to and at the time of diagnosis by OGTT.MethodsWe investigated 646 women, of whom 198 developed GDM, in this prospective cohort study, a secondary analysis of UK Pregnancies Better Eating and Activity Trial (UPBEAT), a multicentre randomised controlled trial of a complex lifestyle intervention in obese pregnant women. Multivariate regression analyses adjusted for multiple testing, and accounting for appropriate confounders including study intervention, were performed to compare obese women with GDM with obese non-GDM women. We measured 163 analytes in serum, plasma or whole blood, including 147 from a targeted NMR metabolome, at time point 1 (mean gestational age 17 weeks 0 days) and time point 2 (mean gestational age 27 weeks 5 days, at time of OGTT) and compared them between groups.ResultsMultiple significant differences were observed in women who developed GDM compared with women without GDM (false discovery rate corrected p values <0.05). Most were evident prior to diagnosis. Women with GDM demonstrated raised lipids and lipoprotein constituents in VLDL subclasses, greater triacylglycerol enrichment across lipoprotein particles, higher branched-chain and aromatic amino acids and different fatty acid, ketone body, adipokine, liver and inflammatory marker profiles compared with those without GDM.Conclusions/interpretationAmong obese pregnant women, differences in metabolic profile, including exaggerated dyslipidaemia, are evident at least 10 weeks prior to a diagnosis of GDM in the late second trimester.
| S-EPMC6448883 | biostudies-literature
Project description:Previous studies have found associations between individual healthy behaviors and reduced risk of gestational diabetes mellitus (GDM); however, the association of composite healthy lifestyle during pregnancy with GDM has not been examined. Participants in the Omega Study (n = 3,005), a pregnancy cohort study conducted in Washington State (1996-2008), reported information on diet, physical activity, smoking, and stress during early pregnancy. Lifestyle components were dichotomized into healthy/unhealthy and then combined into a total lifestyle score (range, 0-4). Regression models were used to determine relative risk of GDM (n = 140 cases) in relation to healthy lifestyle. Twenty percent of participants had a healthy diet, 66% were physically active, 95% were nonsmokers, and 55% had low stress. Each 1-point increase in lifestyle score was associated with a 21% lower risk of GDM (95% confidence interval: 0.65, 0.96) after adjustment for age, race, and nulliparity. Adjustment for prepregnancy body mass index, prepregnancy physical activity, and prepregnancy smoking attenuated the associations slightly. Associations were similar in normal-weight and overweight/obese women. In this study, a composite measure of healthy lifestyle during early pregnancy was associated with substantially lower GDM risk. Public health messaging and interventions promoting multiple aspects of a healthy lifestyle during early pregnancy should be considered for GDM prevention.
| S-EPMC5860043 | biostudies-literature
Project description:Objective:Our aim was to evaluate the relationship between serum vitamin D levels before 20 weeks of pregnancy and the risk of gestational diabetes mellitus. Methods:This study is a retrospective study. We analyzed the relationship between serum 25 (OH) D level before 20 weeks of pregnancy (first antenatal examination) and the risk of gestational diabetes mellitus. Age, parity and pre-pregnancy body mass index were used as confounding factors. 8468 pregnant women were enrolled in this study between January 2018 and March 2020 at the Obstetrics and Gynecology Hospital of Fudan University. Adjusted smoothing splinespline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and gestational diabetes mellitus. Results:After fully adjusting the confounding factors, serum vitamin D is a protective factor in gestational diabetes mellitus (OR?=?0.90). Compared with vitamin D deficiency, vitamin D insufficiency (OR?=?0.78), sufficience (OR?=?0.82) are a protective factor for gestational diabetes mellitus. Conclusion:Sufficience vitamin D before 20 weeks of pregnancy is a protective factor for gestational diabetes mellitus. Vitamin D?>?20 ng/mL can reduce the risk of GDM, which is not much different from the effect of?>?30 ng/mL. The protective effect of vitamin D is more significant in obese pregnant women.
| S-EPMC7574245 | biostudies-literature