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1.
Clin Biochem ; 77: 36-40, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899278

RESUMO

BACKGROUND: Bone turnover markers (BTMs) can be applied to the assessment of bone formation and bone resorption activity. The aim of this study was to investigate the changes in BTMs in women with gestational diabetes mellitus (GDM). METHODS: One hundred and five women with gestational diabetes mellitus defined as the GDM group and 46 healthy pregnant women with normal glucose tolerance selected as the control group were enrolled in this study. Serum samples were collected during regular obstetric examinations and the serum levels of total procollagen type 1 N-terminal propeptide (P1NP), N-terminal midfragment of osteocalcin (N-MID), and ß-C-terminal telopeptide of type 1 collagen (ß-CTX) were measured. An independent-sample t-test, the Mann-Whitney U test, and a Pearson correlation analysis were performed for data analyses. RESULTS: Serum ß-CTX levels in the GDM group were significantly higher than those in the control group (296.00 [235.00-369.00] pg/mL vs. 218.5 [165.25-292.50] pg/mL, p < 0.05), while P1NP and N-MID levels did not differ between the two groups. The Pearson correlation analysis revealed that ß-CTX level was correlated with blood glucose level. CONCLUSIONS: The difference in ß-CTX levels indicated that bone resorption in patients with GDM diabetes was higher than that in pregnant women with normal glucose tolerance. No obvious differences in bone formation markers P1NP and N-MID were found between the two groups.


Assuntos
Diabetes Gestacional/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Remodelação Óssea , Feminino , Humanos , Gravidez
3.
J Agric Food Chem ; 67(48): 13269-13281, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31725275

RESUMO

We studied the long-term influence of gestational diabetes mellitus (GDM) on the pancreas of offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on offspring's pancreas. GDM offspring were divided into three groups: GDM offspring, n-3 PUFA-adequate-GDM offspring, and n-3 PUFA-deficient GDM offspring. All healthy and GDM offspring were fed up to 11 months old. The pancreas of GDM offspring exhibited fatty infiltration at 11 months old, whereas n-3 PUFA improved the pancreatic fatty infiltration. n-3 PUFA lowered the pancreatic oxidative stress and inflammation. Surprisingly, n-3 PUFA postponed pancreatic telomere shortening of GDM offspring at old age. Nontargeted metabolomics showed that many metabolites were altered in the pancreas of GDM offspring at old age, including l-valine, ceramide, acylcarnitines, tocotrienol, cholesteryl acetate, and biotin. n-3 PUFA modulated some altered metabolites and metabolic pathways. Therefore, GDM caused the long-term effects on offspring's pancreas, whereas n-3 PUFA played a beneficial role.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Pâncreas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Animais , Diabetes Gestacional/metabolismo , Gorduras/metabolismo , Feminino , Humanos , Masculino , Metabolômica , Pâncreas/química , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Telômero/metabolismo
4.
Se Pu ; 37(8): 897-903, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31642261

RESUMO

The global increase in the prevalence of gestational diabetes mellitus(GDM)in recent years has prompted the study of the effect of GDM on the metabolism between mother and fetus. In this study, the metabolomic investigation of the umbilical cord blood of mothers presenting GDM was performed using liquid chromatography-mass spectrometry (LC-MS), orthogonal projections to latent structures discriminant analysis (OPLS-DA), and network analysis to assess GDM-related metabolic biomarkers. The results showed that arachidonic acid (AA) played an important role in the key metabolic network while further pathway analysis suggested that GDM induced unsaturated fatty acid metabolic disorder. This study provides the underlying metabolic mechanism of GDM-induced metabolic abnormalities between mother and fetus.


Assuntos
Diabetes Gestacional/metabolismo , Sangue Fetal/metabolismo , Metabolômica , Ácido Araquidônico , Biomarcadores/sangue , Cromatografia Líquida , Feminino , Humanos , Espectrometria de Massas , Gravidez
5.
Int J Mol Sci ; 20(18)2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31505789

RESUMO

It is well known that adipokines are endocrine factors that are mainly secreted by white adipose tissue. Their central role in energy metabolism is currently accepted. More recently, their involvement in fertility regulation and the development of some reproductive disorders has been suggested. Data concerning the role of leptin and adiponectin, the two most studied adipokines, in the control of the reproductive axis are consistent. In recent years, interest has grown about some novel adipokines, chemerin, visfatin, resistin and apelin, which have been found to be strongly associated with obesity and insulin-resistance. Here, we will review their expression and role in male and female reproduction in humans and animal models. According to accumulating evidence, they could regulate the secretion of GnRH (Gonadotropin-Releasing Hormone), gonadotropins and steroids. Furthermore, their expression and that of their receptors (if known), has been demonstrated in the human and animal hypothalamo-pituitary-gonadal axis. Like leptin and adiponectin, these novel adipokines could thus represent metabolic sensors that are able to regulate reproductive functions according to energy balance changes. Therefore, after investigating their role in normal fertility, we will also discuss their possible involvement in some reproductive troubles known to be associated with features of metabolic syndrome, such as polycystic ovary syndrome, gestational diabetes mellitus, preeclampsia and intra-uterine growth retardation in women, and sperm abnormalities and testicular pathologies in men.


Assuntos
Apelina/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Diabetes Gestacional/metabolismo , Retardo do Crescimento Fetal/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Síndrome do Ovário Policístico/metabolismo , Pré-Eclâmpsia/metabolismo , Resistina/metabolismo , Doenças Testiculares/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Humanos , Resistência à Insulina , Masculino , Obesidade/metabolismo , Gravidez
6.
Comput Math Methods Med ; 2019: 6936175, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485258

RESUMO

Gestational diabetes mellitus (GDM) refers to the condition which shows abnormal glucose metabolism that occurs during pregnancy, while normal glucose metabolism before pregnancy. In the present study, a novel analytical procedure was used to explore the key molecule of gestational diabetes mellitus. First, the weighted pathway model was carried out subsequently to eliminate the gene-overlapping effects among pathways. Second, we assessed the enriched pathways by a combination of Fisher's t-test and the Mann-Whitney U test. We carried out the functional principal component analysis by estimating F values of genes to identify the hub genes in the enriched pathways. Results showed that a total of 4 differential pathways were enriched. The key pathway was considered as the insulin secretion pathway. F values of each gene in the key pathway were calculated. Three hub molecules were identified as hub differentially methylated genes, namely, CAMK2B, ADCYAP1, and KCNN2. In addition, by further comparing the gene expression data in a validation cohort, one key molecule was obtained, ADCYAP1. Therefore, ADCYAP1 may serve as a potential target for the treatment of GDM.


Assuntos
Diabetes Gestacional/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Estudos de Casos e Controles , Metilação de DNA , Diabetes Gestacional/metabolismo , Epigênese Genética , Feminino , Redes Reguladoras de Genes , Humanos , Conceitos Matemáticos , Modelos Genéticos , Gravidez , Análise de Componente Principal , Transdução de Sinais , Transcriptoma
8.
Med Sci Monit ; 25: 6128-6152, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31418429

RESUMO

BACKGROUND Gestational diabetes mellitus (GDM) is a pregnancy complication that is diagnosed by the novel onset of abnormal glucose intolerance. Our study aimed to investigate the changes in human breast milk metabolome over the first month of lactation and how GDM affects milk metabolome. MATERIAL AND METHODS Colostrum, transition milk, and mature milk samples from women with normal uncomplicated pregnancies (n=94) and women with GDM-complicated pregnancies (n=90) were subjected to metabolomic profiling by the use of gas chromatography-mass spectrometry (GC-MS). RESULTS For the uncomplicated pregnancies, there were 59 metabolites that significantly differed among colostrum, transition milk, and mature milk samples, while 58 metabolites differed in colostrum, transition milk, and mature milk samples from the GDM pregnancies. There were 28 metabolites that were found to be significantly different between women with normal pregnancies and women with GDM pregnancies among colostrum, transition milk, and mature milk samples. CONCLUSIONS The metabolic profile of human milk is dynamic throughout the first months of lactation. High levels of amino acids in colostrum and high levels of saturated fatty acids and unsaturated fatty acids in mature milk, which may be critical for neonatal development in the first month of life, were features of both normal and GDM pregnancies.


Assuntos
Colostro/química , Diabetes Gestacional/metabolismo , Leite Humano/química , Adulto , Aminoácidos/metabolismo , Índice de Massa Corporal , Aleitamento Materno , China , Colostro/metabolismo , Ácidos Graxos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Lactação/metabolismo , Lactação/fisiologia , Metaboloma/fisiologia , Metabolômica , Leite Humano/metabolismo , Período Pós-Parto/metabolismo , Gravidez
9.
Nutrients ; 11(8)2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31408957

RESUMO

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.


Assuntos
Diabetes Gestacional , Epigênese Genética , Leptina/metabolismo , Síndrome Metabólica , MicroRNAs/metabolismo , Obesidade , Adipogenia/genética , Animais , Metilação de DNA , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Desenvolvimento Fetal , Código das Histonas/genética , Humanos , Hipotálamo/metabolismo , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Obesidade/genética , Obesidade/metabolismo , Gravidez
10.
Eur J Pharmacol ; 859: 172522, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31276667

RESUMO

Gestational diabetes mellitus (GDM) is a temporary form of diabetes during pregnancy, which causes maternal diabetic symptoms and abnormal fetal development, and influence the health of maternal-child in clinical practice. Mangiferin is a bioactive ingredient with anti-inflammation, anti-oxidation and anti-endoplasmic reticulum stress activities. In current study, the effects of mangiferin on GDM were evaluated. We reported that mangiferin greatly improved altered glucose and lipid profile, insulin tolerance, and reproductive outcomes of the GDM mice. Mangiferin ameliorated placental oxidative stress, inflammation and ER stress in GDM mice. Therefore, we demonstrated that mangiferin displayed protective effects on gestational diabetes mellitus symptoms by suppressing placental oxidative stress, inflammation and endoplasmic reticulum stress in GDM mice.


Assuntos
Diabetes Gestacional/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feto/diagnóstico por imagem , Estresse Oxidativo/efeitos dos fármacos , Placenta/efeitos dos fármacos , Placenta/metabolismo , Xantonas/farmacologia , Animais , Aterosclerose/tratamento farmacológico , Diabetes Gestacional/metabolismo , Feminino , Feto/fisiologia , Inflamação/tratamento farmacológico , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Xantonas/uso terapêutico
11.
Nutrients ; 11(7)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340612

RESUMO

The long-term influence of gestational diabetes mellitus (GDM) on offspring and the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on GDM offspring are poorly understood. We studied the long-term diabetic risk in GDM offspring and evaluated the effect of n-3 PUFA intervention. Healthy offspring rats were fed standard diet (soybean oil) after weaning. GDM offspring were divided into three groups: GDM offspring (soybean oil), n-3 PUFA adequate offspring (fish oil), and n-3 PUFA deficient offspring (safflower oil), fed up to 11 months old. The diabetic risk of GDM offspring gradually increased from no change at weaning to obvious impaired glucose and insulin tolerance at 11 months old. N-3 PUFA decreased oxidative stress and inflammation in the liver of older GDM offspring. There was a differential effect of n-3 PUFA and n-6 PUFA on hepatic telomere length in GDM offspring. Non-targeted metabolomics showed that n-3 PUFA played a modulating role in the liver, in which numerous metabolites and metabolic pathways were altered when GDM offspring grew to old age. Many metabolites were related to diabetes risk, such as α-linolenic acid, palmitic acid, ceramide, oxaloacetic acid, tocotrienol, tetrahydro-11-deoxycortisol, andniacinamide. In summary, GDM offspring exhibited obvious diabetes risk at old age, whereas n-3 PUFA decreased this risk.


Assuntos
Diabetes Mellitus/prevenção & controle , Diabetes Gestacional/metabolismo , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Fígado/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Encurtamento do Telômero , Telômero/metabolismo , Fatores Etários , Animais , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Diabetes Gestacional/genética , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/metabolismo , Feminino , Masculino , Gravidez , Ratos Wistar , Fatores de Risco , Telômero/genética , Fatores de Tempo
12.
Diabetes Metab Syndr ; 13(2): 1505-1509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336513

RESUMO

AIM: This study was conducted to illustrate the relation between vitamin D deficiency and glycemic parameters. MATERIALS AND METHODS: The study was carried out on 80 pregnant females who were attending obstetrics and gynecology out-patient clinic in el-Shatby hospital in Alexandria university, Egypt. They were divided into 2 groups: group 1 (n = 40) pregnant females diagnosed with gestational diabetes de novo at week 24-28 and group 2 (n = 40) pregnant females of the same age group who were not suffering from any glucose intolerance (control group). Each patient was subjected to detailed history taking, complete physical examination, One step 75 gm Oral glucose tolerance test, insulin, glycated hemoglobin(HbA1c),homeostatic model assessment of insulin resistance(HOMA-IR), 25 hydroxy-vitamin D, serum calcium, phosphorous and parathormone were assessed. RESULTS: A statistically significant higher fasting blood glucose (FBG), HbA1c%, fasting insulin and HOMA-IR was observed in patients with Gestational diabetes mellitus (GDM) versus control (p < 0.001). However, no significant difference was observed as regards Vitamin D levels in patients with GDM and control group. Among patients with GDM, vitamin D was found to correlate negatively with HbA1c (p < 0.001), insulin(p = 0.019) and HOMA-IR(p = 0.034). CONCLUSION: No definite causal relationship was observed between low vitamin D and subsequent occurrence of GDM.however, a significant correlation was found between the degree of vitamin D deficiency and the insulin resistance in patients with GDM.


Assuntos
Biomarcadores/análise , Glicemia/análise , Diabetes Gestacional/epidemiologia , Resistência à Insulina , Deficiência de Vitamina D/fisiopatologia , Adulto , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Egito , Feminino , Seguimentos , Teste de Tolerância a Glucose , Hemoglobina A Glicada/análise , Humanos , Gravidez , Prognóstico , Estudos Prospectivos
13.
J Assoc Physicians India ; 67(4): 66-70, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31309801

RESUMO

Abstract: Women with a history of Gestational Diabetes Mellitus (GDM) are at increased risk of future diabetes and related Non-Communicable Diseases (NCD) as are their offspring. "Transgenerational transmission occurs". Independent of genetic risk, offspring of hyperglycaemic pregnancies are at increased risk of early onset type 2 diabetes mellitus (Type 2 DM) and obesity. Differences exist in offspring risk of diabetes and obesity based on time and type of diabetes exposure in utero. There is a risk gradient, wherein type 2 DM exposure confers greater risk and reduces time to development of type 2 DM in the offspring compared with exposure to GDM and no diabetes exposure. These data suggest, glucose dose dependence in risk transmission. Given that the age of onset of prediabetes and type 2 DM is declining many reproductive age women may have undiagnosed diabetes or dysglycaemia when they become pregnant. This has great public health significance and it has become imperative that all pregnant women should be screened for hyperglycemia even if they have no symptoms. Ministry of Health, Government of India has developed the national guidelines for testing, diagnosis and management of hyperglycemia in pregnancy. These guidelines recommend early testing at booking, to be repeated again between 24-28 weeks if negative at first testing. The guideline also recommends that GDM can be diagnosed if the 2 hr PG is ≥140mg/dl after 75 gm of oral glucose administration without regard to the time of the last meal (i.e., fasting or non-fasting). This approach has also been endorsed by International Diabetes Federation (IDF), World Health Organization (WHO) and International Federation of Gynaecology and Obstetrics (FIGO) for resource constrained settings.The aim should be to target new born baby's birth weight, appropriate for gestational age (2.5 to 3.5 kg) to prevent the offspring developing NCD in the future. For this to happen early diagnosis and tight maternal glucose control during pregnancy similar to glycaemic level in the normal pregnancy, (FPG between 80 and 90 mg, 2 hr. post prandial between 110 and 120 mg) is necessary.


Assuntos
Diabetes Gestacional/metabolismo , Peso ao Nascer , Diabetes Mellitus Tipo 2 , Feminino , Teste de Tolerância a Glucose , Humanos , Índia , Gravidez , Resultado da Gravidez/epidemiologia
14.
PLoS One ; 14(6): e0218616, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242249

RESUMO

AIM: To isolate and characterize oral extracellular vesicles from gingival crevicular fluid at 11-14 weeks and evaluate their capacity to identify patients at risk of developing gestational diabetes mellitus. METHODS: A case-control study was conducted, including patients who developed gestational diabetes mellitus (n = 11) and healthy pregnant controls (n = 23). Obstetric and periodontal histories were recorded at 11-14 weeks of gestation, and samples of gingival crevicular fluid obtained. Extracellular vesicles were isolated from gingival crevicular fluid by ExoQuick. Nanoparticle tracking analysis, ELISA and transmission electron microscopy were used to characterize extracellular vesicles. RESULTS: Total extracellular vesicles isolated from gingival crevicular fluid were significantly higher in patients who developed gestational diabetes mellitus later in pregnancy compared to normoglycemic pregnant women (6.3x109 vs 1.7 x1010, p value = 0.0026), and the concentration of the extracellular vesicles delivered an area under the ROC curve of 0.81. The distribution size of extracellular vesicles obtained using ExoQuick was around 148 ± 57 nm. There were no significant differences in the periodontal status between cases and controls. The exosome transmembrane protein CD63 was also detected in the extracellular vesicles of gingival crevicular fluid. CONCLUSION: We were able to isolate extracellular vesicles from gingival crevicular fluid using a method that is suitable to be applied in a clinical setting. Our results provide an insight into the potential capacity of first trimester oral extracellular vesicles as early biomarkers for the prediction of gestational diabetes mellitus in pre-symptomatic women.


Assuntos
Diabetes Gestacional/etiologia , Vesículas Extracelulares/ultraestrutura , Líquido do Sulco Gengival/citologia , Adulto , Estudos de Casos e Controles , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Líquido do Sulco Gengival/metabolismo , Humanos , Biópsia Líquida/métodos , Tamanho da Partícula , Periodontite/complicações , Periodontite/metabolismo , Periodontite/patologia , Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos , Fatores de Risco , Tetraspanina 30/metabolismo
15.
BMC Pregnancy Childbirth ; 19(1): 210, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31226953

RESUMO

BACKGROUND: Small for gestational age (SGA) infants are those born small for their gestational age, with weight below the 10th percentile. Not only do SGA infants suffer growth issues after birth, they have elevated risk for the development of metabolic and cardiovascular diseases later in life. Current research has suggested that in cases of SGA infants, maternal milk and breastfeeding are not affected. The mother of an SGA infant was diagnosed with placental insufficiency and Gestational Diabetes Mellitus (GDM) during her pregnancy. The infant was born term, at 38 weeks 3 days, and SGA. The mother had a low milk supply and her milk composition differed from reference values such that the daily infant intake provided less than 50% of the required energy intake at 3 months. CONCLUSION: In cases of SGA and/or GDM, maternal milk quality and quantity may be compromised. This requires follow-up in order to reduce the disease risk for SGA infants and the corresponding public health implications.


Assuntos
Complicações do Diabetes/complicações , Diabetes Gestacional/metabolismo , Transtornos da Lactação/metabolismo , Leite Humano/metabolismo , Valor Nutritivo , Adulto , Aleitamento Materno , Ingestão de Energia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Transtornos da Lactação/etiologia , Leite Humano/química , Gravidez
16.
Am J Physiol Endocrinol Metab ; 317(2): E399-E410, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31237448

RESUMO

Metabolism alters markedly with advancing gestation, characterized by progressive insulin resistance, dyslipidemia, and raised serum bile acids. The nuclear receptor farnesoid X receptor (FXR) has an integral role in bile acid homeostasis and modulates glucose and lipid metabolism. FXR is known to be functionally suppressed in pregnancy. The FXR agonist, obeticholic acid (OCA), improves insulin sensitivity in patients with type 2 diabetes with nonalcoholic fatty liver disease. We therefore hypothesized that OCA treatment during pregnancy could improve disease severity in a mouse model of gestational diabetes mellitus (GDM). C57BL/6J mice were fed a high-fat diet (HFD; 60% kcal from fat) for 4 wk before and throughout pregnancy to induce GDM. The impact of the diet supplemented with 0.03% OCA throughout pregnancy was studied. Pregnant HFD-fed mice displayed insulin resistance and dyslipidemia. OCA significantly reduced plasma cholesterol concentrations in nonpregnant and pregnant HFD-fed mice (by 22.4%, P < 0.05 and 36.4%, P < 0.001, respectively) and reduced the impact of pregnancy on insulin resistance but did not change glucose tolerance. In nonpregnant HFD-fed mice, OCA ameliorated weight gain, reduced mRNA expression of inflammatory markers in white adipose tissue, and reduced plasma glucagon-like peptide 1 concentrations (by 62.7%, P < 0.01). However, these effects were not evident in pregnant mice. OCA administration can normalize plasma cholesterol levels in a mouse model of GDM. However, the absence of several of the effects of OCA in pregnant mice indicates that the agonistic action of OCA is not sufficient to overcome many metabolic consequences of the pregnancy-associated reduction in FXR activity.


Assuntos
Glicemia/efeitos dos fármacos , Ácido Quenodesoxicólico/análogos & derivados , Diabetes Gestacional/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Animais , Glicemia/metabolismo , Ácido Quenodesoxicólico/uso terapêutico , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Dislipidemias/complicações , Dislipidemias/metabolismo , Feminino , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Complicações na Gravidez/tratamento farmacológico , Complicações na Gravidez/metabolismo
17.
Int J Vitam Nutr Res ; 89(1-2): 37-44, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31188080

RESUMO

Background: The aim of this study was to investigate the association of intakes of fruit, vegetable and dairy with gestational diabetes mellitus (GDM). Methods: This prospective study was conducted over a 17 month period, on a random sample of pregnant women (n = 1026), aged 18-45 y, in their first half of pregnancy, attending prenatal clinics in five hospitals' affiliated to universities of medical sciences in different districts of Tehran, Iran. Dietary intakes were assessed during gestational age ≤ 6 weeks using a 168-item validated semi-quantitative food frequency questionnaire. Between 24 and 28 weeks of gestation, all pregnant women underwent a scheduled 100 g 3-h oral glucose tolerance test. Diagnosis of GDM was based on criteria set by the American Diabetes Association. Results: Of 1026 study participants, 71 had GDM, with a mean age and pre-pregnancy BMI of 26.7 ± 4.3 y and 25.4 ± 4.5 Kg/m2, respectively. High fruit and vegetable intakes were negatively associated with GDM risk. Compared with women who consumed < 2.1 servings/day, odds ratio (ORs) for those who consumed ≥ 4.9 servings/day was 0.44 (95% CI: 0.20-0.93), after adjustment for confounding factors. Fruit and vegetable intakes were significantly and inversely associated with the GDM; ORs (95% CIs) for GDM among participants with the highest, compared to the lowest quartiles were 0.48 (0.18-0.89) for fruit and 0.46 (0.22-0.99) for vegetables intake. No association was found between dairy products and GDM. Conclusions: Fruit and vegetable consumption in women of reproductive age have beneficial effects in the prevention of GDM.


Assuntos
Diabetes Gestacional , Frutas , Adolescente , Adulto , Diabetes Gestacional/metabolismo , Feminino , Humanos , Irã (Geográfico) , Gravidez , Estudos Prospectivos , Verduras
18.
Endocrinology ; 160(7): 1684-1700, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31150057

RESUMO

Intrauterine exposure to various adverse conditions during fetal development can lead to epigenetic changes in fetal tissues, predisposing those tissues to disease conditions later in life. An example is gestational diabetes (GD), where the offspring has a higher risk of developing obesity, metabolic disorders, or cardiovascular disease in adult life. In this study, using two well-established GD (streptozotocin- and high-fat and high-sugar-induced) mouse models, we report that female offspring from GD dams are predisposed toward fertility problems later in life. This predisposition to fertility problems is due to altered ovarian expression of a peptide called cocaine- and amphetamine-regulated transcript (CART), which is known to negatively affect folliculogenesis and is induced by elevated leptin levels. Results show that the underlying cause of this altered expression is due to fetal epigenetic modifications involving glucose- and insulin-induced miRNA, miR-101, and the phosphatidylinositol 3-kinase/Akt pathway. These signaling events regulate Ezh2, a histone methyltransferase that promotes H3K27me3, a gene-repressive mark, and CBP/p300, a histone acetyltransferase that promotes H3K27ac, a transcription activation mark, in the fetal ovary. Moreover, the CART promoter has depleted 5-methylcytosine (5mC) and enriched 5-hydroxymethylcytosine (5hmC) levels. The depletion of H3K27me3 and 5mC repressive marks and subsequent increase in H3K27ac and 5hmC gene-activating marks convert the Cartpt promoter to a "superpromoter." This makes the Cartpt promoter more sensitive to leptin levels that predispose the GD offspring to fertility problems. Therefore, this study provides a mechanistic insight about fetal epigenome reprogramming that manifests to ovarian dysfunction and subfertility later in adult life.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Epigênese Genética , Infertilidade/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ovário/metabolismo , Regiões Promotoras Genéticas , Animais , Metilação de DNA , Diabetes Mellitus Experimental/genética , Diabetes Gestacional/genética , Feminino , Histonas/metabolismo , Infertilidade/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Fosfatidilinositol 3-Quinases/metabolismo , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
19.
Arch Endocrinol Metab ; 63(3): 241-249, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31166364

RESUMO

OBJECTIVE: To investigate the relationship of flavonoid intake during pregnancy with maternal excessive body weight and gestational diabetes mellitus (GDM). SUBJECTS AND METHODS: A cross-sectional study was conducted among 785 adult women in singleton pregnancies, and data were collected at the time of the oral glucose tolerance test. For the body mass index (BMI) classification according to the gestational age, the criteria of Atalah was used, and the diagnosis of GDM was based on the World Health Organization of 2014. Two 24-hour dietary recalls were obtained, and the usual intake was determined by the Multiple Source Method. Adjusted multinomial logistic regression was used to investigate the relationship of the flavonoids with overweight and obesity, and adjusted non-conditional logistic regression for the relationship of the flavonoids with GDM. RESULTS: The mean (SD) age of the women was 28 (5) years, 32.1% were overweight, 24.6% were obese and 17.7% were diagnosed with GDM. The median (P25, P75) of total flavonoid intake was 50 (31,75) mg/day. Considering the eutrophic women as the reference, the pregnant women with a higher total flavonoid intake [OR 0.62 (95% CI 0.38; 0.96)] and anthocyanidin intake [OR 0.62 (95% CI 0.40; 0.99)] were less likely to be obese when compared to the women with lower intakes. No association of the flavonoids intake with overweight or GDM was found. CONCLUSION: A very low intake of flavonoids was observed. The data suggest that the intake of foods naturally rich in total flavonoids and anthocyanidin has a beneficial role regarding obesity among pregnant women.


Assuntos
Diabetes Gestacional/metabolismo , Comportamento Alimentar , Flavonoides/administração & dosagem , Obesidade/metabolismo , Adulto , Estudos Transversais , Registros de Dieta , Feminino , Flavonoides/metabolismo , Teste de Tolerância a Glucose , Humanos , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
20.
Histochem Cell Biol ; 152(3): 217-225, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31197456

RESUMO

Gestational diabetes mellitus is a risk factor for congenital heart defects. Our previous results indicated that a decrease in myocardial cells and an increase in apoptotic cells leads to heart defects under hyperglycemia, but much work remains to elucidate this important mechanism of myocardial cell apoptosis induced by high glucose (HG). In this study, we found that a decrease in GSK3ß phosphorylation on Ser9 occurred concomitantly with HG-induced cardiomyocyte apoptosis and in the heart tissues of the offspring of diabetic rats in vitro and in vivo. Decreases in GSK3ß (Ser9) phosphorylation in response to HG were remarkably restored after treatment with SC79, an activator of the Akt signaling pathway. SB216763, an effective inhibitor of the GSK3ß signaling pathway, suppressed HG-induced apoptosis in cardiomyocytes. Further studies showed a decrease in the expression of the anti-apoptotic protein MCL-1 was associated with GSK3ß-mediated apoptosis. MCL-1 overexpression partly inhibits HG-induced apoptosis in cardiomyocytes. Herein, this study revealed the roles of GSK3ß and MCL-1 in modulating HG-induced cardiomyocyte apoptosis and maternal diabetes-induced abnormalities.


Assuntos
Apoptose , Glicemia/metabolismo , Diabetes Gestacional/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Cardiopatias Congênitas/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Gestacional/patologia , Feminino , Cardiopatias Congênitas/patologia , Masculino , Miócitos Cardíacos/patologia , Fosforilação , Gravidez , Ratos , Ratos Sprague-Dawley
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