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Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Gestacional/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Glucose , Humanos , Polimorfismo de Nucleotídeo Único/genética , GravidezRESUMO
Size at birth is known to be influenced by various fetal and maternal factors, including genetic effects. South Asians have a high burden of low birth weight and cardiometabolic diseases, yet studies of common genetic variations underpinning these phenotypes are lacking. We generated independent, weighted fetal genetic scores (fGSs) and maternal genetic scores (mGSs) from 196 birth weight-associated variants identified in Europeans and conducted an association analysis with various fetal birth parameters and anthropometric and cardiometabolic traits measured at different follow-up stages (5-6-year intervals) from seven Indian and Bangladeshi cohorts of South Asian ancestry. The results from these cohorts were compared with South Asians in UK Biobank and the Exeter Family Study of Childhood Health, a European ancestry cohort. Birth weight increased by 50.7 g and 33.6 g per SD of fGS (P = 9.1 × 10-11) and mGS (P = 0.003), respectively, in South Asians. A relatively weaker mGS effect compared with Europeans indicates possible different intrauterine exposures between Europeans and South Asians. Birth weight was strongly associated with body size in both childhood and adolescence (P = 3 × 10-5 to 1.9 × 10-51); however, fGS was associated with body size in childhood only (P < 0.01) and with head circumference, fasting glucose, and triglycerides in adults (P < 0.01). The substantially smaller newborn size in South Asians with comparable fetal genetic effect to Europeans on birth weight suggests a significant role of factors related to fetal growth that were not captured by the present genetic scores. These factors may include different environmental exposures, maternal body size, health and nutritional status, etc. Persistent influence of genetic loci on size at birth and adult metabolic syndrome in our study supports a common genetic mechanism that partly explains associations between early development and later cardiometabolic health in various populations, despite marked differences in phenotypic and environmental factors in South Asians.
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Povo Asiático , Desenvolvimento Fetal , Povo Asiático/genética , Peso ao Nascer/genética , Estudos de Coortes , Humanos , Recém-Nascido , Fatores de RiscoRESUMO
Vitamin B12 has multiple biochemical functions including in the one-carbon cycle generating a methyl group for DNA methylation, and metabolism of fatty acids and amino acids to generate energy via the citric acid cycle. The aim of our study was to use a combined epigenomic and transcriptomic approach to identify novel genes mediating the effect of B12 on adipogenesis.Human pre-adipocytes (CHUB-S7) were treated with a range of B12 (0-500 nM) concentrations from the day of cell seeding until harvesting in discovery and validation experiments prior to genome-wide methylation analysis using the Illumina HumanMethylation 450Beadchip. For transcriptomic analysis, RNA-seq libraries were run on the Illumina HiSeq 2500. To further investigate the expression of any genes on human adipogenesis, a second human preadipocyte strain was studied (SGBS) by real-time quantitative PCR (qRT-PCR).A combined epigenetic and transcriptomic approach in differentiated human pre-adipocyte cell line, CHUB-S7, identified that the Human cartilage chitinase 3-like protein 2 (CHI3L2) gene was hypo-methylated and had increased expression in low B12 conditions. Furthermore, there was an approximately 1000-fold increase in CHI3L2 expression in the early days of adipocyte differentiation, which paralleled an increase of lipid droplets in differentiated SGBS cells and an increased expression level of markers of mature adipocytes.In summary, we have identified a potential role of the human cartilage chitinase 3-like protein 2 (CHI3L2) in adipocyte function in the presence of low B12 levels.
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Quitinases , Adipócitos/metabolismo , Adipogenia/genética , Aminoácidos/genética , Aminoácidos/metabolismo , Aminoácidos/farmacologia , Cartilagem/metabolismo , Diferenciação Celular/genética , Quitinases/genética , Quitinases/metabolismo , Quitinases/farmacologia , Metilação de DNA , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Humanos , Transcriptoma , Vitamina B 12/metabolismo , Vitamina B 12/farmacologiaRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used. OBJECTIVE: We used a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT). METHODS: In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age of 29 y, BMI (in kg/m2) 26.7 and gestational age 33 wk were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine, 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. The independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the HOMA-IR and adjusting for age, GDM status, and BMI. RESULTS: There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (ß = -0.622, P = 0.004), RCF (ß = 0.387, P = 0.018), and BMI (ß = 0.024, P < 0.001) were the significant predictors of HOMA-IR variance. CONCLUSIONS: Significant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other.
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Diabetes Gestacional , Resistência à Insulina , Adulto , Glicemia , Estudos Transversais , Feminino , Ácido Fólico , Glucose , Humanos , Insulina , Gravidez , Terceiro Trimestre da Gravidez , Vitamina B 12RESUMO
AIMS: Gestational diabetes (GDM) is the most common metabolic disorder of pregnancy, requiring complex management and empowerment of those affected. Mobile health (mHealth) applications (apps) are proposed for streamlining healthcare service delivery, extending care relationships into the community, and empowering those affected by prolonged medical disorders to be equal collaborators in their healthcare. This review investigates mHealth apps intended for use with GDM; specifically those powered by artificial intelligence (AI) or providing decision support. METHODS: A scoping review using the novel Survey Tool approach for collaborative literature Reviews (STaR) process was performed. RESULTS: From 18 papers, 11 discrete GDM-based mHealth apps were identified, but only 3 were reasonably mature with only one currently in use in a clinical setting. Two-thirds of the apps provided condition-relevant contextual user feedback that could aid in patient self care. However, although each app targeted one or more components of the GDM clinical pathway, no app addressed the entirety from diagnosis to postpartum. CONCLUSIONS: There are limited mHealth apps for GDM that incorporate AI or AI-based decision support. Many exist only to record patient information like blood glucose readings or diet, provide generic patient education or advice, or to reduce adverse events by providing medication or appointment alerts. Significant barriers remain that continue to limit the adoption of mHealth apps in clinical care settings. Further research and development are needed to deliver intelligent holistic mHealth apps using AI that can truly reduce healthcare resource use and improve outcomes by enabling patient self care in the community.
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Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Diabetes Gestacional/diagnóstico , Aplicativos Móveis , Período Pós-Parto , Telemedicina/métodos , Glicemia/metabolismo , Diabetes Gestacional/sangue , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Betel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome. The aim of our pilot study was to identify gene expression relevant to obesity, T2D and the metabolic syndrome using a genome-wide transcriptomic approach in a human monocyte cell line incubated with arecoline and its nitrosated products. RESULTS: The THP1 monocyte cell line was incubated separately with arecoline and 3-methylnitrosaminopropionaldehyde (MNPA) in triplicate for 24 h and pooled cDNA indexed paired-end libraries were sequenced (Illumina NextSeq 500). After incubation with arecoline and MNPA, 15 and 39 genes respectively had significant changes in their expression (q < 0.05, log fold change 1.5). Eighteen of those genes have reported associations with T2D and obesity in humans; of these genes there was most marked evidence for CLEC10A, MAPK8IP1, NEGR1, NQ01 and INHBE genes. CONCLUSIONS: Our preliminary studies have identified a large number of genes relevant to obesity, T2D and metabolic syndrome whose expression was changed significantly in human TPH1 cells following incubation with betel-nut derived arecoline or with MNPA. These findings require validation by further cell-based work and investigation amongst betel-chewing communities.
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Areca/química , Arecolina/farmacologia , Diabetes Mellitus Tipo 2/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Síndrome Metabólica/genética , Monócitos/metabolismo , Obesidade/genética , Transcriptoma/efeitos dos fármacos , Biomarcadores/análise , Biomarcadores/metabolismo , Seguimentos , Humanos , Monócitos/efeitos dos fármacos , Monócitos/patologia , Projetos Piloto , PrognósticoRESUMO
INTRODUCTION: Mothers with gestational diabetes mellitus (GDM) are at increased risk of pregnancy-related complications and developing type 2 diabetes after delivery. Diet and physical activity-based interventions may prevent GDM, but variations in populations, interventions and outcomes in primary trials have limited the translation of available evidence into practice. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to assess the differential effects and cost-effectiveness of diet and physical activity-based interventions in preventing GDM and its complications. METHODS: The International Weight Management in Pregnancy Collaborative Network database is a living repository of IPD from randomised trials on diet and physical activity in pregnancy identified through a systematic literature search. We shall update our existing search on MEDLINE, Embase, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment Database without language restriction to identify relevant trials until March 2021. Primary researchers will be invited to join the Network and share their IPD. Trials including women with GDM at baseline will be excluded. We shall perform a one and two stage random-effect meta-analysis for each intervention type (all interventions, diet-based, physical activity-based and mixed approach) to obtain summary intervention effects on GDM with 95% CIs and summary treatment-covariate interactions. Heterogeneity will be summarised using I2 and tau2 statistics with 95% prediction intervals. Publication and availability bias will be assessed by examining small study effects. Study quality of included trials will be assessed by the Cochrane Risk of Bias tool, and the Grading of Recommendations, Assessment, Development and Evaluations approach will be used to grade the evidence in the results. A model-based economic analysis will be carried out to assess the cost-effectiveness of interventions to prevent GDM and its complications compared with usual care. ETHICS AND DISSEMINATION: Ethics approval is not required. The study is registered on the International Prospective Register of Systematic Reviews (CRD42020212884). Results will be submitted for publication in peer-reviewed journals.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Análise Custo-Benefício , Diabetes Gestacional/prevenção & controle , Dieta , Exercício Físico , Feminino , Humanos , Metanálise como Assunto , Gravidez , Revisões Sistemáticas como AssuntoRESUMO
AIM: To assess the efficacy of vitamin D3 or B12 supplementation during pregnancy. METHODS: Pregnant women at 6-14 weeks in the intervention arm received oral high dose intermittent vitamin D3 and/or low dose B12 supplementation if they had vitamin D or vitamin B12 deficiency. The control arm received prescribed dietary instruction only. An additional observational arm for those mothers at booking with normal vitamin D and vitamin B12 level was also recruited. All groups received standard care during pregnancy. RESULTS: The primary endpoint of either vitamin D or B12 at term was not met. At baseline 25% participants in both the interventional and control arms had severe D deficiency (<30 nmol/l), reducing to under 3.4% in both groups. No maternal differences in vitamin D or B12 levels were found at delivery between the intervention, control, or observational groups. No significant difference in any of the pregnancy or birth outcomes was observed between three groups. CONCLUSIONS: In this study, oral supplementation of high dose intermittent vitamin D or low dose vitamin B12 regime failed to correct the relevant nutritional deficiencies in Bangladeshi pregnant women as per protocol. Both dietary supplementation and high dose vitamin D corrected severe vitamin deficiency.
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Colecalciferol/uso terapêutico , Suplementos Nutricionais/normas , Vitamina B 12/uso terapêutico , Adolescente , Adulto , Colecalciferol/farmacologia , Feminino , Humanos , Projetos Piloto , Gravidez , Complicações na Gravidez , Vitamina B 12/farmacologia , Adulto JovemRESUMO
Background: The pharmacogenetic effect on cardiovascular disease reduction in response to statin treatment has only been assessed in small studies. In a pharmacogenetic genome wide association study (GWAS) analysis within the Genomic Investigation of Statin Therapy (GIST) consortium, we investigated whether genetic variation was associated with the response of statins on cardiovascular disease risk reduction. Methods: The investigated endpoint was incident myocardial infarction (MI) defined as coronary heart disease death and definite and suspect non-fatal MI. For imputed single nucleotide polymorphisms (SNPs), regression analysis was performed on expected allelic dosage and meta-analysed with a fixed-effects model, inverse variance weighted meta-analysis. All SNPs with p-values <5.0 × 10-4 in stage 1 GWAS meta-analysis were selected for further investigation in stage-2. As a secondary analysis, we extracted SNPs from the Stage-1 GWAS meta-analysis results based on predefined hypotheses to possibly modifying the effect of statin therapy on MI. Results: In stage-1 meta-analysis (eight studies, n = 10,769, 4,212 cases), we observed no genome-wide significant results (p < 5.0 × 10-8). A total of 144 genetic variants were followed-up in the second stage (three studies, n = 1,525, 180 cases). In the combined meta-analysis, no genome-wide significant hits were identified. Moreover, none of the look-ups of SNPs known to be associated with either CHD or with statin response to cholesterol levels reached Bonferroni level of significance within our stage-1 meta-analysis. Conclusion: This GWAS analysis did not provide evidence that genetic variation affects statin response on cardiovascular risk reduction. It does not appear likely that genetic testing for predicting effects of statins on clinical events will become a useful tool in clinical practice.
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Mitochondrial health and cellular metabolism can heavily influence the onset of senescence in T cells. CD8+ EMRA T cells exhibit mitochondrial dysfunction and alterations to oxidative phosphorylation, however, the metabolic properties of senescent CD8+ T cells from people living with type 2 diabetes (T2D) are not known. We show here that mitochondria from T2D CD8+ T cells had a higher oxidative capacity together with increased levels of mitochondrial reactive oxgen species (mtROS), compared to age-matched control cells. While fatty acid uptake was increased, fatty acid oxidation was impaired in T2D CD8+ EMRA T cells, which also showed an accumulation of lipid droplets and decreased AMPK activity. Increasing glucose and fatty acids in healthy CD8+ T cells resulted in increased p-p53 expression and a fragmented mitochondrial morphology, similar to that observed in T2D CD8+ EMRA T cells. The resulting mitochondrial changes are likely to have a profound effect on T cell function. Consequently, a better understanding of these metabolic abnormalities is crucial as metabolic manipulation of these cells may restore correct T cell function and help reduce the impact of T cell dysfunction in T2D.
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Bayesian networks (BNs) have received increasing research attention that is not matched by adoption in practice and yet have potential to significantly benefit healthcare. Hitherto, research works have not investigated the types of medical conditions being modelled with BNs, nor whether there are any differences in how and why they are applied to different conditions. This research seeks to identify and quantify the range of medical conditions for which healthcare-related BN models have been proposed, and the differences in approach between the most common medical conditions to which they have been applied. We found that almost two-thirds of all healthcare BNs are focused on four conditions: cardiac, cancer, psychological and lung disorders. We believe there is a lack of understanding regarding how BNs work and what they are capable of, and that it is only with greater understanding and promotion that we may ever realise the full potential of BNs to effect positive change in daily healthcare practice.
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Atenção à Saúde , Teorema de Bayes , HumanosRESUMO
Information visualisation is transforming data into visual representations to convey information hidden within large datasets. Information visualisation in medicine is underdeveloped. In midwifery, the impact of different graphs on clinicians' and patients' understanding is not well understood. We investigate this gap and its potential consequences.
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Tocologia , Feminino , Humanos , GravidezRESUMO
It remains unclear whether the increased risk of new-onset type 2 diabetes (T2D) seen in statin users is due to low LDL-C concentrations, or due to the statin-induced proportional change in LDL-C. In addition, genetic instruments have not been proposed before to examine whether liability to T2D might cause greater proportional statin-induced LDL-C lowering. Using summary-level statistics from the Genomic Investigation of Statin Therapy (GIST, nmax = 40,914) and DIAGRAM (nmax = 159,208) consortia, we found a positive genetic correlation between LDL-C statin response and T2D using LD score regression (rgenetic = 0.36, s.e. = 0.13). However, mendelian randomization analyses did not provide support for statin response having a causal effect on T2D risk (OR 1.00 (95% CI: 0.97, 1.03) per 10% increase in statin response), nor that liability to T2D has a causal effect on statin-induced LDL-C response (0.20% increase in response (95% CI: -0.40, 0.80) per doubling of odds of liability to T2D). Although we found no evidence to suggest that proportional statin response influences T2D risk, a definitive assessment should be made in populations comprised exclusively of statin users, as the presence of nonstatin users in the DIAGRAM dataset may have substantially diluted our effect estimate.
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LDL-Colesterol/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Análise da Randomização Mendeliana/métodos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/induzido quimicamente , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , MasculinoRESUMO
The worldwide prevalence of diabetes has reached 8.5% among adults, and this is characterised by elevated glucose concentrations and failing insulin secretion. Furthermore, most people with type 2 diabetes are either obese or overweight, with the associated dyslipidaemia contributing to the development of insulin resistance and increased cardiovascular risk. Here we incubated INS-1 pancreatic ß-cells for 72â¯h in RPMI-1640 media, or media supplemented with 28â¯mM glucose, 200⯵M palmitic acid, and 200⯵M oleic acid as a cellular model of diabetic glucolipotoxicity. Illumina HiSeq gene expression analysis showed the trace amine-associated receptor (TAAR) family to be among the most highly downregulated by glucolipotoxicity. Importantly, MetaCore integrated knowledge database, from Clarivate Analytics, indicated potential TAAR impact on insulin secretion through adenylyl cyclase signalling pathways. We therefore investigated the effect of TAAR ligands on cAMP signalling and insulin secretion, and found that only the branch of the TAAR family tree that is activated by isopentylamine, 2-phenylethylamine, p-tyramine, and agmatine significantly increased intracellular cAMP and resulted in increased insulin secretion from INS-1 cells and primary mouse islets under normal conditions. Crucially however, this enhancement was not evident when the receptor family was downregulated by glucolipotoxic conditions. This data indicates that a subset of TAARs are regulators of insulin secretion in pancreatic ß-cells, and that their downregulation contributes to glucolipotoxic inhibition of insulin secretion. As such they may be potential targets for treatment of type 2 diabetes.
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Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ácido Oleico/farmacologia , Ácido Palmítico/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Linhagem Celular Tumoral , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Resistência à Insulina/genética , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ligantes , Masculino , Camundongos , Ratos , Receptores Acoplados a Proteínas G/genéticaRESUMO
BACKGROUND: To assess the maternal characteristics and nutritional status according to body mass index (BMI) at 6-14 weeks of gestation and to examine the relationship between maternal nutritional status in early pregnancy and its impact on neonatal birth weight. METHODS: The investigation was conducted from April 2011 to June 2012 in Dhaka, Bangladesh. A total of 498 primigravida pregnant women participated in the study; women with known diabetes or previous gestational diabetes (GDM) were excluded. Maternal demographic details, pregnancy history and anthropometric measurements were obtained from the mother at the recruitment (6-14 weeks), 2nd visit between 24 and 28 week of gestation and 3rd visit at delivery. Cord venous blood samples of newborns (n = 138) were collected immediately after delivery for blood glucose, insulin, lipid profile, leptin and micronutrients including serum folate, ferritin, homocysteine, vitamin D, and vitamin B12. RESULTS: The prevalence at 6-14 weeks of pregnancy of anemia (Hb, < 11 g/dl), vitamin D deficiency (< 30 nmol/l), vitamin B12 deficiency (< 200 pg/ml), high homocysteine level (> 15 µmol/l), folate deficiency (< 3 ng/ml) and iron deficiency (ferritin < 13 ng/ml) were 19.5, 46.4, 15.1, 1.2, 0.4, and 12.7% respectively. GDM was found in 18.4% women. The prevalence of GDM was higher in overweight women (28.1%) than underweight (16.7%) and normal weight women (16.0%: p < 0.05). The incidence of low birth weight (LBW) and preterm delivery were 11.6 and 5.8% respectively and was not related to maternal BMI at 6-14 weeks of pregnancy. Maternal height was positively (p = 0.02), and homocysteine was negatively associated with neonatal birth weight (p = 0.02). In addition, the newborn's cord serum folate was positively (p = 0.03) and cord triglyceride was negatively (p = 0.03) associated with neonatal birth weight. CONCLUSION: Multiple maternal micronutrient deficiencies were present in early pregnancy. Maternal BMI in early pregnancy was not related to preterm deliveries or LBW. LBW was associated with lower folate, elevated cord triglyceride concentrations of the neonates and mother's height and increase in maternal homocysteine levels. The data has important implications for pregnancy care in Bangladesh and other similar communities.
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Peso ao Nascer/fisiologia , Índice de Massa Corporal , Saúde Materna , Estado Nutricional/fisiologia , Complicações Hematológicas na Gravidez/epidemiologia , Bangladesh/epidemiologia , Biomarcadores/sangue , Feminino , Ácido Fólico/sangue , Idade Gestacional , Homocisteína/sangue , Humanos , Recém-Nascido , Masculino , Gravidez , Complicações Hematológicas na Gravidez/sangue , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. METHODS AND FINDINGS: We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks' gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3-10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0-64.6, p ≤ 0.001) than controls; increased their intake of fish (p < 0.001), white meat (p < 0.001), and pulses (p = 0.05); and reduced their intake of red meat (p < 0.001), butter, margarine, and cream (p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56-1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58-1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47-0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference -1.2 Kg, 95% CI -2.2 to -0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offspring complications between both groups. When we pooled findings from the Effect of Simple, Targeted Diet in Pregnant Women With Metabolic Risk Factors on Pregnancy Outcomes (ESTEEM) trial with similar trials using random effects meta-analysis, we observed a significant reduction in gestational diabetes (odds ratio [OR] 0.67, 95% CI 0.53-0.84, I2 = 0%), with no heterogeneity (2 trials, 2,397 women). The study's limitations include the use of participant reported tools for adherence to the intervention instead of objective biomarkers. CONCLUSIONS: A simple, individualised, Mediterranean-style diet in pregnancy did not reduce the overall risk of adverse maternal and offspring complications but has the potential to reduce gestational weight gain and the risk of gestational diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02218931.
Assuntos
Diabetes Gestacional/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Ganho de Peso na Gestação , Adulto , Técnica Delphi , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/etiologia , Diabetes Gestacional/fisiopatologia , Metabolismo Energético , Inglaterra , Feminino , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Metanálise como Assunto , Estado Nutricional , Valor Nutritivo , Gravidez , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
CONTEXT: Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism. OBJECTIVE: To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3. METHODS: We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4ß,25-dihydroxyvitamin D3 [4ß,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. RESULTS: Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4ß,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4ß,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4ß,25(OH)2D3 to 25(OH)D3 did not differ between groups. CONCLUSIONS: Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.
Assuntos
Colecalciferol/farmacologia , Suplementos Nutricionais , Ergocalciferóis/farmacologia , Vitaminas/farmacologia , 24,25-Di-Hidroxivitamina D 3/sangue , 25-Hidroxivitamina D 2/sangue , Adulto , Idoso , Calcifediol/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Gestational diabetes increases maternal and offspring complications in pregnancy and cardiovascular complications in the long term. The nutritional supplement myo-inositol may prevent gestational diabetes; however, further evaluation is required, especially in multiethnic high-risk mothers. Our pilot trial on myo-inositol to prevent gestational diabetes will evaluate trial processes, assess acceptability to mothers and obtain preliminary estimates of effect and cost data prior to a large full-scale trial. METHODS AND ANALYSIS: EMmY is a multicentre, placebo-controlled, double-blind, pilot, randomised trial, with qualitative evaluation. We will recruit pregnant women at 12-15+6 weeks' gestation, with gestational diabetes risk factors, from five maternity units in England between 2018 and 2019. We will randomise 200 women to take either 2 g of myo-inositol powder (intervention) or placebo, twice daily until delivery. We will assess rates of recruitment, randomisation, adherence to intervention and follow-up. Gestational diabetes will be diagnosed at 24-28 weeks as per the National Institute for Health and Care Excellence (NICE) criteria (fasting plasma glucose: ≥5.6 mmol/L and 2-hour plasma glucose: ≥7.8 mmol/L). We will assess the effects of myo-inositol on glycaemic indices at 28 weeks and on other maternal, fetal and neonatal outcomes at postnatal discharge. Qualitative evaluation will explore the acceptability of the trial and the intervention among women and healthcare professionals. Cost data and health-related quality of life measures will be captured. We will summarise feasibility outcomes using standard methods for proportions and other descriptive statistics, and where appropriate, report point estimates of effect sizes (eg, mean differences and relative risks) and associated 95% CIs. ETHICS AND DISSEMINATION: Ethical approval was obtained through the London Queen Square Research Ethics Committee (17/LO/1741). Study findings will be submitted for publication in peer-reviewed journals. Newsletters will be made available to participants, healthcare professionals and members of Katie's Team (a patient and public advisory group) to disseminate. TRIAL REGISTRATION NUMBER: ISRCTN48872100. PROTOCOL VERSION AND DATE: Version 4.0, 15 January 2018.
Assuntos
Diabetes Gestacional , Inositol , Adulto , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/prevenção & controle , Suplementos Nutricionais , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Inglaterra , Feminino , Idade Gestacional , Índice Glicêmico , Humanos , Inositol/administração & dosagem , Inositol/efeitos adversos , Projetos Piloto , Gravidez , Resultado da Gravidez , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/efeitos adversosRESUMO
OBJECTIVE: To explore the impact of maternal body weight on maternal nutrition and micronutrient status in early pregnancy and potential impact on metabolic status in newborns. METHODOLOGY: The EU FP7 project GIFTS was conducted from Jan 2012 to May 2014. Demographic details and anthropometric measurements of women in the first trimester of pregnancy were obtained. Blood samples were collected for OGTT, insulin, lipid profile, serum folate, ferritin, vitamin D, vitamin B12, and red cell folate. Newborn anthropometric characteristics were observed. Cord blood samples were collected after delivery for glucose, insulin, and lipid profile of newborns. RESULTS: A total of 301 pregnant mothers, 108 overweight, 63 underweight, and 130 normal weight were included. Prevalence of vitamin D deficiency (<30 ng/mL) and low vitamin B12 (<190 ng/l) were high, 44% and 42%, respectively, in the first trimester. Anemic women (due to B12 or iron deficiency) were 79%, while 72% had low ferritin levels. Gestational diabetes was 16%. Differences were observed between underweight and overweight mothers (P < 0.05) for fasting blood glucose, insulin levels, and serum ferritin were observed. No significant difference was observed between vitamin D, serum B12, and red cell folate levels. CONCLUSION: Prevalence of multiple micronutrient deficiencies was common among Pakistani women during early pregnancy despite the nonvegetarian diet that has important implications for pregnancy care in Pakistan and potentially in expatriate communities living abroad. This trial is registered with ISRCTN number 83599025.
Assuntos
Glicemia , Peso Corporal/fisiologia , Insulina/sangue , Lipídeos/sangue , Fenômenos Fisiológicos da Nutrição Materna/fisiologia , Adulto , Diabetes Gestacional/sangue , Feminino , Ferritinas/sangue , Ácido Fólico/sangue , Humanos , Recém-Nascido , Gravidez , Estudos Prospectivos , Vitamina B 12/sangueRESUMO
BACKGROUND: Women's groups interventions in Bangladesh reduced neonatal deaths by 38% and improved hygienic delivery, newborn care practices and breast feeding. We explore the longer-term impact of exposure to women's groups during pregnancy on child growth at 2-4 years. METHODS: We performed a cross-sectional survey of child anthropometric measures (analysed as z-scores) among children born to women who had participated in the women's groups interventions while pregnant, compared with an age-matched and sex-matched sample of children born to control mothers. Results were stratified by maternal body mass index (BMI) and adjusted for possible confounding effects of maternal education, household asset ownership and, in a separate model, mother-child height difference, a proxy for improved survival of small babies in intervention groups. RESULTS: Data were obtained from 2587 mother-child pairs (91% response). After adjustment for asset ownership, maternal education and potential survival effects, children whose mothers were exposed to the women's group intervention had higher head (0.16 (0.04 to 0.28)), mid-upper arm (0.11 (0.04 to 0.19)), abdominal (0.13 (0.00 to 0.26)) and chest (0.18 (0.08 to 0.29)) circumferences than their control counterparts. No significant differences in subcutaneous fat (subscapular and triceps skinfold thickness) were observed. When stratified by maternal BMI, intervention children had higher weight, BMI and circumferences, and these effects decreased with increasing maternal BMI category. CONCLUSIONS: Women's groups appear to have had a lasting, positive impact on child anthropometric outcomes, with most significant results clustering in children of underweight mothers. Observed differences are likely to be of public health significance in terms of the nutritional and metabolic development of children.