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BACKGROUND: A barrier to achieving first trimester antenatal care (ANC) attendance in many countries has been the widespread cultural practice of not discussing pregnancies in the early stages. Motivations for concealing pregnancy bear further study, as the interventions necessary to encourage early ANC attendance may be more complicated than targeting infrastructural barriers to ANC attendance such as transportation, time, and cost. METHODS: Five focus groups with a total of 30 married, pregnant women were conducted to assess the feasibility of conducting a randomised controlled trial to evaluate the effectiveness of early initiation of physical activity and/or yoghurt consumption in reducing Gestational Diabetes Mellitus in pregnant women in The Gambia. Focus group transcripts were coded through a thematic analysis approach, assessing themes as they arose in relation to failure to attend early ANC. RESULTS: Two reasons for the concealment of pregnancies in the first trimester or ahead of a pregnancy's obvious visibility to others were given by focus group participants. These were 'pregnancy outside of marriage' and 'evil spirits and miscarriage.' Concealment on both grounds was motivated through specific worries and fears. In the case of a pregnancy outside of marriage, this was worry over social stigma and shame. Evil spirits were widely considered to be a cause of early miscarriage, and as such, women may choose to conceal their pregnancies in the early stages as a form of protection. CONCLUSION: Women's lived experiences of evil spirits have been under-explored in qualitative health research as they relate specifically to women's access to early antenatal care. Better understanding of how such sprits are experienced and why some women perceive themselves as vulnerable to related spiritual attacks may help healthcare workers or community health workers to identify in a timely manner the women most likely to fear such situations and spirits and subsequently conceal their pregnancies.
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Aborto Espontâneo , Motivação , Feminino , Humanos , Gravidez , Gâmbia , Cognição , Agentes Comunitários de SaúdeRESUMO
BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.
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Tecido Adiposo/crescimento & desenvolvimento , Fatores de Risco de Doenças Cardíacas , Doenças Metabólicas/fisiopatologia , Tecido Adiposo/fisiopatologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Índia , Masculino , Doenças Metabólicas/metabolismoRESUMO
AIMS/HYPOTHESIS: Circulating succinate and 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) were recently shown to promote brown adipocyte thermogenesis and protect against metabolic disorders in rodents. This study aimed to evaluate the associations between plasma levels of these metabolites and adiposity and metabolic profile in humans. METHODS: Fasting plasma succinate and 12,13-diHOME levels were quantified using ultra HPLC-tandem MS in 2248 individuals (50% female, mean age 41.3 ± 5.9 years, mean BMI 26.1 ± 4.6 kg/m2) in addition to fasting plasma biochemistry. Total and regional adiposity were assessed with dual-energy x-ray absorptiometry. An age- and sex-adjusted linear regression model was used to determine the associations between succinate and 12,13-diHOME levels and body composition and metabolic profile. Two-sample Mendelian randomisation was used to assess the associations between genetically determined BMI and metabolic traits with circulating plasma succinate and 12,13-diHOME. RESULTS: A one-SD higher plasma succinate and 12,13-diHOME concentration was associated with a 0.15 SD (95% CI 0.28, 0.03) and 0.08 SD (0.15, 0.01) lower total fat mass respectively. Additionally, a one-SD higher plasma 12,13-diHOME level was associated with a 0.09 SD (0.16, 0.02) lower fasting plasma insulin and 0.10 SD (0.17, 0.04) lower plasma triacylglycerol. In Mendelian randomisation analyses, genetically determined higher BMI, fasting hyperinsulinaemia and elevated lipid levels were not associated with changes in either plasma succinate or plasma 12,13-diHOME concentrations. No indications of bias due to directional pleiotropy were detected in the Mendelian randomisation analyses. CONCLUSIONS/INTERPRETATION: Our findings tentatively suggest that plasma succinate and 12,13-diHOME may play a role in the regulation of energy metabolism and brown adipose tissue activation in humans. Further studies encompassing direct assessment of brown adipose tissue activity and dietary supplementation are necessary to investigate the potential beneficial effects of these metabolites on systemic metabolism.
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Adiposidade , Ácidos Oleicos/metabolismo , Ácido Succínico/química , Termogênese , Adipócitos/metabolismo , Tecido Adiposo Marrom/metabolismo , Adulto , Índice de Massa Corporal , Estudos Transversais , Metabolismo Energético , Feminino , Humanos , Resistência à Insulina , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , ObesidadeRESUMO
PURPOSE OF REVIEW: Upper body abdominal and lower body gluteofemoral fat depot masses display opposing associations with plasma lipid and lipoprotein and cardiovascular disease (CVD) risk profiles. We review developments on adipose tissue fatty acid metabolism in the context of body fat distribution and how that might be related to adverse lipid and lipoprotein profiles and CVD risk. RECENT FINDINGS: Recent data have confirmed the paradoxical relationship of upper abdominal and lower body gluteofemoral adiposity and CVD risk. Mechanistically, this is likely to reflect the different ways fat depots handle lipid storage and release, which impacts directly and indirectly on lipid and lipoprotein metabolism. The upper body enhances immediate fat storage pathway with rapid uptake of dietary-derived fatty acids, whereas the lower body fat depot has a reduced lipid turnover accommodating a slower fat redistribution. Body fat distribution and the fat depots' ability to undergo appropriate expansion when fat storage is required, rather than overall body fatness, appear as the important determinant of metabolic health. SUMMARY: A focus on fat distribution in overweight people, preferably using precise imaging methods, rather than quantifying total body fatness, is likely to provide the medical community with better tools to stratify and treat patients with obesity-related complications.
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Distribuição da Gordura Corporal , Doenças Cardiovasculares/metabolismo , Lipoproteínas/metabolismo , Doenças Cardiovasculares/epidemiologia , Humanos , RiscoRESUMO
BACKGROUND: ABO blood groups have been shown to be associated with increased risks of venous thromboembolic and arterial disease. However, the reported magnitude of this association is inconsistent and is based on evidence from small-scale studies. METHODS AND RESULTS: We used the SCANDAT2 (Scandinavian Donations and Transfusions) database of blood donors linked with other nationwide health data registers to investigate the association between ABO blood groups and the incidence of first and recurrent venous thromboembolic and arterial events. Blood donors in Denmark and Sweden between 1987 and 2012 were followed up for diagnosis of thromboembolism and arterial events. Poisson regression models were used to estimate incidence rate ratios as measures of relative risk. A total of 9170 venous and 24 653 arterial events occurred in 1 112 072 individuals during 13.6 million person-years of follow-up. Compared with blood group O, non-O blood groups were associated with higher incidence of both venous and arterial thromboembolic events. The highest rate ratios were observed for pregnancy-related venous thromboembolism (incidence rate ratio, 2.22; 95% confidence interval, 1.77-2.79), deep vein thrombosis (incidence rate ratio, 1.92; 95% confidence interval, 1.80-2.05), and pulmonary embolism (incidence rate ratio, 1.80; 95% confidence interval, 1.71-1.88). CONCLUSIONS: In this healthy population of blood donors, non-O blood groups explain >30% of venous thromboembolic events. Although ABO blood groups may potentially be used with available prediction systems for identifying at-risk individuals, its clinical utility requires further comparison with other risk markers.
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Sistema ABO de Grupos Sanguíneos/análise , Arteriopatias Oclusivas/epidemiologia , Doadores de Sangue/estatística & dados numéricos , Tromboembolia/epidemiologia , Sistema ABO de Grupos Sanguíneos/genética , Adulto , Arteriopatias Oclusivas/genética , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Complicações Cardiovasculares na Gravidez/genética , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/genética , Recidiva , Análise de Regressão , Risco , Suécia/epidemiologia , Tromboembolia/genética , Trombofilia/genética , Trombose Venosa/epidemiologia , Trombose Venosa/genética , Adulto JovemRESUMO
OBJECTIVES: To investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians. STUDY DESIGN: Data from 2218 adults from the Vellore Birth Cohort were examined for associations of cross-sectional height and body mass index (BMI) and longitudinal growth (independent conditional measures of height and weight gain) in infancy, childhood, adolescence, and adulthood with adult waist circumference (WC), blood pressure (BP), insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR]), and plasma glucose and lipid concentrations. RESULTS: Higher BMI/greater conditional relative weight gain at all ages was associated with higher adult WC, after 3 months with higher adult BP, HOMA-IR, and lipids, and after 15 years with higher glucose concentrations. Taller adult height was associated with higher WC (men ß = 2.32 cm per SD, women ß = 1.63, both P < .001), BP (men ß = 2.10 mm Hg per SD, women ß = 1.21, both P ≤ .001), and HOMA-IR (men ß = 0.08 log units per SD, women ß = 0.12, both P ≤ .05) but lower glucose concentrations (women ß = -0.03 log mmol/L per SD P = .003). Greater height or height gain at all earlier ages were associated with higher adult CVD risk traits. These positive associations were attenuated when adjusted for adult BMI and height. Shorter length and lower BMI at birth were associated with higher glucose concentration in women. CONCLUSIONS: Greater height or weight gain relative to height during childhood or adolescence was associated with a more adverse adult CVD risk marker profile, and this was mostly attributable to larger adult size.
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Estatura , Doenças Cardiovasculares/epidemiologia , Aumento de Peso , Adolescente , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Crescimento , Humanos , Lactente , Masculino , Prognóstico , Estudos Prospectivos , Medição de Risco , Adulto JovemRESUMO
Monoclonal B-cell lymphocytosis (MBL) is a precursor of chronic lymphocytic leukemia (CLL). Observations of MBL in blood donors raise concern that transmitted MBL may cause recipient CLL. Using a database with health information on 1.5 million donors and 2.1 million recipients, we compared CLL occurrence among 7413 recipients of blood from 796 donors diagnosed with CLL after donation cessation, and among 80, 431 recipients of blood from 7477 matched CLL-free donors. During follow-up, 12 and 107 cases of CLL occurred among the exposed and unexposed recipients, respectively, yielding a relative risk of 0.94 (95% confidence interval, 0.52-1.71). Analyses using the entire database showed no evidence of CLL clustering among recipients of blood from individual donors. In conclusion, when donor MBL was approximated by subsequent donor CLL diagnosis, data from 2 countries' entire computerized transfusion experience over more than 30 years indicate that MBL/CLL transmission does not contribute importantly to recipient CLL risk.
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Linfócitos B/patologia , Doadores de Sangue , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/etiologia , Linfocitose/complicações , Reação Transfusional , Seguimentos , Humanos , Contagem de Linfócitos , Prognóstico , Países Escandinavos e NórdicosRESUMO
BACKGROUND: Citrate anticoagulation during apheresis induces transient alterations in calcium homeostasis. It is unknown whether the repeated, transient alterations in calcium homeostasis experienced by repeated apheresis donors affects bone turnover to increase fracture risk. Our aim was to investigate the risk of osteoporotic and nonosteoporotic fracture among voluntary, frequent apheresis donors. STUDY DESIGN AND METHODS: All apheresis donors were identified from the Scandinavian Donations and Transfusions database (SCANDAT2), which includes information on over 1.6 million blood donors from Sweden and Denmark from the years 1968 and 1981, respectively. Only data from Sweden were used for these analyses. Information on fractures was obtained by linking SCANDAT2 to hospital registers. Poisson regression was used to compute incidence rate ratios of fractures in relation to the cumulative number of apheresis donations, both overall and in fixed time windows. RESULTS: In total, 140,289 apheresis donors (67,970 women and 72,319 men) were identified from the SCANDAT2 database and were followed for up to 23 years. We observed no association between the frequency of apheresis donation and the risk of fracture either in the overall study period or during fixed-length time windows. The incidence rate ratio of fractures in donors who had made 100 or more cumulative apheresis donations was 0.99 (95% confidence interval, 0.92-1.06) compared with donors who had made from 9 to 24 donations. The results were similar in analyses stratified by sex and restricted to postmenopausal women. CONCLUSIONS: The absence of an association between repeated apheresis donation and fracture risk indicates that apheresis collection is safe with regard to bone health.
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Remoção de Componentes Sanguíneos/efeitos adversos , Doadores de Sangue , Fraturas Ósseas/epidemiologia , Sistema de Registros , Adulto , Bases de Dados Factuais , Dinamarca/epidemiologia , Feminino , Seguimentos , Fraturas Ósseas/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia/epidemiologiaRESUMO
OBJECTIVE: There is an increasing focus on massive transfusion, but there is a paucity of comprehensive descriptions of the massively transfused patients and their outcomes. The objective of this study is to describe the incidence rate of massive transfusion, patient characteristics, and the mortality of massively transfused patients. DESIGN: Descriptive cohort study. SETTING: Nationwide study with data from Sweden and Denmark. PATIENTS: The study was based on the Scandinavian Donations and Transfusions database, including all patients receiving 10 or more red cell concentrate transfusions in Sweden from 1987 and in Denmark from 1996. A total of 92,057 patients were included. Patients were followed until the end of 2012. MEASUREMENTS AND MAIN RESULTS: Descriptive statistics were used to characterize the patients and indications. Post transfusion mortality was expressed as crude 30-day mortality and as long-term mortality using the Kaplan-Meier method and using standardized mortality ratios. The incidence of massive transfusion was higher in Denmark (4.5 per 10,000) than in Sweden (2.5 per 10,000). The most common indication for massive transfusion was major surgery (61.2%) followed by trauma (15.4%). Massive transfusion due to obstetrical bleeding constituted only 1.8%. The overall 5-year mortality was very high (54.6%), however with large differences between indication groups, ranging from 91.1% among those transfused for a malignant disease without surgery to 1.7% among patients transfused for obstetrical bleeding. The early standardized mortality ratios were high and decreased thereafter, but remained elevated throughout the time period. CONCLUSIONS: This large-scale study based on nationwide data from Sweden and Denmark describes the complete range of massive transfusion. We report a nonnegligible incidence and both a high absolute mortality and high standardized mortality ratio. The general pattern was similar for Sweden and Denmark, and we believe that similar patterns may be found in other high-resource countries. The study provides a relevant background for clinicians and researchers for designing future studies in this field.
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Transfusão de Eritrócitos/estatística & dados numéricos , Complicações Intraoperatórias/epidemiologia , Adulto , Idoso , Estudos de Coortes , Bases de Dados Factuais , Dinamarca/epidemiologia , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/mortalidade , Feminino , Hemorragia/etiologia , Humanos , Incidência , Complicações Intraoperatórias/mortalidade , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suécia/epidemiologiaRESUMO
OBJECTIVE: To establish and utilize a Next-Generation Sequencing (NGS)-based strategy to screen for maturity onset diabetes of the young (MODY) gene mutations in subjects with early-onset diabetes. PATIENTS AND METHODS: Maturity onset diabetes of the young (MODY) genetic testing was carried out in 80 subjects of Asian Indian origin with young onset diabetes to identify mutations in a comprehensive panel of ten MODY genes. A novel multiplex polymerase chain reaction (PCR)-based target enrichment was established, followed by NGS on the Ion Torrent Personal Genome Machine (PGM). All the mutations and rare variants were confirmed by Sanger sequencing. RESULTS: We identified mutations in 11 (19%) of the 56 clinically diagnosed MODY subjects and seven of these mutations were novel. The identified mutations include p.H241Q, p.E59Q, c.-162G>A 5' UTR in NEUROD1, p.V169I cosegregating with c.493-4G>A and c.493-20C>T, p.E271K in HNF4A, p.A501S in HNF1A, p.E440X in GCK, p.V177M in PDX1, p.L92F in HNF1B and p.R31L in PAX4 genes. Interestingly, two patients with NEUROD1 mutation were also positive for the p.E224K mutation in PDX1 gene. These patients with coexisting NEUROD1-PDX1 mutations showed a marked reduction in glucose-induced insulin secretion. All 24 subjects who had not met the clinical criteria of MODY were negative for the mutations. To the best of our knowledge, this is the first report of PDX1, HNF1B, NEUROD1 and PAX4 mutations from India. CONCLUSIONS: Multiplex PCR coupled with NGS provides a rapid, cost-effective and accurate method for comprehensive parallelized genetic testing of MODY. When compared to earlier reports, we have identified a higher frequency and a novel digenic mutation pattern involving NEUROD1 and PDX1 genes.
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Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Regiões 5' não Traduzidas , Adolescente , Adulto , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Índice de Massa Corporal , Biologia Computacional , Análise Mutacional de DNA , Feminino , Biblioteca Gênica , Fator 1-alfa Nuclear de Hepatócito/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Homeodomínio/genética , Humanos , Índia , Insulina/metabolismo , Secreção de Insulina , Masculino , Mutação , Linhagem , Reação em Cadeia da Polimerase , Transativadores/genética , Adulto JovemRESUMO
BACKGROUND: Risks of transfusion-transmitted disease are currently at a record low in the developed world. Still, available methods for blood surveillance might not be sufficient to detect transmission of diseases with unknown etiologies or with very long incubation periods. STUDY DESIGN AND METHODS: We have previously created the anonymized Scandinavian Donations and Transfusions (SCANDAT) database, containing data on blood donors, blood transfusions, and transfused patients, with complete follow-up of donors and patients for a range of health outcomes. Here we describe the re-creation of SCANDAT with updated, identifiable data. We collected computerized data on blood donations and transfusions from blood banks covering all of Sweden and Denmark. After data cleaning, two structurally identical databases were created and the entire database was linked with nationwide health outcomes registers to attain complete follow-up for up to 47 years regarding hospital care, cancer, and death. RESULTS: After removal of erroneous records, the database contained 25,523,334 donation records, 21,318,794 transfusion records, and 3,692,653 unique persons with valid identification, presently followed over 40 million person-years, with possibility for future extension. Data quality is generally high with 96% of all transfusions being traceable to their respective donation(s) and a very high (>97%) concordance with official statistics on annual number of blood donations and transfusions. CONCLUSIONS: It is possible to create a binational, nationwide database with almost 50 years of follow-up of blood donors and transfused patients for a range of health outcomes. We aim to use this database for further studies of donor health, transfusion-associated risks, and transfusion-transmitted disease.
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Doadores de Sangue , Transfusão de Sangue , Bases de Dados Factuais , Dinamarca , Feminino , Humanos , Masculino , SuéciaRESUMO
Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68â g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. ISRCTN registration number: 13432279.
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BACKGROUND: Body composition is associated with bone mineral density (BMD), but the precise associations between body fat distribution and BMD remain unclear. The regional adipose tissue depots have different metabolic profiles. We hypothesized that they would have independent associations with BMD. RESEARCH DESIGN AND METHODS: We used data from 4,900 healthy individuals aged 30-50 years old from the Oxford Biobank to analyze associations between regional fat mass, lean mass and total BMD. RESULTS: Total lean mass was strongly positively associated with BMD. An increase in total BMD was observed with increasing mass of all the fat depots, as measured either by anthropometry or DXA, when accounting for lean mass. However, on adjustment for both total fat mass and lean mass, fat depot specific associations emerged. Increased android and visceral adipose tissue mass in men, and increased visceral adipose tissue mass in women, were associated with lower BMD. CONCLUSIONS: Fat distribution alters the association between adiposity and BMD.
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Bancos de Espécimes Biológicos , Densidade Óssea , Absorciometria de Fóton , Adulto , Distribuição da Gordura Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Non-coding genetic variation at TCF7L2 is the strongest genetic determinant of type 2 diabetes (T2D) risk in humans. TCF7L2 encodes a transcription factor mediating the nuclear effects of WNT signaling in adipose tissue (AT). In vivo studies in transgenic mice have highlighted important roles for TCF7L2 in adipose tissue biology and systemic metabolism. OBJECTIVE: To map the expression of TCF7L2 in human AT, examine its role in human adipose cell biology in vitro, and investigate the effects of the fine-mapped T2D-risk allele at rs7903146 on AT morphology and TCF7L2 expression. METHODS: Ex vivo gene expression studies of TCF7L2 in whole and fractionated human AT. In vitro TCF7L2 gain- and/or loss-of-function studies in primary and immortalized human adipose progenitor cells (APCs) and mature adipocytes (mADs). AT phenotyping of rs7903146 T2D-risk variant carriers and matched controls. RESULTS: Adipose progenitors (APs) exhibited the highest TCF7L2 mRNA abundance compared to mature adipocytes and adipose-derived endothelial cells. Obesity was associated with reduced TCF7L2 transcript levels in whole subcutaneous abdominal AT but paradoxically increased expression in APs. In functional studies, TCF7L2 knockdown (KD) in abdominal APs led to dose-dependent activation of WNT/ß-catenin signaling, impaired proliferation and dose-dependent effects on adipogenesis. Whilst partial KD enhanced adipocyte differentiation, near-total KD impaired lipid accumulation and adipogenic gene expression. Over-expression of TCF7L2 accelerated adipogenesis. In contrast, TCF7L2-KD in gluteal APs dose-dependently enhanced lipid accumulation. Transcriptome-wide profiling revealed that TCF7L2 might modulate multiple aspects of AP biology including extracellular matrix secretion, immune signaling and apoptosis. The T2D-risk allele at rs7903146 was associated with reduced AP TCF7L2 expression and enhanced AT insulin sensitivity. CONCLUSIONS: TCF7L2 plays a complex role in AP biology and has both dose- and depot-dependent effects on adipogenesis. In addition to regulating pancreatic insulin secretion, genetic variation at TCF7L2 might also influence T2D risk by modulating AP function.
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Tecido Adiposo , Diabetes Mellitus Tipo 2 , Proteína 2 Semelhante ao Fator 7 de Transcrição , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliais/metabolismo , Predisposição Genética para Doença , Humanos , Metabolismo dos Lipídeos , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismoRESUMO
OBJECTIVE: Menopause increases the risk of cardiovascular disease (CVD) which in part has been attributed to the rise in cholesterol and blood pressure (BP). This study examined the hypothesis that menopausal changes in body composition and regional fat depots relate to the change in CVD risk factors. METHODS: A prospective recall study was designed to capture premenopausal women to be re-examined soon after menopause. A total of 97 women from the Oxford Biobank underwent dual x-ray absorptiometry, blood biochemistry, and BP readings pre- and postmenopause. RESULTS: Despite minimal changes in body weight over the 5.1â±â0.9 year follow-up period, there was an increase in total fat mass and a decline in lean mass, where the proportional change of regional fat mass was the greatest for the visceral fat depot (+22%, Pâ<â0.01). Plasma ApoB (+12%, Pâ<â0.01) and C-reactive protein (+45%, Pâ<â0.01) increased as did systolic (+7%, Pâ<â0.001) and diastolic BP (+5%, Pâ<â0.001). Plasma nonesterified fatty acids decreased (-20%, Pâ<â0.05) which may reflect on a change in adipose tissue function across the menopause. PCSK-9 decreased (-26%, Pâ<â0.01) which suggests a compensation for the postmenopausal reduction in low-density lipoprotein receptor activity. Using multilinear regression analyses the changes in ApoB and diastolic BP were associated with visceral fat mass change, but this association was lost when adjusted for total fat mass change. CONCLUSION: The increase in CVD risk factor burden across menopause may not be driven by changes in body composition, rather by functional changes in end organs such as adipose tissue and liver.
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Doenças Cardiovasculares , Tecido Adiposo , Composição Corporal , Índice de Massa Corporal , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Menopausa , Estudos Prospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Lifestyle modification is the mainstay of gestational diabetes mellitus (GDM) prevention. However, clinical trials evaluating the safety and efficacy of diet or physical activity (PA) in low-income and middle-income settings such as Africa and India are lacking. This trial aims to evaluate the efficacy of yoghurt consumption and increased PA (daily walking) in reducing GDM incidence in high-risk pregnant women. METHODS AND ANALYSIS: The study is a 2×2 factorial, open-labelled, multicentre randomised controlled trial to be conducted in Vellore, South India and The Gambia, West Africa. 'High-risk' pregnant women (n=1856) aged ≥18 years and ≤16 weeks of gestational age, with at least one risk factor for developing GDM, will be randomised to either (1) yoghurt (2) PA (3) yoghurt +PA or (4) standard antenatal care. Participants will be followed until 32 weeks of gestation with total active intervention lasting for a minimum of 16 weeks. The primary endpoint is GDM incidence at 26-28 weeks diagnosed using International Association of the Diabetes and Pregnancy Study Groups criteria or elevated fasting glucose (≥5.1 mmol/L) at 32 weeks. Secondary endpoints include absolute values of fasting plasma glucose concentration at 32 weeks gestation, maternal blood pressure, gestational weight gain, intrapartum and neonatal outcomes. Analysis will be both by intention to treat and per-protocol. Continuous outcome measurements will be analysed using multiple linear regression and binary variables by logistic regression. ETHICS AND DISSEMINATION: The study is approved by Oxford Tropical Research Ethics Committee (44-18), ethics committees of the Christian Medical College, Vellore (IRB 11367) and MRCG Scientific Coordinating Committee (SCC 1645) and The Gambia Government/MRCG joint ethics committee (L2020.E15). Findings of the study will be published in peer-reviewed scientific journals and presented in conferences. TRIAL REGISTRATION NUMBER: ISRCTN18467720.
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Diabetes Gestacional , Adolescente , Adulto , África , África Ocidental , Países em Desenvolvimento , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/prevenção & controle , Feminino , Gâmbia , Humanos , Índia , Recém-Nascido , Mães , Estudos Multicêntricos como Assunto , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Lower serum 25-hydroxyvitamin D [25(OH)D] is associated with greater adiposity and adverse cardiometabolic risk profile. The evidence is inconsistent among South Asian Indians. We aimed to examine associations between 25(OH)D and cardiovascular (CVD) risk markers in a rural and urban cohort from South India. SUBJECTS/METHODS: In this cross sectional study, 373 individuals (men, n = 205) underwent detailed CVD risk marker assessment including anthropometry [body mass index (BMI), waist, (WC) and hip circumferences (HC)], body composition analysis using dual energy x-ray absorptiometry (DXA), blood pressure and biochemical analysis (glucose, insulin and lipids). The distribution of CVD risk factors were compared across serum 25(OH)D levels, stratified as deficiency (<20 ng/ml), insufficiency (20 to 29 ng/ml) and normal (≥30 ng/ml) levels. Multiple regression analysis, adjusting for potential confounders, was used to study associations of 25(OH)D with adiposity and cardiometabolic traits. RESULTS: The mean and standard deviation (SD) of age, BMI and 25(OH)D levels were 41.4 (1.1) years, 25.5 (4.8) kg/m2 and 23.4 (10.4) ng/ml respectively. The prevalence of 25(OH)D deficiency was 39.9% in this cohort. Individuals in the 25(OH)D deficiency category had significantly higher mean (SD) BMI [26.6 (5.1) kg/m2], waist circumference [89.9 (12.5) cm] and total fat mass [20.6 (7.9) kg] compared with the Vitamin D sufficient group [BMI: 24.0 (4.4); WC 84.7 (12.0); total fat mass: 15.2 (6.8)]. Significantly inverse associations were observed with DXA measured total and regional fat depots with 25(OH)D levels, while anthropometric indices of adiposity showed significant inverse association only in women. After adjusting for total fat mass, no significant associations were observed between 25(OH)D and the cardiometabolic traits. CONCLUSIONS: Our results confirm that lower 25(OH)D is independently associated with both total and regional adiposity, but not with cardiometabolic traits, in this population.
Assuntos
Adiposidade , Fatores de Risco Cardiometabólico , Vitamina D/análogos & derivados , Adulto , Feminino , Humanos , Masculino , Caracteres Sexuais , Vitamina D/sangueRESUMO
INTRODUCTION: India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making. RESEARCH DESIGN AND METHODS: CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) prevalence and incidence were estimated in 962 (male 519) non-migrant adults from Vellore, South India, studied in: (1) 1998-2002 (mean age 28.2 years) and (2) 2013-2014 (mean age 41.7 years). Prevalence was compared with the Non-Communicable Disease Risk Collaboration (global) data. Incidence was compared with another Indian cohort from New Delhi Birth Cohort (NDBC). Regression analysis was used to test baseline predictors of incident CVD risk factors. RESULTS: The prevalence at 28 and 42 years was 17% (95% CI 14% to 19%) and 51% (95% CI 48% to 55%) for overweight/obesity, 19% (95% CI 17% to 22%) and 59% (95% CI 56% to 62%) for central obesity, 3% (95% CI 2% to 4%) and 16% (95% CI 14% to 19%) for T2D, 2% (95% CI 1% to 3%) and 19% (95% CI 17% to 22%) for hypertension and 15% (95% CI 13% to 18%) and 30% (95% CI 27% to 33%) for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high-income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. CONCLUSIONS: A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence. Preventive efforts should target both rural and urban India and should start young.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Adulto , Doenças Cardiovasculares/epidemiologia , Humanos , Incidência , Índia/epidemiologia , Masculino , PrevalênciaRESUMO
INTRODUCTION: There are conflicting results whether elevated hematocrit is associated with an increased risk of thromboembolic events in individuals without polycythemia vera. To assess the risk of vascular events in relation to hemoglobin concentration, we conducted a large population-based cohort study based on Scandinavian health registers. MATERIALS AND METHODS: We included 1,538,019 Swedish and Danish blood donors between 1987 and 2012. Hazard ratios (HRs) of arterial and venous thrombosis were estimated using Cox regression. Additionally, we fitted person-stratified models where each donor was compared only to him-/herself. RESULTS: The risk of myocardial infarction and ischemic stroke increased with higher hemoglobin concentration in both men and women. The HRs for myocardial infarction and ischemic stroke in men with hemoglobin concentration ≥ 17.5 g/dL were 3.52 (95% confidence interval [CI], 2.85-4.36) and 2.36 (95% CI, 1.63-3.43), respectively, compared to the reference group. The corresponding HRs for women with hemoglobin concentration ≥ 16.0 g/dL were 3.22 (2.12-4.89) and 2.35 (1.37-4.02) for myocardial infarction and ischemic stroke, respectively. The risk of venous thrombosis was highest in men with subnormal hemoglobin concentration (<13.0 g/dL), HR 1.69 (95% CI, 1.40-2.04). In the person-stratified model, the association between elevated hemoglobin concentration and risk of myocardial infarction was attenuated but remained significant. CONCLUSIONS: In this large cohort of Scandinavian blood donors, elevated hemoglobin concentration was associated with an increased risk of vascular events, primarily arterial events. Even though associations were weakened when each person served as their own control, a high hemoglobin concentration may serve as a cardiovascular risk marker.