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Introduction Non-alcoholic fatty liver disease (NAFLD) has become a widespread cause of chronic liver disease, ranging from simple steatosis to severe conditions like non-alcoholic steatohepatitis (NASH) and cirrhosis. Despite its similarity to alcohol-induced liver damage, NAFLD affects individuals with no significant alcohol consumption. This study explores the association between NAFLD, bone mineral density (BMD), insulin resistance, and subclinical inflammation, focusing on the Asian Indian population. The primary objective was to investigate the relationship between NAFLD and BMD, insulin levels, and markers of subclinical inflammation, hypothesizing that patients with NAFLD exhibit lower BMD, possibly linked to insulin resistance and inflammation. Methodology A cross-sectional study with 100 subjects aged 18-50 years (50 cases with NAFLD and 50 controls) was conducted. Exclusion criteria included excessive alcohol consumption, drug-induced fatty liver, severe organ dysfunction, infections, pregnancy, and acute or chronic illness. Data were collected through clinical examinations, anthropometric measurements, biochemical investigations, ultrasound diagnosis of NAFLD, and dual-energy X-ray absorptiometry (DEXA) scans for BMD assessment. Statistical analysis employed the chi-squared tests, t-tests, and Wilcoxon rank-sum tests. Results NAFLD patients had higher body mass index (BMI), waist-to-hip ratio, and markers of insulin resistance and inflammation compared to non-NAFLD controls. DEXA scans revealed significantly lower BMD in NAFLD cases, along with a higher prevalence of osteopenia. Positive correlations were observed between BMD and insulin resistance. The study contributes to understanding the link between NAFLD and lower BMD in the Asian Indian population, emphasizing the impact of insulin resistance and inflammation on bone health. The literature review supports the relevance of exploring NAFLD as an independent risk factor for low BMD. Conclusion This case-control study underscores the significant association between NAFLD and lower BMD in the Asian Indian population. Despite limitations, the findings highlight the importance of further research with larger samples and comprehensive assessments to elucidate the interplay between NAFLD, metabolic factors, and bone health.
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BACKGROUND: Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. METHODS: A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. RESULTS: Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. CONCLUSION: Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.
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Apolipoproteínas B , LDL-Colesterol , Humanos , Estudos Transversais , Índia/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , LDL-Colesterol/sangue , Adulto , Apolipoproteínas B/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , PrevalênciaRESUMO
BACKGROUND: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. METHODS: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. RESULTS: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. CONCLUSIONS: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.
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BACKGROUND: Serum adipokines (leptin and adiponectin) are dysregulated before the onset of metabolic syndrome and hence may be useful biomarkers for screening of cardiometabolic late effects in childhood Acute Lymphoblastic Leukemia (cALL) survivors. METHODS: We compared serum adipokine levels between 40 cALL survivors (aged 10-18 years, >2 years from treatment completion) with similar controls. A multivariable logistic regression analysis was then done to assess the association of metabolic syndrome in cALL survivors with variables including adipokines and other metabolic parameters, demographic and treatment details, and Dual-energy X-ray absorptiometry scan-derived variables. RESULTS: Compared to controls, cALL survivors had a higher prevalence of metabolic syndrome (8/40 vs. 2/40, P = .044) and central obesity (11/40 vs. 4/40, P = 0.042). Median Serum Leptin (7.39 vs. 4.23 ng/ml, P = 0.207) levels and derived Leptin-Adiponectin Ratio (1.44 vs. 0.80, P = 0.598), were higher but not statistically different in our survivors compared to controls; Adiponectin levels were similar (6.07 vs. 5.01 µg/ml, P = 0.283). In the cALL survivors, overweight/obesity (odds ratio [OR] 21.9, P = 0.020) or higher Leptin levels (OR 1.11, P = 0.047), were independently associated with metabolic syndrome. CONCLUSIONS: Serum Leptin, independently predictive of metabolic syndrome in our cALL survivors, may be tested in larger studies to assess its utility in surveillance and initiation of early preventive measures.
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Síndrome Metabólica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Leptina , Adipocinas , Adiponectina , Países em Desenvolvimento , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Obesidade/complicações , Sobreviventes , BiomarcadoresRESUMO
The D allele has been identified as being linked to cardiovascular disease since the discovery of an insertion/deletion (I/D) polymorphism in the ACE gene, this polymorphism has been found to have significant associations with a variety of cardiovascular risk factors. Recent findings indicate a rising prevalence of metabolic disorders among rural populations in developing nations. Research on health matters has been predominantly focused on urban populations, with relatively less attention given to their rural counterparts Hence, the present study attempts to estimate the prevalence of ACE gene I/D polymorphism and explore its association with various cardiovascular risk factors among Rural Yadav population from India. In the present study, 207 (Male 47, Female 160) members of the Yadav community participated in the cross-sectional study. All the socio-demographic factors, somatometric (anthropometric) variables, and the intravenous blood was collected and Physiological (blood pressure), and biochemical (fasting glucose and lipid profile) parameters were measured as recommended by the American Heart Association, allele-specific PCR of the ACE gene I/D polymorphism was carried out, the PCR products were genotyped on 2% agarose gel Electrophoresis and ACE gene polymorphism was analysed for its association with various cardiovascular risk factors. Among the analysed individuals, 34 (16.4%) were found to have the II genotype, 58 (28.0%) had the ID genotype, and 115 (55.6%) had the DD genotype. The allele frequency of the I allele was found to be 0.31, and the frequency of the D allele was 0.69. The frequency of the DD genotype was found to be significantly higher among individuals with high TC, high TG, and low non-HDL levels (p value < 0.05). When considered collectively, the findings of this study are consistent with the hypothesis that the DD genotype of ACE polymorphism represents a correlation with cardiovascular disease risk factors in this population.
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Background: Low concentrations of docosahexaenoic acid (DHA) or high n-6 (ω-6):n-3 ratio in pregnant women is associated with poor fetal growth velocity and suboptimal neurodevelopment. However, there is a lack of data on levels of important n-6 and n-3 fatty acids (FAs) at different time points during pregnancy and lactation from India. Data on how much DHA is transferred during actual supplementation are also scarce. Objectives: We report the concentrations of n-6 and n-3 FAs in maternal and infant blood and in breast milk following maternal supplementation with DHA or placebo. Methods: A total of 957 pregnant women (≤20 wk) from Belagavi, Karnataka, were randomly assigned to receive either 400 mg/d of algal DHA or placebo through 6 mo postpartum. Blood samples were collected from the mother at recruitment/baseline, delivery, and 6 mo postpartum and from the infant at birth (cord) and 12 mo (venous). Breast milk samples were collected from a subsample at delivery, 1 mo and 6 mo postpartum. The FA profile was analyzed using gas chromatography. Results: The concentration of DHA appeared to be higher in erythrocyte and breast milk samples of the DHA-supplemented group at all subsequent time points. The n-6:n-3 ratio was lower among women in the DHA group at delivery [DHA: 4.08 (1.79); placebo: 5.84 (3.57); P < 0.001] and at 6 mo postpartum [DHA: 5.34 (2.64); placebo: 7.69 (2.9); P < 0.001]. Infants of DHA-supplemented mothers also had a lower n-6:n-3 ratio at delivery and 12 mo. The n-6:n-3 ratio of breast milk increased from delivery through 1 to 6 mo but remained lower in the DHA-supplemented group than in the placebo. Conclusions: Maternal DHA supplementation with 400 mg/d from early pregnancy through 6 mo postpartum significantly increased circulating DHA in breast milk and infant erythrocyte, whereas decreased erythrocyte and breast milk n-6:n-3 ratio. However, maternal supplementation did not get the ratio to the recommended levels.
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Background & objectives: Vitamin D plays an important role in bone metabolism, and liver is the intermediary site of vitamin D metabolism. The purpose of this study was to study the prevalence of vitamin D deficiency and bone health in patients with cirrhosis. Methods: Prospectively, serum 25-hydroxy vitamin D [25(OH)D] level were assessed in cirrhotics by chemiluminescence method. Endocrine Society Clinical practice guideline was used to define deficiency and insufficiency of vitamin D. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry and the World Health Organization criteria was used to define osteoporosis and osteopenia. The lowest T score at the left hip neck or lumbar spine was taken as osteoporosis or osteopenia. The Child-Turcotte-Pugh score was used to assess the severity of cirrhosis. Results: Cirrhotics (n=350, male: 278, compensated: 210) were included. Mean serum 25(OH)D level was 8.75 ng/ml. The prevalence of vitamin D deficiency (VDD) and low-BMD (osteopenia and osteoporosis) was 89.4 and 86 per cent, respectively. VDD, insufficiency and osteoporosis was found in 86.7, 11.9 and 33.8 per cent, respectively, in patients with compensated cirrhosis; and 93.6, 3.6 and 40 per cent, respectively, in patients with decompensated cirrhosis. Body mass index of >25 kg/m2 was protective for bone health. Interpretation & conclusions: VDD and low-BMD is prevalent in Indian patients with cirrhosis and should be looked for in patients with cirrhosis for its prevention.
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Doenças Ósseas Metabólicas , Osteoporose , Deficiência de Vitamina D , Humanos , Masculino , Densidade Óssea , Vitamina D , Osteoporose/complicações , Osteoporose/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia , Cirrose Hepática/metabolismo , Doenças Ósseas Metabólicas/epidemiologia , Absorciometria de Fóton , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/metabolismo , VitaminasRESUMO
Background: Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH) are prevalent in the community, especially among those with metabolic syndrome. Patients with fibrotic NASH are at increased risk of liver-related-events. Currently available non-invasive tests have not been utilized for screening for fibrotic NASH among the community. We aimed to develop a screening tool for fibrotic NASH among community members. Methods: We included two large cohorts aimed at assessing cardiovascular disease among community members. Fibrotic NASH was defined using the FibroScan-aspartate aminotransferase score of ≥0.67 that identifies ≥F2 fibrosis and a non-alcoholic fatty liver disease activity score ≥4 with a specificity of 90%. Metabolic parameters, biochemical tests and anthropometry were used to develop a multivariate model. Results: The derivation cohort (n = 1660) included a population with a median age 45 years, 42.5% males, metabolic syndrome in 66% and 2.7% (n = 45) with fibrotic NASH. Multivariate analysis identified the four significant variables (Age, body mass index , Diabetes and alanine aminotransferas levels) used to derive an ABDA score. The score had high diagnostic accuracy (the area under receiver-operating characteristic curve, 0.952) with adequate internal validity. An ABDA score ≥-3.52 identified fibrotic NASH in the derivation cohort with a sensitivity and specificity of 88.9% and 88.3%. The score was validated in a second cohort (n = 357) that included 21 patients (5.9%) with fibrotic NASH, where it demonstrated a high area under receiver-operating characteristic curve (0.948), sensitivity (81%) and specificity (89.3%). Conclusions: ABDA score utilizes four easily available parameters to identify fibrotic NASH with high accuracy in the community.
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A diet high in sodium contributes to a significant proportion of Disability Adjusted Life Years (DALYs) due to cardiovascular diseases. This paper describes the awareness, behaviour and determinants related to dietary salt intake in an adult population of 18-69 years that were assessed as part of the National NCD Monitoring Survey (NNMS) in India. A sub-sample of 3000 adults selected through simple random sampling from 150 nationally representative Primary Sampling Units (PSUs) was included. Data regarding awareness and behaviour related to dietary salt intake were collected. Urinary sodium excretion in spot urine samples was estimated and used to calculate dietary salt intake. The dietary salt intake's sociodemographic, behavioural and metabolic determinants were also analysed. Less than one-third of the adults of both genders in all age groups in rural and urban areas were aware that daily high salt intake could affect health. The estimated mean daily salt intake was 8.0 g (8.9 g/day for men and 7.1 g/day for women). The salt intake was significantly higher in men [Adjusted OR = 17.66 (5.24-59.46)], rural areas [Adjusted OR = 6.14 (1.83-20.60)], overweight and obese respondents [Adjusted OR = 17.62 (3.17-98.07)]. The perception of the harmful effects of high salt intake and practices to limit salt intake was low in the study population. The mean daily salt intake was higher than the WHO recommendation of up to 5 g daily. The mean dietary salt intake is high in the Indian population, which calls for planning and implementing control of dietary salt consumption measures.
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Estado Nutricional , Cloreto de Sódio na Dieta , Adulto , Feminino , Humanos , Masculino , Povo Asiático , Índia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , IdosoRESUMO
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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Cellular therapy has shown promise as a strategy for the functional restoration of ischemic tissues through promoting vasculogenesis. Therapy with endothelial progenitor cells (EPCs) has shown encouraging results in preclinical studies, but the limited engraftment, inefficient migration, and poor survival of patrolling endothelial progenitor cells at the injured site hinder its clinical utilization. These limitations can, to some extent, be overcome by co-culturing EPCs with mesenchymal stem cells (MSCs). Studies on the improvement in functional capacity of late EPCs, also referred to as endothelial colony-forming cells (ECFCs), when cultured with MSCs have mostly focused on the angiogenic potential, although migration, adhesion, and proliferation potential also determine effective physiological vasculogenesis. Alteration in angiogenic proteins with co-culturing has also not been studied. We co-cultured ECFCs with MSCs via both direct and indirect means, and studied the impact of the resultant contact-mediated and paracrine-mediated impact of MSCs over ECFCs, respectively, on the functional aspects and the angiogenic protein signature of ECFCs. Both directly and indirectly primed ECFCs significantly restored the adhesion and vasculogenic potential of impaired ECFCs, whereas indirectly primed ECFCs showed better proliferation and migratory potential than directly primed ECFCs. Additionally, indirectly primed ECFCs, in their angiogenesis proteomic signature, showed alleviated inflammation, along with the balanced expression of various growth factors and regulators of angiogenesis.
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OBJECTIVE: To evaluate the prevalence of vitamin D deficiency (VDD) and its correlates among apparently healthy children and adolescents. METHODS: We carried out a secondary analysis of data of Comprehensive National Nutrition Survey 2016-18 to analyze the pre-valence and predictors of VDD among Indian children and adolescents. RESULTS: The over-all prevalence of VDD in preschool children (1-4 years), school age (5-9 years) children, and adolescents (10-19 years) was 13.7%, 18.2%, and 23.9%, respectively. Age, living in urban area, and winter season were significantly associated with VDD. Vegetarian diet and high-income households were the main risk factors observed in 5-19 years age category. Female sex and less than three hour of physical activity/week were independent risk factors among adolescents. CONCLUSION: The prevalence and determinants of VDD across different age-groups are reported, and these should be interpreted and addressed to decrease the burden of VDD in India.
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Deficiência de Vitamina D , Vitamina D , Pré-Escolar , Humanos , Feminino , Adolescente , Criança , Prevalência , Deficiência de Vitamina D/epidemiologia , Estado Nutricional , Índia/epidemiologiaRESUMO
OBJECTIVE: To assess the effect of birth size and postnatal body mass index (BMI) gain from birth to adulthood on leucocytes cellular senescence in adult life. METHODS: Participants were aged 43.04 (± 0.92) y, and were enrolled from the New Delhi Birth Cohort study, who participated in phase 7 of the study (n = 210). Cellular senescence markers, p16 and p21 gene expression were determined by RT-qPCR in leucocytes and their association with birth size and conditional BMI gain at 2, 11, and 29 y were assessed in univariate and multivariate regression models. RESULTS: Birth weight (regression coefficient; B = -0.087, p = 0.011) and birth BMI (unadjusted B = -0.024, p = 0.026; adjusted B = -0.032, p = 0.022) were inversely associated with p21 gene expression in adult life. The p16 gene expression was not associated with any birth parameters. Conditional BMI gain at 2 y, 11 y, and 29 y was not associated with either p16 or p21 gene expression. The p21 gene expression was inversely associated with circulating insulin (B = -0.065, p = 0.026) and C-peptide levels (unadjusted B = -0.097, p = 0.014; adjusted B = -0.133, p = 0.003). CONCLUSION: Small size at birth is associated with accelerated cellular senescence in adult life. An altered senescent state is likely to be one of the links between LBW and adult chronic diseases.
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Peso ao Nascer , Senescência Celular , Doença Crônica , Recém-Nascido de Baixo Peso , Adulto , Humanos , Recém-Nascido , Coorte de Nascimento , Senescência Celular/genética , Estudos de Coortes , Índia/epidemiologia , Doença Crônica/epidemiologia , Biomarcadores , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p21/genéticaRESUMO
BACKGROUND: Diabetes mellitus (DM) and depression are major public health problems globally. Evidence of linkage of common mental disorders (CMDs) including depression and anxiety disorders with DM is sparsely reported from community-based settings. OBJECTIVE: The present study aimed to study the association between CMDs and DM among adult population (>30 years) residing in a rural area of North India. MATERIALS AND METHODS: A community-based case-control study was conducted in 28 villages of Ballabgarh block of Faridabad district of Haryana. Cases (diabetes) were recruited from the community with at least 1 year of diabetes. Age- and sex-matched two neighborhood controls were selected from the same community. Diabetic status was confirmed using glycated hemoglobin. CMDs such as depression and anxiety disorders were screened using PRIME-MD Hindi version. Conditional logistic regression was used to study the relationship between diabetes and CMDs. RESULTS: Total 211 cases (diabetic) and 273 controls (nondiabetic) were approached for the study, of which 173 cases and 175 controls were analyzed. Cases and controls were comparable with respect to age, sex, and socioeconomic status. CMDs were found more among cases as compared to controls (67.5% vs. 37.5%) (P < 0.001). On conditional logistic regression analysis, CMDs were significantly higher among diabetes cases (adjusted odds ratio - 3.2, 95% confidence interval: 1.9-5.2). CONCLUSION: Strong evidence of coexistence of CMDs and DM from this population-based study necessitates the need of incorporation of management of CMDs into diabetes control program in India.
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Diabetes Mellitus , Transtornos Mentais , Humanos , Índia/epidemiologia , Estudos de Casos e Controles , Masculino , Feminino , Adulto , Diabetes Mellitus/epidemiologia , Pessoa de Meia-Idade , Transtornos Mentais/epidemiologia , População Rural/estatística & dados numéricos , Transtornos de Ansiedade/epidemiologia , Fatores Socioeconômicos , Idoso , Modelos LogísticosRESUMO
Background: A heavy burden of cardiometabolic conditions on low- and middle-income countries like India that are rapidly undergoing urbanization remains unaddressed. Indians are known to have high levels of triglycerides and low levels of HDL-C along with moderately higher levels of LDL-C. The genome-wide findings from Western populations need to be validated in an Indian context for a better understanding of the underlying etiology of dyslipidemia in India. Objective: We aim to validate 12 genetic variants associated with lipid levels among rural and urban Indian populations and derive unweighted and weighted genetic risk scores (uGRS and wGRS) for lipid levels among the Indian population. Methods: Assuming an additive model of inheritance, linear regression models adjusted for all the possible covariates were run to examine the association between 12 genetic variants and total cholesterol, triglycerides, HDL-C, LDL-C, and VLDL-C among 2,117 rural and urban Indian participants. The combined effect of validated loci was estimated by allelic risk scores, unweighted and weighted by their effect sizes. Results: The wGRS for triglycerides and VLDL-C was derived based on five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs2293889 at TRPS1, rs4148005 at ABCA8, and rs4420638 at APOC1), which was associated with 36.31 mg/dL of elevated triglyceride and VLDL-C levels (ß = 0.95, SE = 0.16, p < 0.001). Similarly, every unit of combined risk score (rs2293889 at TRPS1 and rs4147536 at ADH1B) was associated with 40.62 mg/dL of higher total cholesterol (ß = 1.01, SE = 0.23, p < 0.001) and 33.97 mg/dL of higher LDL-C (ß = 1.03, SE = 0.19, p < 0.001) based on its wGRS (rs2293889 at TRPS1, rs4147536 at ADH1B, rs4420638 at APOC1, and rs660240 at CELSR2). The wGRS derived from five associated variants (rs174546 at FADS1, rs17482753 at LPL, rs4148005 at ABCA8, rs4420638 at APOC1, and rs7832643 at PLEC) was associated with 10.64 mg/dL of lower HDL-C (ß = -0.87, SE = 0.14, p < 0.001). Conclusion: We confirm the role of eight genome-wide association study (GWAS) loci related to different lipid levels in the Indian population and demonstrate the combined effect of variants for lipid traits among Indians by deriving the polygenic risk scores. Similar studies among different populations are required to validate the GWAS loci and effect modification of these loci by lifestyle and environmental factors related to urbanization.
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Cardiovascular diseases (CVDs) are the leading cause of death in the world. Endothelial progenitor cells (EPCs) are currently being explored in the context of CVD risk. EPCs are bone marrow derived progenitor cells involved in postnatal endothelial repair and neovascularization. A large body of evidence from clinical, animal, and in vitro studies have shown that EPC numbers in circulation and their functionality reflect endogenous vascular regenerative capacity. Traditionally vitamin D is known to be beneficial for bone health and calcium metabolism and in the last two decades, its role in influencing CVD and cancer risk has generated significant interest. Observational studies have shown that low vitamin D levels are associated with an adverse cardiovascular risk profile. Still, Mendelian randomization studies and randomized control trials (RCTs) have not shown significant effects of vitamin D on cardiovascular events. The criticism regarding the RCTs on vitamin D and CVD is that they were not designed to investigate cardiovascular outcomes in vitamin D-deficient individuals. Overall, the association between vitamin D and CVD remains inconclusive. Recent clinical and experimental studies have demonstrated the beneficial role of vitamin D in increasing the circulatory level of EPC as well as their functionality. In this review we present evidence supporting the beneficial role of vitamin D in CVD through its modulation of EPC homeostasis.
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Diabetes mellitus (DM) alters immune responses and given the rising prevalence of DM in tuberculosis (TB) endemic countries; hyperglycemia can be a potential risk factor for active TB development. However, the impact of hyperglycemia on TB-specific innate immune response in terms of macrophage functions remains poorly addressed. We assessed macrophage effector functions in uncontrolled DM patients with or without TB infection (PTB+DM and DM), non-diabetic TB patients (PTB), and non-diabetic-uninfected controls. Phagocytic capacity against BCG and surface expression of different pattern recognition receptors (PRRs) (CD11b, CD14, CD206, MARCO, and TLR-2) were measured via flow cytometry. Effector molecules (ROS and NO) required for bacterial killing were assessed via DCFDA and Griess reaction respectively. A systematic dysregulation in phagocytic capacity with concurrent alterations in the expression pattern of key PRRs (CD11b, MARCO, and CD206) was observed in PTB+DM. These altered PRR expressions were associated with decreased phagocytic capacity of macrophages. Similarly, ROS was aberrantly higher while NO was lower in PTB+DM. These altered macrophage functions were positively correlated with increasing disease severity. Our results highlight several key patterns of immune dysregulation against TB infection under hyperglycemic conditions and highlight a negative impact of hyperglycemia with etiology and progression of TB.
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Diabetes Mellitus , Hiperglicemia , Tuberculose Pulmonar , Tuberculose , Vacina BCG , Humanos , Hiperglicemia/complicações , Hiperglicemia/epidemiologia , Macrófagos , Espécies Reativas de Oxigênio , Receptor 2 Toll-Like , Tuberculose Pulmonar/microbiologiaRESUMO
Background Dietary salt intake is an important modifiable risk factor for cardiovascular diseases. Estimation of 24-hour salt intake using morning urine samples needs to be validated in the Indian context. We examined the performance of INTERSALT, Tanaka and Kawasaki equations for the estimation of 24-hour urinary sodium from morning fasting urine (MFU) samples. Methods We enrolled 486 adults aged 18-69 years from four regions of India with equal rural/urban and sex representation to provide 24-hour urine samples. The next day, a MFU sample was obtained. Based on the volume and sodium content of the 24-hour urine sample, 24-hour sodium excretion (reference method) was calculated. Sodium levels in the MFU samples were measured along with other parameters required, and the above equations were used to estimate 24-hour urinary sodium levels. Intraclass correlation coefficient (ICC) was used to assess the degree of agreement between the estimates from the reference method and the three equations. Bland-Altman (BA) plots were used to identify systematic bias and limits of agreement. A difference of 1 g of salt (0.39 g of sodium) between the mean salt intake by 24-hour urine and as estimated by equations was considered acceptable. Results A total of 346 participants provided both the samples. The mean (SD) daily salt intake estimated by the 24-hour urine sample method was 9.9 (5.8) g. ICC was low for all the three equations: highest for Kawasaki (0.16; 95% CI 0.05-0.26) and least for Tanaka (0.12; 0.02-0.22). Only Tanaka equation provided estimates within 1 g of measured 24-hour salt intake (-0.36 g). BA plots showed that as the mean values increased, all the three equations provided lower estimates of salt intake. Conclusion Tanaka equation provided acceptable values of 24-hour salt intake at the population level. However, poor performance of all the equations highlights the need to understand the reasons and develop better methods for the measurement of sodium intake at the population level.
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Jejum , Cloreto de Sódio na Dieta , Adulto , Comportamento Alimentar , Humanos , Sódio/urina , Urinálise/métodosRESUMO
Data on the effect of vitamin D supplementation on fibroblast growth factor 23 (FGF23), in chronic kidney disease (CKD) are scarce. In a prospective interventional study, the effect of vitamin D supplementation on cFGF23 (C-terminal FGF23) levels in children with CKD stages 2-4 was examined. Forty-one children with CKD and vitamin D insufficiency were administered 600,000 units of cholecalciferol over 3 d; 88% of patients achieved sufficiency at 8 wk. Significant increase in serum cFGF23 and phosphate levels was observed in CKD stage 2 after supplementation, but not in CKD stages 3 and 4. There was no correlation of the change in cFGF23 level with baseline or change in bone health parameters (calcium, phosphate, parathormone or alkaline phosphatase) or with change in flow-mediated dilatation (FMD) of the brachial artery. It is concluded that cholecalciferol supplementation increases serum calcium and reduces PTH, but does not adversely affect FGF23 levels in CKD.
Assuntos
Insuficiência Renal Crônica , Deficiência de Vitamina D , Fosfatase Alcalina , Cálcio , Criança , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Fatores de Crescimento de Fibroblastos , Humanos , Hormônio Paratireóideo , Fosfatos , Estudos Prospectivos , Insuficiência Renal Crônica/terapia , Vitamina D , Deficiência de Vitamina D/tratamento farmacológico , VitaminasRESUMO
PURPOSE: The aim of the present study was to assess the effect of Bacillus coagulans Unique IS-2 supplementation on absorption and utilization of protein in resistance-trained males. METHODS: In this double blind, placebo-control trial, resistance-trained males (21.08 ± 2.84 years) were randomized to consume, either 20 g of whey protein powder {80% whey protein concentrate (WPC80), amounting to 15.4 g protein} with 2 billion CFU Bacillus coagulans Unique IS-2 (supplemental group) or 20 g of whey protein powder and lactose instead of Bacillus coagulans (placebo group) once daily for 60 days with a controlled resistance exercise protocol. The whey protein concentrate (WPC-80) given to both groups had a lactose content of 6.8%. Plasma-free amino acids (PFAAs) were determined at baseline, at 30 and 60 days of supplementation. Muscle strength, hypertrophy, VO2 max, and body composition, and other biochemical parameters were assessed at baseline and end line. RESULTS: A positive effect of probiotic Bacillus coagulans Unique IS-2 supplementation was observed on protein absorption as evidenced by an increase in total PFAA by + 16.1% (p = 0.004). Branched chain amino acids (BCAA) comprising isoleucine (p = 0.016), leucine (p = 0.001), and valine (p = 0.002) were increased by + 33.1% in ITT analysis as compared to placebo after 60 days. At 30 days an increase in isoleucine by + 35% (p = 0.113), leucine by + 43% (p = 0.032), and valine by + 32% (p = 0.017) was observed in ITT analysis. Probiotic effect was shown on exercise performance as evidenced by an increase in one RM of leg press and vertical jump power by + 16.61% (p = 0.024) and + 7.86% (p = 0.007), respectively. CONCLUSION: Significantly increased absorption of BCAA with supplementation of B. coagulans Unique IS-2 along with whey protein and improvement in leg press and vertical jump power was noted indicating the positive effect of the probiotic on muscle power in the lower body. TRIAL REGISTRATION NUMBER: CTRI/2017/03/008117; Date:16.03.2017.