ABSTRACT
BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) leads to nearly 3-fold higher risk of pulmonary tuberculosis (TB), indicating an increasing challenge to public health in low-to-middle income countries. Till now, the risk factor is still uncertain. We carried out this study with the main purpose to identify the risk factors of having TB in DM patients. METHODS AND STUDY DESIGN: A hospital-based matched case-control study was conducted in Qingdao, China from March, 2016 to January, 2018. Cases were DM patients with concurrent TB (DM-TB). Each case was matched with two controls, patients with DM only of similar age, sex and DM course. Cox regression of conditional logistic analysis was used to define the risk factors for having TB in DM, and then sensitivity analysis was carried out. RESULTS: We identified 315 patients, including 105 cases and 210 controls. Smokers had a higher risk of having TB with a multivariable adjusted odds ratio (aOR) of 12.45 than non-smokers. Poor glycemic control (aOR=2.66), frequency of DM re-examination <1 time/year (aOR=3.39), as well as TB contact history was also independently related with higher risk, while BMI ≥24 (aOR=0.42), education level ≥ college (aOR=0.11) showed a negative association. CONCLUSIONS: Poor glycemic control, smoking, low frequency of reexamination was associated with higher risk of having TB in DM, while overweight and obesity, high education levels showed a negative association. These findings provide clues to target DM populations prone to TB, which may be of help to halt the epidemic of TB in high burden countries.
Subject(s)
Diabetes Mellitus, Type 2 , Tuberculosis, Pulmonary , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Hospitals , Humans , Risk Factors , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/epidemiologyABSTRACT
Tuberculosis remains a major global health challenge, particularly in low-to-middle income countries such as China. At the same time, the country is facing a rapidly increasing diabetes incidence over the last 10 years. Diabetes aggravates the tuberculosis epidemic which poses a serious challenge in public health. In recent years, the high prevalence of vitamin D deficiency represents a global health problem, which is also associated with the risk of diabetes, and tuberculosis. Therefore, this review aims to provide an overall and updated understanding of the epidemiology of co-occurrence of tuberculosis and diabetes in China, and to elucidate the possible role of vitamin D deficiency. In conclusion, significant aggravation of the tuberculosis epidemic due to diabetes may exist in China for a relatively long period of time to come. Further, the double burden and its implications to public health in this country may be significantly influenced by the high prevalence of vitamin D deficiency. Bidirectional screening for tuberculosis and diabetes is recommended, and extra vitamin D may benefit especially in a situation of a heavy tuberculosis burden combined with prevalent vitamin D deficiency. Longitudinal studies to verify the role of vitamin D deficiency in the double burden, and trials on the effect of vitamin D supplementation are needed in the future.
Subject(s)
Diabetes Mellitus/epidemiology , Mycobacterium tuberculosis , Tuberculosis/epidemiology , Vitamin D Deficiency/epidemiology , Vitamin D/blood , China , Diabetes Mellitus/blood , Diabetes Mellitus/microbiology , Epidemics , Global Health , Humans , Prevalence , Tuberculosis/blood , Tuberculosis/microbiology , Vitamin D Deficiency/blood , Vitamin D Deficiency/microbiologyABSTRACT
Vitamin D deficiency (VDD) is common in tuberculosis (TB) and may be implicated in the etiology of the disease and in its clinical course. The aim of this study was to investigate the association between leptin, inflammatory markers and VD status in TB patients, stratified for presence or absence of diabetes mellitus (DM). Two hundred ninety-nine TB patients were recruited from October 2015 to August 2016. Also, 91 normal controls were included. The information including socio-demographics, dietary intake and living habits was obtained by face-to-face interview. Serum concentrations of leptin and TNF-α, CRP and IL-6 were compared between TB patients with and without severe VDD (SVDD). Pearson's correlation was used to analyze the association between TNF-α, leptin and 25-hydroxyvitamin D (25(OH)D). A significantly higher prevalence of VDD and SVDD was observed in TB patients compared with normal controls (93.0% vs 70.3%, 65.9% vs 3.3% respectively). Concentration of leptin was significantly lower, while TNF-α higher in TB patients with SVDD compared to those without (p<0.05). After adjustment for confounders, leptin was positively associated with 25(OH)D (r=0.210, p=0.002) with similar correlation in TB patients with DM (r=0.240, p=0.020). A negative association between TNF-α and 25(OH)D was observed (r=-0.197, p=0.003), which was significant only in the subgroup without DM (r=-0.304, p=0.001). Our findings indicate that a higher VD status in TB patients may be related to higher immune activity and less serious tissue damage, and that this relation is different according to presence or absence of DM co-morbidity.
Subject(s)
Leptin/blood , Tuberculosis, Pulmonary/blood , Tumor Necrosis Factor-alpha/blood , Vitamin D Deficiency/blood , Vitamin D/analogs & derivatives , Adolescent , Adult , Aged , C-Reactive Protein/analysis , Cross-Sectional Studies , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Nutritional Status , Prevalence , Tuberculosis, Pulmonary/etiology , Vitamin D/blood , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/microbiology , Young AdultABSTRACT
B vitamins are enzyme cofactors that play an important role in energy metabolism. The aim of this study was to elucidate whether B vitamin administration can reduce body weight (BW) gain by improving energy metabolism-related enzyme activities in rats fed on a highfat diet. Fifty rats were randomly assigned to one of the following five groups: control group (C), including rats fed on standard rat chow; four treatment groups (HO, HI, H2, and H3), in which rats were fed on a high-fat diet. Rats in the HI group were treated daily with 100 mg/kg BW thiamine (VB1), 100 mg/kg BW riboflavin (VB2), and 250 mg/kg BW niacin (VPP); rats in the H2 group were treated daily with 100 mg/kg BW pyridoxine (VB6), 100 mg/kg BW cobalamin (VB12), and 5 mg/kg BW folate (FA); and rats in the H3 group were treated daily with all of the B vitamins administered to the HI and H2 groups. After 12 weeks, the BW gains from the initial value were 154.5±58.4 g and 159.1±53.0 g in the HI and C groups, respectively, which were significantly less than the changes in the HO group (285.2±14.8 g, P<0.05). In the HO group, the plasma total cholesterol (CHO) and triglyceride (TG) levels were 1.59±0.30 mmol/L and 1,55±0.40 mmol/L, respectively, which were significantly greater than those in the HI group (1.19±0.18 mmol/L and 0.76±0.34 mmol/L, respectively, P<0.05). The activities of transketolase (TK), glutathione reductase, and Na+/K+ adenosine triphosphatase were significantly increased in the B vitamin-treated groups and were significantly greater than those in the HO group (P<0.05). Furthermore, the glucose-6-phosphate dehydrogenase, pyruvic acid kinase, and succinate dehydrogenase activities also were increased after treatment with B vitamins. Supplementation with B vitamins could effectively reduce BW gain and plasma levels of lipids by improving energy metabolism-related enzyme activities in rats, thus possibly providing potential benefits to humans.
Subject(s)
Anti-Obesity Agents/pharmacology , Body Weight/drug effects , Obesity/prevention & control , Vitamin B Complex/pharmacology , Vitamins/pharmacology , Animals , Anti-Obesity Agents/administration & dosage , Anti-Obesity Agents/therapeutic use , Cholesterol/blood , Diet, High-Fat/adverse effects , Glucosephosphate Dehydrogenase/blood , Glutathione Reductase/blood , Male , Obesity/blood , Obesity/etiology , Pyruvate Kinase/blood , Rats , Rats, Wistar , Transketolase/blood , Triglycerides/blood , Vitamin B Complex/administration & dosage , Vitamin B Complex/therapeutic use , Vitamins/administration & dosage , Vitamins/therapeutic useABSTRACT
BACKGROUND & AIMS: Tuberculosis (TB) patients have a significant vitamin D deficiency (VDD) endemic, which may be closely related to the onset and progress of the disease. The comorbidity of diabetes (DM) and TB has posed an increasing challenge in recent years. However, the influence of DM on TB and the possible mechanism are still uncertain. We carried out this study to identify the nutritional status of vitamin D (VD) in TB patients in a northern city in China (latitude 36° N) and investigate the possible predictors of severe vitamin D deficiency (SVDD). METHODS: A cross-sectional study including 461 active TB patients (192 with and 269 without DM) were randomly selected from Qingdao Chest Hospital from June 2015 to August 2016. We measured serum 25 hydroxyvitamin D [25(OH)D], and investigated the association between sociodemographic, dietary intake, DM, body mass index (BMI), severity of initial TB signs and symptoms (TB score) and VD status. Multivariate logistic regression analysis was used to define the possible predictors of SVDD. RESULTS: The median serum 25(OH)D concentration was 8.50 ng/mL. Of the 461 TB patients included, 383 (83.1%) had VDD [25(OH)D < 20 ng/mL], and 217 (47.1%) had SVDD [25(OH)D < 8 ng/mL]. The variables associated with serum 25(OH)D concentrations were DM, outdoor activity level, TB score and BMI (p < 0.05). Patients with severe TB score had nearly 5 fold higher risk of having SVDD compared with those in mild subgroup [OR (95% CI) = 4.919 (2.644-9.150), p < 0.001]. Low outdoor activity level also increased the odds of SVDD, while DM and high fish consumption showed protect effects. CONCLUSIONS: Severe hypovitaminosis D is prevalent in active TB patients, and the main predictors of SVDD were severe TB score, low outdoor activity, inadequate fish consumption. Lowered serum 25(OH)D may be associated with increased risk of TB in DM.
Subject(s)
Tuberculosis/epidemiology , Vitamin D Deficiency/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , China , Comorbidity , Cross-Sectional Studies , Diet , Female , Humans , Life Style , Male , Middle Aged , Prevalence , Risk Factors , Severity of Illness Index , Tuberculosis/blood , Vitamin D Deficiency/blood , Young AdultABSTRACT
BACKGROUND: We planned to determine the association of body mass index (BMI) with diabetes mellitus (DM) and impaired fasting glucose (IFG) in Chinese pulmonary tuberculosis (PTB) patients. METHODS: 3,505 newly-diagnosed PTB patients registered in PTB clinics in Linyi of China between September 2010 and March 2013 were enrolled. DM and IFG were identified based on fasting plasma glucose levels. ROC analysis was used to predict the ability of screening of BMI for DM and IFG in PTB patients. RESULTS: Compared with 18.5-23.9 kg/m2, patients with DM and IFG had significantly increased trends when BMI ≥ 24.0 kg/m2, and aORs were 2.28 (95%CI 1.44-3.60) and 1.30 (95%CI 1.04-1.64), respectively. After adjustment for age, gender, and educational level, there was an increased odd in BMI ≥ 23.41 kg/m2 for IFG, and a decreased odd in BMI < 19.82 kg/m2 for DM (p < 0.05). The cut-offs of BMI for screening IFG and DM in PTB patients were 22.22 kg/m2 (AUC 0.56) and 22.34 kg/m2 (AUC 0.59). CONCLUSIONS: In PTB patients, BMI is significantly associated with IFG and DM. However, the predictive power of BMI was not sufficient, so it may only be a limited screening tool for DM and IFG among PTB patients in China.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Obesity/epidemiology , Prediabetic State/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adult , Aged , Blood Glucose/analysis , Body Mass Index , China , Comorbidity , Cross-Sectional Studies , Female , Health Status , Humans , Male , Middle Aged , ROC Curve , Risk FactorsABSTRACT
BACKGROUND AND OBJECTIVES: Although vitamin D is implicated in the generation of anti-microbial peptide cathelicidin, which plays a key role against pulmonary tuberculosis (PTB), and may have an inverse association with the risk of type 2 diabetes (DM), its role in the co-existence of these two diseases (PTB-DM) is still uncertain. This study explored the association of vitamin D status with prevalent PTB, PTB-DM and DM. METHODS AND STUDY DESIGN: We randomly selected 130 PTB patients, 90 PTB-DM, 91 DM and 134 controls. Serum 25(OH)D levels were determined. A structured questionnaire and anthropometric measurements were administered. RESULTS: Serum 25(OH)D levels in PTB and PTB-DM were 12.2±2.2 ng/mL and 12.9±2.5 ng/mL, respectively, which were lower than those in DM and control groups. Odds ratios of PTB and PTB-DM comparing extreme quartiles of 25(OH)D (lower than 8.6 ng/mL versus >=26.6 ng/mL) were 3.26 and 2.27, respectively. These associations remained after adjustment for possible risk factors [OR (95% CI)=4.73 (2.04-10.9) and 2.50 (1.04- 6.02), respectively]. A synergistic interaction was observed between low 25(OH)D and underweight in respect to prevalent PTB-DM [OR=24.6 vs 2.50 for lowest quartile of 25(OH) D and 4.59 for underweight]. CONCLUSIONS: Odds ratios of low serum 25(OH)D levels for PTB and PTB-DM were greater than 1.0, and were even much greater when combined with underweight. However, since the association of serum 25(OH)D levels with PTB was stronger than with PTB-DM, we could not draw the conclusion that vitamin D is a link between PTB and DM.
Subject(s)
Diabetes Mellitus, Type 2/blood , Tuberculosis, Pulmonary/blood , Vitamin D Deficiency/complications , Vitamin D/analogs & derivatives , Adult , Aged , Body Mass Index , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Male , Middle Aged , Nutritional Status , Odds Ratio , Risk Factors , Thinness/complications , Tuberculosis, Pulmonary/epidemiology , Vitamin D/bloodABSTRACT
BACKGROUND: Excessive time between the first presentation of symptoms of pulmonary tuberculosis (PTB) and diagnosis contributes to ongoing transmission and increased risk of infection in the community, as well as to increased disease severity and higher mortality. People with type 2 diabetes mellitus (T2DM) have a higher risk of developing PTB. However, the effect of T2DM on delayed diagnosis of PTB is not fully understood. This study investigated the effects of hyperglycemia (diabetes and prediabetes) and other factors on PTB patient delay in a rural area of China. METHODS: In the present community-based investigation, PTB patients aged ≥16 years newly diagnosed at county tuberculosis dispensaries were recruited consecutively between September 2011 and December 2013. Fasting blood glucose was determined in all subjects, and a structured questionnaire was used to collect basic information. RESULTS: Of the 2280 patients, 605 (26.5 %) had hyperglycemia. The median (interquartile range) time to seeking health care was 44 (59) days. Health care seeking was delayed in 1754 subjects, and hyperglycemia was independently associated with an increased probability (odds ratio 2.10; 95 % confidence interval 1.49-2.97) of patient delay in subjects aged ≥30 years. Other factors associated with patient delay were cough, night sweats, and lack of knowledge regarding typical tuberculosis symptoms. The onset of hemoptysis was negatively correlated with patient delay. CONCLUSIONS: Patient delay appears to be a serious problem in this rural area with a high prevalence of tuberculosis. Hyperglycemia is independently associated with an increased probability of patient delay, which, in turn, may result in more serious clinical manifestations.
Subject(s)
Hyperglycemia/blood , Prediabetic State/blood , Rural Population/statistics & numerical data , Tuberculosis, Pulmonary/blood , Adult , Aged , Asian People , Blood Glucose , China , Cross-Sectional Studies , Delayed Diagnosis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/ethnology , Fasting/blood , Fasting/metabolism , Female , Humans , Hyperglycemia/ethnology , Logistic Models , Male , Middle Aged , Prediabetic State/ethnology , Risk Factors , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/ethnologyABSTRACT
Quantitative insight into species differences in risk assessment is expected to reduce uncertainty and variability related to extrapolation from animals to humans. This paper explores quantification and comparison of gene expression data between tissues and species from intervention studies with isoflavones. Gene expression data from peripheral blood mononuclear cells (PBMCs) and white adipose tissue (WAT) after 8wk isoflavone interventions in postmenopausal women and ovariectomized F344 rats were used. A multivariate model was applied to quantify gene expression effects, which showed 3-5-fold larger effect sizes in rats compared to humans. For estrogen responsive genes, a 5-fold greater effect size was found in rats than in humans. For these genes, intertissue correlations (r = 0.23 in humans, r = 0.22 in rats) and interspecies correlation in WAT (r = 0.31) were statistically significant. Effect sizes, intertissue and interspecies correlations for some groups of genes within energy metabolism, inflammation and cell cycle processes were significant, but weak. Quantification of gene expression data reveals differences between rats and women in effect magnitude after isoflavone supplementation. For risk assessment, quantification of gene expression data and subsequent calculation of intertissue and interspecies correlations within biological pathways will further strengthen knowledge on comparability between tissues and species.
Subject(s)
Adipose Tissue, White/metabolism , Dietary Supplements , Isoflavones/pharmacology , Leukocytes, Mononuclear/metabolism , Transcriptome/drug effects , Adipose Tissue, White/drug effects , Animals , Cross-Over Studies , Double-Blind Method , Female , Humans , Leukocytes, Mononuclear/drug effects , Ovariectomy , Rats , Rats, Inbred F344 , Risk AssessmentABSTRACT
BACKGROUND: Isoflavone supplements, consumed by women experiencing menopausal symptoms, are suggested to have positive effects on menopause-related adiposity and cardiovascular disease risk profile, but discussions about their safety are still ongoing. OBJECTIVE: The objective was to study the effects of an 8-wk consumption of 2 different isoflavone supplements compared with placebo on whole-genome gene expression in the adipose tissue of postmenopausal women. DESIGN: This double-blind, randomized, placebo-controlled crossover intervention consisted of 2 substudies, one with a low-genistein (LG) supplement (56% daidzein + daidzin, 16% genistein + genistin, and 28% glycitein + glycitin) and the other with a high-genistein (HG) supplement (49% daidzein + daidzin, 41% genistein + genistin, and 10% glycitein + glycitin). Both supplements provided â¼ 100 mg isoflavones/d (aglycone equivalents). After the 8-wk isoflavone and placebo period, whole-genome arrays were performed in subcutaneous adipose tissue of postmenopausal women (n = 26 after LG, n = 31 after HG). Participants were randomized by equol-producing phenotype, and data analysis was performed per substudy for equol producers and nonproducers separately. RESULTS: Gene set enrichment analysis showed downregulation of expression of energy metabolism-related genes after LG supplementation (n = 24) in both equol-producing phenotypes and oppositely regulated expression for equol producers (down) and nonproducers (up) after HG supplementation (n = 31). Expression of inflammation-related genes was upregulated in equol producers but downregulated in nonproducers, independent of supplement type. Only 4.4-7.0% of the genes with significantly changed expression were estrogen responsive. Body weight, adipocyte size, and plasma lipid profile were not affected by isoflavone supplementation. CONCLUSIONS: Effects of isoflavones on adipose tissue gene expression were influenced by supplement composition and equol-producing phenotype, whereas estrogen-responsive effects were lacking. LG isoflavone supplementation resulted in a caloric restriction-like gene expression profile for both producer phenotypes and pointed toward a potential beneficial effect, whereas both supplements induced anti-inflammatory gene expression in equol producers. The study was registered at clinicaltrials.gov as NCT01556737.
Subject(s)
Adipose Tissue/drug effects , Dietary Supplements , Equol/metabolism , Isoflavones/administration & dosage , Adipose Tissue/metabolism , Adiposity/drug effects , Aged , Cross-Over Studies , Double-Blind Method , Female , Gene Expression , Genistein/administration & dosage , Humans , Middle Aged , Netherlands , Nutritional Status , Postmenopause , Surveys and QuestionnairesABSTRACT
BACKGROUND: Patients with type 2 diabetes (DM) have a higher risk of developing pulmonary tuberculosis (PTB); moreover, DM co-morbidity in PTB is associated with poor PTB treatment outcomes. Community based prevalence data on DM and prediabetes (pre-DM) among TB patients is lacking, particularly from the developing world. Therefore we conducted a prospective study to investigate the prevalence of DM and pre-DM and evaluated the risk factors for the presence of DM among newly detected PTB patients in rural areas of China. METHODS AND FINDINGS: In a prospective community based study carried out from 2010 to 2012, a representative sample of 6382 newly detected PTB patients from 7 TB clinics in Linyi were tested for DM. A population of 6674 non-TB controls from the same community was similarly tested as well. The prevalence of DM in TB patients (6.3%) was higher than that in non-TB controls (4.7%, p<0.05). PTB patients had a higher odds of DM than non-TB controls (adjusted OR 3.17, 95% CI 1.14-8.84). The prevalence of DM increased with age and was significantly higher in TB patients in the age categories above 30 years (p<0.05). Among TB patients, those with normal weight (BMI 18.5-23.9) had the lowest prevalence of DM (5.8%). Increasing age, family history of DM, positive sputum smear, cavity on chest X-ray and higher yearly income (≥10000 RMB yuan) were positively associated and frequent outdoor activity was negatively associated with DM in PTB patients. CONCLUSIONS: The prevalence of DM in PTB patients was higher than in non-TB controls with a 3 fold higher adjusted odds ratio of having DM. Given the increasing DM prevalence and still high burden of TB in China, this association may represent a new public health challenge concerning the prevention and treatment of both diseases.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Tuberculosis, Pulmonary/epidemiology , Adult , Aged , China/epidemiology , Cohort Studies , Humans , Middle Aged , Prospective StudiesABSTRACT
BACKGROUND: Pulmonary tuberculosis (TB) patients often suffer from anorexia and poor nutrition, causing weight loss. The peptide hormones leptin and its counterpart ghrelin, acting in the regulation of food intake and fat utilization, play an important role in nutritional balance. This study aimed to investigate the association of blood concentrations of leptin, ghrelin and inflammatory cytokines with body mass index (BMI) in TB patients with and without type 2 diabetes mellitus (T2DM). METHODS: BMI, biochemical parameters and plasma levels of leptin, ghrelin and inflammatory cytokines were measured before the start of treatment in 27 incident TB patients with T2DM, 21 TB patients and 23 healthy subjects enrolled in this study. RESULTS: The levels of leptin were significantly higher in TB patients (35.2 ± 19.1 ng/ml) than TB+T2DM (12.6 ± 6.1 ng/ml) and control (16.1 ± 11.1 ng/ml) groups. The level of ghrelin was significantly lower in TB (119.9 ± 46.1 pg/ml) and non-significantly lower in TB+T2DM (127.7 ± 38.6 pg/ml) groups than control (191.6 ± 86.5 pg/ml) group. The levels of TNF-α were higher, while IFN-γ and IL-6 levels were lower in patients than in the control group. Leptin showed a negative correlation with BMI in TB (r=-0.622, p<0.05) and TB+T2DM (r= -0.654, p<0.05) groups, but a positive correlation with BMI in the control group (r=0.521, p<0.05). Contrary ghrelin showed a positive correlation with BMI in TB (r=0.695, p<0.05) and TB+T2DM (r= 0.199, p>0.05) groups, but negative correlation with BMI in the control (r=-0.693, p<0.05) group. Inflammatory cytokines were poorly correlated with BMI in this study. Only IFN-γ showed a significant negative correlation with BMI in the control group (r=-0.545, p<0.05). CONCLUSIONS: This study may suggest that possible abnormalities in ghrelin and leptin regulation (high levels of leptin and low levels of ghrelin) may be associated with low BMI and may account for the poor nutrition associated with TB and TB+T2DM.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Ghrelin/blood , Interferon-gamma/blood , Interleukin-6/blood , Leptin/blood , Tuberculosis, Pulmonary/physiopathology , Tumor Necrosis Factor-alpha/blood , Body Mass Index , Diabetes Mellitus, Type 2/blood , Female , Humans , Inflammation/blood , Inflammation/metabolism , Male , Middle Aged , Tuberculosis, Pulmonary/bloodABSTRACT
Isoflavones (genistein, daidzein, and glycitein) are suggested to have benefits as well as risks for human health. Approximately one-third of the Western population is able to metabolize daidzein into the more potent metabolite equol. Having little endogenous estradiol, equol-producing postmenopausal women who use isoflavone supplements to relieve their menopausal symptoms could potentially be at high risk of adverse effects of isoflavone supplementation. The current trial aimed to study the effects of intake of an isoflavone supplement rich in daidzein compared with placebo on whole-genome gene expression profiles of peripheral blood mononuclear cells (PBMCs) in equol-producing, postmenopausal women. Thirty participants received an isoflavone supplement or a placebo for 8 wk each in a double-blind, randomized cross-over design. The isoflavone supplement was rich in daidzein (60%) and provided 94 mg isoflavones (aglycone equivalents) daily. Gene expression in PBMCs was significantly changed (P < 0.05) in 357 genes after the isoflavone intervention compared with placebo. Gene set enrichment analysis revealed downregulated clusters of gene sets involved in inflammation, oxidative phosphorylation, and cell cycle. The expression of estrogen receptor (ER) target genes and gene sets related to ER signaling were not significantly altered, which may be explained by the low ERα and ERß expression in PBMCs. The observed downregulated gene sets point toward potential beneficial effects of isoflavone supplementation with respect to prevention of cancer and cardiovascular disease. However, whether ER-related effects of isoflavones are beneficial or harmful should be studied in tissues that express ERs.
Subject(s)
Equol/biosynthesis , Isoflavones/adverse effects , Leukocytes, Mononuclear/metabolism , Postmenopause/metabolism , Receptors, Estrogen/physiology , Transcriptome/drug effects , Cross-Over Studies , Dietary Supplements , Double-Blind Method , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Female , Gene Expression , Humans , Isoflavones/administration & dosage , Isoflavones/blood , Placebos , Receptors, Estrogen/geneticsABSTRACT
BACKGROUND: Observational studies have shown that low folate and elevated homocysteine concentrations are risk factors for vascular disease in the general population. Randomized controlled trials in vascular patients have failed to show that folic acid reduces the risk of recurrent vascular disease, whereas such trials are lacking in the general population. OBJECTIVE: The objective was to determine whether folic acid supplementation reduces the progression of atherosclerosis as measured by common carotid intima-media thickness (CIMT)-a validated marker of atherosclerosis and predictor of vascular disease risk. DESIGN: A randomized, double-blind, placebo-controlled study in 819 men and postmenopausal women aged 50-70 y, free-living in the Netherlands, and with a total homocysteine concentration ≥13 µmol/L at screening was conducted. Participants received either 800 µg folic acid or placebo daily for 3 y. Rate of change in CIMT and arterial distensibility were the primary and secondary outcomes, respectively. RESULTS: Compared with placebo, serum folate increased by 577% and plasma total homocysteine concentrations decreased by 26% after 3 y of folic acid supplementation. The mean (±SE) rate of change in CIMT was 1.9 ± 0.9 µm/y in the folic acid arm and 1.3 ± 0.8 µm/y in the placebo arm (mean difference: 0.7 µm/y; 95% CI: -1.8, 3.1 µm/y; P = 0.59). No difference was observed (P = 0.23) between the rates of change in distensibility in the folic acid arm (-0.53 ± 0.06 × 10(-3) kPa(-1)) and in the placebo arm (-0.62 ± 0.06 × 10(-3) kPa(-1)). CONCLUSION: Despite a considerable increase in folate concentrations and a reduction in total homocysteine concentrations, 3-y folic acid supplementation did not slow down atherosclerotic progression or arterial stiffening. This trial was registered at clinicaltrials.gov as NCT00110604.
Subject(s)
Atherosclerosis/prevention & control , Carotid Artery, Common/pathology , Dietary Supplements , Folic Acid Deficiency/drug therapy , Folic Acid/therapeutic use , Tunica Intima/pathology , Tunica Media/pathology , Aged , Atherosclerosis/epidemiology , Atherosclerosis/etiology , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/etiology , Carotid Artery Diseases/prevention & control , Carotid Artery, Common/diagnostic imaging , Disease Progression , Double-Blind Method , Elasticity , Female , Folic Acid/blood , Folic Acid Deficiency/blood , Folic Acid Deficiency/pathology , Folic Acid Deficiency/physiopathology , Homocysteine/blood , Humans , Hyperhomocysteinemia/blood , Hyperhomocysteinemia/drug therapy , Hyperhomocysteinemia/pathology , Hyperhomocysteinemia/physiopathology , Male , Middle Aged , Netherlands/epidemiology , Risk Factors , Tunica Intima/diagnostic imaging , Tunica Media/diagnostic imaging , UltrasonographyABSTRACT
OBJECTIVES: To determine whether a large-scale physical activity intervention could affect body composition in primary school students in Beijing, China. METHODS: The study design was one-year cluster randomized controlled trial of physical activity intervention (20 min of daily exercise in the classroom) with an additional year of follow-up among 4 700 students aged 8-11 years at baseline. RESULTS: After the one-year intervention, BMI increased by 0.56 kg/m(2) (SD 1.15) in the intervention group and by 0.72 kg/m(2) (SD 1.20) in the control group, with a mean difference of -0.15 kg/m(2) (95% CI: -0.28 to -0.02). BMI z score decreased by -0.05 (SD 0.44) in the intervention group, but increased by 0.01 (SD 0.46) in the control group, with a mean difference of -0.07 (-0.13 to -0.01). After another year of follow up, compared to the control group, children in the intervention group had significantly lower BMI (-0.13, -0.25 to -0.01), BMI z score (-0.05, -0.10 to -0.01), fat mass (-0.27 kg, -0.53 to -0.02) and percent body fat (-0.53, -1.00 to -0.05). The intervention had a more pronounced effect on weight, height, BMI, BMI z score, and body composition among obese children than among normal weight or overweight children. Compared to the control group, the intervention group had a significantly higher percentage of children who maintained or reduced their BMI z score at year 1 (P=0.008) and year 2 (P=0.04). CONCLUSIONS: These findings suggest that 20 min of daily moderate to vigorous physical activity during the school year is a feasible and effective way to prevent excessive gain of body weight, BMI, and body fatness in primary school students.
Subject(s)
Body Composition , Exercise , Obesity/prevention & control , Child , China/epidemiology , Female , Humans , Male , Obesity/epidemiologyABSTRACT
Pregnancy is a condition exhibiting increased susceptibility to oxidative stress, and Fe plays a central role in generating harmful oxygen species. The objective of the present study is to investigate the changes in haematological status, oxidative stress and erythrocyte membrane fluidity in anaemic pregnant women after Fe supplementation with and without combined vitamins. The study was a 2 months double-blind, randomised trial. Pregnant women (n 164) were allocated to four groups: group C was the placebo control group; group I was supplemented daily with 60 mg Fe (ferrous sulphate) daily; group IF was supplemented daily with Fe plus 400 µg folic acid; group IM was supplemented daily with Fe plus 2 mg retinol and 1 mg riboflavin, respectively. After the 2-month trial, Hb significantly increased by 15.8, 17.3 and 21.8 g/l, and ferritin by 2.8, 3.6 and 11.0 µg/l, in the I, IF and IM groups compared with placebo. Polarisation (ρ) and microviscosity (η) decreased significantly in other groups compared with placebo, indicating an increase in membrane fluidity. Significant decreases of ρ and η values compared with group C were 0.033 and 0.959 for group I, 0.037 and 1.074 for group IF and 0.064 and 1.865 for group IM, respectively. In addition, significant increases of glutathione peroxidase activities and decreases of malondialdehyde were shown in all treated groups, as well as increases of plasma retinol and urine riboflavin in group IM. The findings show that supplementation with Fe and particularly in combination with vitamins could improve the haematological status as well as oxidative stress and erythrocyte membrane fluidity.
Subject(s)
Anemia/drug therapy , Erythrocyte Membrane/drug effects , Iron, Dietary/administration & dosage , Iron/therapeutic use , Oxidative Stress/drug effects , Pregnancy Complications, Hematologic/drug therapy , Vitamins/therapeutic use , Adult , Anemia/metabolism , Dietary Supplements , Double-Blind Method , Drug Therapy, Combination , Erythrocyte Membrane/metabolism , Female , Ferritins/blood , Folic Acid/pharmacology , Folic Acid/therapeutic use , Glutathione Peroxidase/blood , Hemoglobins/metabolism , Humans , Iron/pharmacology , Malondialdehyde/blood , Micronutrients/pharmacology , Micronutrients/therapeutic use , Pregnancy , Pregnancy Complications, Hematologic/metabolism , Riboflavin/pharmacology , Riboflavin/therapeutic use , Riboflavin/urine , Viscosity , Vitamin A/blood , Vitamin A/pharmacology , Vitamin A/therapeutic use , Vitamins/pharmacology , Young AdultABSTRACT
BACKGROUND: The C282Y mutation of the hemochromatosis (HFE)-gene increases body iron status. Among Caucasians, the carrier frequency of this mutation is 8-9%. C282Y carriers may be more susceptible to iron-induced atherosclerosis due to higher iron levels. It has also been postulated that the C282Y mutation could alter aspects of iron metabolism. We examined the relationship between the C282Y mutation, iron status, and carotid intima-media thickness (IMT) as a marker of atherosclerosis. METHODS AND RESULTS: The present study comprised 764 Dutch men and post-menopausal women aged 50-70 years. Mean and maximum carotid IMT were assessed by B-mode ultrasonography. Blood was sampled for assessment of the C282Y mutation and body iron status. Parameters of iron status (e.g. ferritin and non-transferrin bound iron) were significantly higher in C282Y carriers (n=80; 10%) compared to non-carriers (P-values <0.001), however, there was no difference in the carotid IMT measures. Among non-smokers (n=222), carotid IMT was 0.051 mm (95% CI: 0.005; 0.096) lower in carriers compared to non-carriers (P=0.03), which remained after adjustment for iron parameters. Within the subgroup of carriers, higher carotid IMT values were observed across sex-specific quartiles of ferritin (mean IMT: 0.789, 0.787, 0.814, and 0.865 mm; P-trend=0.08), whereas this association was absent in non-carriers. CONCLUSION: Overall, we found no association of HFE genotype with carotid IMT, despite higher iron status. Interestingly, C282Y carriers may be hyper responsive to vascular damage which needs to be confirmed in prospective cohort studies.
Subject(s)
Atherosclerosis/genetics , Carotid Arteries/pathology , Hemochromatosis/genetics , Heterozygote , Histocompatibility Antigens Class I/genetics , Iron/pharmacology , Membrane Proteins/genetics , Mutation , Aged , Cohort Studies , Female , Hemochromatosis Protein , Humans , Male , Middle Aged , Prospective Studies , Tunica Intima/pathology , Tunica Media/pathologyABSTRACT
BACKGROUND: Weekly fish consumption has been related to a lower risk of fatal coronary heart disease (CHD) and incident stroke in populations with a low fish intake. This relation has mainly been attributed to n-3 fatty acids in fish, that is, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). It is at present unclear whether alpha-linolenic acid (ALA), a n-3 fatty acid from vegetable origin, could also be protective against cardiovascular diseases (CVDs). There is a need for food-based trials to establish the efficacy of low doses of n-3 fatty acids in CVD prevention. OBJECTIVES: The aim of the study was to evaluate the effect of an additional daily intake of 400 mg of EPA + DHA and 2 g of ALA on CVD morbidity and mortality in free-living subjects with a history of myocardial infarction. DESIGN: The multicenter Alpha Omega Trial is a randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design. Between May 2002 and December 2006, we enrolled a total of 4,837 men and women aged 60 through 80 who experienced a myocardial infarction within 10 years before entering the study. Subjects were randomized to 1 of 4 margarine spreads that were enriched with EPA + DHA and/or ALA, or placebo. Compliance was monitored via tub counts and assessment of n-3 fatty acids in plasma. Subjects were observed for 40 months for the occurrence of fatal and nonfatal CVD. RESULTS: The cohort was on average 69 years old at the start of the study and comprised 22% women. Subjects had their (last) myocardial infarction approximately 4 years before enrollment. Mean body mass index was 27.7 kg/m(2), and 17% smoked. Average serum total and high-density lipoprotein cholesterol were 4.7 and 1.3 mmol/L, respectively, and 85% used statins. Mean blood pressure was 142/80 mm Hg, and most subjects were on antihypertensive medication (88%). Diabetes mellitus was reported by 17% of the subjects, and 7% reported a history of stroke. The overall mortality rate during the trial period was 23 per 1,000 person-years, with approximately 40% due to CVD. CURRENT STATUS: Follow-up of the patients was completed in November 2009, and findings will be reported in the second part of 2010.
Subject(s)
Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Fatty Acids, Omega-3/pharmacology , Aged , Aged, 80 and over , Cardiovascular Diseases/mortality , Double-Blind Method , Female , Humans , Male , Middle Aged , Myocardial Infarction/drug therapy , Risk Factors , Treatment OutcomeABSTRACT
BACKGROUND: The increased prevalence of overweight and obesity warrants preventive actions, particularly among people in transitional stages associated with lifestyle changes, such as occupational retirement. The purpose is to investigate the effect of a one year low-intensity computer-tailored energy balance programme among recent retirees on waist circumference, body weight and body composition, blood pressure, physical activity and dietary intake. METHODS: A randomised controlled trial was conducted among recent retirees (N = 413; mean age 59.5 years). Outcome measures were assessed using anthropometry, bio-impedance, blood pressure measurement and questionnaires. RESULTS: Waist circumference, body weight and blood pressure decreased significantly in men of the intervention and control group, but no significant between-group-differences were observed at 12 or at 24-months follow-up. A significant effect of the programme was only observed on waist circumference (-1.56 cm (95%CI: -2.91 to -0.21)) at 12 month follow up among men with low education (n = 85). Physical activity and dietary behaviours improved in both the intervention and control group during the intervention period. Although, these behaviours changed more favourably in the intervention group, these between-group-differences were not statistically significant. CONCLUSIONS: The multifaceted computer-tailored programme for recent retirees did not appear to be effective. Apparently the transition to occupational retirement and/or participation in the study had a greater impact than the intervention programme. TRIAL REGISTRATION: Clinical Trials NCT00122213.
Subject(s)
Body Composition , Diet , Energy Metabolism/physiology , Health Promotion/methods , Life Style , Aged , Cluster Analysis , Exercise/physiology , Female , Follow-Up Studies , Health Promotion/standards , Humans , Male , Middle Aged , Netherlands , Program Evaluation , Retirement , Weight Loss/physiologyABSTRACT
BACKGROUND: Little is known about the effect of different types of dairy food products on the development of hypertension. OBJECTIVE: The objective was to determine whether the incidence of hypertension in older Dutch subjects is associated with intake of dairy products. DESIGN: We examined the relation between dairy intake and incident hypertension in 2245 participants of the Rotterdam Study aged > or =55 y with complete dietary and blood pressure data, who were free of hypertension at baseline (1990-1993). Blood pressure was reexamined in 1993-1995 and in 1997-1999. Hazard ratios (HRs) with 95% CIs for 2- and 6-y incidence of hypertension were obtained in quartiles of energy-adjusted dairy intake, with adjustment for age, sex, BMI, smoking, educational level, dietary factors, and intake of alcohol and total energy. RESULTS: Risk of hypertension after 2 y of follow-up (664 incident cases) was inversely associated with dairy product intake. After adjustment for confounders, HRs (95% CIs) were 1.00, 0.82 (0.67, 1.02), 0.67 (0.54, 0.84), and 0.76 (0.61, 0.95) in consecutive quartiles of total dairy product intake (P for trend = 0.008). Corresponding HRs for low-fat dairy products were 1.00, 0.75 (0.60, 0.92), 0.77 (0.63, 0.96), and 0.69 (0.56, 0.86) (P for trend = 0.003). Analysis of specific types of dairy products showed an inverse association with milk and milk products (P for trend = 0.07) and no association with high-fat dairy or cheese (P > 0.6). After 6 y of follow-up (984 incident cases), the associations with hypertension were attenuated to risk reductions of approximately 20% for both total and low-fat dairy products between the extreme quartiles of intake (P for trend = 0.07 and 0.09, respectively). CONCLUSION: Intake of low-fat dairy products may contribute to the prevention of hypertension at an older age.