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Sample records for metabolic disease cohort

  1. Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.

    PubMed

    Chang, Yoosoo; Ryu, Seungho; Choi, Yuni; Zhang, Yiyi; Cho, Juhee; Kwon, Min-Jung; Hyun, Young Youl; Lee, Kyu-Beck; Kim, Hyang; Jung, Hyun-Suk; Yun, Kyung Eun; Ahn, Jiin; Rampal, Sanjay; Zhao, Di; Suh, Byung-Seong; Chung, Eun Cheol; Shin, Hocheol; Pastor-Barriuso, Roberto; Guallar, Eliseo

    2016-03-01

    The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. Prospective cohort study. Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal-weight participants were -4.0 (95% CI, -7.8 to -0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. Chronic kidney disease was identified by a single measurement at each visit. Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. None.

  2. Metabolic Syndrome, Components, and Cardiovascular Disease Prevalence in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

    PubMed Central

    Townsend, Raymond R.; Anderson, Amanda H.; Chen, Jing; Gadebegku, Crystal A.; Feldman, Harold I.; Fink, Jeffrey C.; Go, Alan S.; Joffe, Marshall; Nessel, Lisa A.; Ojo, Akinlolu; Rader, Daniel J.; Reilly, Muredach P.; Teal, Valerie; Teff, Karen; Wright, Jackson T.; Xie, Dawei

    2011-01-01

    Background/Aims Metabolic syndrome may increase the risk for incident cardiovascular disease (CVD) and all-cause mortality in the general population. It is unclear whether, and to what degree, metabolic syndrome is associated with CVD in chronic kidney disease (CKD). We determined metabolic syndrome prevalence among individuals with a broad spectrum of kidney dysfunction, examining the role of the individual elements of metabolic syndrome and their relationship to prevalent CVD. Methods We evaluated four models to compare metabolic syndrome or its components to predict prevalent CVD using prevalence ratios in the Chronic Renal Insufficiency Cohort (CRIC) Study. Results Among 3,939 CKD participants, the prevalence of metabolic syndrome was 65% and there was a significant association with prevalent CVD. Metabolic syndrome was more common in diabetics (87.5%) compared with non-diabetics (44.3%). Hypertension was the most prevalent component, and increased triglycerides the least prevalent. Using the bayesian information criterion, we found that the factors defining metabolic syndrome, considered as a single interval-scaled variable, was the best of four models of metabolic syndrome, both for CKD participants overall and for diabetics and non-diabetics separately. Conclusion The predictive value of this model for future CVD outcomes will subsequently be validated in longitudinal analyses. PMID:21525746

  3. Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study.

    PubMed

    Kim, Gi Hyun; Chung, Jung Wha; Lee, Jong Ho; Ok, Kyeong Sam; Jang, Eun Sun; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Jeong, Sook-Hyang; Kim, Nayoung; Lee, Dong Ho; Kim, Jin-Wook

    2015-12-01

    Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome. A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85). The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period. Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.

  4. Identification of Metabolic risk phenotypes predisposing to Non-Alcoholic Fatty Liver Disease in a Pakistani Cohort

    PubMed Central

    Ghani, Rizwana Abdul; Saqlain, Muhammad; Zafar, Muhammad Mobeen; Jabeen, Shagufta; Naqvi, Syed Muhammad Saqlan; Raja, Ghazala Kaukab

    2017-01-01

    Objectives: Non-alcoholic fatty liver disease (NAFLD) has emerged in the last two decades with worldwide prevalence of 25.24%. Due to its increasing frequency in Pakistan, it was aimed to identify disease predisposing metabolic risks and their association with NAFLD. Methods: Anthropometric and biochemical investigations were collected from 1366 subjects with minor metabolic disturbances. Comparative analyses were performed to compute frequencies of common metabolic risk phenotypes while their associations with NAFLD were explored using regression analyses. The prevalence of NAFLD was also estimated in total, age, and gender-based population cohorts. Results: Among metabolic risk phenotypes obesity, hyperglycemia, hypertension, and dyslipidemia significantly associated (p<0.001) with NAFLD risk irrespective of age, gender, and BMI. Prevalence of NAFLD in total study cohort was 14.8%, 16.1% in males, 13.4% in females, 19.9% in ≥40 years and 8.7% in ≤40 years respectively. Conclusion: General Pakistani populations experiencing common metabolic disturbances are at high risk of NAFLD development, especially male gender and advanced age. Based on these parameters the stratified NAFLD population could be treated accordingly. PMID:28367184

  5. Effect of vitamin E in nonalcoholic fatty liver disease with metabolic syndrome: A propensity score-matched cohort study

    PubMed Central

    Kim, Gi Hyun; Chung, Jung Wha; Lee, Jong Ho; Ok, Kyeong Sam; Jang, Eun Sun; Kim, Jaihwan; Shin, Cheol Min; Park, Young Soo; Hwang, Jin-Hyeok; Jeong, Sook-Hyang; Kim, Nayoung; Lee, Dong Ho

    2015-01-01

    Background/Aims Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome. Methods A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85). Results The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period. Conclusions Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E. PMID:26770927

  6. Metabolic and Body Composition Risk Factors Associated with Metabolic Syndrome in a Cohort of Women with a High Prevalence of Cardiometabolic Disease

    PubMed Central

    Norris, Shane A.; Jaff, Nicole G.; Crowther, Nigel J.

    2016-01-01

    Background The aetiology of the metabolic syndrome and the inter-relationship between risk factors for this syndrome are poorly understood. The purpose of this investigation was to determine the risk factors for metabolic syndrome and their interactions in a cohort of women with a high prevalence of metabolic syndrome. Materials and Methods Abdominal and whole body composition (ultrasound and dual-energy X-ray absorptiometry), blood pressure, and cardiometabolic and demographic factors were measured in a cross-sectional study of 702 black African women from Soweto, Johannesburg. Data was analysed using multivariate logistic regression. Results Metabolic syndrome was present in 49.6% of the study cohort. Logistic regression analysis demonstrated that adiponectin (odds ratio [95% CIs]: 0.84 [0.77, 0.92], p<0.0005) and abdominal subcutaneous fat (0.56 [0.39, 0.79], p = 0.001) reduced metabolic syndrome risk whilst insulin resistance (1.31 [1.16, 1.48], p<0.0005) and trunk fat-free soft-tissue mass (1.34 [1.10, 1.61], p = 0.002) increased risk. Within this group of risk factors, the relationship of adiponectin with metabolic syndrome risk, when analysed across adiponectin hexiles, was the least affected by adjustment for the other risk factors. Conclusions Adiponectin has a significant protective role against metabolic syndrome and is independent of other risk factors. The protective and possible augmentive effects of abdominal subcutaneous fat and lean trunk mass, respectively on metabolic syndrome risk demonstrate the existence of novel interactions between body composition and cardiometabolic disease. PMID:27589387

  7. Eosinophil Count Is a Common Factor for Complex Metabolic and Pulmonary Traits and Diseases: The LifeLines Cohort Study

    PubMed Central

    Bashirova, Dinara; Prins, Bram P.; Corpeleijn, Eva; Bruinenberg, Marcel; Franke, Lude; van der Harst, Pim; Navis, Gerjan; Wolffenbuttel, Bruce H. R.; Stolk, Ronald P.; Wijmenga, Cisca; Postma, Dirkje S.; Koppelman, Gerard H.; Boezen, H. Marike; Vonk, Judith; Snieder, Harold; Alizadeh, Behrooz Z.

    2016-01-01

    There is ongoing debate on the association between eosinophil count and diseases, as previous studies were inconsistent. We studied the relationship of eosinophil count with 22 complex metabolic, cardiac, and pulmonary traits and diseases. From the population-based LifeLines Cohort Study (N = 167,729), 13,301 individuals were included. We focused on relationship of eosinophil count with three classes of metabolic (7 traits, 2 diseases), cardiac (6 traits, 2 diseases), and pulmonary (2 traits, 2 diseases) outcomes. Regression analyses were applied in overall, women and men, while adjusted for age, sex, BMI and smoking. A p-value of <0.00076 was considered statistically significant. 58.2% of population were women (mean±SD 51.3±11.1 years old). In overall, one-SD higher of ln-eosinophil count was associated with a 0.04 (±SE ±0.002;p = 6.0×10−6) SD higher levels in ln-BMI, 0.06 (±0.007;p = 3.1×10−12) SD in ln-TG, 0.04 (±0.003;p = 7.0×10−6) SD in TC, 0.04 (±0.004;p = 6.3×10−7) SD in LDL, 0.04 (±0.006;p = 6.0×10−6) SD in HbA1c; and with a 0.05 (±0.004;p = 1.7×10−8) SD lower levels in HDL, 0.05 (±0.007;p = 3.4×10−23) SD in FEV1, and 0.09 (±0.001;p = 6.6×10−28) SD in FEV1/FVC. A higher ln-eosinophil count was associated with 1.18 (95%CI 1.09–1.28;p = 2.0×10−5) odds ratio of obesity, 1.29 (1.19–1.39;p = 1.1×10−10) of metabolic syndrome, 1.40 (1.25–1.56;p = 2.7×10−9) of COPD and 1.81 (1.61–2.03;p = 1.0×10−23) of asthma. Similar results were found in women. We found no association between ln-eosinophil count either with blood pressure indices in overall, women and men; or with BMI, LDL, HbA1c and obesity in men. In a large population based cohort, we confirmed eosinophil count as a potential factor implicated in metabolic and pulmonary outcomes. PMID:27978545

  8. New biomarkers for early diagnosis of Lesch-Nyhan disease revealed by metabolic analysis on a large cohort of patients.

    PubMed

    Ceballos-Picot, Irène; Le Dantec, Aurélia; Brassier, Anaïs; Jaïs, Jean-Philippe; Ledroit, Morgan; Cahu, Julie; Ea, Hang-Korng; Daignan-Fornier, Bertrand; Pinson, Benoît

    2015-01-23

    Lesch-Nyhan disease is a rare X-linked neurodevelopemental metabolic disorder caused by a wide variety of mutations in the HPRT1 gene leading to a deficiency of the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). The residual HGprt activity correlates with the various phenotypes of Lesch-Nyhan (LN) patients and in particular with the different degree of neurobehavioral disturbances. The prevalence of this disease is considered to be underestimated due to large heterogeneity of its clinical symptoms and the difficulty of diagnosing of the less severe forms of the disease. We therefore searched for metabolic changes that would facilitate an early diagnosis and give potential clues on the disease pathogenesis and potential therapeutic approaches. Lesch-Nyhan patients were diagnosed using HGprt enzymatic assay in red blood cells and identification of the causal HPRT1 gene mutations. These patients were subsequently classified into the three main phenotypic subgroups ranging from patients with only hyperuricemia to individuals presenting motor dysfunction, cognitive disability and self-injurious behavior. Metabolites from the three classes of patients were analyzed and quantified by High Performance Ionic Chromatography and biomarkers of HGprt deficiency were then validated by statistical analyses. A cohort of 139 patients, from 112 families, diagnosed using HGprt enzymatic assay in red blood cells, was studied. 98 displayed LN full phenotype (86 families) and 41 (26 families) had attenuated clinical phenotypes. Genotype/phenotype correlations show that LN full phenotype was correlated to genetic alterations resulting in null enzyme function, while variant phenotypes are often associated with missense mutations allowing some residual HGprt activity. Analysis of metabolites extracted from red blood cells from 56 LN patients revealed strong variations specific to HGprt deficiency for six metabolites (AICAR mono- and tri

  9. Predicting the development of diabetes using the product of triglycerides and glucose: the Chungju Metabolic Disease Cohort (CMC) study.

    PubMed

    Lee, Seung-Hwan; Kwon, Hyuk-Sang; Park, Yong-Moon; Ha, Hee-Sung; Jeong, Seung Hee; Yang, Hae Kyung; Lee, Jin-Hee; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Yoon, Kun-Ho

    2014-01-01

    To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9 ± 0.6 vs. 8.6 ± 0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701-6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes.

  10. Association of osteoporosis susceptibility genes with bone mineral density and bone metabolism related markers in Koreans: the Chungju Metabolic Disease Cohort (CMC) study.

    PubMed

    Park, Se Eun; Oh, Ki Won; Lee, Won Young; Baek, Ki Hyun; Yoon, Kun Ho; Son, Ho Young; Lee, Won Chul; Kang, Moo Il

    2014-01-01

    In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

  11. Post-mortem whole-exome analysis in a large sudden infant death syndrome cohort with a focus on cardiovascular and metabolic genetic diseases.

    PubMed

    Neubauer, Jacqueline; Lecca, Maria Rita; Russo, Giancarlo; Bartsch, Christine; Medeiros-Domingo, Argelia; Berger, Wolfgang; Haas, Cordula

    2017-04-01

    Sudden infant death syndrome (SIDS) is described as the sudden and unexplained death of an apparently healthy infant younger than one year of age. Genetic studies indicate that up to 35% of SIDS cases might be explained by familial or genetic diseases such as cardiomyopathies, ion channelopathies or metabolic disorders that remained undetected during conventional forensic autopsy procedures. Post-mortem genetic testing by using massive parallel sequencing (MPS) approaches represents an efficient and rapid tool to further investigate unexplained death cases and might help to elucidate pathogenic genetic variants and mechanisms in cases without a conclusive cause of death. In this study, we performed whole-exome sequencing (WES) in 161 European SIDS infants with focus on 192 genes associated with cardiovascular and metabolic diseases. Potentially causative variants were detected in 20% of the SIDS cases. The majority of infants had variants with likely functional effects in genes associated with channelopathies (9%), followed by cardiomyopathies (7%) and metabolic diseases (1%). Although lethal arrhythmia represents the most plausible and likely cause of death, the majority of SIDS cases still remains elusive and might be explained by a multifactorial etiology, triggered by a combination of different genetic and environmental risk factors. As WES is not substantially more expensive than a targeted sequencing approach, it represents an unbiased screening of the exome, which could help to investigate different pathogenic mechanisms within the genetically heterogeneous SIDS cohort. Additionally, re-analysis of the datasets provides the basis to identify new candidate genes in sudden infant death.

  12. Body weight, metabolic dysfunction, and risk of type 2 diabetes in patients at high risk for cardiovascular events or with manifest cardiovascular disease: a cohort study.

    PubMed

    Franssens, Bas T; van der Graaf, Yolanda; Kappelle, L Jaap; Westerink, Jan; de Borst, Gert J; Cramer, Maarten J; Visseren, Frank L J

    2015-10-01

    To quantify the role of BMI and metabolic dysfunction in the risk of development of type 2 diabetes in patients at high risk or with manifest vascular disease. A total of 6,997 patients participating in the prospective Secondary Manifestations of ARTerial disease (SMART) cohort study were classified according to BMI and metabolic dysfunction, defined as three or more of the modified National Cholesterol Education Program (NCEP) metabolic syndrome criteria (waist circumference replaced by hs-CRP ≥2 mg/L). Risk of type 2 diabetes (assessed with biannually questionnaires) was estimated with Cox proportional hazards analysis. During a median follow-up of 6.0 years (interquartile range 3.1-9.1 years), 519 patients developed type 2 diabetes (incidence rate 12/1,000 person-years). In the absence of metabolic dysfunction (≤2 NCEP criteria), adiposity increased the risk of type 2 diabetes compared with normal-weight patients (HR 2.5 [95% CI 1.5-4.2] for overweight and HR 4.3 [95% CI 2.2-8.6] for obese patients). In the presence of metabolic dysfunction (≥3 NCEP criteria), an increased risk of type 2 diabetes was observed in patients with normal weight (HR 4.7 [95% CI 2.8-7.8]), overweight (HR 8.5 [95% CI 5.5-13.4]), and obesity (HR 16.3 [95% CI 10.4-25.6]) compared with normal-weight patients without metabolic dysfunction. Adiposity, even in the absence of metabolic dysfunction, is a risk factor for type 2 diabetes. Moreover, presence of metabolic dysfunction increases the risk of type 2 diabetes in all BMI categories. This supports the assessment of adiposity and metabolic dysfunction in patients with vascular disease or at high risk for cardiovascular events. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Prognostic value of metabolic syndrome for the development of cardiovascular disease in a cohort of premenopausal women with systemic lupus erythematosus.

    PubMed

    García-Villegas, Elsy Aidé; Lerman-Garber, Israel; Flores-Suárez, Luis Felipe; Aguilar-Salinas, Carlos; Márquez González, Horacio; Villa-Romero, Antonio Rafael

    2015-04-08

    Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE. Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD). The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD. We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Mineral metabolism in heart disease.

    PubMed

    Heine, Gunnar H

    2015-07-01

    Strong experimental and clinical evidence points towards a substantial contribution of mineral metabolism disorders to the initiation and progression of cardiovascular disease. Vice versa, recent work suggests that cardiovascular disease may also cause mineral metabolism alterations. Experimental studies suggest that hyperphosphatemia, elevated plasma levels of phosphaturic hormones--parathyroid hormone and fibroblast growth factor-23 (FGF-23)--and hypovitaminosis D exert detrimental effects on vascular tissue and on the myocardium. Accordingly, in longitudinal clinical cohort studies, individuals with high plasma levels of phosphate, parathyroid hormone and FGF-23, and with low vitamin D levels, face worst cardiovascular prognosis.Notably, recent evidence suggests that cardiovascular disease may not only follow but also induce mineral metabolism disorders: severe derangements in mineral metabolism were observed in patients with acute heart failure, who face a tremendous increase in plasma FGF-23. Unfortunately, few prospective studies have been completed hitherto that specifically target components of the mineral metabolism for cardiovascular disease prevention or treatment. A bidirectional interaction exists between mineral metabolism disorders and cardiovascular disease. However, clinical evidence for a cardiovascular benefit of therapeutic interventions into mineral metabolism is outstanding.

  15. The Relationship of Metabolic Syndrome with Stress, Coronary Heart Disease and Pulmonary Function - An Occupational Cohort-Based Study

    PubMed Central

    Nowobilski, Roman; Dropinski, Jerzy; Kotula-Horowitz, Katarzyna; Laskowicz, Bartosz; Stanisz, Andrzej; Lelakowski, Jacek

    2015-01-01

    Background and Aims Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. Design and Methods The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. Results Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24–5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07–29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24–66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03–1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001–1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96–0.99; p = 0.02). MetS subjects had significantly lower values of certain

  16. Anthropometric and Metabolic Risk Factors for ESRD Are Disease-Specific: Results from a Large Population-Based Cohort Study in Austria

    PubMed Central

    Zitt, Emanuel; Pscheidt, Constanze; Concin, Hans; Kramar, Reinhard; Lhotta, Karl; Nagel, Gabriele

    2016-01-01

    Background Anthropometric and metabolic risk factors for all-cause end-stage renal disease (ESRD) may vary in their impact depending on the specific primary renal disease. Methods In this Austrian population-based prospective cohort study (n = 185,341; 53.9% women) the following data were collected between 1985 and 2005: age, sex, body mass index (BMI), fasting blood glucose (FBG) from 1988, blood pressure, total cholesterol (TC), triglycerides (TG), gamma-glutamyl transferase (GGT) and smoking status. These data were merged with the Austrian Dialysis and Transplant Registry to identify ESRD patients. Cox proportional hazards models were applied to calculate hazard ratios (HR) for all-cause ESRD as well as for cause-specific ESRD due to the following primary renal diseases: autosomal dominant polycystic kidney disease (ADPKD), vascular nephropathy (VN), diabetic nephropathy (DN) and other diseases (OD). Results During a mean follow-up of 17.5 years 403 participants developed ESRD (ADPKD 36, VN 97, DN 86, and OD 184). All parameters except TG and GGT were significantly associated with all-cause ESRD risk. Particular cause-specific ESRD risk factor patterns were found: for ADPKD increased risk from hypertension (HR 11.55); for VN from smoking (HR 1.81), hypertension (HR 2.37), TG (≥5.70 vs. <1.17 mmol/L: HR 9.27); for DN from smoking (HR 1.77), BMI (≥30 vs. 18.5–24.9 kg/m2: HR 7.55), FBG (≥6.94 vs. <5.55 mmol/L: HR 7.67), hypertension (HR 1.08), TG (≥5.70 vs. <1.17 mmol/L: HR 2.02), GGT (HR 2.14); and for OD from hypertension (HR 2.29), TG (≥5.70 vs. <1.17 mmol/L: HR 6.99) and TC (≥6.22 vs. <5.18 mmol/L: HR 1.56). Conclusions Particular anthropometric and metabolic ESRD risk factors differ in importance depending on the primary renal disease. This needs to be considered for future preventive and therapeutic strategies addressing cause-specific ESRD. PMID:27537361

  17. Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease

    PubMed Central

    Gallicchio, Lisa; Berndt, Sonja I; McSorley, Meghan A; Newschaffer, Craig J; Thuita, Lucy W; Argani, Pedram; Hoffman, Sandra C; Helzlsouer, Kathy J

    2006-01-01

    Background A cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer. Methods Among participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries. Results Among all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 – 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32). Conclusion The results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer. PMID:16808847

  18. Disease fatality and bias in survival cohorts.

    PubMed

    Barry, Vaughn; Klein, Mitchel; Winquist, Andrea; Darrow, Lyndsey A; Steenland, Kyle

    2015-07-01

    Simulate how the effect of exposure on disease occurrence and fatality influences the presence and magnitude of bias in survivor cohorts, motivated by an actual survivor cohort under study. We simulated a cohort of 50,000 subjects exposed to a disease-causing exposure over time and followed forty years, where disease incidence was the outcome of interest. We simulated this 'inception' cohort under different assumptions about the effect of exposure on disease occurrence and fatality after disease occurrence. We then created a corresponding 'survivor' (or 'cross-sectional') cohort, where cohort enrollment took place at a specific date after exposure began in the inception cohort; subjects dying prior to that enrollment date were excluded. The disease of interest caused all deaths in our simulations, but was not always fatal. In the survivor cohort, person-time at risk began before enrollment for all subjects who did not die prior to enrollment. We compared exposure-disease associations in each inception cohort to those in corresponding survivor cohorts to determine how different assumptions impacted bias in the survivor cohorts. All subjects in both inception and survivor cohorts were considered equally susceptible to the effect of exposure in causing disease. We used Cox proportional hazards regression to calculate effect measures. There was no bias in survivor cohort estimates when case fatality among diseased subjects was independent of exposure. This was true even when the disease was highly fatal and more highly exposed subjects were more likely to develop disease and die. Assuming a positive exposure-response in the inception cohort, survivor cohort rate ratios were biased downwards when case fatality was greater with higher exposure. Survivor cohort effect estimates for fatal outcomes are not always biased, although precision can decrease. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Diseases of Phenylalanine Metabolism

    PubMed Central

    Parker, Charles E.

    1979-01-01

    Continuing investigation of the system that hydroxylates phenylalanine to tyrosine has led to new insights into diseases associated with the malfunction of this system. Good evidence has confirmed that phenylketonuria (PKU) is not caused by a simple lack of phenylalanine hydroxylase. Dihydropteridine reductase deficiency as well as defects in biopterin metabolism may also cause the clinical features of phenylketonuria. Furthermore, these diseases do not respond to the standard treatment for phenylketonuria. PMID:388868

  20. The prevalence of metabolic syndrome increases with serum high sensitivity C-reactive protein concentration in individuals without a history of cardiovascular disease: a report from a large Persian cohort.

    PubMed

    Kazemi-Bajestani, Seyyed Mr; Tayefi, Maryam; Ebrahimi, Mahmoud; Heidari-Bakavoli, Ali R; Moohebati, Mohsen; Parizadeh, Seyyed Mr; Esmaeili, Habibollah; Ferns, Gordon Aa; Ghayour-Mobarhan, Majid

    2017-01-01

    Background Metabolic syndrome is defined by a clustering of cardiovascular risk factors and is associated with a heightened inflammatory state. A raised serum high-sensitivity C-reactive protein, a marker of inflammation, is also known to associate with cardiovascular risk. We have investigated the relationship between the presence of metabolic syndrome and serum high-sensitivity C-reactive protein concentration in a large representative Persian population cohort without a history of cardiovascular disease. Methods The MASHAD study population cohort comprised 9778 subjects, who were recruited from the city of Mashhad, Iran, between 2007 and 2008. Several cardiovascular risk factors were measured in this population without cardiovascular disease. Individuals were categorized into quartiles of serum high-sensitivity C-reactive protein concentration: first quartile - 0.72 (0.59-0.85) (median [range]) mg/L, second quartile - 1.30 (1.14-1.4) mg/L, third quartile - 2.29 (1.92-2.81) mg/L and fourth quartile - 6.63 (4.61-11.95) mg/L, respectively. The prevalence of metabolic syndrome in each quartile was determined using either International Diabetes Federation or Adult Treatment Panel III criteria. Results The prevalence of metabolic syndrome was highest in the fourth quartile for serum high-sensitivity C-reactive protein (1220 subjects [50.0%]), and significantly higher than that in the first quartile (reference group) (634 subjects [25.9%]) ( P < 0.001). A positive smoking habit (OR, 1.47 [1.26-1.70], P < 0.001) and the presence of either metabolic syndrome-International Diabetes Federation (OR, 1.35 [1.18-1.55], P < 0.001) or metabolic syndrome-ATPIII (OR, 1.40 [1.18-1.50], P < 0.001) were strong predictors of a fourth quartile for serum high-sensitivity C-reactive protein concentration. Conclusions There was a significant association between high concentrations of serum high-sensitivity C-reactive protein and the presence of metabolic syndrome among

  1. [Metabolic bone diseases].

    PubMed

    Jakob, F

    2007-10-01

    Osteomalacia is caused by impaired vitamin D receptor (VDR) signaling, calcium deficiency, and altered bone mineralization. This can be due to insufficient sunlight exposure, malabsorption, reduced D hormone activation in chronic kidney disease, and rare alterations of VDR signaling and phosphate metabolism. Leading symptoms are bone pain, muscular cramps, and increased incidence of falls in the elderly. The adequate respective countermeasures are to optimize the daily intake of calcium and vitamin D3 and to replace active D hormone and phosphate if deficient. Osteoporosis is characterized by bone fragility fractures upon minor physical impact. Indications for diagnosis and treatment can be established by estimating the absolute fracture risk, taking into account bone mineral density, age, gender, and individual risk factors. Exercise, intervention programs to avoid falls, and specific drugs are capable of substantially reducing fracture risk even in the elderly. Secondary osteoporosis primarily requires both bone-altering medications and effective treatment of underlying diseases.

  2. Alterations of lipid metabolism in Wilson disease

    PubMed Central

    2011-01-01

    Introduction Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b-/- and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date. Patients and Methods This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination). Results A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides. Conclusion Contradictory to previous reports using WD animal models (Atp7b-/- and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment. PMID:21595966

  3. Nuclear Receptors: Decoding Metabolic Disease

    PubMed Central

    Sonoda, Junichiro; Pei, Liming; Evans, Ronald M.

    2008-01-01

    Nuclear receptors (NR) are a superfamily of ligand-activated transcription factors that regulate development, reproduction, and metabolism of lipids, drugs and energy. The importance of this family of proteins in metabolic disease is exemplified by NR ligands used in the clinic or under exploratory development for the treatment of diabetes mellitus, dyslipidemia, hypercholesterolemia, or other metabolic abnormalities. Genetic studies in humans and rodents support the notion that NRs control a wide variety of metabolic processes by regulating the expression of genes encoding key enzymes, transporters and other proteins involved in metabolic homeostasis. Current knowledge of complex NR metabolic networks is summarized here. PMID:18023286

  4. The cohort effect in childhood disease dynamics.

    PubMed

    He, Daihai; Earn, David J D

    2016-07-01

    The structure of school terms is well known to influence seasonality of transmission rates of childhood infectious diseases in industrialized countries. A less well-studied aspect of school calendars that influences disease dynamics is that all children enter school on the same day each year. Rather than a continuous inflow, there is a sudden increase in the number of susceptible individuals in schools at the start of the school year. Based on the standard susceptible-exposed-infectious-recovered (SEIR) model, we show that school cohort entry alone is sufficient to generate a biennial epidemic pattern, similar to many observed time series of measles incidence. In addition, cohort entry causes an annual decline in the effective transmission that is evident in observed time series, but not in models without the cohort effect. Including both cohort entry and school terms yields a model fit that is significantly closer to observed measles data than is obtained with either cohort entry or school terms alone (and just as good as that obtained with Schenzle's realistic age-structured model). Nevertheless, we find that the bifurcation structure of the periodically forced SEIR model is nearly identical, regardless of whether forcing arises from cohort entry, school terms and any combination of the two. Thus, while detailed time-series fits are substantially improved by including both cohort entry and school terms, the overall qualitative dynamic structure of the SEIR model appears to be insensitive to the origin of periodic forcing.

  5. Diagnosis of metabolic bone disease

    SciTech Connect

    Grech, P.; Martin, T.J.; Barrington, N.A.; Ell, P.J.

    1986-01-01

    This book presents a reference on the radiologic evaluation, features, and differential diagnosis of metabolic diseases involving the whole skeleton, calcium deficiencies resulting from pharmacologic agents, and bone changes related to endocrine disturbances. It also stresses how radiology, nuclear medicine, and biochemistry - either alone or in concert - contribute to clinical diagnosis. It covers renal bone disease, Paget's disease, hyperphosphatasia, extraskeletal mineralization, metabolic bone disorders related to malnutrition, tumors, plus radionuclide studies including materials and methods.

  6. Metabolic syndrome and eye diseases.

    PubMed

    Poh, Stanley; Mohamed Abdul, Riswana Banu Binte; Lamoureux, Ecosse L; Wong, Tien Y; Sabanayagam, Charumathi

    2016-03-01

    Metabolic syndrome is becoming a worldwide medical and public health challenge as it has been seen increasing in prevalence over the years. Age-related eye diseases, the leading cause of blindness globally and visual impairment in developed countries, are also on the rise due to aging of the population. Many of the individual components of the metabolic syndrome have been shown to be associated with these eye diseases. However, the association of metabolic syndrome with eye diseases is not clear. In this review, we reviewed the evidence for associations between metabolic syndrome and certain ocular diseases in populations. We also reviewed the association of individual metabolic syndrome components with ocular diseases due to a paucity of research in this area. Besides, we also summarised the current understanding of etiological mechanisms of how metabolic syndrome or the individual components lead to these ocular diseases. With increasing evidence of such associations, it may be important to identify patients who are at risk of developing metabolic syndrome as prompt treatment and intervention may potentially decrease the risk of developing certain ocular diseases.

  7. Phosphate Metabolism in Cardiorenal Metabolic Disease

    PubMed Central

    Gupta, Deepashree; Brietzke, Stephen; Hayden, M.R.; Kurukulasuriya, L. Romayne; Sowers, James R.

    2011-01-01

    Hyperphosphatemia is a major risk factor for cardiovascular disease, abnormalities of mineral metabolism and bone disease, and the progression of renal insufficiency in patients with chronic renal disease. In early renal disease, serum phosphate levels are maintained within the ‘normal laboratory range’ by compensatory increases in phosphaturic hormones such as fibroblast growth factor-23 (FGF-23). An important co-factor for FGF-23 is Klotho; a deficiency in Klotho plays an important role in the pathogenesis of hyperphosphatemia, renal tubulointerstitial disease, and parathyroid and bone abnormalities. Clinical hyperphosphatemia occurs when these phosphaturic mechanisms cannot counterbalance nephron loss. Hyperphosphatemia is associated with calcific uremic arteriolopathy and uremic cardiomyopathy, which may explain, in part, the epidemiologic connections between phosphate excess and cardiovascular disease. However, no clinical trials have been conducted to establish a causal relationship, and large, randomized trials with hard endpoints are urgently needed to prove or disprove the benefits and risks of therapy. In summary, hyperphosphatemia accelerates renal tubulointerstitial disease, renal osteodystrophy, as well as cardiovascular disease, and it is an important mortality risk factor in patients with chronic kidney disease. PMID:22096458

  8. [Metabolic bone and joint diseases].

    PubMed

    Endo, Itsuro

    2014-10-01

    Metabolic bone and joint diseases in adults include osteomalacia, rheumatoid arthritis, gouty arthritis. Recently, the newest molecular biology procedures and the clinical observation studies can produce good results for understanding of these diseases. From this perspective, the author introduced updated information of the pathophysiology, the latest diagnostic criteria and the therapy of these diseases.

  9. Lysophosphatidylinositol Signalling and Metabolic Diseases

    PubMed Central

    Arifin, Syamsul A.; Falasca, Marco

    2016-01-01

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis. PMID:26784247

  10. Lysophosphatidylinositol Signalling and Metabolic Diseases.

    PubMed

    Arifin, Syamsul A; Falasca, Marco

    2016-01-15

    Metabolism is a chemical process used by cells to transform food-derived nutrients, such as proteins, carbohydrates and fats, into chemical and thermal energy. Whenever an alteration of this process occurs, the chemical balance within the cells is impaired and this can affect their growth and response to the environment, leading to the development of a metabolic disease. Metabolic syndrome, a cluster of several metabolic risk factors such as abdominal obesity, insulin resistance, high cholesterol and high blood pressure, and atherogenic dyslipidaemia, is increasingly common in modern society. Metabolic syndrome, as well as other diseases, such as diabetes, obesity, hyperlipidaemia and hypertension, are associated with abnormal lipid metabolism. Cellular lipids are the major component of cell membranes; they represent also a valuable source of energy and therefore play a crucial role for both cellular and physiological energy homeostasis. In this review, we will focus on the physiological and pathophysiological roles of the lysophospholipid mediator lysophosphatidylinositol (LPI) and its receptor G-protein coupled receptor 55 (GPR55) in metabolic diseases. LPI is a bioactive lipid generated by phospholipase A (PLA) family of lipases which is believed to play an important role in several diseases. Indeed LPI can affect various functions such as cell growth, differentiation and motility in a number of cell-types. Recently published data suggest that LPI plays an important role in different physiological and pathological contexts, including a role in metabolism and glucose homeostasis.

  11. Historical cohort studies and the early origins of disease hypothesis: making sense of the evidence.

    PubMed

    Wells, Jonathan C K

    2009-05-01

    The hypothesis that early-life growth patterns contribute to non-communicable diseases initially emerged from historical cohort studies, consistently associating low birth weight and infant weight gain with later disease risk. Cohort studies offer crucial life-course data on disease aetiology, but also suffer from important limitations, including the difficulty of adjusting for confounding factors and the challenge of interpreting data on early growth. Prospective randomised trials of infant diet appear to provide evidence in direct contradiction to cohort studies, associating faster early growth with disease risk. The present article attempts to resolve this contradiction on two grounds. First, insufficient attention has been directed to inconsistency of outcomes between cohort studies and prospective trials. Cohort studies can assess actual mortality, whereas prospective trials investigate proxies for disease risk. These proxies are often aspects of phenotype that reflect the 'normalisation' of metabolism in response to growth, and not all those displaying normalisation in adolescence and early adulthood may go on to develop disease. Second, a distinction is made between 'metabolic capacity', defined as organ development that occurs in early life, and 'metabolic load', which is imposed by subsequent growth. Disease risk is predicted to be greatest when there is extreme disparity between metabolic capacity and metabolic load. Whereas cohort studies link disease risk with poor metabolic capacity, prospective trials link it with increased metabolic load. Infancy is a developmental period in which nutrition can affect both metabolic capacity and metabolic load; this factor accounts for reported associations of both slow and fast infant growth with greater disease risk.

  12. Metabolic mediators of the effects of body-mass index, overweight, and obesity on coronary heart disease and stroke: a pooled analysis of 97 prospective cohorts with 1·8 million participants

    PubMed Central

    2014-01-01

    Summary Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23–1·31) for coronary heart disease and 1·18 (1·14–1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12–1·18) for coronary heart disease and 1·04 (1·01–1·08) for stroke, suggesting that 46% (95% CI 42–50) of the excess risk of BMI for coronary heart disease and 76% (65–91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28–35) of the excess risk for coronary heart disease and 65% (56–75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a

  13. Metabolic syndrome in rheumatological diseases.

    PubMed

    Pereira, Rosa Maria Rodrigues; de Carvalho, Jozélio Freire; Bonfá, Eloísa

    2009-03-01

    Metabolic syndrome is characterized by a combination of various cardiovascular risk factors (age, gender, smoking, hypertension and dyslipidemia) that imply additional cardiovascular morbidity that is greater than the sum of the risks associated with each individual component. Herein, the authors review the rheumatological diseases in which metabolic syndrome has been studied: gout, osteoarthritis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome and ankylosing spondylitis. The prevalence of metabolic syndrome in these disorders varies from 14% to 62.8%. The great majority of these studies demonstrated that this frequency was higher in rheumatological diseases than in the control populations, suggesting that either the presence or the treatment of those diseases seems to influence the risk of developing metabolic syndrome.

  14. A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation.

    PubMed

    Wolf, Myles; Weir, Matthew R; Kopyt, Nelson; Mannon, Roslyn B; Von Visger, Jon; Deng, Hongjie; Yue, Susan; Vincenti, Flavio

    2016-01-01

    Kidney transplantation corrects or improves many complications of chronic kidney disease, but its impact on disordered mineral metabolism is incompletely understood. We performed a multicenter, prospective, observational cohort study of 246 kidney transplant recipients in the United States to investigate the evolution of mineral metabolism from pretransplant through the first year after transplantation. Participants were enrolled into 2 strata defined by their pretransplant levels of parathyroid hormone (PTH), low PTH (>65 to ≤300 pg/mL; n = 112), and high PTH (>300 pg/mL; n = 134) and underwent repeated, longitudinal testing for mineral metabolites. The prevalence of posttransplant, persistent hyperparathyroidism (PTH >65 pg/mL) was 89.5%, 86.8%, 83.1%, and 86.2%, at months 3, 6, 9, and 12, respectively, among participants who remained untreated with cinacalcet, vitamin D sterols, or parathyroidectomy. The results did not differ across the low and high PTH strata, and rates of persistent hyperparathyroidism remained higher than 40% when defined using a higher PTH threshold greater than 130 pg/mL. Rates of hypercalcemia peaked at 48% at week 8 in the high PTH stratum and then steadily decreased through month 12. Rates of hypophosphatemia (<2.5 mg/dL) peaked at week 2 and then progressively decreased through month 12. Levels of intact fibroblast growth factor 23 decreased rapidly during the first 3 months after transplantation in both PTH strata and remained less than 40 pg/mL thereafter. Persistent hyperparathyroidism is common after kidney transplantation. Further studies should determine if persistent hyperparathyroidism or its treatment influences long-term posttransplantation clinical outcomes.

  15. Transgenerational inheritance of metabolic disease.

    PubMed

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.

  16. Transgenerational Inheritance of Metabolic Disease

    PubMed Central

    Stegemann, Rachel; Buchner, David A.

    2015-01-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. PMID:25937492

  17. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  18. Alzheimer's as a metabolic disease.

    PubMed

    Demetrius, Lloyd A; Driver, Jane

    2013-12-01

    Empirical evidence indicates that impaired mitochondrial energy metabolism is the defining characteristic of almost all cases of Alzheimer's disease (AD). Evidence is reviewed supporting the general hypothesis that the up-regulation of OxPhos activity, a metabolic response to mitochondrial dysregulation, drives the cascade of events leading to AD. This mode of metabolic alteration, called the Inverse Warburg effect, is postulated as an essential compensatory mechanism of energy production to maintain the viability of impaired neuronal cells. This article appeals to the inverse comorbidity of cancer and AD to show that the amyloid hypothesis, a genetic and neuron-centric model of the origin of sporadic forms of AD, is not consistent with epidemiological data concerning the age-incidence rates of AD. A view of Alzheimer's as a metabolic disease-a condition consistent with mitochondrial dysregulation and the Inverse Warburg effect, will entail a radically new approach to diagnostic and therapeutic strategies.

  19. Cancer as a metabolic disease

    PubMed Central

    2010-01-01

    Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including aerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease will impact approaches to cancer management and prevention. PMID:20181022

  20. The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies

    PubMed Central

    2014-01-01

    Background Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies. Methods Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18–80 years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI ≥ 30 kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease. Results Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes. Conclusions Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics

  1. Gene Therapy for Metabolic Diseases

    PubMed Central

    Chandler, Randy J.; Venditti, Charles P.

    2016-01-01

    SUMMARY Gene therapy has recently shown great promise as an effective treatment for a number of metabolic diseases caused by genetic defects in both animal models and human clinical trials. Most of the current success has been achieved using a viral mediated gene addition approach, but gene-editing technology has progressed rapidly and gene modification is being actively pursued in clinical trials. This review focuses on viral mediated gene addition approaches, because most of the current clinical trials utilize this approach to treat metabolic diseases. PMID:27853673

  2. [The Idiopathic Parkinson's disease: A metabolic disease?].

    PubMed

    Rieu, I; Boirie, Y; Morio, B; Derost, P; Ulla, M; Marques, A; Debilly, B; Bannier, S; Durif, F

    2010-10-01

    Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient.

  3. Metabolic Syndrome and Urologic Diseases

    PubMed Central

    Gorbachinsky, Ilya; Akpinar, Haluk; Assimos, Dean G

    2010-01-01

    Metabolic syndrome (MetS) is a complex entity consisting of multiple interrelated factors including insulin resistance, central adiposity, dyslipidemia, endothelial dysfunction and atherosclerotic disease, low-grade inflammation, and in males, low testosterone levels. MetS has been linked to a number of urologic diseases including nephrolithiasis, benign prostatic hyperplasia and lower urinary tract symptoms, erectile dysfunction, male infertility, female incontinence, and prostate cancer. This article reviews the relationships between MetS and these entities. Urologists need to be cognizant of the impact that MetS has on urologic diseases as well as on overall patient health. PMID:21234260

  4. Gut microbiome and metabolic diseases.

    PubMed

    Fukuda, Shinji; Ohno, Hiroshi

    2014-01-01

    The prevalence of obesity and obesity-related disorders is increasing worldwide. In the last decade, the gut microbiota has emerged as an important factor in the development of obesity and metabolic syndrome, through its interactions with dietary, environmental, and host genetic factors. Various studies have shown that alteration of the gut microbiota, shifting it toward increased energy harvest, is associated with an obese phenotype. However, the molecular mechanisms by which the gut microbiota affects host metabolism are still obscure. In this review, we discuss the complexity of the gut microbiota and its relationship to obesity and obesity-related diseases. Furthermore, we discuss the anti-obesity potential of probiotics and prebiotics.

  5. Impact of disease-management programs on metabolic control in patients with type 1 diabetes mellitus: A cohort study in Shantou, China.

    PubMed

    Lin, Kun; Yang, Xiaoping; Wu, Yixi; Chen, Shuru; Yin, Guoshu; Zhan, Jianjun; Lin, Chujia; Xu, Wencan; Chen, Yongsong; Lin, Dan; Xie, Peiwen; Fang, Yishan; Lin, Qiuqiang; Lin, Shaoda

    2016-12-01

    The aim of this study is to evaluate the effect of diabetes disease management program (DMP) on glycemic control in type 1 diabetes mellitus (T1DM) patients in Shantou China.A sample of 240 participants recruited from 3C study Shantou subgroup was followed up in DMP for 3 years. The DMP provided self-management education, individualized therapy plan, diabetes complications screening, and laboratory examination periodical according to clinical practice guidelines. Primary outcomes were changes in hemoglobin A1C (HbA1c).Two hundred one of the participants completed the follow-up. There was a significant decrease in the HbA1c levels after DMP implemented. The mean (± SD) pre- and post-intervention HbA1c levels were 10.26% ± 3.30% and 8.57% ± 1.57% respectively with a P value <0.001. General linear mixed model analyse demonstrated that changes in glycemic control were associated with insulin treatment regimen, frequency of Self-Monitoring of Blood Glucose (SMBG), diabetes diet adherence, physical activity, and duration of diabetes.DMP helped to improve glycemic control and should be general implemented in China's T1DM. Individuals with basal-bolus regimen (multiple daily injections or pump therapy), more frequency of SMBG, following a diabetes diet, more physical activity, shorter diabetes duration may derive greater benefits from DMP.

  6. Thiazolidinediones and Parkinson Disease: A Cohort Study.

    PubMed

    Connolly, John G; Bykov, Katsiaryna; Gagne, Joshua J

    2015-12-01

    Thiazolidinediones, a class of medications indicated for the treatment of type 2 diabetes mellitus, reduce inflammation and have been shown to provide a therapeutic benefit in animal models of Parkinson disease. We examined the association between treatment with thiazolidinediones and the onset of Parkinson disease in older individuals. We performed a cohort study of 29,397 Medicare patients enrolled in state pharmaceutical benefits programs who initiated treatment with thiazolidinediones or sulfonylureas during the years 1997 through 2005 and had no prior diagnosis of Parkinson disease. New users of thiazolidinediones were propensity score matched to new users of sulfonylureas and followed to determine whether they were diagnosed with Parkinson disease. We used Cox proportional hazards models to compare time to diagnosis of Parkinson disease in the propensity score-matched populations. To assess the association with duration of use, we performed several analyses that required longer continuous use of medications. In the primary analysis, thiazolidinedione users had a hazard ratio for a diagnosis of Parkinson disease of 1.09 (95% confidence interval: 0.71, 1.66) when compared with sulfonylurea users. Increasing the duration-of-use requirements to 10 months did not substantially change the association; the hazard ratios ranged from 1.00 (95% confidence interval: 0.49, 2.05) to 1.17 (95% confidence interval: 0.60, 2.25). Thiazolidinedione use was not associated with a longer time to diagnosis of Parkinson disease than was sulfonylurea use, regardless of duration of exposure.

  7. Sirtuin and metabolic kidney disease.

    PubMed

    Wakino, Shu; Hasegawa, Kazuhiro; Itoh, Hiroshi

    2015-10-01

    Sirtuin is a nicotinamide adenine dinucleotide-dependent deacetylase. One of its isoforms, Sirt1, is a key molecule in glucose, lipid, and energy metabolism. The renal protective effects of Sirt1 are found in various models of renal disorders with metabolic impairment, such as diabetic nephropathy. Protective effects include the maintenance of glomerular barrier function, anti-fibrosis effects, anti-oxidative stress effects, and regulation of mitochondria function and energy metabolism. Various target molecules subject to direct deacetylation or epigenetic gene regulation have been identified as effectors of the renal protective function of sirtuin. Recently, it was demonstrated that Sirt1 expression decreases in proximal tubules before albuminuria in a mouse model of diabetic nephropathy, and that albuminuria is suppressed in proximal tubule-specific mice overexpressing Sirt1. These findings suggest that decreased Sirt1 expression in proximal tubular cells causes abnormal nicotine metabolism and reduces the supply of nicotinamide mononucleotide from renal tubules to glomeruli. This further decreases expression of Sirt1 in glomerular podocytes and increases expression of a tight junction protein, claudin-1, which results in albuminuria. Activators of the sirtuin family of proteins, including resveratrol, may be important in the development of new therapeutic strategies for treating metabolic kidney diseases, including diabetic nephropathy.

  8. PPARs: diverse regulators in energy metabolism and metabolic diseases.

    PubMed

    Wang, Yong-Xu

    2010-02-01

    The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.

  9. Cholesterol metabolism in Huntington disease.

    PubMed

    Karasinska, Joanna M; Hayden, Michael R

    2011-09-06

    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  10. Metabolic Imaging in Parkinson Disease.

    PubMed

    Meles, Sanne K; Teune, Laura K; de Jong, Bauke M; Dierckx, Rudi A; Leenders, Klaus L

    2017-01-01

    This review focuses on recent human (18)F-FDG PET studies in Parkinson disease. First, an overview is given of the current analytic approaches to metabolic brain imaging data. Next, we discuss how (18)F-FDG PET studies have advanced understanding of the relation between distinct brain regions and associated symptoms in Parkinson disease, including cognitive decline. In addition, the value of (18)F-FDG PET studies in differential diagnosis, identifying prodromal patients, and the evaluation of treatment effects are reviewed. Finally, anticipated developments in the field are addressed. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  11. Glutathione metabolism and Parkinson's disease.

    PubMed

    Smeyne, Michelle; Smeyne, Richard Jay

    2013-09-01

    It has been established that oxidative stress, defined as the condition in which the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson disease. Glutathione is a ubiquitous thiol tripeptide that acts alone or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals, and peroxynitrites. In this review, we examine the synthesis, metabolism, and functional interactions of glutathione and discuss how these relate to the protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson disease.

  12. Metabolic Syndrome in Adults With Congenital Heart Disease.

    PubMed

    Deen, Jason F; Krieger, Eric V; Slee, April E; Arslan, Alex; Arterburn, David; Stout, Karen K; Portman, Michael A

    2016-02-12

    Metabolic syndrome increases risk for atherosclerotic coronary artery disease, and its prevalence increases with increasing age and body mass index. Adults with congenital heart disease (ACHD) are now living longer and accruing coronary artery disease risk factors. However, the prevalence of metabolic syndrome in ACHD patients is unknown. We conducted a retrospective cohort study of ACHD patients at our center to quantify the prevalence of metabolic syndrome in an ACHD population. Using case-control matching, we constructed a comparable control group from a population-based sample of 150 104 adults. International Diabetes Federation criteria were used to define metabolic syndrome. We used logistic regression to compare the risk of metabolic syndrome across the resulting cohorts, which were composed of 448 ACHD patients and 448 controls matched by age and sex. Mean age of both groups was 32.4±11.3 years, and 51.3% were female. Obesity was present in 16.1% of the ACHD patients and 16.7% of the controls. Metabolic syndrome was more common in ACHD patients than in controls (15.0% versus 7.4%; odds ratio 1.82, 95% CI 1.25-2.65). Our data suggest that metabolic syndrome is more common among adults with congenital heart disease than in the general population. Thus, patients with congenital heart disease should be screened for metabolic syndrome and risk factors mitigated where possible to prevent atherosclerotic coronary artery disease. Preventive cardiology should be included during routine ACHD care. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  13. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism.

    PubMed

    Germain, Arnaud; Ruppert, David; Levine, Susan M; Hanson, Maureen R

    2017-01-31

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remains a continuum spectrum disease without biomarkers or simple objective tests, and therefore relies on a diagnosis from a set of symptoms to link the assortment of brain and body disorders to ME/CFS. Although recent studies show various affected pathways, the underlying basis of ME/CFS has yet to be established. In this pilot study, we compare plasma metabolic signatures in a discovery cohort, 17 patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins. This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361 (P < 0.05), and 35 significantly altered after statistical correction (Q < 0.15). The latter list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients. Pathway analysis points to a few pathways with high impact and therefore potential disturbances in patients, mainly taurine metabolism and glycerophospholipid metabolism, combined with primary bile acid metabolism, as well as glyoxylate and dicarboxylate metabolism and a few other pathways, all involved broadly in fatty acid metabolism. Purines, including ADP and ATP, pyrimidines and several amino acid metabolic pathways were found to be significantly disturbed. Finally, glucose and oxaloacetate were two main metabolites affected that have a major effect on sugar and energy levels. Our work provides a prospective path for diagnosis and understanding of the underlying mechanisms of ME/CFS.

  14. Intestinal microflora and metabolic diseases.

    PubMed

    Serino, M; Luche, E; Chabo, C; Amar, J; Burcelin, R

    2009-09-01

    Recent advances in molecular sequencing technology have allowed researchers to answer major questions regarding the relationship between a vast genomic diversity-such as found in the intestinal microflora-and host physiology. Over the past few years, it has been established that, in obesity, type 1 diabetes and Crohn's disease-to cite but a few-the intestinal microflora play a pathophysiological role and can induce, transfer or prevent the outcome of such conditions. A few of the molecular vectors responsible for this regulatory role have been determined. Some are related to control of the immune, vascular, endocrine and nervous systems located in the intestines. However, more important is the fact that the intestinal microflora-to-host relationship is bidirectional, with evidence of an impact of the host genome on the intestinal microbiome. This means that the ecology shared by the host and gut microflora should now be considered a new player that can be manipulated, using pharmacological and nutritional approaches, to control physiological functions and pathological outcomes. What now remains is to demonstrate the molecular connection between the intestinal microflora and metabolic diseases. We propose here that the proinflammatory lipopolysaccharides play a causal role in the onset of metabolic disorders.

  15. Ageing, metabolism and cardiovascular disease.

    PubMed

    Costantino, Sarah; Paneni, Francesco; Cosentino, Francesco

    2016-04-15

    Age is one of the major risk factors associated with cardiovascular disease (CVD). About one-fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66(Shc) , JunD and NF-kB. This overview will provide the background for attractive molecular targets to prevent age-driven pathology in the vasculature and the heart. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  16. Ageing, metabolism and cardiovascular disease

    PubMed Central

    Costantino, Sarah; Paneni, Francesco

    2015-01-01

    Abstract Age is one of the major risk factors associated with cardiovascular disease (CVD). About one‐fifth of the world population will be aged 65 or older by 2030, with an exponential increase in CVD prevalence. It is well established that environmental factors (overnutrition, smoking, pollution, sedentary lifestyles) may lead to premature defects in mitochondrial functionality, insulin signalling, endothelial homeostasis and redox balance, fostering early senescent features. Over the last few years, molecular investigations have unveiled common signalling networks which may link the ageing process with deterioration of cardiovascular homeostasis and metabolic disturbances, namely insulin resistance. These different processes seem to be highly interconnected and their interplay may favour adverse vascular and cardiac phenotypes responsible for myocardial infarction, stroke and heart failure. In the present review, we carefully describe novel molecular cues underpinning ageing, metabolism and CVD. In particular, we describe a dynamic interplay between emerging pathways such as FOXOs, AMPK, SIRT1, p66Shc, JunD and NF‐kB. This overview will provide the background for attractive molecular targets to prevent age‐driven pathology in the vasculature and the heart. PMID:26391109

  17. Opportunities for genetic improvement of metabolic diseases

    USDA-ARS?s Scientific Manuscript database

    Metabolic disorders are disturbances to one or more of the metabolic processes in dairy cattle. Dysfunction of any of these processes is associated with the manifestation of metabolic diseases or disorders. In this review, data recording, incidences, genetic parameters, predictors and status of gene...

  18. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  19. Bone scan in metabolic bone diseases. Review.

    PubMed

    Abdelrazek, Saeid; Szumowski, Piotr; Rogowski, Franciszek; Kociura-Sawicka, Agnieszka; Mojsak, Małgorzata; Szorc, Małgorzata

    2012-08-25

    Metabolic bone disease encompasses a number of disorders that tend to present a generalized involvement of the whole skeleton. The disorders are mostly related to increased bone turnover and increased uptake of radiolabelled diphosphonate. Skeletal uptake of 99mTc-labelled diphosphonate depends primarily upon osteoblastic activity, and to a lesser extent, skeletal vascularity. A bone scan image therefore presents a functional display of total skeletal metabolism and has valuable role to play in the assessment of patients with metabolic bone disorders. However, the bone scan appearances in metabolic bone disease are often non-specific, and their recognition depends on increased tracer uptake throughout the whole skeleton. It is the presence of local lesions, as in metastatic disease, that makes a bone scan appearance obviously abnormal. In the early stages, there will be difficulty in evaluating the bone scans from many patients with metabolic bone disease. However, in the more severe cases scan appearances can be quite striking and virtually diagnostic.

  20. Maternal cholestasis during pregnancy programs metabolic disease in offspring.

    PubMed

    Papacleovoulou, Georgia; Abu-Hayyeh, Shadi; Nikolopoulou, Evanthia; Briz, Oscar; Owen, Bryn M; Nikolova, Vanya; Ovadia, Caroline; Huang, Xiao; Vaarasmaki, Marja; Baumann, Marc; Jansen, Eugene; Albrecht, Christiane; Jarvelin, Marjo-Riitta; Marin, Jose J G; Knisely, A S; Williamson, Catherine

    2013-07-01

    The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

  1. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  2. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease.

  3. Influence of Metabolism on Epigenetics and Disease

    PubMed Central

    Kaelin, William G.; McKnight, Steven L.

    2013-01-01

    Chemical modifications of histones and DNA, such as histone methylation, histone acetylation, and DNA methylation, play critical roles in epigenetic gene regulation. Many of the enzymes that add or remove such chemical modifications are known, or might be suspected, to be sensitive to changes in intracellular metabolism. This knowledge provides a conceptual foundation for understanding how mutations in the metabolic enzymes SDH, FH, and IDH can result in cancer and, more broadly, for how alterations in metabolism and nutrition might contribute to disease. Here, we review literature pertinent to hypothetical connections between metabolic and epigenetic states in eukaryotic cells. PMID:23540690

  4. Achieving Synergy: Linking an Internet-Based Inflammatory Bowel Disease Cohort to a Community-Based Inception Cohort and Multicentered Cohort in Inflammatory Bowel Disease.

    PubMed

    Kochar, Bharati; Aldridge, Molly; Cook, Suzanne Follan; Bright, Renee; Mallette, Meaghan; Moniz, Heather; Shah, Samir A; LeLeiko, Neal S; Shapiro, Jason; Sands, Bruce E; Chen, Wenli; Jaeger, Elizabeth; Galanko, Joseph; Long, Millie D; Martin, Christopher F; Sandler, Robert S; Kappelman, Michael D

    2016-06-03

    Traditional cohort studies are important contributors to our understanding of inflammatory bowel diseases, but they are labor intensive and often do not focus on patient-reported outcomes. Internet-based studies provide new opportunities to study patient-reported outcomes and can be efficiently implemented and scaled. If a traditional cohort study was linked to an Internet-based study, both studies could benefit from added synergy. Existing cohort studies provide an opportunity to develop and test processes for cohort linkage. The Crohn's and Colitis Foundation of America's (CCFA) Partners study is an Internet-based cohort of more than 14,000 participants. The Ocean State Crohn's and Colitis Area Registry (OSCCAR) is an inception cohort. The Sinai-Helmsley Alliance for Research Excellence (SHARE) is a multicentered cohort of inflammatory bowel disease patients. Both the later cohorts include medical record abstraction, patient surveys, and biospecimen collection. Given the complementary nature of these existing cohorts, we sought to corecruit and link data. Eligible OSCCAR and SHARE participants were invited to join the CCFA Partners study and provide consent for data sharing between the 2 cohorts. After informed consent, participants were directed to the CCFA Partners website to complete enrollment and a baseline Web-based survey. Participants were linked across the 2 cohorts by the matching of an email address. We compared demographic and clinical characteristics between OSCCAR and SHARE participants who did and did not enroll in CCFA Partners and the data linkage. Of 408 participants in the OSCCAR cohort, 320 were eligible for participation in the CCFA Partners cohort. Of these participants, 243 consented to participation; however, only 44 enrolled in CCFA Partners and completed the linkage. OSCCAR participants who enrolled in CCFA Partners were better educated (17% with doctoral degrees) than those who did not (3% with doctoral degrees, P=.01). In the SHARE

  5. Abnormal erythrocyte metabolism in hepatic disease.

    PubMed

    Smith, J R; Kay, N E; Gottlieb, A J; Oski, F A

    1975-12-01

    Erythrocyte (RBC) metabolic studies were done on 114 patients with severe hepatic disease. Heinz body formation after incubation of RBCs with acetyl phenylhydrazine was found to be significantly higher in patients than in controls. RBC-reduced glutathione levels were lower than those of controls both before and after incubation with acetyl phenylhydrazine, and patients with the highest Heinz body counts had the lowest reduced glutathione levels. RBC methylene blue-stimulated hexose monophosphate (HMP) shunt metabolism and glucose recycling through the shunt were significantly lower in patients with active hepatic disease than in controls. There was no difference in resting HMP shunt activity or in resting recycling of glucose. Despite impairment of shunt metabolism, total glucose consumption was greater in patients than in controls. The patients with the lowest stimulated HMP shunt metabolism and glucose recycling had the highest Heinz body counts, lowest reduced glutathione, and highest total glucose consumption. A continuum of abnormal shunt metabolism was seen, from a mild reduction of stimulated HMP shunt activity to a severe combined decrease in both the HMP shunt and glucose recycling. When measured, glutathione reductase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, and transketolase were normal or increased. Sequential studies were done on 11 patients who had abnormal metabolic studies. Coincident with improvement of HMP shunt metabolism, the Heinz body counts became lower, reduced glutathione higher, hematocrit higher, and liver function improved. Impaired HMP shunt metabolism appears to be a common, acquired RBC abnormality in patients with severe, active liver disease.

  6. Regulation of pyruvate metabolism and human disease.

    PubMed

    Gray, Lawrence R; Tompkins, Sean C; Taylor, Eric B

    2014-07-01

    Pyruvate is a keystone molecule critical for numerous aspects of eukaryotic and human metabolism. Pyruvate is the end-product of glycolysis, is derived from additional sources in the cellular cytoplasm, and is ultimately destined for transport into mitochondria as a master fuel input undergirding citric acid cycle carbon flux. In mitochondria, pyruvate drives ATP production by oxidative phosphorylation and multiple biosynthetic pathways intersecting the citric acid cycle. Mitochondrial pyruvate metabolism is regulated by many enzymes, including the recently discovered mitochondria pyruvate carrier, pyruvate dehydrogenase, and pyruvate carboxylase, to modulate overall pyruvate carbon flux. Mutations in any of the genes encoding for proteins regulating pyruvate metabolism may lead to disease. Numerous cases have been described. Aberrant pyruvate metabolism plays an especially prominent role in cancer, heart failure, and neurodegeneration. Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.

  7. Night eating behavior and metabolic heath in mothers and fathers enrolled in the QUALITY cohort study.

    PubMed

    Gallant, Annette; Drapeau, Vicky; Allison, Kelly C; Tremblay, Angelo; Lambert, Marie; O'Loughlin, Jennifer; Lundgren, Jennifer D

    2014-04-01

    Desynchrony between eating and sleeping patterns and poor sleep quality have been associated with obesity and metabolic abnormalities. This study examined the metabolic health correlates of night eating syndrome in adults enrolled in the QUALITY cohort study. Night eating symptoms were assessed in 310 women (mean age = 40.3 ± 5.1 years, mean BMI = 28.8 ± 6.2 kg/m(2)) and 305 men (mean age = 42.5 ± 5.9 years, mean BMI = 30.3 ± 5.0 kg/m(2)). Anthropometric measures, fasting blood samples and blood pressure were used to diagnose metabolic syndrome (MetS) and type 2 diabetes (T2D) diagnosis was self-report. Correlational and case/control comparisons assessed night eating symptoms in persons with and without MetS and T2D. Night eating questionnaire (NEQ) scores were positively correlated with BMI. When controlling for BMI, NEQ scores were significantly negatively correlated with blood pressure in women and positively correlated with waist circumference and triglycerides in men. MetS diagnosis was associated with morning anorexia in both women and men and urges to eat at night in women only. T2D was associated with a depressed mood in women and with insomnia in men. Symptoms of night eating syndrome are associated with higher BMI and poor metabolic health. Future research is needed to determine if night eating syndrome per se is a unique causal pathway in the development of obesity and metabolic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Metabolic Disturbances in Diseases with Neurological Involvement

    PubMed Central

    Duarte, João M. N.; Schuck, Patrícia F.; Wenk, Gary L.; Ferreira, Gustavo C.

    2014-01-01

    Degeneration of specific neuronal populations and progressive nervous system dysfunction characterize neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. These findings are also reported in inherited diseases such as phenylketonuria and glutaric aciduria type I. The involvement of mitochondrial dysfunction in these diseases was reported, elicited by genetic alterations, exogenous toxins or buildup of toxic metabolites. In this review we shall discuss some metabolic alterations related to the pathophysiology of diseases with neurological involvement and aging process. These findings may help identifying early disease biomarkers and lead to more effective therapies to improve the quality of life of the patients affected by these devastating illnesses. PMID:25110608

  9. [Hearing and balance in metabolic bone diseases].

    PubMed

    Zatoński, Tomasz; Temporale, Hanna; Krecicki, Tomasz

    2012-03-01

    There are reports that hearing loss is one of the clinical manifestations of metabolic bone diseases. Demineralization can lead to a reduction in ossicular mass. Paget's disease can reveal loss of mineral density of the cochlear bone. Ear bone remodeling in osteoporosis is similar to the changes in otosclerosis. Moreover, osteoporosis, osteogenesis imperfecta and otosclerosis have a similar genetic mechanism. According to some researchers osteopenia and osteoporosis may well be associated with idiopathic benign positional vertigo (BPV). Dysfunction of the organ of hearing and balance in patients with renal insufficiency may be due to disturbances in calcium phosphate balance and renal osteodystrophy in the course of the disease. Proving the presence of hearing loss in patients with metabolic bone diseases may lead to determining the new indications for bone densitometry in some patients with hearing impairment. Furthermore, audiological examination in patients with osteoporosis may be important because of the impact of hearing loss on prognosis for patients with metabolic bone diseases.

  10. Nutrient sensing and inflammation in metabolic diseases.

    PubMed

    Hotamisligil, Gökhan S; Erbay, Ebru

    2008-12-01

    The proper functioning of the pathways that are involved in the sensing and management of nutrients is central to metabolic homeostasis and is therefore among the most fundamental requirements for survival. Metabolic systems are integrated with pathogen-sensing and immune responses, and these pathways are evolutionarily conserved. This close functional and molecular integration of the immune and metabolic systems is emerging as a crucial homeostatic mechanism, the dysfunction of which underlies many chronic metabolic diseases, including type 2 diabetes and atherosclerosis. In this Review we provide an overview of several important networks that sense and manage nutrients and discuss how they integrate with immune and inflammatory pathways to influence the physiological and pathological metabolic states in the body.

  11. Hepatic diseases related to triglyceride metabolism.

    PubMed

    Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

    2013-10-01

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis.

  12. Imbalanced cholesterol metabolism in Alzheimer's disease.

    PubMed

    Xue-shan, Zhao; Juan, Peng; Qi, Wu; Zhong, Ren; Li-hong, Pan; Zhi-han, Tang; Zhi-sheng, Jiang; Gui-xue, Wang; Lu-shan, Liu

    2016-05-01

    Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

  13. Paternal epigenetic programming: evolving metabolic disease risk.

    PubMed

    Hur, Suzy S J; Cropley, Jennifer E; Suter, Catherine M

    2017-04-01

    Parental health or exposures can affect the lifetime health outcomes of offspring, independently of inherited genotypes. Such 'epigenetic' effects occur over a broad range of environmental stressors, including defects in parental metabolism. Although maternal metabolic effects are well documented, it has only recently been established that that there is also an independent paternal contribution to long-term metabolic health. Both paternal undernutrition and overnutrition can induce metabolic phenotypes in immediate offspring, and in some cases, the induced phenotype can affect multiple generations, implying inheritance of an acquired trait. The male lineage transmission of metabolic disease risk in these cases implicates a heritable factor carried by sperm. Sperm-based transmission provides a tractable system to interrogate heritable epigenetic factors influencing metabolism, and as detailed here, animal models of paternal programming have already provided some significant insights. Here, we review the evidence for paternal programming of metabolism in humans and animal models, and the available evidence on potential underlying mechanisms. Programming by paternal metabolism can be observed in multiple species across animal phyla, suggesting that this phenomenon may have a unique evolutionary significance.

  14. Peripheral cholesterol, metabolic disorders and Alzheimer's disease.

    PubMed

    Ledesma, Maria Dolores; Dotti, Carlos Gerardo

    2012-01-01

    Strong correlations have been made between high levels of blood cholesterol and the risk to suffer Alzheimer's disease (AD). The question arises on how a peripheral event contributes to a disease that so severely affects the integrity and function of the Central Nervous System. Hypercholesterolemia has been also associated to peripheral metabolic disorders like diabetes, obesity or atherosclerosis that, in turn, predispose to AD. Here we review data, which point to alterations in blood cholesterol levels as a link between these metabolic disorders and AD. We describe and discuss common, cholesterol-related, molecular mechanisms and strategies to fight these conditions that, altogether, constitute a major cause of death in our societies.

  15. Blood Metabolic Signatures of Body Mass Index: A Targeted Metabolomics Study in the EPIC Cohort.

    PubMed

    Carayol, Marion; Leitzmann, Michael F; Ferrari, Pietro; Zamora-Ros, Raul; Achaintre, David; Stepien, Magdalena; Schmidt, Julie A; Travis, Ruth C; Overvad, Kim; Tjønneland, Anne; Hansen, Louise; Kaaks, Rudolf; Kühn, Tilman; Boeing, Heiner; Bachlechner, Ursula; Trichopoulou, Antonia; Bamia, Christina; Palli, Domenico; Agnoli, Claudia; Tumino, Rosario; Vineis, Paolo; Panico, Salvatore; Quirós, J Ramón; Sánchez-Cantalejo, Emilio; Huerta, José María; Ardanaz, Eva; Arriola, Larraitz; Agudo, Antonio; Nilsson, Jan; Melander, Olle; Bueno-de-Mesquita, Bas; Peeters, Petra H; Wareham, Nick; Khaw, Kay-Tee; Jenab, Mazda; Key, Timothy J; Scalbert, Augustin; Rinaldi, Sabina

    2017-09-01

    Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.

  16. Neurodegenerative disorders and metabolic disease.

    PubMed

    Pierre, Germaine

    2013-08-01

    Most genetic causes of neurodegenerative disorders in childhood are due to neurometabolic disease. There are over 200 disorders, including aminoacidopathies, creatine disorders, mitochondrial cytopathies, peroxisomal disorders and lysosomal storage disorders. However, diagnosis can pose a challenge to the clinician when patients present with non-specific problems like epilepsy, developmental delay, autism, dystonia and ataxia. The variety of specialist tests involved can also be daunting. This review aims to give a practical approach to the investigation and diagnosis of neurometabolic disease from the neonatal period to late childhood while prioritising disorders where there are therapeutic options. In particular, patients who have a complex clinical picture of several neurological and non-neurological features should be investigated.

  17. A revised definition of the metabolic syndrome predicts coronary artery disease and ischemic stroke after adjusting for low density lipoprotein cholesterol in a 13-year cohort study of Japanese: the Suita study.

    PubMed

    Okamura, Tomonori; Kokubo, Yoshihiro; Watanabe, Makoto; Higashiyama, Aya; Ono, Yuu; Nishimura, Kunihiro; Okayama, Akira; Miyamoto, Yoshihiro

    2011-07-01

    Recently, several major organizations have proposed a unified definition for the metabolic syndrome (MetS), which should be evaluated in multiethnic groups. The effect of Mets on the incidence of cardiovascular disease needs to be assessed after adjusting for serum low density lipoprotein cholesterol (LDLC), a major risk factor for atherosclerotic diseases. This is especially needed to be evaluated in Asian populations with low incidence of coronary artery disease (CAD). We conducted a 13-year prospective study of 4939 Japanese living in an urban area. The MetS was defined using a unified classification that included cut-off points for waist circumference in Asians. The multivariable adjusted hazard ratios (HRs) of MetS for CAD and stroke were calculated using a Cox proportional model adjusted for other potential confounding factors with LDLC. During the follow-up period, there were 155 cases of CAD and 204 of stroke including 118 cerebral infarctions. In participants under 65 years old, the multivariable HRs of MetS for CAD were 1.21 (95% C.I., 0.64-2.28) in men and 4.44 (95% C.I., 1.73-11.4) in women; the HRs for ischemic stroke were 3.24 (95% C.I., 1.55-6.77) in men and 3.99 (95% C.I., 1.34-11.8) in women. In participants aged 65 years old and over, MetS only showed a significant association with CAD in men (HR 1.89, 95% C.I., 1.11-3.21). Serum LDLC was associated with increased risk of CAD in men irrespective of age group; however, it was not associated with CAD in women. There was no association between serum LDLC and ischemic stroke in any group stratified by sex and the age of 65. These results indicate that the new uniform MetS definition is useful for detecting high risk individuals, especially for middle-aged population. However, continuous screening for hypercholesterolemia is necessary to prevent CAD, especially in men, even in Asian countries such as Japan. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  18. Brain Iron Metabolism Dysfunction in Parkinson's Disease.

    PubMed

    Jiang, Hong; Wang, Jun; Rogers, Jack; Xie, Junxia

    2017-05-01

    Dysfunction of iron metabolism, which includes its uptake, storage, and release, plays a key role in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease, and Huntington's disease. Understanding how iron accumulates in the substantia nigra (SN) and why it specifically targets dopaminergic (DAergic) neurons is particularly warranted for PD, as this knowledge may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for this disease. In this review, we begin with a brief introduction describing brain iron metabolism and its regulation. We then provide a detailed description of how iron accumulates specifically in the SN and why DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on the possible mechanisms involved in iron-induced cell death of DAergic neurons in the SN. Finally, we present evidence in support that iron chelation represents a plausable therapeutic strategy for PD.

  19. Metabolomics reveals metabolic biomarkers of Crohn's disease

    SciTech Connect

    Jansson, J.K.; Willing, B.; Lucio, M.; Fekete, A.; Dicksved, J.; Halfvarson, J.; Tysk, C.; Schmitt-Kopplin, P.

    2009-06-01

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  20. A Metabolic Study of Huntington's Disease.

    PubMed

    Nambron, Rajasree; Silajdžić, Edina; Kalliolia, Eirini; Ottolenghi, Chris; Hindmarsh, Peter; Hill, Nathan R; Costelloe, Seán J; Martin, Nicholas G; Positano, Vincenzo; Watt, Hilary C; Frost, Chris; Björkqvist, Maria; Warner, Thomas T

    2016-01-01

    Huntington's disease patients have a number of peripheral manifestations suggestive of metabolic and endocrine abnormalities. We, therefore, investigated a number of metabolic factors in a 24-hour study of Huntington's disease gene carriers (premanifest and moderate stage II/III) and controls. Control (n = 15), premanifest (n = 14) and stage II/III (n = 13) participants were studied with blood sampling over a 24-hour period. A battery of clinical tests including neurological rating and function scales were performed. Visceral and subcutaneous adipose distribution was measured using magnetic resonance imaging. We quantified fasting baseline concentrations of glucose, insulin, cholesterol, triglycerides, lipoprotein (a), fatty acids, amino acids, lactate and osteokines. Leptin and ghrelin were quantified in fasting samples and after a standardised meal. We assessed glucose, insulin, growth hormone and cortisol concentrations during a prolonged oral glucose tolerance test. We found no highly significant differences in carbohydrate, protein or lipid metabolism markers between healthy controls, premanifest and stage II/III Huntington's disease subjects. For some markers (osteoprotegerin, tyrosine, lysine, phenylalanine and arginine) there is a suggestion (p values between 0.02 and 0.05) that levels are higher in patients with premanifest HD, but not moderate HD. However, given the large number of statistical tests performed interpretation of these findings must be cautious. Contrary to previous studies that showed altered levels of metabolic markers in patients with Huntington's disease, our study did not demonstrate convincing evidence of abnormalities in any of the markers examined. Our analyses were restricted to Huntington's disease patients not taking neuroleptics, anti-depressants or other medication affecting metabolic pathways. Even with the modest sample sizes studied, the lack of highly significant results, despite many being tested, suggests that the majority

  1. Inflammatory mechanisms linking obesity and metabolic disease.

    PubMed

    Saltiel, Alan R; Olefsky, Jerrold M

    2017-01-03

    There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.

  2. Metabolic Syndrome Prevalence and Associations in a Bariatric Surgery Cohort from the Longitudinal Assessment of Bariatric Surgery-2 Study

    PubMed Central

    Selzer, Faith; Smith, Mark D.; Berk, Paul D.; Courcoulas, Anita P.; Inabnet, William B.; King, Wendy C.; Pender, John; Pomp, Alfons; Raum, William J.; Schrope, Beth; Steffen, Kristine J.; Wolfe, Bruce M.; Patterson, Emma J.

    2014-01-01

    Abstract Background: Metabolic syndrome is associated with higher risk for cardiovascular disease, sleep apnea, and nonalcoholic steatohepatitis, all common conditions in patients referred for bariatric surgery, and it may predict early postoperative complications. The objective of this study was to determine the prevalence of metabolic syndrome, defined using updated National Cholesterol Education Program criteria, in adults undergoing bariatric surgery and compare the prevalence of baseline co-morbid conditions and select operative and 30-day postoperative outcomes by metabolic syndrome status. Methods: Complete metabolic syndrome data were available for 2275 of 2458 participants enrolled in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2), an observational cohort study designed to evaluate long-term safety and efficacy of bariatric surgery in obese adults. Results: The prevalence of metabolic syndrome was 79.9%. Compared to those without metabolic syndrome, those with metabolic syndrome were significantly more likely to be men, to have a higher prevalence of diabetes and prior cardiac events, to have enlarged livers and higher median levels of liver enzymes, a history of sleep apnea, and a longer length of stay after surgery following laparoscopic Roux-en-Y gastric bypass (RYGB) and gastric sleeves but not open RYGB or laparoscopic adjustable gastric banding. Metabolic syndrome status was not significantly related to duration of surgery or rates of composite end points of intraoperative events and 30-day major adverse surgical outcomes. Conclusions: Nearly four in five participants undergoing bariatric surgery presented with metabolic syndrome. Establishing a diagnosis of metabolic syndrome in bariatric surgery patients may identify a high-risk patient profile, but does not in itself confer a higher risk for short-term adverse postsurgery outcomes. PMID:24380645

  3. Achieving Synergy: Linking an Internet-Based Inflammatory Bowel Disease Cohort to a Community-Based Inception Cohort and Multicentered Cohort in Inflammatory Bowel Disease

    PubMed Central

    Aldridge, Molly; Cook, Suzanne Follan; Bright, Renee; Mallette, Meaghan; Moniz, Heather; Shah, Samir A; LeLeiko, Neal S; Shapiro, Jason; Sands, Bruce E; Chen, Wenli; Jaeger, Elizabeth; Galanko, Joseph; Long, Millie D; Martin, Christopher F; Sandler, Robert S; Kappelman, Michael D

    2016-01-01

    Background Traditional cohort studies are important contributors to our understanding of inflammatory bowel diseases, but they are labor intensive and often do not focus on patient-reported outcomes. Internet-based studies provide new opportunities to study patient-reported outcomes and can be efficiently implemented and scaled. If a traditional cohort study was linked to an Internet-based study, both studies could benefit from added synergy. Existing cohort studies provide an opportunity to develop and test processes for cohort linkage. The Crohn’s and Colitis Foundation of America’s (CCFA) Partners study is an Internet-based cohort of more than 14,000 participants. The Ocean State Crohn’s and Colitis Area Registry (OSCCAR) is an inception cohort. The Sinai-Helmsley Alliance for Research Excellence (SHARE) is a multicentered cohort of inflammatory bowel disease patients. Both the later cohorts include medical record abstraction, patient surveys, and biospecimen collection. Objective Given the complementary nature of these existing cohorts, we sought to corecruit and link data. Methods Eligible OSCCAR and SHARE participants were invited to join the CCFA Partners study and provide consent for data sharing between the 2 cohorts. After informed consent, participants were directed to the CCFA Partners website to complete enrollment and a baseline Web-based survey. Participants were linked across the 2 cohorts by the matching of an email address. We compared demographic and clinical characteristics between OSCCAR and SHARE participants who did and did not enroll in CCFA Partners and the data linkage. Results Of 408 participants in the OSCCAR cohort, 320 were eligible for participation in the CCFA Partners cohort. Of these participants, 243 consented to participation; however, only 44 enrolled in CCFA Partners and completed the linkage. OSCCAR participants who enrolled in CCFA Partners were better educated (17% with doctoral degrees) than those who did not (3% with

  4. [Serum sclerostin levels and metabolic bone diseases].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2013-06-01

    Serum sclerostin levels are being investigated in various metabolic bone diseases. Since serum sclerostin levels are decreased in primary hyperparathyroidism and elevated in hypoparathyroidism, parathyroid hormone (PTH) is thought to be a regulatory factor for sclerostin. Serum sclerostin levels exhibit a significant positive correlation with bone mineral density. On the other hand, a couple of studies on postmenopausal women have shown that high serum sclerostin levels are a risk factor for fracture. Although glucocorticoid induced osteoporosis and diabetes are both diseases that reduce bone formation, serum sclerostin levels have been reported to be decreased in the former and elevated in the latter, suggesting differences in the effects of sclerostin in the two diseases. Serum sclerostin levels are correlated with renal function, and increase with reduction in renal function. Serum sclerostin level may be a new index of bone assessment that differs from bone mineral density and bone metabolic markers.

  5. Mediterranean-style dietary pattern, reduced risk of metabolic syndrome traits, and incidence in the Framingham Offspring Cohort123

    PubMed Central

    Rumawas, Marcella E; Meigs, James B; Dwyer, Johanna T; McKeown, Nicola M

    2009-01-01

    Background: The benefit of the Mediterranean-style dietary pattern in mitigating metabolic risk factors for type 2 diabetes and cardiovascular disease has not been well investigated among nondiabetic Americans. Objective: The aim of this study was to examine the prospective association between the Mediterranean-style dietary pattern and metabolic syndrome. Design: The Mediterranean-style dietary pattern score (MSDPS) was used to characterize a Mediterranean-style dietary pattern in the Framingham Heart Study Offspring Cohort. We examined the longitudinal association between MSDPS and metabolic syndrome traits (including homeostasis model assessment–insulin resistance, fasting glucose, waist circumference, triglyceride, HDL cholesterol, and systolic and diastolic blood pressure) among 2730 participants of the Framingham Heart Study Offspring Cohort without type 2 diabetes (baseline median age: 54 y; 55% women), who were followed from the fifth (baseline) to the seventh study examinations (mean follow-up time: 7 y), and metabolic syndrome incidence (according to the National Cholesterol Education Program Adult Treatment Panel III definition) in 1918 participants free of the condition at baseline. Results: A higher MSDPS was associated with lower homeostasis model assessment–insulin resistance (P = 0.02), waist circumference (P < 0.001), fasting plasma glucose (P = 0.03), and triglycerides (P < 0.001) and higher HDL cholesterol (P = 0.02) after adjustment for the corresponding baseline values and for several confounding factors associated with type 2 diabetes risk. Participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome than those in the lowest quintile category (38.5% compared with 30.1%; P = 0.01). Conclusion: Our study suggests that the consumption of a diet consistent with the principles of the Mediterranean-style diet may protect against metabolic syndrome in Americans. PMID:19828705

  6. Mitochondria: mitochondrial RNA metabolism and human disease.

    PubMed

    Nicholls, Thomas J; Rorbach, Joanna; Minczuk, Michal

    2013-04-01

    Post-transcriptional control of RNA stability, processing, modification, and degradation is key to the regulation of gene expression in all living cells. In mitochondria, these post-transcriptional processes are also vital for proper expression of the thirteen proteins encoded by the mitochondrial genome, as well as mitochondrial tRNAs and rRNAs. Our knowledge on mitochondrial RNA (mt-RNA) metabolic pathways, however, is far from complete. All the proteins involved in mt-RNA metabolism are encoded by the nucleus, and must be imported into the organelle. Mutations in these nuclear genes can lead to perturbations in mitochondrial RNA processing, modification, stability and decay and thus are a cause of human mitochondrial disease. This review summarises the current knowledge on mt-RNA metabolism and its links with human mitochondrial pathologies.

  7. Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

    PubMed

    Delitala, Alessandro P; Fanciulli, Giuseppe; Maioli, Margherita; Delitala, Giuseppe

    2017-03-01

    Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism.

  8. Obesity and Metabolic Disease After Childhood Cancer

    PubMed Central

    Barnea, Dana; Raghunathan, Nirupa; Friedman, Danielle Novetsky; Tonorezos, Emily S.

    2016-01-01

    As care for the childhood cancer patient has improved significantly, there is an increasing incidence of treatment-related late effects. Obesity and type 2 diabetes mellitus are common and significant metabolic conditions in some populations of adult survivors of childhood cancer. Results from the Childhood Cancer Survivor Study and other large cohorts of childhood cancer survivors reveal that long-term survivors of acute lymphoblastic leukemia and those who received total body irradiation or abdominal radiotherapy are at highest risk. The potential mechanisms for the observed increase in risk, including alterations in leptin and adiponectin, pancreatic insufficiency, poor dietary habits, sedentary lifestyle, and perhaps changes in the composition of the gut microbiota, are reviewed. Discussion of exercise and diet intervention studies shows that further research about the barriers to a healthy lifestyle and other interventions in childhood cancer survivors is warranted. PMID:26568532

  9. Leptospirosis and Peripheral Artery Occlusive Disease: A Nationwide Cohort Analysis.

    PubMed

    Chiu, Chun-Hsiang; Lin, Cheng-Li; Lee, Feng-You; Wang, Ying-Chuan; Kao, Chia-Hung

    2016-03-01

    Data on the association between peripheral artery occlusive disease (PAOD) and leptospirosis are limited. We conducted a retrospective cohort study for determining whether leptospirosis is one of the possible risk factors for PAOD. Patients diagnosed with leptospirosis by using 2000 to 2010 data from the Taiwan National Health Insurance Research Database. Patients with leptospirosis without a history of PAOD were selected. For each leptospirosis patient, 4 controls without a history of leptospirosis and PAOD were randomly selected and frequency-matched for sex, age, the year of the index date, and comorbidity diseases. The follow-up period was from the time of the initial diagnosis of leptospirosis to the diagnosis date of PAOD, or December 31, 2011. The Cox proportional hazard regression models were used for analyzing the risk of PAOD. During the follow-up period, the cumulative incidence of PAOD was higher among the patients from the leptospirosis cohort than among the nonleptospirosis cohort (log-rank test, P < 0.001). In total, 29 patients with PAOD from the leptospirosis cohort and 81 from the nonleptospirosis cohort were observed with the incidence rates of 2.1 and 1.3 per 1000 person-years, respectively, yielding a crude hazards ratio (HR) of 1.62 (95% confidence interval [CI] = 1.44-1.81) and adjusted HR (aHR) of 1.75 (95% CI = 1.58-1.95).The risk of PAOD was 1.75-fold higher in the patients with leptospirosis than in the general population.

  10. Employment characteristics of a complex adult congenital heart disease cohort.

    PubMed

    Pickup, L; Gaffey, T; Clift, P; Bowater, S; Thorne, S; Hudsmith, L

    2017-08-01

    Due to advances in surgical techniques and subsequent management, there have been remarkable improvements in the survival of patients with congenital heart disease. In particular, larger numbers of patients with complex disease are now living into adulthood and are entering the workforce. To establish the types of employment complex adult congenital heart disease (ACHD) patients are engaged in, based on the largest cohort of patients with a single-ventricle circulation in the UK. Records of all patients with a univentricular (Fontan) circulation at the Queen Elizabeth Hospital were reviewed. Employment status was categorized according to the Standard Occupational Classification criteria (2010). A total of 210 patient records were reviewed. There was the same proportion of professionals in our cohort compared to the rest of the UK (20% versus 20%). There were greater proportions working in the caring, leisure and other service occupations (15% versus 9%), the elementary occupations (17% versus 11%), sales and customer service occupations (14% versus 8%) and administrative and secretarial occupations (12% versus 11%). The reverse trend was observed for associate professions and technical occupations (7% versus 14%), skilled trades (10% versus 11%), process, plant and machine operatives (3% versus 6%) and managers, directors and senior officials (2% versus 10%). The data show that ACHD patients with a single ventricle are engaged in a diverse range of occupations. It is essential that early education and employment advice are given to this cohort to maximize future employment potential.

  11. Kynurenine pathway metabolism and neuroinflammatory disease

    PubMed Central

    Braidy, Nady; Grant, Ross

    2017-01-01

    Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response. Under physiological conditions, QUIN is metabolized to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+), which represents an important metabolic cofactor and electron transporter. NAD+ also serves as a substrate for the DNA ‘nick sensor’ and putative nuclear repair enzyme, poly(ADP-ribose) polymerase (PARP). Free radical initiated DNA damage, PARP activation and NAD+ depletion may contribute to brain dysfunction and cell death in neuroinflammatory disease. PMID:28250737

  12. Dissecting the association between metabolic syndrome and prostate cancer risk: analysis of a large clinical cohort.

    PubMed

    Bhindi, Bimal; Locke, Jennifer; Alibhai, Shabbir M H; Kulkarni, Girish S; Margel, David S; Hamilton, Robert J; Finelli, Antonio; Trachtenberg, John; Zlotta, Alexandre R; Toi, Ants; Hersey, Karen M; Evans, Andrew; van der Kwast, Theodorus H; Fleshner, Neil E

    2015-01-01

    A biologic rationale exists for the association between metabolic syndrome (MetS) and prostate cancer (PCa). However, epidemiologic studies have been conflicting. To evaluate the association between MetS and the odds of PCa diagnosis in men referred for biopsy. Patients without prior PCa diagnosis undergoing prostate biopsy were identified from a large prostate biopsy cohort (in Toronto, Canada). The definition of MetS was based on the most recent interim joint consensus definition, requiring any three of five components (obesity, elevated blood pressure, diabetes or impaired fasting glucose, low high-density lipoprotein-cholesterol, and hypertriglyceridemia). Both the individual components of MetS and the cumulative number of MetS components were evaluated. The outcomes were PCa detection overall, clinically significant PCa (CSPC; defined as any Gleason pattern ≥ 4, >50% involvement of a single biopsy core, or more than one of three total number of cores involved), and intermediate- or high-grade PCa (I-HGPC; Gleason 7-10). Tests for trend and multivariable logistic regression analyses were performed. Of 2235 patients, 494 (22.1%) had MetS. No individual MetS component was independently associated with PCa. However, increasing number of MetS components was associated with higher PCa grade (p<0.001), as well as progressively higher odds of PCa outcomes (three or more; ie, MetS) compared with no MetS components: Odds ratios were 1.54 for PCa overall (95% confidence interval [CI], 1.17-2.04; p=0.002), 1.56 for CSPC (95% CI, 1.17-2.08; p=0.002), and 1.56 for I-HGPC (95% CI, 1.16-2.10; p=0.003) in multivariable analyses. The main limitation is the retrospective design. Although the individual MetS components are not independently associated with PCa outcomes, MetS is significantly associated with higher odds of PCa diagnosis, CSPC, and I-HGPC. There is a biologic gradient between the number of MetS components and the risk of PCa, as well as cancer grade. Metabolic

  13. Early growth in children with coeliac disease: a cohort study.

    PubMed

    Kahrs, Christian R; Magnus, Maria C; Stigum, Hein; Lundin, Knut E A; Størdal, Ketil

    2017-06-13

    We aimed to study growth during the first 2 years of life in children later diagnosed with coeliac disease compared with children without, in a time with changing epidemiology and improved diagnostics. A prospective population-based pregnancy cohort study. The nationwide Norwegian Mother and Child Cohort Study. 58 675 children born between 2000 and 2009 with prospectively collected growth data. Coeliac disease was identified through combined data from questionnaires and the Norwegian Patient Register. The differences in height and weight at age 0, 3, 6, 8, 12, 15-18 and 24 months using internally standardised age and gender-specific z-scores. Linear regression and mixed models were used. During a median follow-up of 8.6 years (range 4.6-14.2), 440 children (0.8%) were diagnosed with coeliac disease at a mean age of 4.4 years (range 1.5-8.5). Children with coeliac disease had significantly lower z-scores for height from 12 months (-0.09 standard deviation scores (SDS), 95% CI -0.18 to -0.01) and weight from 15 to 18 months of life (-0.09 SDS, 95% CI -0.18 to -0.01) compared with cohort controls. The longitudinal analysis from 0 to 24 months yielded a significant reduction in height z-score per year (-0.07 SDS, 95% CI -0.13 to -0.01) but not for weight among children with coeliac disease. Excluding children diagnosed before age 2 years gave similar results. This study indicates that growth retardation in children later diagnosed with coeliac disease commonly starts at 12 months of age, and precedes clinical symptoms that usually bring the suspicion of diagnosis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

    PubMed Central

    Wang, Zeneng; Klipfell, Elizabeth; Bennett, Brian J.; Koeth, Robert; Levison, Bruce S.; DuGar, Brandon; Feldstein, Ariel E.; Britt, Earl B.; Fu, Xiaoming; Chung, Yoon-Mi; Wu, Yuping; Schauer, Phil; Smith, Jonathan D.; Allayee, Hooman; Tang, W. H. Wilson; DiDonato, Joseph A.; Lusis, Aldons J.; Hazen, Stanley L.

    2011-01-01

    Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease. PMID:21475195

  15. Alzheimer's disease and smoking: bias in cohort studies.

    PubMed

    Debanne, Sara M; Bielefeld, Roger A; Cheruvu, Vinay K; Fritsch, Thomas; Rowland, Douglas Y

    2007-06-01

    The discrepancy between cohort and case-control studies regarding the association between smoking and Alzheimer's disease (AD) has been attributed to the competing risk of early mortality of smokers. A simulation study was conducted to show that the bias favoring smokers acts also on cohort studies. In the model, individuals {grow older} and have smoking habits according to published year-age-gender-specific patterns, with morbidity and mortality according to their demographic and smoking profiles. Those individuals dying of smoking-related causes ("phantoms") remain at risk of AD and of death from other causes. Three scenarios were considered: no association of AD and smoking, increased risk for smokers, and decreased risk for smokers. For each simulation of a cohort study, two incidence density ratios (IDR) were computed: one including the phantoms that developed AD (thus ignoring smoking-related deaths) and another excluding them (thus mimicking real-life studies). For all scenarios, the simulations show that smoking-related death creates a bias, resulting in smokers having an understated risk of AD compared to non-smokers. The speculation that the conflicting results of case-control and cohort studies are solely due to the increased mortality in smokers thus appears unjustified. Other factors must also be considered to explain the discrepancy in results.

  16. The Intestinal Microbiota in Metabolic Disease

    PubMed Central

    Woting, Anni; Blaut, Michael

    2016-01-01

    Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet–host–microbe interactions. PMID:27058556

  17. Metabolic syndrome and chronic kidney disease.

    PubMed

    Bhowmik, D; Tiwari, S C

    2008-01-01

    Obesity is fast becoming a bane for the present civilization, as a result of sedentary lifestyle, atherogenic diet, and a susceptible thrifty genotype. The concept of metabolic syndrome, which is a constellation of metabolic disturbances, has crystallized over the last 80 years with the aim of identifying those at greater risk of developing type 2 diabetes and cardiovascular disease. These patients have visceral obesity and insulin resistance characterized by hypertyriglyceridemia. Recently, it has been realized that they are also at an increased risk of chronic renal disease. Release of adipocytokines leads to endothelial dysfunction. There is also activation of systemic and local renin-angiotensin-aldosterone system, oxidative stress, and impaired fibrinolysis. This leads to glomerular hyperfiltration, proteinuria, focal segmental glomerulosclerosis (FSGS), and ultimately end-stage renal disease (ESRD). Treatment consists of lifestyle modifications along with optimal control of blood pressure, blood sugar and lipids. Metformin and thiazolidenidiones reduce insulin resistance; while angiotensin converting enzyme inhibitors and angiotensin receptor blockers reduce proteinuria and have a renoprotective effect. Exciting new medical therapies on the horizon include rimonabant a cannabinoid receptor type 1 antagonist, soy proteins, and peroxisome proliferator-activated receptor (PPAR) agonist. Bariatric surgery for morbid obesity has also been shown to be effective in treating metabolic syndrome.

  18. [Validity of self-reported metabolic syndrome components in a cohort study].

    PubMed

    Fernández-Montero, Alejandro; Beunza, Juan J; Bes-Rastrollo, Maira; Barrio, María T; de la Fuente-Arrillaga, Carmen; Moreno-Galarraga, Laura; Martínez-González, Miguel A

    2011-01-01

    To assess the accuracy of self-reported data needed to constitute the metabolic syndrome in the University of Navarra Follow-Up [Seguimiento Universidad de Navarra (SUN)] cohort. The SUN project is a multi-purpose prospective cohort, formed by more than 20,000 university graduates, followed-up using surface mail questionnaires every 2 years. In a sample of 287 cohort participants, self-reported data on the criteria needed to define the metabolic syndrome (waist circumference, blood pressure, triglycerides, high-density lipoprotein-cholesterol and glucose) were compared with the same biometric data obtained by blood tests or measured by trained medical staff. Intra-class correlation coefficients with 95% confidence intervals (95% CI), relative mean error and agreement limits according to the method proposed by Bland and Altman were calculated for each variable studied. High intraclass correlations were found for the values of waist circumference (r=0.86, 95% CI: 0.80-0.90) and triglycerides (r=0.71, 95%CI: 0.61-0.79). Moderate intraclass correlations were found (between 0.46 and 0.63) for the other factors. Relative mean errors were always<2.5%, and >91% of values were within the limits of agreement for all variables. The results suggest that self-declared data on the criteria of metabolic syndrome obtained in the SUN cohort, though with some caution, are sufficiently accurate to be used in epidemiological studies. Copyright © 2010 SESPAS. Published by Elsevier Espana. All rights reserved.

  19. Glutathione Metabolism and Parkinson’s Disease

    PubMed Central

    Smeyne, Michelle

    2013-01-01

    It has been established that oxidative stress, defined as the condition when the sum of free radicals in a cell exceeds the antioxidant capacity of the cell, contributes to the pathogenesis of Parkinson’s disease. Glutathione is a ubiquitous thiol tripeptide that acts alone, or in concert with enzymes within cells to reduce superoxide radicals, hydroxyl radicals and peroxynitrites. In this review, we examine the synthesis, metabolism and functional interactions of glutathione, and discuss how this relates to protection of dopaminergic neurons from oxidative damage and its therapeutic potential in Parkinson’s disease. PMID:23665395

  20. Ozone and Survival in Four Cohorts with Potentially Predisposing Diseases

    PubMed Central

    Schwartz, Joel

    2011-01-01

    Rationale: Time series studies have reported associations between ozone and daily deaths. Only one cohort study has reported the effect of long-term exposures on deaths, and little is known about effects of chronic ozone exposure on survival in susceptible populations. Objectives: We investigated whether ozone was associated with survival in four cohorts of persons with specific diseases in 105 United States cities, treating ozone as a time varying exposure. Methods: We used Medicare data (1985–2006), and constructed cohorts of persons hospitalized with chronic conditions that might predispose to ozone effects: chronic obstructive pulmonary disease, diabetes, congestive heart failure, and myocardial infarction. Yearly warm-season average ozone was merged to the individual follow-up in each city. We applied Cox proportional hazard model for each cohort within each city, adjusting for individual risk factors, temperature, and city-specific long-term trends. Measurements and Main Results: We found significant associations with a hazard ratio for mortality of 1.06 (95% confidence interval [CI], 1.03–1.08) per 5-ppb increase in summer average ozone for persons with congestive heart failure; of 1.09 (95% CI, 1.06–1.12) with myocardial infarction; of 1.07 (95% CI, 1.04–1.09) with chronic obstructive pulmonary disease; and of 1.07 (95% CI, 1.05–1.10) for diabetics. We also found that the effect varied by region, but that this was mostly explained by mean temperature, which is likely a surrogate of air conditioning use, and hence exposure. Conclusions: This is the first study that follows persons with specific chronic conditions, and shows that long-term ozone exposure is associated with increased risk of death in these groups. PMID:21700916

  1. Metabolic Syndrome and Breast Cancer Risk: A Case-Cohort Study Nested in a Multicentre Italian Cohort

    PubMed Central

    Agnoli, Claudia; Grioni, Sara; Sieri, Sabina; Sacerdote, Carlotta; Ricceri, Fulvio; Tumino, Rosario; Frasca, Graziella; Pala, Valeria; Mattiello, Amalia; Chiodini, Paolo; Iacoviello, Licia; De Curtis, Amalia; Panico, Salvatore; Krogh, Vittorio

    2015-01-01

    Background Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies – most confined to postmenopausal women – have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women. Methods We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models. Results Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004). Conclusions These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of

  2. Metabolic syndrome and breast cancer risk: a case-cohort study nested in a multicentre italian cohort.

    PubMed

    Agnoli, Claudia; Grioni, Sara; Sieri, Sabina; Sacerdote, Carlotta; Ricceri, Fulvio; Tumino, Rosario; Frasca, Graziella; Pala, Valeria; Mattiello, Amalia; Chiodini, Paolo; Iacoviello, Licia; De Curtis, Amalia; Panico, Salvatore; Krogh, Vittorio

    2015-01-01

    Metabolic syndrome (defined as at least three among abdominal obesity, high blood triglycerides, low high-density lipoprotein cholesterol, high blood glucose, and high blood pressure) is emerging as a risk factor for breast cancer; however few studies - most confined to postmenopausal women - have investigated associations between breast cancer risk and metabolic syndrome. The purpose of this study was to examine the association between metabolic syndrome and its components, and risk of breast cancer in postmenopausal and premenopausal women. We performed a case-cohort study on 22,494 women recruited in 1993-1998 to four Italian centres (Turin, Varese, Naples, Ragusa) of the European Prospective Investigation into Cancer and Nutrition (EPIC) and followed-up for up to 15 years. A random subcohort of 565 women was obtained and 593 breast cancer cases were diagnosed. Hazard ratios (HR) with 95% confidence intervals (CI), adjusted for potential confounders, were estimated by Prentice-weighted Cox proportional hazards models. Presence of metabolic syndrome was associated with significantly increased breast cancer risk in all women (HR 1.52, 95%CI 1.14-2.02). When the analyses were repeated separately for menopausal status, the association was limited to postmenopausal women (HR 1.80, 95%CI 1.22-2.65) and absent in premenopausal women (HR 0.71, 95%CI 0.43-1.16); P for interaction between metabolic syndrome and menopausal status was 0.001. Of metabolic syndrome components, only high blood glucose was significantly associated with increased breast cancer risk in all women (HR 1.47, 95%CI 1.13-1.91) and postmenopausal women (HR 1.89, 95%CI 1.29-2.77), but not premenopausal women (HR 0.80, 95%CI 0.52-1.22; P interaction=0.004). These findings support previous data indicating that metabolic syndrome is an important risk factor for breast cancer in postmenopausal women, but not in premenopausal women, and suggest that prevention of metabolic syndrome through lifestyle changes

  3. Predictors of kidney disease in a cohort of pediatric patients with lupus.

    PubMed

    Sule, S D; Moodalbail, D G; Burnham, J; Fivush, B; Furth, S L

    2015-07-01

    Children with systemic lupus erythematosus (SLE) have an increased prevalence of kidney disease compared to their adult counterparts. Our goal was to identify potential clinical and laboratory predictors of renal disease. We performed a cohort study of incident and prevalent patients with SLE aged ≤19 years. Retrospective data from initial presentation until study enrollment was also collected. Laboratory and clinic data were recorded from each clinic visit including disease activity indices, autoantibodies, urinalyses, blood counts, and metabolic profile. Kidney disease was defined as the presence of abnormal renal biopsy or by American College of Rheumatology case definition for lupus nephritis. Logistic regression analyses were used to determine the association between clinical and laboratory data with kidney disease in those who had renal involvement within 30 days of SLE diagnosis. We also performed a time to event analysis to identify antecedents of renal disease. Forty-seven children and adolescents with SLE were followed in the cohort, 91% female and 68% black. All of the males in the cohort developed renal disease, and all within one month of the diagnosis of SLE. In logistic regression, low serum albumin (odds ratio (OR): 4.8, 95% CI: 1.9-12.5) and positive dsDNA antibodies (OR: 3.2, 95% CI: 1.7-5.9) were associated with kidney disease. In longitudinal analyses, isolated sterile pyuria (hazard ratio (HR): 3, 95% CI: 1.1-6.4) and low serum albumin (HR: 3.4, 95% CI: 1.7-6.9) were predictors of future kidney disease. The presence of antibodies against Ro were protective against renal disease (HR: 0.2, 95% CI: 0.05-0.5). We identified variables associated with kidney disease, both at initial diagnosis of SLE and in longitudinal follow-up in a cohort of children with SLE. The recognition of these abnormal laboratory values may help clinicians identify patients at risk for kidney disease before its onset thus preventing long-term complications. © The Author

  4. [Microbiotes and metabolic diseases: the bases for therapeutic strategies].

    PubMed

    Burcelin, Rémy; Nicolas, Simon; Blasco-Baque, Vincent

    2016-11-01

    After more than one and a half century, i.e. since Louis Pasteur work on microbes, fermentation, and diseases, biological science has made a giant step in bacteria knowledge. Thanks to an ultra-powerful "microscope", i.e. ultra-fast DNA sequencing, scientists have been able to read and group within a catalog over the last decade, the gene code of bacteria, i.e. the metagenome at the surface of our epithelia. More recently, live bacteria within adipose tissue, defining a tissue microbiota, as well as bacterial fragments such as DNA within the liver, the brain and the blood have been identified. Metagenomic analyses from large cohorts of patients have uncovered tight correlations between bacterial genes within our intestine and mouth and diseases such as metabolic diseases, diabetes, obesity, some liver diseases, kidney and heart failure as well as vascular diseases. Some causal mechanisms have been proposed in rodents and can set the soil for novel therapeutic strategies that could interfere with both the microbes and the corresponding host targets.

  5. Iron metabolism: from health to disease.

    PubMed

    Oliveira, Fernando; Rocha, Sara; Fernandes, Rúben

    2014-05-01

    Iron is vital for almost all living organisms by participating in a wide range of metabolic processes. However, iron concentration in body tissues must be tightly regulated since excessive iron may lead to microbial infections or cause tissue damage. Disorders of iron metabolism are among the most common human diseases and cover several conditions with varied clinical manifestations. An extensive literature review on the basic aspects of iron metabolism was performed, and the most recent findings on this field were highlighted as well. New insights on iron metabolism have shed light into its real complexity, and its role in both healthy and pathological states has been recognized. Important discoveries about the iron regulatory machine and imbalances in its regulation have been made, which may lead in a near future to the development of new therapeutic strategies against iron disorders. Besides, the toxicity of free iron and its association with several pathologies has been addressed, although it requires further investigations. This review will provide students in the fields of biochemistry and health sciences a brief and clear overview of iron physiology and toxicity, as well as imbalances in the iron homeostasis and associated pathological conditions. © 2014 Wiley Periodicals, Inc.

  6. Cohort profile: the Finnish Medication and Alzheimer's disease (MEDALZ) study

    PubMed Central

    Tolppanen, Anna-Maija; Taipale, Heidi; Koponen, Marjaana; Lavikainen, Piia; Tanskanen, Antti; Tiihonen, Jari; Hartikainen, Sirpa

    2016-01-01

    Purpose The aim of the Medicine use and Alzheimer's disease (MEDALZ) study is to investigate the changes in medication and healthcare service use among persons with Alzheimer's disease (AD) and to evaluate the safety and effectiveness of medications in this group. This is important, because the number of persons with AD is rapidly growing and even though they are a particularly vulnerable patient group, the number of representative, large-scale studies with adequate follow-up time is limited. Participants MEDALZ contains all residents of Finland who received a clinically verified diagnosis of AD between 2005 and 2011 and were community-dwelling at the time of diagnosis (N=70 719). The diagnosis is based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCS-ADRDA) and Diagnostic and Statistical Manual Fourth Edition (DSM-IV) criteria for Alzheimer's disease. The cohort contains socioeconomic data (education, occupational status and taxable income, 1972–2012) and causes of death (2005–2012), data from the prescription register (1995–2012), the special reimbursement register (1972–2012) and the hospital discharge register (1972–2012). Future updates are planned. The average age was 80.1 years (range 34.5–104.6 years). The majority of cohort (65.2%) was women. Currently, the average length of follow-up after AD diagnosis is 3.1 years and altogether 26 045 (36.8%) persons have died during the follow-up. Findings Altogether 53% of the cohort had used psychotropic drugs within 1 year after AD diagnoses. The initiation rate of for example, benzodiazepines and related drugs and antidepressants began to increase already before AD diagnosis. Future plans We are currently assessing if these, and other commonly used medications are related to adverse events such as death, hip fractures, head injuries and pneumonia. PMID:27412109

  7. Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

    PubMed

    Williams, Tracy

    2015-08-01

    Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  8. Phosphatidylethanolamine Metabolism in Health and Disease

    PubMed Central

    Calzada, Elizabeth; Onguka, Ouma; Claypool, Steven M.

    2016-01-01

    Phosphatidylethanolamine (PE) is the second most abundant glycerophospholipid in eukaryotic cells. The existence of four only partially redundant biochemical pathways that produce PE, highlights the importance of this essential phospholipid. The CDP-ethanolamine and phosphatidylserine decarboxylase pathways occur in different subcellular compartments and are the main sources of PE in cells. Mammalian development fails upon ablation of either pathway. Once made, PE has diverse cellular functions that include serving as a precursor for phosphatidylcholine and a substrate for important posttranslational modifications, influencing membrane topology, and promoting cell and organelle membrane fusion, oxidative phosphorylation, mitochondrial biogenesis, and autophagy. The importance of PE metabolism in mammalian health has recently emerged following its association with Alzheimer's disease, Parkinson's disease, nonalcoholic liver disease, and the virulence of certain pathogenic organisms. PMID:26811286

  9. Polyamine metabolism in Menkes kinky hair disease.

    PubMed

    Rennert, O M; Chan, W Y; Hidalgo, H; Cushing, W; Griesmann, G

    1980-05-09

    Clinical investigations of the urinary excretion of putrescine and the polyamines spermidine and spermine in a patient with Menkes kinky hair disease are reported. This disorder, characterized by intra- and extracellular copper deficiency, is associated with significant depression of diamine oxidase and monoamine oxidase activity. Urinary excretion of diamine and polyamines, monitored over a 2-month interval in a 4-month old patient with Menkes kinky hair disease, documented a 3- to 10-fold increase in the excretion of free putrescine, spermidine and spermine as well as the conjugated derivatives of putrescine and spermidine. These observations suggest that abnormalities in diamine and polyamine concentration occur in disease states in which the metabolic transformation of these compounds is impaired.

  10. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  11. AMPK/Mitochondria in Metabolic Diseases.

    PubMed

    Bullon, Pedro; Marin-Aguilar, Fabiola; Roman-Malo, Lourdes

    The obtaining of nutrients is the most important task in our lives. Energy is central to life's evolutions; this was one of the aspect that induced the selection of the more adaptable and more energetically profitable species. Nowadays things have changed in our modern society. A high proportion of people has access to plenty amount of food and the obesity appear as one of the pathological characteristics of our society. Energy is obtained essentially in the mitochondria with the transfer of protons across the inner membrane that produce ATP. The exactly regulation of the synthesis and degradation of ATP (ATP ↔ ADP + phosphate) is essential to all form of life. This task is performed by the 5' adenosine monophosphate-activated protein kinase (AMPK). mtDNA is highly exposed to oxidative damage and could play a central role in human health and disease. This high potential rate of abnormalities is controlled by one of the most complex mechanism: the autophagy. AMPK appears to be the key cellular energy sensor involved in multiple cellular mechanisms and is essential to have a good metabolic homeostasis to face all the aggression and start the inflammatory reaction. Therefore its disturbances have been related with multiple diseases. Recent findings support the role of AMPK in inflammation and immunity such as Metabolic Syndrome, Obesity and Diabetes. All these Metabolic Disorders are considered pandemics and they need an adequate control and prevention. One important way to achieve it is deepen in the pathogenic mechanisms. Mitochondria and AMPK are the key elements through which it happen, their knowledge and research allow us to a better management. The discovery and use of drugs that can modulate them is imperative to improve our way of manage the metabolic disorders.

  12. Inflammatory links between obesity and metabolic disease

    PubMed Central

    Lumeng, Carey N.; Saltiel, Alan R.

    2011-01-01

    The obesity epidemic has forced us to evaluate the role of inflammation in the health complications of obesity. This has led to a convergence of the fields of immunology and nutrient physiology and the understanding that they are inextricably linked. The reframing of obesity as an inflammatory condition has had a wide impact on our conceptualization of obesity-associated diseases. In this Review, we highlight the cellular and molecular mechanisms at play in the generation of obesity-induced inflammation. We also emphasize how defining the immune regulation in metabolic tissues has broadened the understanding of the diversity of inflammatory responses. PMID:21633179

  13. Plasma IL6 levels, metabolic dysfunction, and asthma severity: a cross-sectional analysis of two cohorts

    PubMed Central

    Peters, Michael C.; McGrath, Kelly Wong; Hawkins, Gregory A.; Hastie, Annette T.; Levy, Bruce D.; Israel, Elliot; Phillips, Brenda R.; Mauger, David T.; Comhair, Suzy A.; Erzurum, Serpil C.; Johansson, Mats W.; Jarjour, Nizar N.; Coverstone, Andrea M.; Castro, Mario; Holguin, Fernando; Wenzel, Sally E.; Woodruff, Prescott G.; Bleecker, Eugene R.; Fahy, John V.

    2016-01-01

    Background Severe asthma is a complex heterogeneous disease associated with older age and obesity. The presence of eosinophilic (type 2) inflammation in some but not all patients with severe asthma predicts responsiveness to current treatments, but new treatment approaches will require better understanding of non-type 2 mechanisms of severe asthma. We considered the possibility that systemic inflammation - which occurs in subgroups of obese and older patients - modifies asthma to make it worse. Interleukin 6 (IL6) is a biomarker of systemic inflammation and metabolic dysfunction, and we aimed to explore the relationship between IL6, metabolic dysfunction, and asthma severity. Methods We generated a reference range in health for plasma IL6 in a cohort of healthy controls (n=93). We compared the clinical characteristics of asthmatics with plasma IL6 levels below and above the upper limit of normal (“IL6 low” and “IL-high” asthma) in two asthma cohorts - predominantly non-severe asthmatics recruited at the University of California San Francisco (UCSF)(n=249) and predominantly severe asthmatics recruited by the Severe Asthma Research Program (SARP)(n=387). Findings The upper 95th centile value for plasma IL6 in the healthy cohort was 3·1pg/mL, and 14% of UCSF cohort and 26% of the SARP cohort had plasma IL6 levels above this upper limit. The “IL6-high” patients in both asthma cohorts had a significantly higher body mass index and a higher prevalence of metabolic disease than the IL6-low patients (all p values < 0.01). IL6-high patients also had significantly lower lung function and more frequent asthma exacerbations than IL6-low patients (all p values < 0·01). Although 75% of IL6-high asthmatics were obese, 63% of obese patients were IL6-low. Among obese patients, the forced expired volume in one second (FEV1) was significantly lower in IL6-high than in IL6-low patients (mean FEV1 70·8 [S.D. 19·5] vs. 78·1 [19·7] % predicted, p = 0·002), and the

  14. Metabolic phenotyping and systems biology approaches to understanding metabolic syndrome and fatty liver disease.

    PubMed

    Dumas, Marc-Emmanuel; Kinross, James; Nicholson, Jeremy K

    2014-01-01

    Metabolic syndrome, a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease, is becoming an increasing global health concern. Insulin resistance is often associated with metabolic syndrome and also typical hepatic manifestations such as nonalcoholic fatty liver disease. Profiling of metabolic products (metabolic phenotyping or metabotyping) has provided new insights into metabolic syndrome and nonalcoholic fatty liver disease. Data from nuclear magnetic resonance spectroscopy and mass spectrometry combined with statistical modeling and top-down systems biology have allowed us to analyze and interpret metabolic signatures in terms of metabolic pathways and protein interaction networks and to identify the genomic and metagenomic determinants of metabolism. For example, metabolic phenotyping has shown that relationships between host cells and the microbiome affect development of the metabolic syndrome and fatty liver disease. We review recent developments in metabolic phenotyping and systems biology technologies and how these methodologies have provided insights into the mechanisms of metabolic syndrome and nonalcoholic fatty liver disease. We discuss emerging areas of research in this field and outline our vision for how metabolic phenotyping could be used to study metabolic syndrome and fatty liver disease. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Metabolism and Skeletal Muscle Homeostasis in Lung Disease.

    PubMed

    Ceco, Ermelinda; Weinberg, Samuel E; Chandel, Navdeep S; Sznajder, Jacob I

    2017-07-01

    There is increased awareness that patients with lung diseases develop muscle dysfunction. Muscle dysfunction is a major contributor to a decreased quality of life in patients with chronic pulmonary diseases. Furthermore, muscle dysfunction exacerbates lung disease outcome, as a decrease in muscle mass and function are associated with increased morbidity, often long after critical illness or lung disease has been resolved. As we are learning more about the role of metabolism in health and disease, we are appreciating more the direct role of metabolism in skeletal muscle homeostasis. Altered metabolism is associated with numerous skeletal muscle pathologies and, conversely, skeletal muscle diseases are associated with significant changes in metabolic pathways. In this review, we highlight the role of metabolism in the regulation of skeletal muscle homeostasis. Understanding the metabolic pathways that underlie skeletal muscle wasting is of significant clinical interest for critically ill patients as well as patients with chronic lung disease, in which proper skeletal muscle function is essential to disease outcome.

  16. Obesity and Metabolic Comorbidities: Environmental Diseases?

    PubMed Central

    Lubrano, Carla; Genovesi, Giuseppe; Specchia, Palma; Costantini, Daniela; Mariani, Stefania; Petrangeli, Elisa; Lenzi, Andrea; Gnessi, Lucio

    2013-01-01

    Obesity and metabolic comorbidities represent increasing health problems. Endocrine disrupting compounds (EDCs) are exogenous agents that change endocrine function and cause adverse health effects. Most EDCs are synthetic chemicals; some are natural food components as phytoestrogens. People are exposed to complex mixtures of chemicals throughout their lives. EDCs impact hormone-dependent metabolic systems and brain function. Laboratory and human studies provide compelling evidence that human chemical contamination can play a role in obesity epidemic. Chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes. EDCs can alter methylation patterns and normal epigenetic programming in cells. Oxidative stress may be induced by many of these chemicals, and accumulating evidence indicates that it plays important roles in the etiology of chronic diseases. The individual sensitivity to chemicals is variable, depending on environment and ability to metabolize hazardous chemicals. A number of genes, especially those representing antioxidant and detoxification pathways, have potential application as biomarkers of risk assessment. The potential health effects of combined exposures make the risk assessment process more complex compared to the assessment of single chemicals. Techniques and methods need to be further developed to fill data gaps and increase the knowledge on harmful exposure combinations. PMID:23577225

  17. Vascular and metabolic reserve in Alzheimer's disease.

    PubMed

    Nagata, K; Kondoh, Y; Atchison, R; Sato, M; Satoh, Y; Watahiki, Y; Hirata, Y; Yokoyama, E

    2000-01-01

    Vascular and metabolic reserve were analyzed in probable Alzheimer's disease (AD) and vascular dementia (VaD). Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen (CMRO(2)), and oxygen extraction fraction (OEF) were measured quantitatively with positron emission tomography (PET). Vascular reactivity (VR) was also calculated by comparing the CBF during 5% CO(2) inhalation with the CBF during normal breathing. Vascular transit time (VTT) that was calculated as a ratio of CBV/CBF and VR reflect vasodilating capacity of the small resistance vessels, whereas OEF designates metabolic (oxygen-extraction) reserve in threatening brain ischemia. Significant increase in OEF was seen in the parieto-temporal cortex and both VTT and VR were preserved in AD patients. By constrast, there was no significant increase in OEF whereas VTT was prolonged and VR was markedly depressed in VaD patients. The increase of OEF and preserved VTT and VR seen in AD patients indicate the possible participation of vascular factors in the pathogenesis of AD perhaps at the capillary level.

  18. CYP2C9 allelic variants and frequencies in a pediatric sickle cell disease cohort: implications for NSAIDs pharmacotherapy.

    PubMed

    Jaja, Cheedy; Patel, Niren; Scott, Stuart A; Gibson, Robert; Kutlar, Abdullah

    2014-10-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism-PCR assays and the Tag-It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate-specific effects of variant alleles common in populations with genetic susceptibility to SCD. © 2014 Wiley Periodicals, Inc.

  19. CYP2C9 Allelic Variants and Frequencies in a Pediatric Sickle Cell Disease Cohort: Implications for NSAIDs Pharmacotherapy

    PubMed Central

    Patel, Niren; Scott, Stuart A.; Gibson, Robert; Kutlar, Abdullah

    2014-01-01

    Abstract Nonsteroidal anti‐inflammatory drugs (NSAIDs) used to treat pain in patients with sickle cell disease (SCD) are metabolized by the CYP2C9 enzyme. Racial differences in CYP2C9 allele frequencies impact NSAIDs efficacy and safety. We determined the frequencies of CYP2C9 alleles in an African American pediatric SCD cohort. Genomic DNA was isolated from blood samples of 30 patients aged between 7 and 17 years. Genotyping of nine CYP2C9 alleles (*1,*2, *3, *4, *5, *6, *8, *11, and *13) was performed using restriction fragment length polymorphism‐PCR assays and the Tag‐It™ Mutation Detection System. The wild type *1 allele frequency was 0.850. The most common variant allele detected was CYP2C9*8 (0.067). The combined frequency of the *2, *5, *6, *8, and *11 variants was 0.151. Seventy percent of the study cohort were predicted extensive metabolizers (*1/*1) and 30% were intermediate metabolizers due mainly to the *1/*8 genotype. Analysis of CYP2C9 using an expanded assay panel facilitated improved classification of predicted drug metabolic phenotypes in our cohort. However, the pharmacokinetic effects of the CYP2C9*5,*6,*8, and *11 alleles on NSAIDs metabolism has not been evaluated and underscores the need for studies on substrate‐specific effects of variant alleles common in populations with genetic susceptibility to SCD. PMID:24889181

  20. [Nutritional and metabolic aspects of neurological diseases].

    PubMed

    Planas Vilà, Mercè

    2014-01-01

    The central nervous system regulates food intake, homoeostasis of glucose and electrolytes, and starts the sensations of hunger and satiety. Different nutritional factors are involved in the pathogenesis of several neurological diseases. Patients with acute neurological diseases (traumatic brain injury, cerebral vascular accident hemorrhagic or ischemic, spinal cord injuries, and cancer) and chronic neurological diseases (Alzheimer's Disease and other dementias, amyotrophic lateral sclerosis, Parkinson's Disease) increase the risk of malnutrition by multiple factors related to nutrient ingestion, abnormalities in the energy expenditure, changes in eating behavior, gastrointestinal changes, and by side effects of drugs administered. Patients with acute neurological diseases have in common the presence of hyper metabolism and hyper catabolism both associated to a period of prolonged fasting mainly for the frequent gastrointestinal complications, many times as a side effect of drugs administered. During the acute phase, spinal cord injuries presented a reduction in the energy expenditure but an increase in the nitrogen elimination. In order to correct the negative nitrogen balance increase intakes is performed with the result of a hyper alimentation that should be avoided due to the complications resulting. In patients with chronic neurological diseases and in the acute phase of cerebrovascular accident, dysphagia could be present which also affects intakes. Several chronic neurological diseases have also dementia, which lead to alterations in the eating behavior. The presence of malnutrition complicates the clinical evolution, increases muscular atrophy with higher incidence of respiratory failure and less capacity to disphagia recuperation, alters the immune response with higher rate of infections, increases the likelihood of fractures and of pressure ulcers, increases the incapacity degree and is an independent factor to increase mortality. The periodic nutritional

  1. Metabolic profiling of Alzheimer's disease brains

    NASA Astrophysics Data System (ADS)

    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  2. Chromium in metabolic and cardiovascular disease.

    PubMed

    Hummel, M; Standl, E; Schnell, O

    2007-10-01

    Chromium is an essential mineral that appears to have a beneficial role in the regulation of insulin action, metabolic syndrome, and cardiovascular disease. There is growing evidence that chromium may facilitate insulin signaling and chromium supplementation therefore may improve systemic insulin sensitivity. Tissue chromium levels of subjects with diabetes are lower than those of normal control subjects, and a correlation exists between low circulating levels of chromium and the incidence of type 2 diabetes. Controversy still exists as to the need for chromium supplementation. However, supplementation with chromium picolinate, a stable and highly bioavailable form of chromium, has been shown to reduce insulin resistance and to help reduce the risk of cardiovascular disease and type 2 diabetes. Since chromium supplementation is a safe treatment, further research is necessary to resolve the confounding data. The existing data suggest to concentrate future studies on certain forms as chromium picolinate and doses as at least 200 mcg per day.

  3. Metabolically healthy obesity and depressive symptoms: 16-year follow-up of the Gazel cohort study.

    PubMed

    Hinnouho, Guy-Marino; Singh-Manoux, Archana; Gueguen, Alice; Matta, Joane; Lemogne, Cedric; Goldberg, Marcel; Zins, Marie; Czernichow, Sébastien

    2017-01-01

    The health correlates of the metabolically healthy obese (MHO) phenotype, particularly in relation to depressive symptoms remains unclear. Accordingly, we examined the risk of depressive symptoms in this phenotype using a 16-year follow-up prospective study. A sample of 14 475 participants (75% men), aged 44-59 years in 1996, was drawn from the Gazel cohort. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 and metabolic health as having none of the self-reported following cardiovascular risk factors: hypertension, type 2 diabetes and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale in 1996, 1999, 2002, 2005, 2008 and 2012. Generalized Estimating Equations (GEE) were used to estimate the risk of depressive symptoms during a follow-up of 16 years. In multivariate analyses, metabolically unhealthy normal weight [Odds Ratio (OR) = 1.37; 95% Confidence Interval (CI): 1.25-1.51], overweight [1.44 (1.31-1.59)] and obese [1.30 (1.10-1.54)] but not MHO participants [1.04 (0.81-1.32)] had higher risk of depressive symptoms at the start of follow-up compared to metabolically healthy normal weight individuals. Depressive symptoms decreased over time in metabolically healthy normal weight individuals [0.52 (0.50-0.55)], this decrease was less marked only in metabolically unhealthy obese participants [1.22 (1.07-1.40)]. Compared to MHO participants, metabolically unhealthy obese individuals were at increased risk of depression at the start of follow-up, but with a similar reduction of this risk over time. Poor metabolic health, irrespective of BMI was associated with greater depressive symptoms at the start of follow-up, whereas a poorer course of depressive symptoms over time was observed only in those with both obesity and poor metabolic health.

  4. The impact of obesity and metabolic syndrome on alcoholic liver disease.

    PubMed

    Chiang, Dian J; McCullough, Arthur J

    2014-02-01

    Alcoholic liver disease (ALD) remains a major cause of chronic liver diseases and liver failure. Population-based prospective studies and patient cohort studies have demonstrated that obesity and the metabolic syndrome exacerbate progression of ALD and increase hepatocellular carcinoma (HCC) incidence and mortality. Emerging evidence also suggests a synergism between alcohol and obesity in mortality and HCC incidence. Recognition of these increased risks and detection of early-stage liver disease may offer the opportunity to address these modifiable risk factors and prevent disease progression in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Sodium-chloride Difference and Metabolic Syndrome: A Population-based Large-scale Cohort Study.

    PubMed

    Kimura, Toshihiro; Hashimoto, Yoshitaka; Tanaka, Muhei; Asano, Mai; Yamazaki, Masahiro; Oda, Yohei; Toda, Hitoshi; Marunaka, Yoshinori; Nakamura, Naoto; Fukui, Michiaki

    Objective Metabolic syndrome (MetS) is associated with cardiovascular disease, which is the leading cause of mortality and morbidity. Hypernatremia and hypochloremia are also associated with an increased mortality. Thus, the aim of this study was to evaluate the association between the sodium-chloride difference (Na(+)-Cl(-)) and MetS. Methods In this cross-sectional and retrospective cohort study, we enrolled 3,875 subjects and evaluated the relationship between Na(+)-Cl(-) and MetS using logistic regression analyses. MetS was diagnosed according to the joint interim statement when a subject had three or more of the following criteria: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein (HDL) cholesterol; and abdominal obesity. Results There were 3,354 subjects without MetS and 521 subjects with MetS at baseline. The highest Na(+)-Cl(-) quartile (≥43 mmol/L) was associated with an increased risk of the presence of MetS compared to the lowest Na(+)-Cl(-) quartile (≤38 mmol/L) after adjusting for covariates, including age, sex, the body mass index, systolic blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol, creatinine, uric acid and lifestyle factors [multivariate odds ratio (OR) 1.81, 95% confidence interval (CI) 1.17-2.84, p=0.0078]. After an 8-year follow-up, 658 out of 3,352 subjects were newly diagnosed with MetS. The highest Na(+)-Cl(-) quartile (≥43 mmol/L) was associated with an increased risk of the development of MetS compared to the lowest Na(+)-Cl(-) quartiles (≤38 mmol/L) after adjusting for covariates (multivariate OR 1.76, 95% CI 1.27-2.45, p=0.0007). Conclusion The sodium and chloride difference is associated with MetS.

  6. Determinants of Incident Metabolic Syndrome in a Middle Eastern Population: Isfahan Cohort Study.

    PubMed

    Hosseini, Naeimeh; Talaei, Mohammad; Dianatkhah, Minoo; Sadeghi, Masoumeh; Oveisgharan, Shahram; Sarrafzadegan, Nizal

    2017-09-01

    To identify the associated risk factors with development of metabolic syndrome (MetS) in a longitudinal prospective cohort study in an Iranian population. A total of 1994 participants, aged ≥35 years, free of MetS, diabetes, and cardiovascular disease at baseline were followed up for 7 years. Physical examination, laboratory studies, and interview about lifestyle factors were performed, and MetS was defined based on harmonized definition at both time points. Logistic regression was used to calculate odds ratio (OR) and corresponding 95% confidence interval (CI). MetS occurred in 27% of subjects with an incidence rate of 39.2 and 46.6 per 1000 person-year in men and women, respectively (P = 0.04). Among the components of MetS, triglyceride (TG) alone (OR 2.59, 95% CI 1.78-3.78) or in combination with waist circumference (WC; OR 5.01, 95% CI 3.59-7.01) was the strongest predictor of incident MetS compared to those free of components. In multivariable analysis, all components were associated with higher risk except fasting plasma glucose in both genders and high-density lipoprotein cholesterol in men. Impaired glucose tolerance was associated with two (95% CI 1.11-3.65) times increased risk in women. The multivariable adjusted OR (95% CI) of overweight and obesity was 1.68 (1.13-2.50) and 2.88 (1.73-4.78) in women and 2.46 (1.74-3.46) and 2.47 (1.38-4.43) in men, respectively. Unhealthy diet [1.57 (1.02-2.41)] and weekly Cola consumption [1.50 (1.05, 2.14)] increased the risk in women only. TG and WC components showed the highest predictive values for MetS incidence, while general obesity was independently associated with it.

  7. Adipokines, Metabolic Syndrome and Rheumatic Diseases

    PubMed Central

    Abella, Vanessa; Scotece, Morena; López, Verónica; Lazzaro, Verónica; Pino, Jesús; Gómez-Reino, Juan J.; Gualillo, Oreste

    2014-01-01

    The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases. PMID:24741591

  8. Adipokines, metabolic syndrome and rheumatic diseases.

    PubMed

    Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Lazzaro, Verónica; Pino, Jesús; Gómez-Reino, Juan J; Gualillo, Oreste

    2014-01-01

    The metabolic syndrome (MetS) is a cluster of cardiometabolic disorders that result from the increasing prevalence of obesity. The major components of MetS include insulin resistance, central obesity, dyslipidemia, and hypertension. MetS identifies the central obesity with increased risk for cardiovascular diseases (CVDs) and type-2 diabetes mellitus (T2DM). Patients with rheumatic diseases, such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis, have increased prevalence of CVDs. Moreover, CVD risk is increased when obesity is present in these patients. However, traditional cardiovascular risk factors do not completely explain the enhanced cardiovascular risk in this population. Thus, MetS and the altered secretion patterns of proinflammatory adipokines present in obesity could be the link between CVDs and rheumatic diseases. Furthermore, adipokines have been linked to the pathogenesis of MetS and its comorbidities through their effects on vascular function and inflammation. In the present paper, we review recent evidence of the role played by adipokines in the modulation of MetS in the general population, and in patients with rheumatic diseases.

  9. Nutrigenomic programming of cardiovascular and metabolic diseases.

    PubMed

    Ozanne, Susan

    2014-10-01

    Over twenty five years ago epidemiological studies revealed that there was a relationship between patterns of early growth and subsequent risk of diseases such as type 2 diabetes, cardiovascular disease and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, discordant siblings and animal models have provided strong evidence that the early environment plays an important role in mediating these relationships. Early nutrition is one such important environmental factor. The concept of early life programming is therefore widely accepted and the underlying mechanisms starting to emerge. These include: (1) Permanent structural changes in an organ due to exposure to suboptimal levels of essential hormones or nutrients during a critical period of development leading to permanent changes in tissue function (2) Persistent epigenetic changes such as DNA methylation and histone modifications and miRNAs leading to changes in gene expression. (3) Permanent effects on regulation of cellular ageing through increases in oxidative stress and mitochondrial dysfunction leading to DNA damage and telomere shortening. Further understanding of these processes will enable the development of preventative and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease.

  10. Contribution of gut bacterial metabolism to human metabolic disease.

    PubMed

    Bain, M D; Jones, M; Borriello, S P; Reed, P J; Tracey, B M; Chalmers, R A; Stacey, T E

    1988-05-14

    Metronidazole, an antibiotic with specific activity against anaerobic bacteria, was of clinical and biochemical benefit in two patients with methylmalonic aciduria. The virtual elimination of propionic acid from the stool suggested that propionic acid derived from faecal bacterial metabolism contributes substantially to methylmalonate production. These findings point to a novel avenue of treatment for these disorders of intermediary metabolism, and indicate the importance of microbial gut flora in normal human metabolism.

  11. Household Fuel Use and Cardiovascular Disease Mortality: Golestan Cohort Study

    PubMed Central

    Mitter, Sumeet S.; Vedanthan, Rajesh; Islami, Farhad; Pourshams, Akram; Khademi, Hooman; Kamangar, Farin; Abnet, Christian C.; Dawsey, Sanford M.; Pharoah, Paul D.; Brennan, Paul; Fuster, Valentin; Boffetta, Paolo; Malekzadeh, Reza

    2016-01-01

    Background Household air pollution is the third largest risk factor for global disease burden, but direct links with cardiovascular disease mortality are limited. This study aimed to evaluate the relationship between household fuel use and cardiovascular disease mortality. Methods and Results The Golestan Cohort Study in northeastern Iran enrolled 50045 individuals aged 40 to 75 years between 2004 and 2008, and collected data on lifetime household fuel use and other baseline exposures. Participants were followed through 2012 with a 99% successful follow-up rate. Cox proportional hazards models were fitted to calculate hazard ratios (HRs) for associations between pehen (local dung), wood, kerosene/diesel, or natural gas burning for cooking and heating and all-cause and cause-specific mortality, adjusting for lifetime exposure to each of these fuels and potential confounders. 3073 participants (6%) died during follow-up, 78% of which were attributable to non-communicable diseases, including cardiovascular, oncologic and respiratory illnesses. Adjusted 10-year HRs from kerosene/diesel burning were 1.06 (95% CI 1.02-1.10), and 1.11 (1.06-1.17), respectively, for all-cause and cardiovascular mortality. Subtype-specific analyses revealed a significant increase in ischemic heart disease (10-year HR 1.14 (1.06-1.21)) and a trend toward cerebrovascular accident (10-year HR 1.08 (0.99-1.17)) mortality. Stratification by sex revealed a potential signal for increased risk for all-cause and cardiovascular disease mortality among women versus men, with similar risk for ischemic heart disease mortality. Conclusions Household exposure to high-pollution fuels was associated with increased risk for all-cause and cardiovascular disease mortality. Replicating these results worldwide would support efforts to reduce such exposures. PMID:27297340

  12. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.

    PubMed

    Sabatti, Chiara; Service, Susan K; Hartikainen, Anna-Liisa; Pouta, Anneli; Ripatti, Samuli; Brodsky, Jae; Jones, Chris G; Zaitlen, Noah A; Varilo, Teppo; Kaakinen, Marika; Sovio, Ulla; Ruokonen, Aimo; Laitinen, Jaana; Jakkula, Eveliina; Coin, Lachlan; Hoggart, Clive; Collins, Andrew; Turunen, Hannu; Gabriel, Stacey; Elliot, Paul; McCarthy, Mark I; Daly, Mark J; Järvelin, Marjo-Riitta; Freimer, Nelson B; Peltonen, Leena

    2009-01-01

    Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

  13. Glucose tolerance status is a better predictor of diabetes and cardiovascular outcomes than metabolic syndrome: a prospective cohort study

    PubMed Central

    2012-01-01

    Backround To evaluate the importance of oral glucose tolerance test (OGTT) in predicting diabetes and cardiovascular disease in patients with and without Metabolic Syndrome from a population treated in a primary care unit. Research design and methods A prospective cohort study was conducted with subjects regularly attending the primary care unit of Hospital de Clínicas de Porto Alegre. Participants underwent a 75 g OGTT. Metabolic syndrome definition was based on the criteria of IDF/AHA/NHLBI-2010. Results Participants mean age was 61 ± 12 years (males: 38%; whites: 67%). Of the 148 subjects included, 127 (86%) were followed for 36 ± 14 months, 21 (14%) were lost. Subjects were classified into four groups based on baseline OGTT: 29% normal (n = 43), 28% impaired fasting glucose (IFG; n = 42), 26% impaired glucose tolerance (IGT; n = 38), and 17% diabetes (n = 25). Metabolic syndrome prevalence was lower in normal group (28%), intermediate in IFG (62%) and IGT (65%) groups, and higher among subjects with diabetes (92%; P <0.001). Incidence of diabetes increased along with the stages of glucose metabolism disturbance (normal: 0%, IFG: 16%, IGT: 28%; P = 0.004). No patient with normal OGTT developed diabetes, regardless metabolic syndrome presence. Diabetes at baseline was the major determinant of cardiovascular disease occurrence (normal: 0%, IFG: 4%, IGT: 0%, diabetes: 24%; P = 0.001). In Cox-regression analysis, only the 2 h OGTT results were associated with diabetes (OR = 1.03; 95%CI 1.01–1.06; P <0.001) and cardiovascular disease development (OR = 1.013; 95%CI 1.002–1.025; P = 0.024). Conclusions In this sample of subjects undergoing diabetes screening, the OGTT predicted diabetes and cardiovascular disease more effectively than the metabolic syndrome status. PMID:22682107

  14. The Nakuru eye disease cohort study: methodology & rationale

    PubMed Central

    2014-01-01

    Background No longitudinal data from population-based studies of eye disease in sub-Saharan-Africa are available. A population-based survey was undertaken in 2007/08 to estimate the prevalence and determinants of blindness and low vision in Nakuru district, Kenya. This survey formed the baseline to a six-year prospective cohort study to estimate the incidence and progression of eye disease in this population. Methods/Design A nationally representative sample of persons aged 50 years and above were selected between January 2007 and November 2008 through probability proportionate to size sampling of clusters, with sampling of individuals within clusters through compact segment sampling. Selected participants underwent detailed ophthalmic examinations which included: visual acuity, autorefraction, visual fields, slit lamp assessment of the anterior and posterior segments, lens grading and fundus photography. In addition, anthropometric measures were taken and risk factors were assessed through structured interviews. Six years later (2013/2014) all subjects were invited for follow-up assessment, repeating the baseline examination methodology. Discussion The methodology will provide estimates of the progression of eye diseases and incidence of blindness, visual impairment, and eye diseases in an adult Kenyan population. PMID:24886366

  15. Podocyte energy metabolism and glomerular diseases.

    PubMed

    Imasawa, Toshiyuki; Rossignol, Rodrigue

    2013-09-01

    Mitochondria are crucial organelles that produce and deliver adenosine triphosphate (ATP), by which all cellular processes are driven. Although the mechanisms that control mitochondrial biogenesis, function and dynamics are complex process and vary among different cell types, recent studies provided many new discoveries in this field. Podocyte injury is a crucial step in the development of a large number of glomerular diseases. Glomerular podocytes are unique cells with complex foot processes that cover the outer layer of the glomerular basement membrane, and are the principle cells composing filtration barriers of glomerular capillaries. Little is known on the modalities and the regulation of podocyte's energetics as well as the type of energy substrate primarily used for their activity, recent studies revealed that dysfunction of energy transduction in podocytes may underlie the podocyte injury associated with numerous glomerular diseases. We herein review and discuss the importance of a fine regulation of energy metabolism in podocytes for maintaining their cellular structure and related kidney function. In the future, understanding these mechanisms will open up new areas of treatment for glomerular diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Immune regulation of metabolic homeostasis in health and disease

    PubMed Central

    Brestoff, Jonathan R.; Artis, David

    2015-01-01

    Obesity is an increasingly prevalent disease worldwide. While genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases, emerging studies indicate that innate and adaptive immune cell responses in adipose tissue have critical roles in the regulation of metabolic homeostasis. In the lean state, type 2 cytokine-associated immune cell responses predominate in white adipose tissue and protect against weight gain and insulin resistance through direct effects on adipocytes and elicitation of beige adipose. In obesity, these metabolically beneficial immunologic pathways become dysregulated, and adipocytes and other factors initiate metabolically deleterious type 1 inflammation that impairs glucose metabolism. This review discusses our current understanding of the functions of different types of adipose tissue, how immune cells regulate adipocyte function and metabolic homeostasis in the context of health and disease, and highlights the potential of targeting immuno-metabolic pathways as a therapeutic strategy to treat obesity and associated diseases. PMID:25815992

  17. Blood monoamine metabolism in Huntington's disease.

    PubMed

    Belendiuk, K; Belendiuk, G W; Freedman, D X

    1980-03-01

    In 25 patients with Huntington's disease (HD), the mean blood concentration of serotonin (5-HT) and percentage of plasma free tryptophan were significantly increased while plasma concentrations of total and protein-bound tryptophan were significantly decreased. The pattern of changes in tryptophan concentrations was related to clinical severity but not to 5-HT levels. Platelet monoamine oxidase (MAO) activity was significantly increased in patients with HD; kinetic and marker enzyme studies suggested an increased enzyme concentration. Offspring at risk for HD also had elevated platelet MAO activity but normal concentrations of blood 5-HT and plasma tryptophan. In ten patients, plasma epinephrine concentrations were significantly increased; plasma dopamine and norepinephrine concentrations were positively related to MAO activity. The finding of peripheral neurotransmitter abnormalities in HD raises the question of an interaction between CNS and peripheral processes or a systemic disorder of neurotransmitter metabolism.

  18. Leukocyte set points in metabolic disease.

    PubMed

    Odegaard, Justin I; Chawla, Ajay

    2012-01-01

    Vertebrate tissues comprise precise admixtures of parenchymal and hematopoietic cells, whose interactions are vital to proper tissue function. By regulating this interaction, vertebrates are able to mitigate environmental stress and coordinate dramatic physiologic adaptations. For instance, under conditions of chronic nutrient excess, leukocyte recruitment and activation increase in an effort to decrease excess nutrient storage and alleviate adipocyte stress. While basal equilibria may be reestablished upon normalization of nutrient intake, a new set point characterized by insulin resistance and chronic inflammation is established if the stress persists. Consequently, although this response is adaptive in settings of acute overfeeding and infection, it has catastrophic health consequences in the modern context of obesity. Understanding how leukocyte set points (numbers and activation status) are established, maintained, and regulated in tissues is, thus, critical to our understanding of, and intervention in, chronic metabolic diseases, such as obesity and diabetes.

  19. Oral manifestations of metabolic bone disease: vitamin D and osteoporosis.

    PubMed

    Zachariasen, R

    1990-10-01

    Metabolic bone diseases are disorders of bone remodeling and characteristically involve the entire bony skeleton. Metabolic bone diseases exhibit their effects throughout all skeletal tissue, and very often are first diagnosed from abnormalities appearing in the oral cavity or on dental radiographs. This article presents major metabolic bone diseases that are often manifested in the oral cavity. It discusses the physiology of vitamin D and the major bone disorders associated with abnormal levels of this hormone. Osteoporosis, the most common metabolic bone disease in elderly patients, also will be discussed. With the expanding older population, osteoporosis has become a major health problem and poses special concerns for the dental practitioner.

  20. Metabolic syndrome and cardiovascular diseases in Korea.

    PubMed

    Suh, Sunghwan; Lee, Moon-Kyu

    2014-01-01

    There has been a rapid increase in the prevalence of obesity, type 2 diabetes and metabolic syndrome(MetS) over the past two to three decades in most Asian countries. According to the Korean National Health and Nutrition Examination Survey(KNHANES), the prevalence of MetS significantly increased from 24.9% to 31.3% between 1998 and 2007. The clinical significance of MetS is based on the increased risk for the development of cardiovascular disease(CVD). We analyzed the 8-year follow-up data of 2,435 healthy subjects and found that MetS was associated with an increased risk of CVD in both men and women(OR: 1.98, 95% CI: 1.30-3.03 in men; OR: 4.04, 95% CI: 1.78-9.14 in women). MetS was significantly associated with the risk for future coronary heart disease(CHD) in men(OR: 3.68; 95% CI: 1.93-7.01) and stroke in women(OR: 3.96; 95% CI: 1.58- 9.94). We also analyzed the echocardiographic findings of 1,600 healthy subjects to evaluate the relationship between metabolic syndrome and left ventricular diastolic dysfunction(LVDD). The patients with MetS exhibited significant differences in parameters of cardiac structure and the LV diastolic function compared to that observed in the patients without MetS. MetS was associated with an increased risk of LVDD(OR: 1.67; 95% CI: 1.18-2.37). These results suggest that the presence of MetS is associated with an increased risk for the development of serious CVD and abnormal changes in the LV structure and diastolic function, even before the development of overt CVD.

  1. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort

    PubMed Central

    Schreuder, Tim C. M. A.; Dullaart, Robin P. F.; Faber, Klaas Nico; Alizadeh, Behrooz Z.; Blokzijl, Hans

    2017-01-01

    Background & aims Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the largest population-based cohort to date. Methods Biochemical characteristics, type 2 diabetes mellitus and metabolic syndrome were determined in the Lifelines Cohort Study (N = 167,729), a population-based cohort in the North of the Netherlands. Non-alcoholic fatty liver disease was defined as Fatty Liver Index (FLI)≥60. Exclusion criteria were age <18 years, immigrants, missing data to assess FLI and metabolic syndrome, excessive alcohol use, previous-diagnosed hepatitis or cirrhosis and non-fasting blood sampling. Results Out of 37,496 included participants (median age 44 years, 62.1% female), 8,259 (22.0%) had a FLI≥60. Individuals with a FLI≥60 were more often male, older, obese, had higher levels of hemoglobinA1c, fasting glucose, liver enzymes, total cholesterol, low-density lipoprotein cholesterol, triglycerides, c-reactive protein and leucocytes and lower high-density lipoprotein cholesterol (all P<0.0001). Participants with a FLI≥60 showed higher prevalence of type 2 diabetes mellitus (9.3% vs. 1.4%), metabolic syndrome (54.2% vs. 6.2%), impaired renal function (20.1% vs. 8.7%) and cardiovascular disease (4.6% vs. 1.6%) (all P<0.0001). Multivariable logistic analysis showed that smoking, hemoglobin, leucocytes, c-reactive protein, platelets, alanine aminotransferase, alkaline phosphatase, albumin, impaired renal function (OR 1.27, 95%CI 1.15–1.41), metabolic syndrome (OR 11.89, 95%CI 11.03–12.82) and its individual components hyperglycemia (OR 2.53, 95%CI 2.34–2.72), hypertension (OR 1.89, 95%CI 1.77–2.01) and reduced high-density lipoprotein cholesterol (OR 3.44, 95%CI 3.22–3.68) were independently associated with suspected non-alcoholic fatty

  2. The Implications of Relationships between Human Diseases and Metabolic Subpathways

    PubMed Central

    Li, Jing; Han, Junwei; Miao, Yingbo; Wang, Yan; Wang, Qianghu; Li, Wei; Wu, Chao; Zhang, Yunpeng; Li, Xiang; Yao, Qianlan

    2011-01-01

    One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the “k-clique” subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations between network topology and genes within disease-related metabolic subpathways, and found that within a disease-related subpathway in the DMSPN, the ratio of disease genes and the ratio of tissue-specific genes significantly increased as the number of diseases caused by the subpathway increased. Surprisingly, the ratio of essential genes significantly decreased and the ratio of housekeeping genes remained relatively unchanged. Furthermore, the coexpression levels between disease genes and other types of genes were calculated for each subpathway in the DMSPN. The results indicated that those genes intensely influenced by disease genes, including essential genes and tissue-specific genes, might be significantly associated with the disease diversity of subpathways, suggesting that different kinds of genes within a disease-related subpathway may play significantly

  3. Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community-Based Cohorts: A Meta-Analysis.

    PubMed

    Brant, Luisa C C; Wang, Na; Ojeda, Francisco M; LaValley, Michael; Barreto, Sandhi M; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S; Palmisano, Joseph N; Münzel, Thomas; Blankenberg, Stefan; Wild, Philipp S; Zeller, Tanja; Ribeiro, Antonio L P; Schnabel, Renate B; Hamburg, Naomi M

    2017-03-08

    Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. We meta-analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19-90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometry (PAT), were calculated. Individuals were classified as normal-weight, overweight, or obese by body mass index (BMI) and stratified by healthy or unhealthy metabolic status based on metabolic syndrome using the ATP-III criteria. Male sex, BMI, and metabolic risk factors were associated with higher baseline pulse amplitude and lower PAT ratio. There was stepwise impairment of vascular measures from normal weight to obesity in both metabolic status strata. Metabolically healthy obese individuals had more impaired vascular function than metabolically healthy normal-weight individuals (baseline pulse amplitude 6.12±0.02 versus 5.61±0.01; PAT ratio 0.58±0.01 versus 0.76±0.01, all P<0.0001). Metabolically unhealthy obese individuals had more impaired vascular function than metabolically healthy obese individuals (baseline pulse amplitude 6.28±0.01 versus 6.12±0.02; PAT ratio 0.49±0.01 versus 0.58±0.01, all P<0.0001). Metabolically healthy obese individuals have impaired microvascular function, though the degree of impairment is less marked than in metabolically unhealthy obese individuals. Our findings suggest that obesity is detrimental to vascular health irrespective of metabolic status. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  4. Tyrosine Metabolism in Patients with Liver Disease*

    PubMed Central

    Levine, Robert J.; Conn, Harold O.

    1967-01-01

    Plasma levels of tyrosine were assayed in the fasting state and after oral administration of either tyrosine (tyrosine tolerance test) or phenylalanine (phenlyalanine conversion test) in normal subjects and in patients with hepatitis, biliary obstruction, or cirrhosis. Fasting tyrosine levels tended to be slightly increased in patients with hepatitis and biliary obstruction and markedly increased in patients with cirrhosis. Tyrosine tolerance tests in patients with cirrhosis were characterized by larger than normal increments in tyrosine levels and by delayed returns toward fasting levels. The results of phenylalanine conversion tests were abnormal in approximately one-half of patients with either hepatitis or biliary obstruction and four-fifths of patients with cirrhosis. Abnormalities were characterized by elevated fasting plasma tyrosine levels, or small and delayed increments in tyrosine levels, or both. Abnormal phenylalanine conversion test results in patients with cirrhosis did not correlate closely with any clinical feature of cirrhosis or with the results of any standard liver function test; there was positive correlation only with abnormal ammonia tolerance, a test of portalsystemic shunting. Tests of tyrosine metabolism do not appear to be useful for routine clinical assessment of liver function. Tyrosine tolerance tests and phenylalanine conversion tests done for purposes of diagnosis of other diseases may yield misleading results in patients with liver disease. PMID:6074004

  5. Omentin: linking metabolic syndrome and cardiovascular disease.

    PubMed

    Zhou, Ji-Yin; Chan, Lawrence; Zhou, Shi-Wen

    2014-01-01

    Omentin is an adipokine preferentially produced by visceral adipose tissue with insulin-sensitizing effects. Its expression is reduced in obesity, insulin resistance and type 2 diabetes. Omentin is also positively related with adiponectin, high-density lipoprotein levels and negatively related with body mass index, waist circumference, insulin resistance, triglyceride and leptin levels. Lower plasma omentin levels contribute to the pathogenesis of insulin resistance, type 2 diabetes and cardiovascular diseases in obese or overweight patients. Omentin has anti-inflammatory, antiatherogenic, anti-cardiovascular disease and antidiabetic properties. With respect to vascular biology, omentin causes vasodilatation of blood vessels and attenuates C-reactive protein-induced angiogenesis. The ability of omentin to reduce insulin resistance in conjunction with its anti-inflammatory and anti-atherogenic properties makes it a promising therapeutic target. Thus, omentin may have beneficial effects on the metabolic syndrome and could potentially be used as a biologic marker and/or pharmacologic agent/target in this respect.

  6. Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study.

    PubMed

    Little, Mark P; Zablotska, Lydia B; Brenner, Alina V; Lipshultz, Steven E

    2016-03-01

    High-dose ionizing radiation is associated with circulatory disease. Risks from lower-dose fractionated exposures, such as from diagnostic radiation procedures, remain unclear. In this study we aimed to ascertain the relationship between fractionated low-to-medium dose radiation exposure and circulatory disease mortality in a cohort of 13,568 tuberculosis patients in Massachusetts, some with fluoroscopy screenings, between 1916 and 1961 and follow-up until the end of 2002. Analysis of mortality was in relation to cumulative thyroid (cerebrovascular) or lung (all other circulatory disease) radiation dose via Poisson regression. Over the full dose range, there was no overall radiation-related excess risk of death from circulatory disease (n = 3221; excess relative risk/Gy -0.023; 95% CI -0.067, 0.028; p = 0.3574). Risk was somewhat elevated in hypertensive heart disease (n = 89; excess relative risk/Gy 0.357; 95% CI -0.043, 1.030, p = 0.0907) and slightly decreased in ischemic heart disease (n = 1950; excess relative risk/Gy -0.077; 95% CI -0.130, -0.012; p = 0.0211). However, under 0.5 Gy, there was a borderline significant increasing trend for all circulatory disease (excess relative risk/Gy 0.345; 95% CI -0.032, 0.764; p = 0.0743) and for ischemic heart disease (excess relative risk/Gy 0.465; 95% CI, -0.032, 1.034, p = 0.0682). Pneumolobectomy increased radiation-associated risk (excess relative risk/Gy 0.252; 95% CI 0.024, 0.579). Fractionation of dose did not modify excess risk. In summary, we found no evidence of radiation-associated excess circulatory death risk overall, but there are indications of excess circulatory death risk at lower doses (<0.5 Gy). Although consistent with other radiation-exposed groups, the indications of higher risk at lower doses are unusual and should be confirmed against other data.

  7. Trend in the prevalence of the metabolic syndrome and its impact on cardiovascular disease incidence: the San Antonio Heart Study.

    PubMed

    Lorenzo, Carlos; Williams, Ken; Hunt, Kelly J; Haffner, Steven M

    2006-03-01

    With the current obesity epidemic, one would expect a prevalence increase in the metabolic syndrome. Therefore, in the San Antonio Heart Study, a population-based study with worsening obesity, we examined the metabolic syndrome and its effect on incident cardiovascular disease (CVD). We enrolled 5,158 subjects in two cohorts: 1979-1982 and 1984-1988. We reexamined 3,682 (71.4%) subjects in 1987-1990 (cohort 1) and 1991-1996 (cohort 2) and assessed a 7.5-year incidence of CVD in 4,635 (90.0%) participants. We used the metabolic syndrome definition of the National Cholesterol Education Program-Adult Treatment Panel III. At baseline, the metabolic syndrome was less prevalent in cohort 1 than in cohort 2: in men, 20.4 vs. 29.3% (P < 0.001); in women, 16.3 vs. 26.3% (P < 0.001). The prevalence increased in men and women of both Mexican-American and non-Hispanic white ethnic groups between 1979-1982 and 1991-1996 (P for trend <0.001 for each of the groups). There was an excess of incident CVD in cohort 2 relative to cohort 1 (odds ratio 1.37 [95% CI 1.02-1.84]) after adjustment for age, sex, ethnic origin, socioeconomic status, history of CVD, diabetes, total cholesterol, smoking, and family history of heart attack. Further adjustment for the metabolic syndrome reduced this difference (1.26 [0.93-1.71]) because the metabolic syndrome predicted incident CVD (1.58 [1.14-2.18]). In San Antonio, Texas, an increase in the prevalence of the metabolic syndrome between 1979-1982 and 1984-1988 contributes to explain a higher CVD incidence.

  8. Periodontal disease: the influence of metabolic syndrome

    PubMed Central

    2012-01-01

    Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that include obesity, impaired glucose tolerance or diabetes, hyperinsulinemia, hypertension, and dyslipidemia. Recently, more attention has been reserved to the correlation between periodontitis and systemic health. MetS is characterized by oxidative stress, a condition in which the equilibrium between the production and the inactivation of reactive oxygen species (ROS) becomes disrupted. ROS have an essential role in a variety of physiological systems, but under a condition of oxidative stress, they contribute to cellular dysfunction and damage. Oxidative stress may act as a common link to explain the relationship between each component of MetS and periodontitis. All those conditions show increased serum levels of products derived from oxidative damage, promoting a proinflammatory state. Moreover, adipocytokines, produced by the fat cells of fat tissue, might modulate the balance between oxidant and antioxidant activities. An increased caloric intake involves a higher metabolic activity, which results in an increased production of ROS, inducing insulin resistance. At the same time, obese patients require more insulin to maintain blood glucose homeostasis – a state known as hyperinsulinemia, a condition that can evolve into type 2 diabetes. Oxidation products can increase neutrophil adhesion and chemotaxis, thus favoring oxidative damage. Hyperglycemia and an oxidizing state promote the genesis of advanced glycation end-products, which could also be implicated in the degeneration and damage of periodontal tissue. Thus, MetS, the whole of interconnected factors, presents systemic and local manifestations, such as cardiovascular disease and periodontitis, related by a common factor known as oxidative stress. PMID:23009606

  9. UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells

    ClinicalTrials.gov

    2017-04-03

    Adrenoleukodystrophy; Batten Disease; Mucopolysaccharidosis II; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Neimann Pick Disease; Pelizaeus-Merzbacher Disease; Sandhoff Disease; Tay-Sachs Disease; Brain Diseases, Metabolic, Inborn

  10. Postmenopausal hormone therapy and Alzheimer disease: A prospective cohort study.

    PubMed

    Imtiaz, Bushra; Tuppurainen, Marjo; Rikkonen, Toni; Kivipelto, Miia; Soininen, Hilkka; Kröger, Heikki; Tolppanen, Anna-Maija

    2017-03-14

    To explore the association between postmenopausal hormone therapy (HT) and Alzheimer disease (AD). Twenty-year follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention study cohort were used. Self-administered questionnaires were sent to all women aged 47-56 years, residing in Kuopio Province starting in 1989 until 2009, every 5th year. Register-based information on HT prescriptions was available since 1995. Probable AD cases, based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, were identified from the special reimbursement register (1999-2009). The study population included 8,195 women (227 cases of incident AD). Postmenopausal estrogen use was not associated with AD risk in register-based or self-reported data (hazard ratio/95% confidence interval 0.92/0.68-1.2, 0.99/0.75-1.3, respectively). Long-term self-reported postmenopausal HT was associated with reduced AD risk (0.53/0.31-0.91). Similar results were obtained with any dementia diagnosis in the hospital discharge register as an outcome. Our results do not provide strong evidence for a protective association between postmenopausal HT use and AD or dementia, although we observed a reduced AD risk among those with long-term self-reported HT use. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  11. NLRP3 inflammasomes link inflammation and metabolic disease.

    PubMed

    De Nardo, Dominic; Latz, Eicke

    2011-08-01

    A strong link between inflammation and metabolism is becoming increasingly evident. A number of recent landmark studies have implicated the activation of the NLRP3 inflammasome, an interleukin-1β family cytokine-activating protein complex, in a variety of metabolic diseases including obesity, atherosclerosis and type 2 diabetes. Here, we review these new developments and discuss their implications for a better understanding of inflammation in metabolic disease, and the prospects of targeting the NLRP3 inflammasome for therapeutic intervention.

  12. Metabolically healthy obesity and depressive symptoms: 16-year follow-up of the Gazel cohort study

    PubMed Central

    Gueguen, Alice; Matta, Joane; Lemogne, Cedric; Goldberg, Marcel; Zins, Marie

    2017-01-01

    Aims The health correlates of the metabolically healthy obese (MHO) phenotype, particularly in relation to depressive symptoms remains unclear. Accordingly, we examined the risk of depressive symptoms in this phenotype using a 16-year follow-up prospective study. Methods A sample of 14 475 participants (75% men), aged 44–59 years in 1996, was drawn from the Gazel cohort. Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 and metabolic health as having none of the self-reported following cardiovascular risk factors: hypertension, type 2 diabetes and dyslipidemia. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale in 1996, 1999, 2002, 2005, 2008 and 2012. Generalized Estimating Equations (GEE) were used to estimate the risk of depressive symptoms during a follow-up of 16 years. Results In multivariate analyses, metabolically unhealthy normal weight [Odds Ratio (OR) = 1.37; 95% Confidence Interval (CI): 1.25–1.51], overweight [1.44 (1.31–1.59)] and obese [1.30 (1.10–1.54)] but not MHO participants [1.04 (0.81–1.32)] had higher risk of depressive symptoms at the start of follow-up compared to metabolically healthy normal weight individuals. Depressive symptoms decreased over time in metabolically healthy normal weight individuals [0.52 (0.50–0.55)], this decrease was less marked only in metabolically unhealthy obese participants [1.22 (1.07–1.40)]. Compared to MHO participants, metabolically unhealthy obese individuals were at increased risk of depression at the start of follow-up, but with a similar reduction of this risk over time. Conclusion Poor metabolic health, irrespective of BMI was associated with greater depressive symptoms at the start of follow-up, whereas a poorer course of depressive symptoms over time was observed only in those with both obesity and poor metabolic health. PMID:28384219

  13. Physical activity and risk of Metabolic Syndrome in an urban Mexican cohort

    PubMed Central

    Méndez-Hernández, Pablo; Flores, Yvonne; Siani, Carole; Lamure, Michel; Dosamantes-Carrasco, L Darina; Halley-Castillo, Elizabeth; Huitrón, Gerardo; Talavera, Juan O; Gallegos-Carrillo, Katia; Salmerón, Jorge

    2009-01-01

    Background In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. Methods The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. Results The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57–0.95) and women (OR 0.78; 95%CI 0.64–0.94) who reported an amount of ≥30 minutes/day of leisure

  14. Physical activity and risk of metabolic syndrome in an urban Mexican cohort.

    PubMed

    Méndez-Hernández, Pablo; Flores, Yvonne; Siani, Carole; Lamure, Michel; Dosamantes-Carrasco, L Darina; Halley-Castillo, Elizabeth; Huitrón, Gerardo; Talavera, Juan O; Gallegos-Carrillo, Katia; Salmerón, Jorge

    2009-07-31

    In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio-respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self-administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57-0.95) and women (OR 0.78; 95%CI 0.64-0.94) who reported an amount of >or=30 minutes/day of leisure-time activity, and among women

  15. Defects in RNA metabolism in mitochondrial disease.

    PubMed

    Siira, Stefan J; Shearwood, Anne-Marie J; Bracken, Cameron P; Rackham, Oliver; Filipovska, Aleksandra

    2017-04-01

    The expression of mitochondrially-encoded genes requires the efficient processing of long precursor RNAs at the 5' and 3' ends of tRNAs, a process which, when disrupted, results in disease. Two such mutations reside within mt-tRNA(Leu(UUR)); a m.3243A>G transition, which is the most common cause of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), and m.3302A>G which often causes mitochondrial myopathy (MM). We used parallel analysis of RNA ends (PARE) that captures the 5' terminal end of 5'-monophosphorylated mitochondrial RNAs to compare the effects of the m.3243A>G and m.3302A>G mutations on mitochondrial tRNA processing and downstream RNA metabolism. We confirmed previously identified RNA processing defects, identified common internal cleavage sites and new sites unique to the m.3243A>G mutants that do not correspond to transcript ends. These sites occur in regions of predicted RNA secondary structure, or are in close proximity to such regions, and may identify regions of importance to the processing of mtRNAs.

  16. [Metabolic syndrome in inflammatory rheumatic diseases].

    PubMed

    Malesci, D; Valentini, G; La Montagna, G

    2006-01-01

    Toward the end of the last century a better knowledge of cardiovascular (CV) risk factors and their associations led investigators to propose the existence of a unique pathophysiological condition called "metabolic" or "insulin resistance syndrome". Among all, insulin-resistance and compensatory hyperinsulinemia are considered its most important treatment targets. Different definitions have been provided by World Health Organization (WHO) and by The Third Report of The National Cholesterol Education Program's Adult Treatment Panel (NCEP-ATP III). In particular, abdominal obesity, hypertension, low HDL cholesterol and hyperglicemia are the most common items used for its definition. The presence of MetS is effective in predicting the future risk of diabetes and coronaropathies. The evidence of a higher CV risk rate among different rheumatic inflammatory diseases has recently been associated with high prevalence of MetS in some cases. Rheumatoid or psoriatic arthritis have the large series among arthritis, whereas systemic lupus erythematosus among connective tissue disorders. This review analyses all most important studies about the evidence of MetS in rheumatic patients and the main clinical and prognostic significance of this relation.

  17. Sedentary bout durations and metabolic syndrome among working adults: a prospective cohort study.

    PubMed

    Honda, Takanori; Chen, Sanmei; Yonemoto, Koji; Kishimoto, Hiro; Chen, Tao; Narazaki, Kenji; Haeuchi, Yuka; Kumagai, Shuzo

    2016-08-26

    This study aimed to examine the associations between time spent in prolonged and non-prolonged sedentary bouts and the development of metabolic syndrome. We used data from a prospective study of Japanese workers. Baseline examination was conducted between 2010 and 2011. A total of 430 office workers (58 women) aged 40-64 years without metabolic syndrome were followed up by annual health checkups until 2014. Metabolic syndrome was defined as having ≥ 3 out of 5 diagnostic criteria from the Joint Interim Statement 2009 definition. Sedentary time was assessed using a tri-axial accelerometer. Time spent in total, prolonged (accumulated ≥ 30 min) and non-prolonged sedentary bouts (accumulated < 30 min) was calculated. Cox proportional hazards models were used to estimate the risk of developing metabolic syndrome. During a median follow-up of 3 years, 83 participants developed metabolic syndrome. After adjustment for age, sex, education, smoking, and family income, positive associations were observed between time spent in prolonged sedentary bouts and the development of metabolic syndrome. After additional adjustment for moderate-to-vigorous physical activity, those in the three highest quartiles of time spent in prolonged sedentary bouts showed higher risk of metabolic syndrome compared to the lowest quartile group, with adjusted hazard ratios (95 % confidence intervals) of 2.72 (1.30 - 5.73), 2.42 (1.11 - 5.50), and 2.85 (1.31 - 6.18), respectively. No associations were seen for time spent in total and non-prolonged sedentary bouts. Sedentary behavior accumulated in a prolonged manner was associated with an increased risk of metabolic syndrome. In devising public health recommendations for the prevention of metabolic disease, the avoidance of prolonged uninterrupted periods of sedentary behavior should be considered.

  18. Inflammasomes and Metabolic Disorders: Old Genes in Modern Diseases

    PubMed Central

    Robbins, Gregory R.; Wen, Haitao; Ting, Jenny P.-Y.

    2014-01-01

    Summary Modern medical and hygienic practices have greatly improved human health and longevity; however, increased human lifespan occurs concomitantly with the emergence of metabolic and age-related diseases. Studies over the past decade have strongly linked host inflammatory responses to the etiology of several metabolic diseases including atherosclerosis, type 2 diabetes (T2D), obesity and gout. A common immunological factor to these diseases is the activation of the inflammasome and release of pro-inflammatory cytokines that promote disease progression. Here we review the molecular mechanism(s) of inflammasome activation in response to metabolic damage associated molecular patterns (DAMPs) and discuss potential targets for therapeutic intervention. PMID:24766894

  19. Childhood stunting and the metabolic syndrome components in young adults from a Brazilian birth cohort study

    PubMed Central

    Grillo, L P; Gigante, D P; Horta, B L; de Barros, F C F

    2016-01-01

    Background/Objectives: The aim of this study was to investigate the association between stunting in the second year of life and metabolic syndrome components in early adulthood among subjects who have been prospectively followed-up since birth, in a city in Southern Brazil. Subjects/Methods: In 1984, we attempted to follow-up the entire cohort; the subjects were examined and their mothers interviewed. Stunting was defined by a length-for-age Z-score 2 s.d. or more below the mean, in accordance with the World Health Organization reference. Between 2004 and 2005, we again tried to follow the entire cohort; during this period the subjects were evaluated for the following metabolic syndrome components: high-density lipoprotein (HDL) cholesterol, triglycerides, random blood glucose, waist circumference and systolic and diastolic blood pressure. Family income at the time of the baby's birth, asset index, mother's education, mother's smoking during pregnancy and duration of breastfeeding were considered possible confounders. Linear regression was used in the unadjusted and adjusted analyses. Results: Among men, stunting was inversely associated with triglycerides (β=−11.90, confidence interval (CI)=−22.33 to −1.48) and waist circumference (β=−4.29, CI=−5.62 to −2.97), whereas for women stunting was negatively related to HDL-cholesterol (β=−4.50, CI=−6.47 to −2.52), triglycerides (β=−9.61, CI=−17.66 to −1.56) and waist circumference (β=−1.14, CI=−4.22 to −1.02). However, after controlling for confounding variables, these associations vanished. Conclusions: The findings suggest that stunting in childhood is not associated with metabolic syndrome components in young adults. PMID:26733042

  20. Metabolic risk score and cancer risk: pooled analysis of seven cohorts

    PubMed Central

    Stocks, Tanja; Bjørge, Tone; Ulmer, Hanno; Manjer, Jonas; Häggström, Christel; Nagel, Gabriele; Engeland, Anders; Johansen, Dorthe; Hallmans, Göran; Selmer, Randi; Concin, Hans; Tretli, Steinar; Jonsson, Håkan; Stattin, Pär

    2015-01-01

    Background: There are few data on the joint influence of metabolic factors on risk of separate cancers. Methods: We analysed data on body mass index, blood pressure and plasma levels of glucose, total cholesterol and triglycerides from seven European cohorts comprising 564 596 men and women with a mean age of 44 years. We weighted those factors equally into a standardized metabolic risk score [MRS, mean = 0, standard deviation (SD) = 1], with an individual’s level indicated as SDs from the sex- and cohort-specific means. Cancer hazard ratios were calculated by Cox regression with age as timescale and with relevant adjustments including smoking status. All statistical tests were two-sided. Results: During a mean follow-up of 12 years, 21 593 men and 14 348 women were diagnosed with cancer. MRS was linearly and positively associated with incident cancer in total and at sites (P < 0.05). In men, risk per SD MRS was increased by 43% (95% confidence interval: 27–61) for renal cell cancer, 43% (16–76) for liver cancer, 29% (20–38) for colon cancer, 27% (5–54) for oesophageal cancer, 20% (9–31) for rectal cancer, 19% (4–37) for leukaemias, 15% (1–30) for oral cancer and 10% (2–19) for bladder cancer. In women, risk increases per SD MRS were 56% (42–70) for endometrial cancer, 53% (29–81) for pancreatic cancer, 40% (16–67) for renal cell cancer, 27% (9–47) for cervical cancer and 17% (3–32) for rectal cancer. Conclusion: This largest study to date on the joint influence of metabolic factors on risk of separate cancers showed increased risks for several cancers, in particular renal cell and liver cancer in men and endometrial and pancreatic cancer in women. PMID:25652574

  1. Increased prevalence of autoimmune disease within C9 and FTD/MND cohorts

    PubMed Central

    Sturm, Virginia E.; Camsari, Gamze Balci; Karydas, Anna; Yokoyama, Jennifer S.; Grinberg, Lea T.; Boxer, Adam L.; Rosen, Howard J.; Rankin, Katherine P.; Gorno-Tempini, Maria Luisa; Coppola, Giovanni; Geschwind, Daniel H.; Rademakers, Rosa; Seeley, William W.; Graff-Radford, Neill R.; Miller, Bruce L.

    2016-01-01

    Objective: To determine the prevalence of autoimmune disease in symptomatic C9ORF72 (C9) mutation carriers and frontotemporal dementia with motor neuron disease (FTD/MND) cohorts. Methods: In this case-control study, we reviewed the clinical histories of 66 patients with FTD/MND and 57 symptomatic C9 carriers (24 overlapping cases), a total of 99 charts, for history of autoimmune disease. The prevalence of autoimmune disease in C9 and FTD/MND cohorts was determined by χ2 and Fisher exact comparisons between the combined C9 and FTD/MND group with normal control, Alzheimer disease, and progressive supranuclear palsy cohorts, as well as comparisons within C9 and FTD/MND cohorts. Results: Our combined C9 and FTD/MND cohort has a 12% prevalence of nonthyroid autoimmune disease. The prevalence of nonthyroid autoimmune disease in C9 and FTD/MND is similar to the rates in previously detailed progranulin and semantic variant primary progressive aphasia cohorts and elevated in comparison to previously collected normal control and typical Alzheimer disease cohorts, as well as a newly screened progressive supranuclear palsy cohort. Furthermore, the types of autoimmune disease in this combined C9 and FTD/MND cohort cluster within the same 3 categories previously described in progranulin and semantic variant primary progressive aphasia: inflammatory arthritides, cutaneous conditions, and gastrointestinal disorders. Conclusions: The association between selective autoimmune disease and neurodegenerative disorders unified by the underlying pathology frontotemporal lobar degeneration with TDP-43–positive inclusions (FTLD-TDP) extends to C9 and FTD/MND cohorts, providing further evidence that select autoimmune inflammation may be intrinsically linked to FTLD-TDP pathophysiology. PMID:27844039

  2. Metabolic syndrome in rheumatic diseases: epidemiology, pathophysiology, and clinical implications.

    PubMed

    Sidiropoulos, Prodromos I; Karvounaris, Stylianos A; Boumpas, Dimitrios T

    2008-01-01

    Subjects with metabolic syndrome--a constellation of cardiovascular risk factors of which central obesity and insulin resistance are the most characteristic--are at increased risk for developing diabetes mellitus and cardiovascular disease. In these subjects, abdominal adipose tissue is a source of inflammatory cytokines such as tumor necrosis factor-alpha, known to promote insulin resistance. The presence of inflammatory cytokines together with the well-documented increased risk for cardiovascular diseases in patients with inflammatory arthritides and systemic lupus erythematosus has prompted studies to examine the prevalence of the metabolic syndrome in an effort to identify subjects at risk in addition to that conferred by traditional cardiovascular risk factors. These studies have documented a high prevalence of metabolic syndrome which correlates with disease activity and markers of atherosclerosis. The correlation of inflammatory disease activity with metabolic syndrome provides additional evidence for a link between inflammation and metabolic disturbances/vascular morbidity.

  3. [Bone and calcium metabolism in life-style related diseases].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2016-03-01

    Accumulating evidence shows that life-style related diseases such as diabetes mellitus, hypertension, dyslipidemia are associated with bone and calcium metabolism. Patients with diabetes mellitus have increased fracture risks, independently of bone mineral density, with abnormality of parathyroid hormone secretion and impaired osteoblastic function. On the other hand, osteocalcin secreted from bone is reported to regulate glucose metabolism. Thus, bone, calcium and glucose metabolism may be deeply associated with each other. In this review, we describe the association between life-style related diseases, especially diabetes mellitus, and metabolism of bone and calcium.

  4. Optimization of Inflammatory Bowel Disease Cohort Studies in Asia

    PubMed Central

    2015-01-01

    With the incidence of inflammatory bowel disease (IBD) increasing rapidly in many Asian countries, including Hong Kong, it is important that patient characteristics are better understood. For example, are the phenotypes, behaviors, complications, and even treatment responses found in Asian patients similar to those of their Western counterparts? To formally address these questions, a properly designed local cohort study is needed. Whilst IBD is still relatively uncommon in Asia, the establishment of a local IBD registry will significantly contribute to the answering of these questions. The Hong Kong IBD registry was established to fill the gap in the understanding of IBD patients, and to foster research into IBD in Hong Kong. The Hong Kong IBD registry is a territory-wide registry that includes all public hospitals in Hong Kong. We included all IBD patients who were currently receiving medical care at these hospitals. With the help of the central computer medical record system of the Hospital Authority of Hong Kong, all clinical events, medications usage, endoscopy records, and laboratory results of patients in the registry were captured. Apart from data collection, the registry is also establishing a bio-specimen bank of blood and stool samples of IBD patients for future research. The IBD registry is a very useful platform for population-based studies on IBD in Asia. PMID:26130994

  5. Optimization of Inflammatory Bowel Disease Cohort Studies in Asia.

    PubMed

    Leung, Wai K

    2015-07-01

    With the incidence of inflammatory bowel disease (IBD) increasing rapidly in many Asian countries, including Hong Kong, it is important that patient characteristics are better understood. For example, are the phenotypes, behaviors, complications, and even treatment responses found in Asian patients similar to those of their Western counterparts? To formally address these questions, a properly designed local cohort study is needed. Whilst IBD is still relatively uncommon in Asia, the establishment of a local IBD registry will significantly contribute to the answering of these questions. The Hong Kong IBD registry was established to fill the gap in the understanding of IBD patients, and to foster research into IBD in Hong Kong. The Hong Kong IBD registry is a territory-wide registry that includes all public hospitals in Hong Kong. We included all IBD patients who were currently receiving medical care at these hospitals. With the help of the central computer medical record system of the Hospital Authority of Hong Kong, all clinical events, medications usage, endoscopy records, and laboratory results of patients in the registry were captured. Apart from data collection, the registry is also establishing a bio-specimen bank of blood and stool samples of IBD patients for future research. The IBD registry is a very useful platform for population-based studies on IBD in Asia.

  6. Weight for gestational age and metabolically healthy obesity in adults from the Haguenau cohort

    PubMed Central

    Matta, Joane; Carette, Claire; Levy Marchal, Claire; Bertrand, Julien; Pétéra, Mélanie; Zins, Marie; Pujos-Guillot, Estelle; Comte, Blandine; Czernichow, Sébastien

    2016-01-01

    Background An obesity subphenotype, named ‘metabolically healthy obese’ (MHO) has been recently defined to characterise a subgroup of obese individuals with less risk for cardiometabolic abnormalities. To date no data are available on participants born with small weight for gestational age (SGA) and the risk of metabolically unhealthy obesity (MUHO). Objective Assess the risk of MUHO in SGA versus appropriate for gestational age (AGA) adult participants. Methods 129 young obese individuals (body mass index ≥30 kg/m²) from data of an 8-year follow-up Haguenau cohort (France), were identified out of 1308 participants and were divided into 2 groups: SGA (n=72) and AGA (n=57). Metabolic characteristics were analysed and compared using unpaired t-test. The HOMA-IR index was determined for the population and divided into quartiles. Obese participants within the first 3 quartiles were considered as MHO and those in the fourth quartile as MUHO. Relative risks (RRs) and 95% CI for being MUHO in SGA versus AGA participants were computed. Results The SGA-obese group had a higher risk of MUHO versus the AGA-obese group: RR=1.27 (95% CI 1.10 to 1.6) independently of age and sex. Conclusions In case of obesity, SGA might confer a higher risk of MUHO compared with AGA. PMID:27580829

  7. Antipsychotic Use Among Adult Outpatients and Venous Thromboembolic Disease: A Retrospective Cohort Study.

    PubMed

    Ferraris, Augusto; Szmulewicz, Alejandro G; Vazquez, Fernando J; Vollmer, William M; Angriman, Federico

    2017-08-01

    Treatment with antipsychotic (AP) agents is associated with incident thromboembolic events. However, the underpinnings of this association remain unknown. We sought to evaluate the effect of AP agents-categorized by their metabolic/sedative and hyperprolactinemia adverse effect profile-on the risk of venous thromboembolic disease during long-term follow-up. A retrospective cohort study of adult patients initiating AP treatment for the first time was conducted. Primary outcome was defined as the time to venous thromboembolism (VTE) (either deep venous thrombosis or acute pulmonary embolism). Antipsychotic agents were categorized by their risk (high vs low) of either drug-induced (a) sedation/metabolic adverse event or (b) hyperprolactinemia. We used a propensity score-adjusted Cox proportional hazards model to control for confounding. One thousand eight patients (mean age, 72.4 y) were followed for a median of 36 months. Incident VTE occurred in 6.25% of patients, corresponding to an incidence rate of 184 cases per 10,000 person-years. We found no difference in the hazard of VTE during follow-up between high- and low-risk groups (hazard ratio, 1.23 [95% confidence interval, 0.74-2.04] for drug-induced sedation/metabolic adverse event risk categories, and hazard ratio 0.81 [95% confidence interval, 0.50-1.35] for high versus low hyperprolactinemia risk). These results suggest that the risk of thromboembolic events in older adults who started AP treatment for the first time does not seem to be related to these drugs' risk of either sedation/metabolic adverse events or hyperprolactinemia. However, VTE remains a common problem in this subgroup of patients.

  8. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome.

    PubMed

    Lonardo, Amedeo; Ballestri, Stefano; Marchesini, Giulio; Angulo, Paul; Loria, Paola

    2015-03-01

    The conventional paradigm of nonalcoholic fatty liver disease representing the "hepatic manifestation of the metabolic syndrome" is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty liver disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty liver disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty liver disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty liver disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty liver disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty liver disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.

  9. RNA metabolism in the pathogenesis of Parkinson׳s disease.

    PubMed

    Lu, Bingwei; Gehrke, Stephan; Wu, Zhihao

    2014-10-10

    Neurodegenerative diseases such as Parkinson׳s disease are progressive disorders of the nervous system that affect the function and maintenance of specific neuronal populations. While most disease cases are sporadic with no known cause, a small percentage of disease cases are caused by inherited genetic mutations. The identification of genes associated with the familial forms of the diseases and subsequent studies of proteins encoded by the disease genes in cellular or animal models have offered much-needed insights into the molecular and cellular mechanisms underlying disease pathogenesis. Recent studies of the familial Parkinson׳s disease genes have emphasized the importance of RNA metabolism, particularly mRNA translation, in the disease process. It is anticipated that continued studies on the role of RNA metabolism in Parkinson׳s disease will offer unifying mechanisms for understanding the cause of neuronal dysfunction and degeneration and facilitate the development of novel and rational strategies for treating this debilitating disease.

  10. Metabolic Abnormalities and Coronary Heart Disease Risk in Human Immunodeficiency Virus–Infected Adults

    PubMed Central

    Aouizerat, Bradley E.; Gay, Caryl; Coggins, Traci; Movsesyan, Irina; Davis, Harvey; Kane, John P.; Portillo, Carmen; Lee, Kathryn A.

    2010-01-01

    Abstract Background Metabolic syndrome is a combination of risk factors for cardiovascular disease and diabetes, It has been reported to be increased in human immunodeficiency virus (HIV)–infected individuals. Methods In a cohort of HIV-infected adults we examined parameters that contribute to defining the metabolic syndrome and to estimating the 10-year risk of coronary heart disease (CHD). The study group consisted of 296 participants (217 men and 79 women) of mixed ethnicity with a mean age of 45.3 years. Results There was an appreciable prevalence of metabolic syndrome (30.0%), with the frequency increasing to 42.5% in those over 50 years of age. Those with the metabolic syndrome had a lower viral load. More women had abdominal obesity (59.5%) than men (20.7%, P < 0.001). The frequency of elevated plasma glucose was higher in females (37.2%) compared to males (16.9%, P = 0.004). High frequencies of decreased high-density lipoprotein cholesterol (HDL-C) and elevated blood pressure were seen in both sexes. Hypertriglyceridemia was less prevalent in African Americans. In those under 50 years of age, the 10-year CHD risk score for men was double that for women (6.2% vs 2.7%, P < 0.001). In older participants, the risk was similar between the sexes, with a third having scores over 10%. Conclusions The prevalence of metabolic syndrome was higher than in most other HIV cohorts. Those with the syndrome had significantly lower viral loads. Mean 10-year Framingham Cardiovascular Risk (FCR) scores were nearly doubled for those with metabolic syndrome. Both researchers and clinicians should consider age as well as sex when assessing patients with HIV infection for risks associated with metabolic syndrome. PMID:20235745

  11. Metabolic diseases and pro- and prebiotics: Mechanistic insights.

    PubMed

    Nakamura, Yukiko K; Omaye, Stanley T

    2012-06-19

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual's behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases.

  12. Metabolic diseases and pro- and prebiotics: Mechanistic insights

    PubMed Central

    2012-01-01

    Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual’s behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases. PMID:22713169

  13. Cancer as a metabolic disease: implications for novel therapeutics.

    PubMed

    Seyfried, Thomas N; Flores, Roberto E; Poff, Angela M; D'Agostino, Dominic P

    2014-03-01

    Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual's unique physiology.

  14. Cancer as a metabolic disease: implications for novel therapeutics

    PubMed Central

    Seyfried, Thomas N.

    2014-01-01

    Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. When viewed as a mitochondrial metabolic disease, the evolutionary theory of Lamarck can better explain cancer progression than can the evolutionary theory of Darwin. Cancer growth and progression can be managed following a whole body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broad-based cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology. PMID:24343361

  15. Interconnectivity of human cellular metabolism and disease prevalence

    NASA Astrophysics Data System (ADS)

    Lee, Deok-Sun

    2010-12-01

    Fluctuations of metabolic reaction fluxes may cause abnormal concentrations of toxic or essential metabolites, possibly leading to metabolic diseases. The mutual binding of enzymatic proteins and ones involving common metabolites enforces distinct coupled reactions, by which local perturbations may spread through the cellular network. Such network effects at the molecular interaction level in human cellular metabolism can reappear in the patterns of disease occurrence. Here we construct the enzyme-reaction network and the metabolite-reaction network, capturing the flux coupling of metabolic reactions caused by the interacting enzymes and the shared metabolites, respectively. Diseases potentially caused by the failure of individual metabolic reactions can be identified by using the known disease-gene association, which allows us to derive the probability of an inactivated reaction causing diseases from the disease records at the population level. We find that the greater the number of proteins that catalyze a reaction, the higher the mean prevalence of its associated diseases. Moreover, the number of connected reactions and the mean size of the avalanches in the networks constructed are also shown to be positively correlated with the disease prevalence. These findings illuminate the impact of the cellular network topology on disease development, suggesting that the global organization of the molecular interaction network should be understood to assist in disease diagnosis, treatment, and drug discovery.

  16. Energy metabolism and rheumatic diseases: from cell to organism

    PubMed Central

    2012-01-01

    In rheumatic and other chronic inflammatory diseases, high amounts of energy for the activated immune system have to be provided and allocated by energy metabolism. In recent time many new insights have been gained into the control of the immune response through metabolic signals. Activation of immune cells as well as reduced nutrient supply and hypoxia in inflamed tissues cause stimulation of glycolysis and other cellular metabolic pathways. However, persistent cellular metabolic signals can promote ongoing chronic inflammation and loss of immune tolerance. On the organism level, the neuroendocrine immune response of the hypothalamic-pituitary adrenal axis and sympathetic nervous system, which is meant to overcome a transient inflammatory episode, can lead to metabolic disease sequelae if chronically activated. We conclude that, on cellular and organism levels, a prolonged energy appeal reaction is an important factor of chronic inflammatory disease etiology. PMID:22747923

  17. Relation of aortic valve calcium to chronic kidney disease (from the Chronic Renal Insufficiency Cohort Study).

    PubMed

    Guerraty, Marie A; Chai, Boyang; Hsu, Jesse Y; Ojo, Akinlolu O; Gao, Yanlin; Yang, Wei; Keane, Martin G; Budoff, Matthew J; Mohler, Emile R

    2015-05-01

    Although subjects with chronic kidney disease (CKD) are at markedly increased risk for cardiovascular mortality, the relation between CKD and aortic valve calcification has not been fully elucidated. Also, few data are available on the relation of aortic valve calcification and earlier stages of CKD. We sought to assess the relation of aortic valve calcium (AVC) with estimated glomerular filtration rate (eGFR), traditional and novel cardiovascular risk factors, and markers of bone metabolism in the Chronic Renal Insufficiency Cohort (CRIC) Study. All patients who underwent aortic valve scanning in the CRIC study were included. The relation between AVC and eGFR, traditional and novel cardiovascular risk factors, and markers of calcium metabolism were analyzed using both unadjusted and adjusted regression models. A total of 1,964 CRIC participants underwent computed tomography for AVC quantification. Decreased renal function was independently associated with increased levels of AVC (eGFR 47.11, 44.17, and 39 ml/min/1.73 m2, respectively, p<0.001). This association persisted after adjusting for traditional, but not novel, AVC risk factors. Adjusted regression models identified several traditional and novel risk factors for AVC in patients with CKD. There was a difference in AVC risk factors between black and nonblack patients. In conclusion, our study shows that eGFR is associated in a dose-dependent manner with AVC in patients with CKD, and this association is independent of traditional cardiovascular risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Psychosocial risk factors for the metabolic syndrome: A prospective cohort study.

    PubMed

    Pedersen, Jolene Masters; Lund, Rikke; Andersen, Ingelise; Clark, Alice Jessie; Prescott, Eva; Rod, Naja Hulvej

    2016-07-15

    Metabolic deregulations and development of metabolic syndrome may be an important pathway underlying the relationship between stress and cardiovascular disease. We aim to estimate the effect of a comprehensive range of psychosocial factors on the risk of developing metabolic syndrome in men and women. The study population consisted of 3621 men and women from the Copenhagen City Heart Study who were free of metabolic syndrome at baseline and reexamined after 10years. The data was analyzed by multivariable logistic regression models adjusted for age, education, income, menopausal status and life style factors. We found major life events in adult life (OR 1.48, 95% CI 0.93 to 2.36) and major life events at work (OR 2.75, 95% CI 1.38 to 5.50), lacking a confidant (OR 1.94, 95% CI 1.07 to 3.53) and dissatisfaction with social network (OR 1.53, 95% CI 1.11 to 2.11) to be risk factors for developing the metabolic syndrome in women, while vital exhaustion (OR 2.09, 95% CI 0.95 to 4.59) and intake of sleep medications (OR 2.54, 95% CI 0.92 to 5.96) may play a more important role in men. Experiencing major life events in work and adult life and/or dysfunctional social networks is a risk factor for metabolic syndrome in women, and stress reactions such as vital exhaustion and intake of sleep medications may play a more important role in the development of metabolic syndrome men. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Veganism does not reduce the risk of the metabolic syndrome in a Taiwanese cohort.

    PubMed

    Shang, Penghui; Shu, Zheng; Wang, Yanfang; Li, Na; Du, Songming; Sun, Feng; Xia, Yinyin; Zhan, Siyan

    2011-01-01

    The purpose of the present study was to assess the risk of the metabolic syndrome (MS) with vegan, pescovegetarian, lactovegetarian and nonvegetarian diets in Taiwan. The design was a retrospective cohort study using secondary data analysis from a Taiwan longitudinal health check-up database provided by MJ Health Screening Center during 1996-2006. A total of 93209 participants were classified as vegans (n=1116), pescovegetarians (n=2461), lactovegetarians (n=4313) and nonvegetarians (n=85319) by food frequency list of self-administered questionnaire at baseline. The association between MS or MS components and different dietary groups was evaluated using Cox proportional-hazards regression models with adjustment for confounders. During the mean 3.75 years of follow up, a total 8006 MS incident cases occurred and the incidence of MS was 229 (95% CI, 224, 234) per 10000 person year. Compared with vegans, hazard ratios of MS for nonvegetarians, pescovegetarians, lactovegetarians were 0.75 (95% CI, 0.64, 0.88), 0.68 (95% CI, 0.55, 0.83) and 0.81 (95% CI, 0.67, 0.97) after adjusting for sex, age, education status, smoking status, drinking status, physical activity at work and leisure, respectively. As for MS components, nonvegetarians and pescovegetarians had 0.72 (95% CI, 0.62, 0.84), 0.70 (95% CI, 0.57, 0.84) times risk of developing low high density lipoprotein cholesterol (HDL-C), while nonvegetarians had 1.16 (95% CI, 1.02, 1.32) times risk of developing high fasting plasma glucose. Our data suggest that the vegan diets did not decrease the risk of metabolic syndrome compared with pescovegetarian, lactovegetarian and nonvegetarian diets in a Taiwanese cohort.

  20. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort.

    PubMed

    Pivovarova, Olga; Nikiforova, Victoria J; Pfeiffer, Andreas F H; Rudovich, Natalia

    2009-02-01

    In the present study, we aimed to validate the type 2 diabetes (T2DM) susceptibility alleles identified in the first genome-wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837). Furthermore, we investigated quantitative metabolic risk phenotypes of these two variants for association with three key components of the insulin metabolism: insulin secretion, insulin sensitivity and insulin degradation. Two HHEX polymorphisms were genotyped in 1026 subjects from the German MESYBEPO cohort. Complete OGTT data were available for a subset of 420 with normal glucose tolerance (NGT), 282 with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) and 146 diabetic subjects. We validated association of both HHEX polymorphisms with T2DM. In the non-diabetic subcohort including NGT and IFG/IGT subjects, the risk alleles of rs7923837 and rs1111875 were significantly associated with decreased first and second phases of insulin secretion and lower insulinogenic index after oral glucose loading. In healthy, normal glucose-tolerant subjects, the same association of HHEX SNP rs1111875 with OGTT-derived phases of insulin secretion were detectable, however, rs7923837 was only weakly associated with reduced insulinogenic index. For both polymorphisms, no significant correlations with insulin sensitivity were obtained. Reduced insulin clearance was also observed in heterozygous carriers of rs1111875. We validated the association of polymorphisms of the HHEX gene with T2DM in the MESYBEPO cohort. Importantly, variations within the HHEX gene conferred the impaired insulin secretion and changes of insulin degradation but no alteration in insulin sensitivity in carriers of risk alleles. Copyright (c) 2008 John Wiley & Sons, Ltd.

  1. Obesity and the metabolic syndrome in a student cohort from Southern Italy.

    PubMed

    Noto, D; Niglio, T; Cefalù, A B; Martino, E; Fayer, F; Mina, M; Valenti, V; Notarbartolo, A; Averna, M; Martino, F

    2009-11-01

    Cardiovascular (CV) risk factors present in childhood predict future CV events. Few data regarding the metabolic syndrome (MS) prevalence are available in adolescents from Mediterranean areas where obesity is becoming a social emergency. This study presents data of MS prevalence in a student cohort from southern Italy. 1629 students between 7 and 14 years of age underwent anthropometric measurements and a blood sample was obtained to assess biochemical parameters. MS risk factors were calculated based on age and gender adjusted percentiles of parameter distributions. MS prevalence rate was 0.022 using paediatric, age-adjusted criteria; the rate increased to 0.029 using a 90th percentile criteria for fasting blood glucose instead of >100mg/dL. Using the criteria issued by the International Diabetes Federation the MS prevalence rate dropped to 0.005. The exploratory factor analysis identified four factors: age/fat related, lipids, blood pressure and blood glucose. Family history of type 2 diabetes mellitus was associated with triglyceride [OR=1.55 (1.0-2.3)] and BMI [OR=1.71 (1.2-2.4)] but not to blood glucose by logistic regression analysis. In a student cohort from Southern Italy, obesity is associated with the features of MS.

  2. Recent developments in metabolic bone diseases: a gnathic perspective.

    PubMed

    Raubenheimer, Erich J; Noffke, Claudia E; Hendrik, Hilde D

    2014-12-01

    Metabolic bone diseases often are asymptomatic and progress sub clinically. Many patients present at a late stage with catastrophic skeletal and extra skeletal complications. In this article, we provide an overview of normal bone remodeling and a synopsis of recent developments in the following conditions: osteoporosis, rickets/osteomalacia, endocrine-induced bone disease, chronic kidney disease-mineral bone disorder and Paget's disease of bone. Our discussion will emphasize the clinical and microscopic manifestations of these diseases in the jaws.

  3. Clinical features of celiac disease: a prospective birth cohort.

    PubMed

    Agardh, Daniel; Lee, Hye-Seung; Kurppa, Kalle; Simell, Ville; Aronsson, Carin Andrén; Jörneus, Ola; Hummel, Michael; Liu, Edwin; Koletzko, Sibylle

    2015-04-01

    To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort. Children from 6 clinical centers in 4 countries positive for HLA-DR3-DQ2 or DR4-DQ8 were annually screened for tissue transglutaminase antibodies (tTGA) and assessed for symptoms by questionnaires. Associations of symptoms with anthropometrics, known risk factors for CD, tTGA levels, and mucosal lesions in those biopsied were examined. Of 6706 screened children, 914 developed persistent positive tTGA, 406 underwent biopsies, and 340 had CD. Compared with age-matched tTGA-negative children, those with persistent tTGA were more likely to have symptoms at 2 (34% vs 19%, P < .001) and 3 years of age (28% vs 19%, P = .009) but not at 4 years (27% vs 21%, NS). Z-scores for height, weight, and BMI did not differ between groups. In children with persistent tTGA, having ≥ 1 symptom was associated with family history of CD (odds ratio = 2.59, 95% confidence interval, 1.21-5.57) but not with age, gender, or HLA-DR3-DQ2 homozygosity. At seroconversion, tTGA levels were higher in symptomatic than asymptomatic children (P < .001), in those from CD families (P < .001), and in US participants (P < .001) but not associated with age, gender, or HLA genotype. tTGA levels correlated with severity of mucosal lesions both in symptomatic (r = 0.53, P < .001) and asymptomatic children (r = 0.22, P = .01). A majority of children detected with persistent tTGA in screenings are asymptomatic and have normal growth by age 4 years. tTGA levels correlate more strongly with severity of mucosal lesions in symptomatic as compared with asymptomatic children. Copyright © 2015 by the American Academy of Pediatrics.

  4. Algorithm for employing physical forces in metabolic bone diseases.

    PubMed

    Massari, Leo

    2011-04-01

    Metabolic bone diseases, especially osteoporosis, demand a multidisciplinary approach. The physical forces find a rationale in the treatment of local alterations in bone-cartilage metabolism. In integrated treatment of vertebral fractures caused by fragility, stimulation with electrical fields has been observed to be effective in reducing pain and improving patients' quality of life.

  5. Fatty acid metabolism: Implications for diet, genetic variation, and disease

    PubMed Central

    Suburu, Janel; Gu, Zhennan; Chen, Haiqin; Chen, Wei; Zhang, Hao; Chen, Yong Q.

    2014-01-01

    Cultures across the globe, especially Western societies, are burdened by chronic diseases such as obesity, metabolic syndrome, cardiovascular disease, and cancer. Several factors, including diet, genetics, and sedentary lifestyle, are suspected culprits to the development and progression of these health maladies. Fatty acids are primary constituents of cellular physiology. Humans can acquire fatty acids by de novo synthesis from carbohydrate or protein sources or by dietary consumption. Importantly, regulation of their metabolism is critical to sustain balanced homeostasis, and perturbations of such can lead to the development of disease. Here, we review de novo and dietary fatty acid metabolism and highlight recent advances in our understanding of the relationship between dietary influences and genetic variation in fatty acid metabolism and their role in chronic diseases. PMID:24511462

  6. [Perceived stress and cardiovascular disease mortality. The Ohsaki Cohort Study].

    PubMed

    Kowata, Emi; Hozawa, Atsushi; Kakizaki, Masako; Tomata, Yasutake; Nagai, Masato; Sugawara, Yumi; Kuriyama, Shinichi; Tsuji, Ichiro

    2012-02-01

    Previous studies have indicated that stress can affect the circulatory system. Although prospective studies have examined the association between perceived stress and cardiovascular disease (CVD) mortality, the results are still controversial. The purpose of the present study was to elucidate the relationship with stratified analyses by alcohol intake category and smoking status. The prospective Ohsaki Cohort Study covered all National Health Insurance beneficiaries aged 40 to 79 years living in the precinct of Ohsaki Public Health Center, Miyagi, Japan. A total of 45,293 Japanese (21,552 men and 23,741 women), without a history of cancer, ischemic heart disease or stroke, and who answered all items related to stress level at the baseline in 1994, were followed prospectively. Over 12 years of follow-up, 1,751 deaths from CVD occurred (994 men and 757 women). We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for CVD mortality according to the perceived stress categories. The low stress category was used as the reference in all analyses. Perceived stress demonstrated a significant positive association with CVD mortality for men; the multivariate adjusted HR for high versus low stress was 1.43 (95% CI: 1.19, 1.87, P = 0.006). No significant relationship was noted for women. With current smokers, perceived high stress versus low had a pronounced association for both men (HR = 1.76, 95% CI: 1.28, 2.41, P = 0.001) and women (HR = 1.61, 95% CI: 1.20, 2.16, P = 0.004), and a similar tendency was noted for current drinking (HR = 1.56, 95% CI: 1.16, 2.09, P = 0.006, HR = 1.42, 95% CI: 1.08, 1.87, P = 0.001). Additionally, for both smoking and drinking men, those reporting high stress had 2 times the risk of CVD mortality of their low stress counterparts (P for trend < 0.001). The interaction of perceived stress with smoking for CVD mortality was of borderline statistical significance only for men (P for interaction

  7. Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil

    DTIC Science & Technology

    2007-04-01

    and Metabolic Disease: Orexin and Modafinil PRINCIPAL INVESTIGATOR: Stephen C. Benoit, Ph.D. CONTRACTING ORGANIZATION: University of...NUMBER Molecular Connections Between Arousal and Metabolic Disease: Orexin and Modafinil 5b. GRANT NUMBER W81XWH-06-2-0019 5c. PROGRAM...the central orexin system may modulate energy balance. Ongoing studies are assessing the effects of treatment on insulin sensitivity and also the

  8. Disturbed Tryptophan Metabolism in Cardiovascular Disease

    PubMed Central

    Mangge, H.; Stelzer, I.; Reininghaus, E.; Weghuber, D.; Postolache, T.T.; Fuchs, D.

    2016-01-01

    cardiovascular morbidity and mortality. Accelerated catabolism of TRP is further involved in the pathogenesis of the anemia of scLGI. The pro-inflammatory cytokine IFN-γ suppresses growth and differentiation of erythroid progenitor cells, and the depletion of TRP limits protein synthesis and thus hemoglobin production, and, through reduction in oxygen supply, may contribute to ischemic vascular disease. In this review we discuss the impact of TRP breakdown and the related complex mechanisms on the prognosis and individual course of CVD. Measurement of TRP, KYN concentrations, and calculation of the KYN/TRYP ratio will contribute to a better understanding of the interplay between inflammation, metabolic syndrome, mood disturbance, and anemia, all previously described as significant predictors of an unfavorable outcome in patients with CVD. The review leads to a novel framework for successful therapeutic modification of several cardinal pathophysiological processes leading to adverse cardiovascular outcome. PMID:24606499

  9. Dietary magnesium intake and risk of incident coronary heart disease in men: A prospective cohort study.

    PubMed

    Kokubo, Yoshihiro; Saito, Isao; Iso, Hiroyasu; Yamagishi, Kazumasa; Yatsuya, Hiroshi; Ishihara, Junko; Maruyama, Koutatsu; Inoue, Manami; Sawada, Norie; Tsugane, Shoichiro

    2017-08-12

    The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. We studied 85,293 Japanese subjects by questionnaire at baseline (age 45-74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50-0.99) and 0.66 (0.44-0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39-0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. Metabolic resting-state brain networks in health and disease.

    PubMed

    Spetsieris, Phoebe G; Ko, Ji Hyun; Tang, Chris C; Nazem, Amir; Sako, Wataru; Peng, Shichun; Ma, Yilong; Dhawan, Vijay; Eidelberg, David

    2015-02-24

    The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the "DMN-like" dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer's disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer's disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease.

  11. Metabolically Healthy Obese and Incident Cardiovascular Disease Events Among 3.5 Million Men and Women.

    PubMed

    Caleyachetty, Rishi; Thomas, G Neil; Toulis, Konstantinos A; Mohammed, Nuredin; Gokhale, Krishna M; Balachandran, Kumarendran; Nirantharakumar, Krishnarajah

    2017-09-19

    Previous studies have been unclear about the cardiovascular risks for metabolically healthy obese individuals. This study examined the associations among metabolically healthy obese individuals and 4 different presentations of incident cardiovascular disease in a contemporary population. We used linked electronic health records (1995 to 2015) in The Health Improvement Network (THIN) to assemble a cohort of 3.5 million individuals, 18 years of age or older and initially free of cardiovascular disease. We created body size phenotypes defined by body mass index categories (underweight, normal weight, overweight, and obesity) and 3 metabolic abnormalities (diabetes, hypertension, and hyperlipidemia). The primary endpoints were the first record of 1 of 4 cardiovascular presentations (coronary heart disease [CHD], cerebrovascular disease, heart failure, and peripheral vascular disease). During a mean follow-up of 5.4 years, obese individuals with no metabolic abnormalities had a higher risk of CHD (multivariate-adjusted hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.45 to 1.54), cerebrovascular disease (HR: 1.07; 95% CI: 1.04 to 1.11), and heart failure (HR: 1.96; 95% CI: 1.86 to 2.06) compared with normal weight individuals with 0 metabolic abnormalities. Risk of CHD, cerebrovascular disease, and heart failure in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities. Metabolically healthy obese individuals had a higher risk of coronary heart disease, cerebrovascular disease, and heart failure than normal weight metabolically healthy individuals. Even individuals who are normal weight can have metabolic abnormalities and similar risks for cardiovascular disease events. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. A multiregional Italian cohort of 24-hour urine metabolic evaluation in renal stone formers.

    PubMed

    Esperto, Francesco; Marangella, Martino; Trinchieri, Alberto; Petrarulo, Michele; Miano, Roberto

    2017-09-07

    Nephrolithiasis is a common condition with several studies documenting an increased prevalence over the past four decades. EAU and AUA guidelines recommend 24-hour urine metabolic evaluation in high-risk stone formers. Aim of this study is to retrospectively evaluate the first three years of experience with Lithotest® (Biohealth Italia Srl, Turin, Italy) through the analysis of demographic, clinical and biochemical data collected from a large cohort of patients with kidney stones. We retrospectively analysed data from the LithoCenter database, including data from outpatient consultations, between January 2007 and December 2009 from all over Italy. Lithotest® was performed through a 24-h urine collection and included measurements of urine volume and pH, 24-h excretion of creatinine as well as main cations and anions, including calcium, magnesium sodium potassium, ammonium, uric acid, oxalate, citrate, phosphate, inorganic sulphate and chloride. Urine state of saturation for calcium oxalate (ßCaOx), calcium hydrogen phosphate or brushite (ßbsh) and uric acid (ßUA) were also calculated by means of the computer program Lithorisk. Brand's test for cystinuria was also carried out. Statistical analysis was performed using the S-PSS 22.0 software. The number of patients with data available for analysis was 435, 236 males (54%) and 199 females (46%). Complete 24-h urine measurements were available for all 435 patients. Compared to men, women had significantly lower values for creatinine, irate, oxalate, phosphate, sodium, potassium, magnesium and chloride excretion, whereas 24-hour pH and citrate excretion were higher. No significant differences were found for the other examined variables. ßCaOx and ßUA were significantly higher in men than women, whereas no significant difference was found for ßbsh. There was a direct relationship between calcium and sodium urine excretion. Excessive sodium excretion was recorded in 191 patients (44%) and low urine volumes in 201

  13. The role of RNA metabolism in neurological diseases

    PubMed Central

    Abou Al-Shaar, H; Shariff, RK; Albakr, A

    2015-01-01

    Abstract Neurodegenerative disorders are commonly encountered in medical practices. Such diseases can lead to major morbidity and mortality among the affected individuals. The molecular pathogenesis of these disorders is not yet clear. Recent literature has revealed that mutations in RNA-binding proteins are a key cause of several human neuronal-based diseases. This review discusses the role of RNA metabolism in neurological diseases with specific emphasis on roles of RNA translation and microRNAs in neurodegeneration, RNA-mediated toxicity, repeat expansion diseases and RNA metabolism, molecular pathogenesis of amyotrophic lateral sclerosis and frontotemporal dementia, and neurobiology of survival motor neuron (SMN) and spinal muscular atrophy. PMID:27785391

  14. Medical Problems in Obstetrics: Inherited Metabolic Disease.

    PubMed

    Murphy, Elaine

    2015-07-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Although, in general, outcomes for women and their children are good, there are a number of issues that need to be considered. Currently, limited specific guidance on the management of these conditions in pregnancy is available. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in disorders of energy metabolism or intoxication significantly reduced. Multidisciplinary management, and close liaison between obstetricians and other specialists, is required for those women in whom there is cardiac, renal, respiratory, joint or other organ involvement.

  15. Pregnancy in women with inherited metabolic disease

    PubMed Central

    2015-01-01

    An increasing number of women with rare inherited disorders of metabolism are becoming pregnant. Whilst, in general, outcomes for women and their children are good, there are issues that need to be considered. Due to the rarity of many conditions, there is limited specific guidance available on best management. Prepregnancy counselling with information on inheritance, options for reproduction, teratogenicity risk, potential impact on maternal health and long-term health of children should be offered. With appropriate specialist management, the teratogenic risk of conditions such as maternal phenylketonuria (PKU) can be eliminated, and the risk of metabolic decompensation in other disorders of intoxication or energy metabolism significantly reduced. Newer therapies, such as enzyme replacement therapy, appear to be safe in pregnancy, but specific advice should be sought. Multidisciplinary management, and close liaison between obstetricians and other specialists is required for women in whom there is cardiac, renal, respiratory, joint or other organ involvement. PMID:27512458

  16. Tissue-specific insulin signaling, metabolic syndrome and cardiovascular disease

    PubMed Central

    Rask-Madsen, Christian; Kahn, C. Ronald

    2012-01-01

    Summary Impaired insulin signaling is central to the development of the metabolic syndrome and can promote cardiovascular disease indirectly through development of abnormal glucose and lipid metabolism, hypertension and a proinflammatory state. However, insulin action directly on vascular endothelium, atherosclerotic plaque macrophages, and in the heart, kidney, and retina has now been described, and impaired insulin signaling in these locations can alter progression of cardiovascular disease in the metabolic syndrome and affect development of microvascular complications of diabetes. Recent advances in our understanding of the complex pathophysiology of insulin’s effects on vascular tissues offer new opportunities for preventing these cardiovascular disorders. PMID:22895666

  17. Metabolic bone diseases during long-term total parenteral nutrition.

    PubMed

    Acca, M; Ragno, A; Francucci, C M; D'Erasmo, E

    2007-01-01

    Long-term total parenteral nutrition (TPN) is a procedure commonly applied to patients with advanced forms of intestinal malabsorption. Among TPN complications, bone metabolic diseases, such as osteoporosis and osteomalacia, are a common finding. Initially considered to be a manifestation of aluminium toxicity which followed massive contamination with the element of the solutions used in TPN, metabolic osteopathy during TPN is currently considered a multiform syndrome, with a multifactorial pathogenesis, which may manifest itself with vague or clear clinical pictures. In this review, we analyse clinical, pathogenetic, and therapeutic aspects of the most common bone metabolic diseases in patients undergoing long-term TPN.

  18. The emerging role of the intestine in metabolic diseases.

    PubMed

    Bradley, William D; Zwingelstein, Catherine; Rondinone, Cristina M

    2011-07-01

    The intestine is an important metabolic organ that has gained attention in recent years for the newly identified role that it plays in the pathophysiology of various metabolic diseases including obesity, insulin resistance and diabetes. Recent insights regarding the role of enteroendocrine hormones, such as GIP, GLP-1, and PYY in metabolic diseases, as well as the emerging role of the gut microbial community and gastric bypass bariatric surgeries in modulating metabolic function and dysfunction have sparked a wave of interest in understanding the mechanisms involved, in an effort to identify new therapeutics and novel regulators of metabolism. This review summarizes the current evidence that the gastrointestinal tract has a key role in the development of obesity, inflammation, insulin resistance and diabetes and discusses the possible players that can be targeted for therapeutic intervention.

  19. Metabolic Modulators in Heart Disease: Past, Present, and Future.

    PubMed

    Lopaschuk, Gary D

    2017-07-01

    Ischemic heart disease and heart failure are leading causes of mortality and morbidity worldwide. They continue to be major burden on health care systems throughout the world, despite major advances made over the past 40 years in developing new therapeutic approaches to treat these debilitating diseases. A potential therapeutic approach that has been underutilized in treating ischemic heart disease and heart failure is "metabolic modulation." Major alterations in myocardial energy substrate metabolism occur in ischemic heart disease and heart failure, and are associated with an energy deficit in the heart. A metabolic shift from mitochondrial oxidative metabolism to glycolysis, as well as an uncoupling between glycolysis and glucose oxidation, plays a crucial role in the development of cardiac inefficiency (oxygen consumed per work performed) and functional impairment in ischemic heart disease as well as in heart failure. This has led to the concept that optimizing energy substrate use with metabolic modulators can be a potentially promising approach to decrease the severity of ischemic heart disease and heart failure, primarily by improving cardiac efficiency. Two approaches for metabolic modulator therapy are to stimulate myocardial glucose oxidation and/or inhibit fatty acid oxidation. In this review, the past, present, and future of metabolic modulators as an approach to optimizing myocardial energy substrate metabolism and treating ischemic heart disease and heart failure are discussed. This includes a discussion of pharmacological interventions that target enzymes involved in fatty acid uptake, fatty acid oxidation, and glucose oxidation in the heart, as well as enzymes involved in ketone and branched chain amino acid catabolism in the heart. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  20. Pathogenic role of ganglioside metabolism in neurodegenerative diseases.

    PubMed

    Ariga, Toshio

    2014-10-01

    Ganglioside metabolism is altered in several neurodegenerative diseases, and this may participate in several events related to the pathogenesis of these diseases. Most changes occur in specific areas of the brain and their distinct membrane microdomains or lipid rafts. Antiganglioside antibodies may be involved in dysfunction of the blood-brain barrier and disease progression in these diseases. In lipid rafts, interactions of glycosphingolipids, including ganglioside, with proteins may be responsible for the misfolding events that cause the fibril and/or aggregate processing of disease-specific proteins, such as α-synuclein, in Parkinson's disease, huntingtin protein in Huntington's disease, and copper-zinc superoxide dismutase in amyotrophic lateral sclerosis. Targeting ganglioside metabolism may represent an underexploited opportunity to design novel therapeutic strategies for neurodegeneration in these diseases. © 2014 Wiley Periodicals, Inc.

  1. Bile Acid Signaling in Metabolic Disease and Drug Therapy

    PubMed Central

    Li, Tiangang

    2014-01-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid–activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein–coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver. PMID:25073467

  2. Bile acid signaling in metabolic disease and drug therapy.

    PubMed

    Li, Tiangang; Chiang, John Y L

    2014-10-01

    Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates hepatobiliary secretion of lipids, lipophilic metabolites, and xenobiotics. In the intestine, bile acids are essential for the absorption, transport, and metabolism of dietary fats and lipid-soluble vitamins. Extensive research in the last 2 decades has unveiled new functions of bile acids as signaling molecules and metabolic integrators. The bile acid-activated nuclear receptors farnesoid X receptor, pregnane X receptor, constitutive androstane receptor, vitamin D receptor, and G protein-coupled bile acid receptor play critical roles in the regulation of lipid, glucose, and energy metabolism, inflammation, and drug metabolism and detoxification. Bile acid synthesis exhibits a strong diurnal rhythm, which is entrained by fasting and refeeding as well as nutrient status and plays an important role for maintaining metabolic homeostasis. Recent research revealed an interaction of liver bile acids and gut microbiota in the regulation of liver metabolism. Circadian disturbance and altered gut microbiota contribute to the pathogenesis of liver diseases, inflammatory bowel diseases, nonalcoholic fatty liver disease, diabetes, and obesity. Bile acids and their derivatives are potential therapeutic agents for treating metabolic diseases of the liver.

  3. Gestational dating by metabolic profile at birth: a California cohort study.

    PubMed

    Jelliffe-Pawlowski, Laura L; Norton, Mary E; Baer, Rebecca J; Santos, Nicole; Rutherford, George W

    2016-04-01

    Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11-20 weeks' gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and term births. Using a linear discriminate

  4. Gestational dating by metabolic profile at birth: a California cohort study

    PubMed Central

    Jelliffe-Pawlowski, Laura L.; Norton, Mary E.; Baer, Rebecca J.; Santos, Nicole; Rutherford, George W.

    2016-01-01

    Background Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. Objective We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. Study Design We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11–20 weeks’ gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Results Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and

  5. Gamma images in benign and metabolic bone diseases: volume 1

    SciTech Connect

    Sy, W.M.

    1981-01-01

    Volume 1 of ''Gamma images in benign and metabolic bone diseases'' comprises chapters devoted to: general remarks and considerations, radiopharmaceuticals, Paget disease, osteomyelitis, trauma, benign bone tumors, chronic renal dialysis, acute renal failure, osteomalacia and rickets, and osteoporosis. Although published in 1981, the most recent references in the book were 1978 and most are 1977 or earlier. One of the strongest aspects of the volume are tables which categorize diseases, pathophysiology of disease, and image abnormalities. (JMT)

  6. Burden of nonalcoholic fatty liver disease and advanced fibrosis in a Texas Hispanic community cohort

    PubMed Central

    Pan, Jen-Jung; Fisher-Hoch, Susan P; Chen, Chaoru; Feldstein, Ariel E; McCormick, Joseph B; Rahbar, Mohammad H; Beretta, Laura; Fallon, Michael B

    2015-01-01

    AIM: To investigate the potential burden of nonalcoholic steatohepatitis (NASH) and advanced fibrosis in a hispanic community. METHODS: Four hundred and forty two participants with available ultrasonography data from the Cameron County Hispanic Cohort were included in this study. Each participant completed a comprehensive questionnaire regarding basic demographic information, medical history, medication use, and social and family history including alcohol use. Values of the nonalcoholic fatty liver disease fibrosis score (NFS), FIB4 index, BARD score, and Aspartate aminotransferase to Platelet Ratio Index (APRI) were computed using the blood samples collected within 6 mo of liver ultrasonography from each participant. Hepatic steatosis was determined by ultrasonography. As part of univariable analysis, for continuous variables, comparisons among groups were performed with student-t test, one way analysis of variance, and Mann-Whitney test. Pearson χ2 and the Fisher exact test are used to assess differences in categorical variables. For multivariable analyses, logistic regression analyses were performed to identify characteristics associated with hepatic steatosis. All reported P values are based two-sided tests, and a P value of less than 0.05 was considered to indicate statistical significance. RESULTS: The mean age and body mass index (BMI) of the study participants were 49.1 years and 31.3 kg/m2, respectively. Among them, 65.6% were females, 52% had hepatic steatosis, 49.5% had metabolic syndrome, and 29% had elevated aminotransferases. Based on established cut-offs for diagnostic panels, between 17%-63% of the entire cohort was predicted to have NASH with indeterminate or advanced fibrosis. Participants with hepatic steatosis had significantly higher BMI (32.9 ± 5.6 kg/m2 vs 29.6 ± 6.1 kg/m2, P < 0.001) and higher prevalence rates of elevation of ALT (42.2% vs 14.6%, P < 0.001), elevation of aspartate aminotransferase (38.7% vs 18.9%, P < 0.001), and

  7. Cardiovascular disease in kidney donors: matched cohort study.

    PubMed

    Garg, Amit X; Meirambayeva, Aizhan; Huang, Anjie; Kim, Joseph; Prasad, G V Ramesh; Knoll, Greg; Boudville, Neil; Lok, Charmaine; McFarlane, Philip; Karpinski, Martin; Storsley, Leroy; Klarenbach, Scott; Lam, Ngan; Thomas, Sonia M; Dipchand, Christine; Reese, Peter; Doshi, Mona; Gibney, Eric; Taub, Ken; Young, Ann

    2012-03-01

    To determine whether people who donate a kidney have an increased risk of cardiovascular disease. Retrospective population based matched cohort study. All people who were carefully selected to become a living kidney donor in the province of Ontario, Canada, between 1992 and 2009. The information in donor charts was manually reviewed and linked to provincial healthcare databases. Matched non-donors were selected from the healthiest segment of the general population. A total of 2028 donors and 20,280 matched non-donors were followed for a median of 6.5 years (maximum 17.7 years). Median age was 43 at the time of donation (interquartile range 34-50) and 50 at the time of follow-up (42-58). The primary outcome was a composite of time to death or first major cardiovascular event. The secondary outcome was time to first major cardiovascular event censored for death. The risk of the primary outcome of death and major cardiovascular events was lower in donors than in non-donors (2.8 v 4.1 events per 1000 person years; hazard ratio 0.66, 95% confidence interval 0.48 to 0.90). The risk of major cardiovascular events censored for death was no different in donors than in non-donors (1.7 v 2.0 events per 1000 person years; 0.85, 0.57 to 1.27). Results were similar in all sensitivity analyses. Older age and lower income were associated with a higher risk of death and major cardiovascular events in both donors and non-donors when each group was analysed separately. The risk of major cardiovascular events in donors is no higher in the first decade after kidney donation compared with a similarly healthy segment of the general population. While we will continue to follow people in this study, these interim results add to the evidence base supporting the safety of the practice among carefully selected donors.

  8. Synthetic biology-inspired therapies for metabolic diseases.

    PubMed

    Teixeira, Ana Palma; Fussenegger, Martin

    2017-10-01

    Our ability to engineer mammalian cells with effective therapeutic behaviors has brought new hope for treating metabolic diseases. Synthetic gene networks have been customized to interface with the host metabolism, discriminate between healthy and diseased states, and respond by producing an adjusted dose of the therapeutic molecule. Such devices have the potential to treat a range of dysfunctions that are simply not addressable using conventional therapies. Recently, the repurposing of native signaling pathways has formed the basis of autonomous therapeutic programs genetically installed in mammalian cells and has greatly expanded the possibilities to effectively tackle metabolic disorders. Here, we outline network topologies that have been successfully validated in animal models of metabolic diseases and discuss future developments that will be important for bringing this technology closer to clinical application. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Microbiome and metabolic disease: revisiting the bacterial phylum Bacteroidetes.

    PubMed

    Johnson, Elizabeth L; Heaver, Stacey L; Walters, William A; Ley, Ruth E

    2017-01-01

    Bacterial species composition in the gut has emerged as an important factor in obesity and its related metabolic diseases such as type 2 diabetes. Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes. Members of the Bacteroidetes in particular have been associated with human metabolic diseases. However, their associations with disease are not always consistent between studies. Delving deeper into the diversity within the Bacteroidetes reveals a vast diversity in genomes and capacities, which partly explain how not all members respond equally to similar environmental conditions in their hosts. Here, we discuss the Bacteroidetes phylum, associations of its members with metabolic phenotypes, and efforts to characterize functionally their interactions with their hosts. Harnessing the Bacteroidetes to promote metabolic health will require a nuanced understanding of how specific strains interact with their microbial neighbors and their hosts under various conditions.

  10. Prevalence of the metabolic syndrome in children with psoriatic disease.

    PubMed

    Goldminz, Ari M; Buzney, Catherine D; Kim, Noori; Au, Shiu-Chung; Levine, Danielle E; Wang, Andrew C; Volf, Eva M; Yaniv, Shimrat S; Kerensky, Todd A; Bhandarkar, Manasa; Dumont, Nicole M; Lizzul, Paul F; Loo, Daniel S; Kulig, John W; Brown, Mary E; Lopez-Benitez, Jorge M; Miller, Laurie C; Gottlieb, Alice B

    2013-01-01

    Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS) and cardiovascular disease (CVD), but few studies have investigated the prevalence of MetS and other risk factors for CVD in children with psoriasis. In an assessor-blinded study, 20 children ages 9-17 years with a current or previously documented history of psoriasis involving 5% or more of their body surface area or psoriatic arthritis were compared with a cohort of age- and sex-matched controls with benign nevi, warts, or acne. MetS, our primary endpoint, was defined by the presence of abnormal values in at least three of the following measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1 mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no statistically significant differences in the other four components of MetS, BMI, BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that children with psoriasis have higher rates of MetS than age- and sex-matched controls. It may therefore be important to evaluate children with psoriasis for components of MetS to prevent future CVD morbidity and mortality.

  11. Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study.

    PubMed

    Lu, Na; Dubreuil, Maureen; Zhang, Yuqing; Neogi, Tuhina; Rai, Sharan K; Ascherio, Alberto; Hernán, Miguel A; Choi, Hyon K

    2016-03-01

    While gout is associated with cardiovascular (CV)-metabolic comorbidities and their sequelae, the antioxidant effects of uric acid may have neuroprotective benefits. We evaluated the potential impact of incident gout on the risk of developing Alzheimer's disease (AD) in a general population context. We conducted an age-matched, sex-matched, entry-time-matched and body mass index (BMI)-matched cohort study using data from The Health Improvement Network, an electronic medical record database representative of the UK general population, from 1 January 1995 to 31 December 2013. Up to five non-gout individuals were matched to each case of incident gout by age, sex, year of enrolment and BMI. We compared incidence rates of AD between the gout and comparison cohorts, excluding individuals with prevalent gout or dementia at baseline. Multivariate hazard ratios (HRs) were calculated, while adjusting for smoking, alcohol use, physician visits, social deprivation index, comorbidities and medication use. We repeated the same analysis among patients with incident osteoarthritis (OA) as a negative control exposure. We identified 309 new cases of AD among 59 224 patients with gout (29% female, mean age 65 years) and 1942 cases among 238 805 in the comparison cohort over a 5-year median follow up (1.0 vs 1.5 per 1000 person-years, respectively). Univariate (age-matched, sex-matched, entry-time-matched and BMI-matched) and multivariate HRs for AD among patients with gout were 0.71 (95% CI 0.62 to 0.80) and 0.76 (95% CI 0.66 to 0.87), respectively. The inverse association persisted among subgroups stratified by sex, age group (<75 and ≥75 years), social deprivation index and history of CV disease. The association between incident OA and the risk of incident AD was null. These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, supporting the purported potential neuroprotective role of uric acid

  12. Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study.

    PubMed

    Hackett, Ruth A; Kivimäki, Mika; Kumari, Meena; Steptoe, Andrew

    2016-02-01

    The hypothalamic pituitary-adrenal axis is thought to play a role in type 2 diabetes (T2D). However, evidence for an association between cortisol and future glucose disturbance is sparse. The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. This is a prospective cohort study of salivary cortisol measured at the 2002-2004 clinical examination of the Whitehall II study, United Kingdom. We measured cortisol (nmol/l) from six saliva samples obtained over the course of a day: at waking, +30 minutes, +2.5 hours, +8 hours, +12 hours, and bedtime. Participants who were normoglycemic in 2002-2004 (phase 7) were reexamined in 2012-2013 (phase 11). The occupational cohort was originally recruited in 1985-1988. A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002-2004). Incident T2D and impaired fasting glucose in 2012-2013 were measured. Raised evening cortisol at phase 7 was predictive of new-onset T2D at phase 11 (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01-1.37) with a trend for a flatter slope in participants with incident T2D (odds ratio, 1.15; 95% CI, 0.99-1.33). When expanding this analysis to a broader category of glucose disturbance we found that a flattened diurnal cortisol slope at phase 7 was predictive of future impaired fasting glucose or T2D at phase 11 (OR, 1.12; 95% CI, 1.02-1.22), as was high bedtime cortisol (OR, 1.10; 95% CI, 1.01-1.20). In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance.

  13. Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders.

    PubMed

    Cai, Huan; Cong, Wei-na; Ji, Sunggoan; Rothman, Sarah; Maudsley, Stuart; Martin, Bronwen

    2012-01-01

    Alzheimer's disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer's disease, Huntington's disease, and Parkinson's disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and 'eumetabolic' activities may possess superior efficacies compared to less pluripotent remedies.

  14. Homocysteine Metabolism, Atherosclerosis, and Diseases of Aging.

    PubMed

    McCully, Kilmer S

    2015-12-15

    The importance of homocysteine in vascular function and arteriosclerosis was discovered by demonstration of arteriosclerotic plaques in children with homocystinuria caused by inherited enzymatic deficiencies of cystathionine synthase, methionine synthase, or methylene-tetrahydrofolate reductase. According to the homocysteine theory of arteriosclerosis, an elevated blood homocysteine level is an important risk factor for atherosclerosis in subjects without these rare enzymatic abnormalities. The homocysteine theory is supported by demonstration of arterial plaques in experimental animals with hyperhomocysteinemia, by discovery of a pathway for conversion of homocysteine thiolactone to sulfate in cell cultures from children with homocystinuria, and by demonstration of growth promotion by homocysteic acid in normal and hypophysectomized animals. Studies with cultured malignant cells revealed abnormal homocysteine thiolactone metabolism, resulting in homocysteinylation of proteins, nucleic acids, and glycosaminoglycans, explaining the abnormal oxidative metabolism, abnormalities of cellular membranes, and altered genetic expression observed in malignancy. Abnormal homocysteine metabolism in malignant cells is attributed to deficiency of thioretinamide, the amide synthesized from retinoic acid and homocysteine thiolactone. Two molecules of thioretinamide combine with cobalamin to form thioretinaco. Based on the molecular structure of thioretinaco, a theory of oxidative phosphorylation was proposed, involving oxidation to a disulfonium derivative by ozone, and binding of oxygen, nicotinamide adenine dinucleotide and phosphate as the active site of adenosine triphosphate synthesis in mitochondria. Obstruction of vasa vasorum by aggregates of microorganisms with homocysteinylated low-density lipoproteins is proposed to cause ischemia of arterial wall and a microabscess of the intima, the vulnerable atherosclerotic plaque.

  15. Modeling Metabolism and Disease in Bioarcheology.

    PubMed

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data.

  16. Modeling Metabolism and Disease in Bioarcheology

    PubMed Central

    Qualls, Clifford; Appenzeller, Otto

    2015-01-01

    We examine two important measures that can be made in bioarcheology on the remains of human and vertebrate animals. These remains consist of bone, teeth, or hair; each shows growth increments and each can be assayed for isotope ratios and other chemicals in equal intervals along the direction of growth. In each case, the central data is a time series of measurements. The first important measures are spectral estimates in spectral analyses and linear system analyses; we emphasize calculation of periodicities and growth rates as well as the comparison of power in bands. A low frequency band relates to the autonomic nervous system (ANS) control of metabolism and thus provides information about the life history of the individual of archeological interest. Turning to nonlinear system analysis, we discuss the calculation of SM Pinus' approximate entropy (ApEn) for short or moderate length time series. Like the concept that regular heart R-R interval data may indicate lack of health, low values of ApEn may indicate disrupted metabolism in individuals of archeological interest and even that a tipping point in deteriorating metabolism may have been reached just before death. This adds to the list of causes of death that can be determined from minimal data. PMID:26347356

  17. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  18. Living at a Geographically Higher Elevation Is Associated with Lower Risk of Metabolic Syndrome: Prospective Analysis of the SUN Cohort

    PubMed Central

    Lopez-Pascual, Amaya; Bes-Rastrollo, Maira; Sayón-Orea, Carmen; Perez-Cornago, Aurora; Díaz-Gutiérrez, Jesús; Pons, Juan J.; Martínez-González, Miguel A.; González-Muniesa, Pedro; Martínez, J. Alfredo

    2017-01-01

    Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456 m) exhibited a significantly lower risk of developing MetS compared to those in the lowest tertile (<122 m) of altitude of residence [Model 2: Hazard ratio = 0.75 (95% Confidence interval: 0.58–0.97); p for trend = 0.029]. Living at geographically higher altitude was associated with a lower risk of developing MetS in the SUN project. Our findings suggest that geographical elevation may be an important factor linked to metabolic diseases. PMID:28101063

  19. Living at a Geographically Higher Elevation Is Associated with Lower Risk of Metabolic Syndrome: Prospective Analysis of the SUN Cohort.

    PubMed

    Lopez-Pascual, Amaya; Bes-Rastrollo, Maira; Sayón-Orea, Carmen; Perez-Cornago, Aurora; Díaz-Gutiérrez, Jesús; Pons, Juan J; Martínez-González, Miguel A; González-Muniesa, Pedro; Martínez, J Alfredo

    2016-01-01

    Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456 m) exhibited a significantly lower risk of developing MetS compared to those in the lowest tertile (<122 m) of altitude of residence [Model 2: Hazard ratio = 0.75 (95% Confidence interval: 0.58-0.97); p for trend = 0.029]. Living at geographically higher altitude was associated with a lower risk of developing MetS in the SUN project. Our findings suggest that geographical elevation may be an important factor linked to metabolic diseases.

  20. GPR120 agonism as a countermeasure against metabolic diseases.

    PubMed

    Cornall, Lauren M; Mathai, Michael L; Hryciw, Deanne H; McAinch, Andrew J

    2014-05-01

    Obesity, type 2 diabetes mellitus and cardiovascular disease are at epidemic proportions in developed nations globally, representing major causes of ill-health and premature death. The search for drug targets to counter the growing prevalence of metabolic diseases has uncovered G-protein-coupled receptor 120 (GPR120). GPR120 agonism has been shown to improve inflammation and metabolic health on a systemic level via regulation of adiposity, gastrointestinal peptide secretion, taste preference and glucose homeostasis. Therefore, GPR120 agonists present as a novel therapeutic option that could be exploited for the treatment of impaired metabolic health. This review summarizes the current knowledge of GPR120 functionality and the potential applications of GPR120-specific agonists for the treatment of disease states such as obesity, type 2 diabetes mellitus and cardiovascular disease.

  1. Socioeconomic inequalities in lipid and glucose metabolism in early childhood in a population-based cohort: the ABCD-Study

    PubMed Central

    2012-01-01

    Background Socioeconomic inequalities in cardiovascular disease are pervasive, yet much remains to be understood about how they originate. The objective of this study was to explore the relations of socioeconomic status to lipid and glucose metabolism as indicators of cardiovascular health in 5–6 year olds. Additionally to explore the explanatory role of maternal factors, birth outcome, and child factors. Methods In 1308 5–6 year old ethnic Dutch children from the ABCD cohort study, lipids (cholesterol, LDL, HDL, triglycerides), glucose and C-peptide were measured after an overnight-fast. Results There were no differences in cholesterol, HDL, LDL, and triglycerides between socioeconomic groups, as indicated by maternal education and income adequacy. However, children of low educated mothers had on average a higher glucose (β = 0.15; 95% confidence interval (CI) 0.03 – 0.27), logC-peptide (β = 0.07; 95% CI 0.04 – 0.09), and calculated insulin resistance (HOMA-IR) (β = 0.15; 95% CI 0.08 – 0.22) compared to children of high educated mothers. Only childhood BMI partly explained these differences (models controlled for age, height, and sex). Conclusions The socioeconomic gradient in cardiovascular risk factors seems to emerge in early childhood. In absence of underlying mechanisms these empirical findings are relevant for public health care and further explanatory research. PMID:22852830

  2. Metabolic profiling distinguishes three subtypes of Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.

    2015-01-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

  3. NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy.

    PubMed

    Kalra, S P; Kalra, P S

    2004-08-01

    Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.

  4. Abdominal obesity and metabolic syndrome burden in adolescents--Penn State Children Cohort study.

    PubMed

    He, Fan; Rodriguez-Colon, Sol; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N; Bixler, Edward O; Berg, Arthur; Imamura Kawasawa, Yuka; Sawyer, Marjorie D; Liao, Duanping

    2015-01-01

    To investigate the association between abdominal obesity and metabolic syndrome (MetS) burden in a population-based sample of adolescents, we used data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. Dual-energy x-ray absorptiometry (DXA) was used to assess abdominal obesity, as measured by android/gynoid fat ratio (A/G ratio), android/whole body fat proportion (A/W proportion), visceral (VAT) and subcutaneous fat (SAT) areas. Continuous metabolic syndrome score (cMetS), calculated as the sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components, was used to assess the MetS burden. Linear regression models were used to analyze the impact of DXA measures on cMetS components. All models were adjusted for age, race, sex, and general obesity. We found abdominal obesity is significantly associated with increased cMetS. With 1 standard deviation (SD) increase in A/G ratio, A/W proportion, VAT area, and SAT area, cMetS increased by 1.34 (SE=0.17), 1.25 (SE=0.19), 1.67 (SE=0.17), and 1.84 (SE=0.20) units, respectively. At individual component level, strongest association was observed between abdominal obesity and insulin resistance (IR) than lipid-based or blood pressure-based components. VAT and SAT had a stronger impact on IR than android ratio-based DXA measurements. In conclusion, abdominal obesity is associated with higher MetS burden in adolescent population. The association between abdominal obesity and IR measure is the strongest, suggesting the key impact of abdominal obesity on IR in adolescents MetS burden.

  5. Abdominal Obesity and Metabolic Syndrome Burden in Adolescents-Penn State Children Cohort Study

    PubMed Central

    He, Fan; Rodriguez-Colon, Sol; Fernandez-Mendoza, Julio; Vgontzas, Alexandros N.; Bixler, Edward O.; Berg, Arthur; Kawasawa, Yuka Imamura; Sawyer, Marjorie D.; Liao, Duanping

    2014-01-01

    INTRODUCTION To investigate the association between abdominal obesity and metabolic syndrome (MetS) burden in a population-based sample of adolescents. METHODS We used the data from 421 adolescents who completed the follow-up examination in the Penn State Children Cohort study. Dual-energy x-ray absorptiometry (DXA) was used to assess abdominal obesity, as measured by android/gynoid fat ratio (A/G ratio), android/whole body fat proportion (A/W proportion), visceral (VAT) and subcutaneous fat (SAT) areas. Continuous metabolic syndrome score (cMetS), calculated as the sum of the age and sex-adjusted standardized residual (Z-score) of five established MetS components, was used to assess the MetS burden. Linear regression models were used to analyze the impact of DXA measures on cMetS and individual cMetS components. All models were adjusted for age, race, sex, and general obesity. RESULTS Abdominal obesity is significantly associated with increased cMetS. With 1 standard deviation (SD) increase in A/G ratio, A/W proportion, VAT area, and SAT area, cMetS increased by 1.34 (SE=0.17), 1.25 (SE=0.19), 1.67 (SE=0.17), and 1.84 (SE=0.20) units, respectively. At individual component level, strongest association was observed between abdominal obesity and insulin resistance than lipid-based or blood pressure-based components. VAT and SAT had a stronger impact on insulin resistance than android ratio-based DXA measurements. CONCLUSIONS Abdominal obesity is associated with higher MetS burden in adolescent population. The association between abdominal obesity and insulin resistance measure is the strongest, suggesting the key impact of abdominal obesity on insulin resistance in adolescents Mets burden. PMID:25220887

  6. Consumption of fried foods and risk of metabolic syndrome: the SUN cohort study.

    PubMed

    Sayon-Orea, C; Martinez-Gonzalez, M A; Gea, A; Flores-Gomez, E; Basterra-Gortari, F J; Bes-Rastrollo, M

    2014-06-01

    There is scarce evidence from long-term prospective studies relating the consumption of fried foods with the incidence of Metabolic Syndrome (MS). The aim of this study was to assess the association between fried food consumption and the incidence of MS. We followed 8289 participants (2813 men and 5476 women, mean age = 35.9 y, SD = 10.4) during a median period of 8.3-y. They were initially free of any MS criteria. MS was defined according to the American Heart Association and the International Diabetes Federation criteria as outlined in the harmonized definition for MS. Each component of the MS was assessed at the 6th and 8th-y of follow-up. The outcome was defined as the presence of ≥3 of the components of MS after ≥6 years of follow-up. During 65335 person-years, 420 incident cases of MS were identified. Frequent consumption of fried foods was not associated with the incidence of MS [HR = 0.98 (95% CI: 0.77-1.26) p for trend = 0.862]. However, two components of the MS, central adiposity and high blood pressure were positively associated with fried food consumption [HR for consumption >4 times/week compared with ≤2 times/week = 1.10 (95% CI: 1.01-1.19) (p for trend 0.022) and HR = 1.16 (95% CI: 1.02-1.32) (p for trend 0.011), respectively] after multivariable adjustment. In this Mediterranean cohort of relatively young adults, frequent consumption of fried foods was not associated with MS. Two out of five components of MS (central adiposity and high blood pressure) were positively associated with frequent fried food consumption. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  7. Dietary indexes, food patterns and incidence of metabolic syndrome in a Mediterranean cohort: The SUN project

    PubMed Central

    Pimenta, Adriano M.; Toledo, Estefanía; Rodriguez-Diez, Maria C.; Gea, Alfredo; Lopez-Iracheta, Roberto; Shivappa, Nitin; Hébert, James R.; Martinez-Gonzalez, Miguel A.

    2016-01-01

    SUMMARY Background & aims We prospectively assessed the association between adherence to several a priori defined healthy food patterns and risk of metabolic syndrome (MetS). Methods We assessed 6851 participants of a Spanish dynamic prospective cohort of university graduates, initially free of any MetS-specific definition criteria, and followed-up for a median of 8.3 years. We calculated the adherence to thirteen different a priori defined food patterns or dietary indexes. MetS was classified according to the updated harmonizing criteria. We estimated multivariable-adjusted Incidence Rate Ratios (IRR) of metabolic syndrome and their 95% Confidence Intervals (95% CI), using Poisson regression models. Results The cumulative incidence of MetS was 5.0%. Moderate adherence to the Pro-Vegetarian Diet (PVEG) was significantly associated with a lower risk for developing MetS (IRR = 0.75, 95% CI = 0.59–0.97). Among women, an inverse association with the PVEG was significant not only for a moderate adherence (IRR = 0.54, 95% CI = 0.36–0.82), but also for higher adherence (IRR = 0.63, 95% CI = 0.43 –0.93). A higher adherence to the Dietary Approaches to Stop Hypertension (DASH) diet showed an inverse association with the MetS among participants, but only if they had low alcohol intake (RR = 0.41, 95% CI = 0.20–0.85). Conclusions Our findings support the adoption of a PVEG dietary pattern for the reduction of MetS risk. The same statement can be applied in relation to the DASH diet, insofar a limited consumption of alcoholic beverages is also maintained. PMID:24975512

  8. Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.

    PubMed

    Kelsen, Judith; Bittinger, Kyle; Pauly-Hubbard, Helen; Posivak, Leah; Grunberg, Stephanie; Baldassano, Robert; Lewis, James D; Wu, Gary D; Bushman, Frederic D

    2015-12-01

    Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric patients with CD initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. Pediatric patients with CD were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodulators, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). Most subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared with healthy controls after 8 weeks of therapy. Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance.

  9. Fatigue in Parkinson's disease: The contribution of cerebral metabolic changes.

    PubMed

    Cho, Sang Soo; Aminian, Kelly; Li, Crystal; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

    2017-01-01

    Fatigue is a common and disabling non-motor symptom in Parkinson's disease associated with a feeling of overwhelming lack of energy. The aim of this study was to identify the neural substrates that may contribute to the development of fatigue in Parkinson's disease. Twenty-three Parkinson's disease patients meeting UK Brain Bank criteria for the diagnosis of idiopathic Parkinson's disease were recruited and completed the 2-[(18) F]fluoro-2-deoxy-D-glucose (FDG)-PET scan. The metabolic activities of Parkinson's disease patients with fatigue were compared to those without fatigue using statistical parametric mapping analysis. The Parkinson's disease group exhibiting higher level of fatigue showed anti-correlated metabolic changes in cortical regions associated with the salience (i.e., right insular region) and default (i.e., bilateral posterior cingulate cortex) networks. The metabolic abnormalities detected in these brain regions displayed a significant correlation with level of fatigue and were associated with a disruption of the functional correlations with different cortical areas. These observations suggest that fatigue in Parkinson's disease may be the expression of metabolic abnormalities and impaired functional interactions between brain regions linked to the salience network and other neural networks. Hum Brain Mapp 38:283-292, 2017. © 2016 Wiley Periodicals, Inc.

  10. Non alcoholic fatty liver disease and metabolic syndrome

    PubMed Central

    Paschos, P; Paletas, K

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seems to have common pathophysiological mechanisms, with focus on insulin resistance as a key factor. This review summarizes the current knowledge on the epidemiology, pathophysiology and diagnosis of both NAFLD and metabolic syndrome and the findings that strongly support the association of nonalcoholic fatty liver disease as a possible component in the cluster of metabolic syndrome. PMID:19240815

  11. Vitamin-dependent methionine metabolism and alcoholic liver disease.

    PubMed

    Halsted, Charles H; Medici, Valentina

    2011-09-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencies in ALD and how they interact with chronic ethanol exposure to alter hepatic methionine metabolism. Subsequent sections focus on molecular mechanisms for the interactions of aberrant methionine metabolism with ethanol in the pathogenesis of ALD, in particular the role of S-adenosylmethionine (SAM) in regulating the epigenetic expressions of genes relevant to pathways of liver injury. The review will conclude with descriptions of studies on the efficacy of SAM in the treatment of ALD and with discussion of potentially fruitful future avenues of research.

  12. Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease1

    PubMed Central

    Halsted, Charles H.; Medici, Valentina

    2011-01-01

    Emerging evidence indicates that ethanol-induced alterations in hepatic methionine metabolism play a central role in the pathogenesis of alcoholic liver disease (ALD). Because malnutrition is a universal clinical finding in this disease and hepatic methionine metabolism is dependent upon dietary folate and vitamins B-6 and B-12, ALD can be considered an induced nutritional disorder that is conditioned by alcohol abuse. The present review describes the etiologies of these 3 vitamin deficiencies in ALD and how they interact with chronic ethanol exposure to alter hepatic methionine metabolism. Subsequent sections focus on molecular mechanisms for the interactions of aberrant methionine metabolism with ethanol in the pathogenesis of ALD, in particular the role of S-adenosylmethionine (SAM) in regulating the epigenetic expressions of genes relevant to pathways of liver injury. The review will conclude with descriptions of studies on the efficacy of SAM in the treatment of ALD and with discussion of potentially fruitful future avenues of research. PMID:22332083

  13. Antecedent ADHD, dementia, and metabolic dysregulation: A U.S. based cohort analysis.

    PubMed

    Fluegge, Keith; Fluegge, Kyle

    2017-08-12

    Epidemiological and genetic studies have reported a link between antecedent ADHD and dementia. The underpinning mechanisms of these associations are not known and have generated considerable speculation. We have extracted hospitalization discharge data on dementia and ADHD (representing a severe phenotype) from the Healthcare Cost and Utilization Project (HCUPnet) and utilized a Poisson regression with two-ways fixed effects to investigate this association. An unadjusted ten-year lagged measure of a severe ADHD phenotype increases hospitalization risk for an all-listed Lewy Body Dementia (LBD) diagnosis (IRR: 1.21, 95% C.I. 1.08-1.35) and Alzheimer's disease (AD) discharge diagnosis (IRR: 1.15, 95% C.I.: 1.05-1.27). However, these relationships may be dependent upon the extent of metabolic dysregulation in a subtype-specific manner, as controlling for diabetes removes the significant association between antecedent ADHD and risk of AD but not LBD. These results indicate that the association between antecedent ADHD and dementia risk may be uniquely influenced by metabolic dysregulation, building upon prior discussion in this journal of a purported link between AD and diabetes. We tie the current findings to environmental risk factors that we have previously implicated in the etiology of ADHD to generate testable hypotheses on the underlying brain neurochemistry that may facilitate the link between metabolic dysregulation and dementia subtype risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort.

    PubMed

    Org, Elin; Blum, Yuna; Kasela, Silva; Mehrabian, Margarete; Kuusisto, Johanna; Kangas, Antti J; Soininen, Pasi; Wang, Zeneng; Ala-Korpela, Mika; Hazen, Stanley L; Laakso, Markku; Lusis, Aldons J

    2017-04-13

    The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships.

  15. [Magnesium disorder in metabolic bone diseases].

    PubMed

    Ishii, Akira; Imanishi, Yasuo

    2012-08-01

    Magnesium is abundantly distributed among the body. The half of the magnesium exists in the bone. In addition, magnesium is the second most abundant intracellular cation in vertebrates and essential for maintaining physiological function of the cells. Epidemiologic studies have demonstrated that magnesium deficiency is a risk factor for osteoporosis. The mechanism of bone fragility caused by magnesium deficiency has been intensely studied using animal models of magnesium deficiency. Magnesium deficiency causes decreased osteoblastic function and increased number of osteoclasts. Magnesium deficiency also accelerates mineralization in bone. These observations suggest that disturbed bone metabolic turnover and mineralization causes bone fragility.

  16. Patients with celiac disease have a lower prevalence of non-insulin-dependent diabetes mellitus and metabolic syndrome.

    PubMed

    Kabbani, Toufic A; Kelly, Ciaran P; Betensky, Rebecca A; Hansen, Joshua; Pallav, Kumar; Villafuerte-Gálvez, Javier A; Vanga, Rohini; Mukherjee, Rupa; Novero, Aileen; Dennis, Melinda; Leffler, Daniel A

    2013-05-01

    We investigated whether risk for non-insulin-dependent diabetes mellitus (NIDDM) and metabolic syndrome are affected by celiac disease. We examined the prevalence of NIDDM and metabolic syndrome among adults with celiac disease, compared with matched controls. We assessed medical records of 840 patients with biopsy-proven celiac disease for diagnoses of NIDDM, hypertension, or hyperlipidemia; body mass index (BMI); lipid profile; and levels of glucose or glycosylated hemoglobin, to identify those with metabolic syndrome. Patients without celiac disease were matched for age, sex, and ethnicity (n = 840 controls). The prevalence of NIDDM and metabolic syndrome in the celiac disease cohort was compared with that of the controls and subjects included in the National Health and Nutrition Examination Survey. Twenty-six patients with celiac disease (3.1%) had NIDDM compared with 81 controls (9.6%) (P < .0001). Similarly, the prevalence of metabolic syndrome was significantly lower among patients with celiac disease than controls (3.5% vs 12.7%; P < .0001). The mean BMI of patients with celiac disease was significantly lower than that of controls (24.7 vs 27.5; P < .0001). However, celiac disease was still associated with a lower risk of NIDDM, after controlling for BMI. The prevalence of NIDDM and metabolic syndrome are lower among patients with celiac disease than in matched controls and the general population. These differences are not explained by differences in BMI. Studies are needed to determine the mechanisms by which celiac disease affects the risk for NIDDM and metabolic syndrome. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1

    PubMed Central

    Zietek, Tamara; Rath, Eva

    2016-01-01

    Chronic diseases, such as obesity and diabetes, cardiovascular, and inflammatory bowel diseases (IBD) share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways, such as the unfolded protein response (UPR), alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular, the L-cell-derived incretin hormone glucagon-like peptide 1 (GLP-1) has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D). Yet, accumulating data indicate a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment, including the microbiota via receptors and transporters. Subsequently, mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling. This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity, and disease. PMID:27148273

  18. Longitudinal assessment of neuroimaging and clinical markers in autosomal dominant Alzheimer's disease: a prospective cohort study.

    PubMed

    Yau, Wai-Ying Wendy; Tudorascu, Dana L; McDade, Eric M; Ikonomovic, Snezana; James, Jeffrey A; Minhas, Davneet; Mowrey, Wenzhu; Sheu, Lei K; Snitz, Beth E; Weissfeld, Lisa; Gianaros, Peter J; Aizenstein, Howard J; Price, Julie C; Mathis, Chester A; Lopez, Oscar L; Klunk, William E

    2015-08-01

    The biomarker model of Alzheimer's disease postulates a dynamic sequence of amyloidosis, neurodegeneration, and cognitive decline as an individual progresses from preclinical Alzheimer's disease to dementia. Despite supportive evidence from cross-sectional studies, verification with long-term within-individual data is needed. For this prospective cohort study, carriers of autosomal dominant Alzheimer's disease mutations (aged ≥21 years) were recruited from across the USA through referrals by physicians or from affected families. People with mutations in PSEN1, PSEN2, or APP were assessed at the University of Pittsburgh Alzheimer's Disease Research Center every 1-2 years, between March 23, 2003, and Aug 1, 2014. We measured global cerebral amyloid β (Aβ) load using (11)C-Pittsburgh Compound-B PET, posterior cortical metabolism with (18)F-fluorodeoxyglucose PET, hippocampal volume (age and sex corrected) with T1-weighted MRI, verbal memory with the ten-item Consortium to Establish a Registry for Alzheimer's Disease Word List Learning Delayed Recall Test, and general cognition with the Mini Mental State Examination. We estimated overall biomarker trajectories across estimated years from symptom onset using linear mixed models, and compared these estimates with cross-sectional data from cognitively normal control individuals (age 65-89 years) who were negative for amyloidosis, hypometabolism, and hippocampal atrophy. In the mutation carriers who had the longest follow-up, we examined the within-individual progression of amyloidosis, metabolism, hippocampal volume, and cognition to identify progressive within-individual changes (a significant change was defined as an increase or decrease of more than two Z scores standardised to controls). 16 people with mutations in PSEN1, PSEN2, or APP, aged 28-56 years, completed between two and eight assessments (a total of 83 assessments) over 2-11 years. Significant differences in mutation carriers compared with controls (p<0

  19. Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

    PubMed Central

    Wang, Hansong; Park, Sungshim L.; Stram, Daniel O.; Haiman, Christopher A.; Wilkens, Lynne R.; Hecht, Stephen S.; Kolonel, Laurence N.; Murphy, Sharon E.; Le Marchand, Loïc

    2015-01-01

    Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10−6) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10−7, smallest P = 1.5 × 10−9), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. PMID:26568573

  20. Metabolic Vulnerability in the Neurodegenerative Disease Glaucoma

    PubMed Central

    Inman, Denise M.; Harun-Or-Rashid, Mohammad

    2017-01-01

    Axons can be several orders of magnitude longer than neural somas, presenting logistical difficulties in cargo trafficking and structural maintenance. Keeping the axon compartment well supplied with energy also presents a considerable challenge; even seemingly subtle modifications of metabolism can result in functional deficits and degeneration. Axons require a great deal of energy, up to 70% of all energy used by a neuron, just to maintain the resting membrane potential. Axonal energy, in the form of ATP, is generated primarily through oxidative phosphorylation in the mitochondria. In addition, glial cells contribute metabolic intermediates to axons at moments of high activity or according to need. Recent evidence suggests energy disruption is an early contributor to pathology in a wide variety of neurodegenerative disorders characterized by axonopathy. However, the degree to which the energy disruption is intrinsic to the axon vs. associated glia is not clear. This paper will review the role of energy availability and utilization in axon degeneration in glaucoma, a chronic axonopathy of the retinal projection. PMID:28424571

  1. Postpartum metabolic control in a cohort of women with type 1 diabetes.

    PubMed

    Quirós, Carmen; Patrascioiu, Ioana; Perea, Verónica; Bellart, Jordi; Conget, Ignacio; Vinagre, Irene

    2015-03-01

    Pregnancy in women with type 1 diabetes (T1D) involves greater risks as compared to non-diabetic women, but less information is available about blood glucose and weight control after delivery. Our aim was to evaluate the postpartum metabolic profile (blood glucose and weight control) of women with T1D and the factors related to those metabolic outcomes. A retrospective, observational study of 36 women with T1D during pregnancy and for up to one year after delivery. Fifty percent of patients attended a preconceptional planning program (PPP), and 44.4% of women were treated with continuous subcutaneous insulin infusion. Mean preconceptional HbA1c and body mass index (BMI) were 7.2±1.2% and 23.8±5.0 respectively. In the total cohort, blood glucose control significantly worsened one year after delivery (HbA1c: 7.2±1.2 vs 7.6±1.2%, P<0.001). Lower preconceptional HbA1c values were found in patients who attended PPP (6.6±0.5 vs. 7.8±1.4%; P=0.02), and were maintained for one year after delivery. No differences were found in body mass index (BMI) from the pregestational period to one year after delivery in any of two groups (No PPP 22.5±4.6 vs 23.2±4.8, P=0.078; PPP 25.4±3.4 vs 25.5±3.4 kg/m(2), P=0.947). Preconceptional HbA1c was shown to be the most important determinant of metabolic control (β=0.962, p<0.001) and weight one year after delivery (β=0.524, p=0.025) and weight gain during pregnancy (β=0.633, p=0.004). Pregnant women with T1D return to prepregnancy body weight one year after delivery, especially those with lower HbA1c levels and BMI before pregnancy. However, blood glucose control deteriorates after delivery, suggesting the need for changes in clinical practice after delivery. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  2. Gut microbiota drives metabolic disease in immunologically altered mice.

    PubMed

    Chassaing, Benoit; Aitken, Jesse D; Gewirtz, Andrew T; Vijay-Kumar, Matam

    2012-01-01

    The mammalian intestine harbors trillions of microbes collectively known as the microbiota, which can be viewed as an anaerobic metabolic organ that benefits the host in a number of ways. The homeostasis of this large microbial biomass is a prerequisite to maintaining host health by maximizing symbiotic interrelations and minimizing the risk of living in a close relationship. The cooperation between the innate and adaptive immune systems of the host maintains homeostasis of the microbiota. The dysregulation/alteration of microbiota in various immunodeficiency states including both innate and adaptive deficiency results in metabolic disease. This review examines the influence of microbiota on host metabolic health in immunologically altered mice. Accumulated data from a variety of immune-deficient murine models indicate that altered microbiota can play a key role in origination of metabolic diseases through the following potential mechanisms: (i) increasing calorie extraction resulting in adiposity, (ii) inducing low-grade chronic inflammation in the gut directly or increasing systemic loads of microbial ligands via leaky guts, (iii) generating toxic metabolites from dietary components, and (iv) inducing a switch from pro-metabolic to pro-immune phenotype that drives malabsorption of lipids resulting in muscle wastage and weight loss-particularly upon states of adaptive immune deficiency. Further, these murine models demonstrate that altered microbiota is not purely a consequence of metabolic disease but plays a key role in driving this disorder.

  3. Modulators of nucleoside metabolism in the therapy of brain diseases.

    PubMed

    Boison, Detlev

    2011-01-01

    Nucleoside receptors are known to be important targets for a variety of brain diseases. However, the therapeutic modulation of their endogenous agonists by inhibitors of nucleoside metabolism represents an alternative therapeutic strategy that has gained increasing attention in recent years. Deficiency in endogenous nucleosides, in particular of adenosine, may causally be linked to a variety of neurological diseases and neuropsychiatric conditions ranging from epilepsy and chronic pain to schizophrenia. Consequently, augmentation of nucleoside function by inhibiting their metabolism appears to be a rational therapeutic strategy with distinct advantages: (i) in contrast to specific receptor modulation, the increase (or decrease) of the amount of a nucleoside will affect several signal transduction pathways simultaneously and therefore have the unique potential to modify complex neurochemical networks; (ii) by acting on the network level, inhibitors of nucleoside metabolism are highly suited to fine-tune, restore, or amplify physiological functions of nucleosides; (iii) therefore inhibitors of nucleoside metabolism have promise for the "soft and smart" therapy of neurological diseases with the added advantage of reduced systemic side effects. This review will first highlight the role of nucleoside function and dysfunction in physiological and pathophysiological situations with a particular emphasis on the anticonvulsant, neuroprotective, and antinociceptive roles of adenosine. The second part of this review will cover pharmacological approaches to use inhibitors of nucleoside metabolism, with a special emphasis on adenosine kinase, the key regulator of endogenous adenosine. Finally, novel gene-based therapeutic strategies to inhibit nucleoside metabolism and focal treatment approaches will be discussed.

  4. Modulators of Nucleoside Metabolism in the Therapy of Brain Diseases

    PubMed Central

    Boison, Detlev

    2010-01-01

    Nucleoside receptors are known to be important targets for a variety of brain diseases. However, the therapeutic modulation of their endogenous agonists by inhibitors of nucleoside metabolism represents an alternative therapeutic strategy that has gained increasing attention in recent years. Deficiency in endogenous nucleosides, in particular of adenosine, may causally be linked to a variety of neurological diseases and neuropsychiatric conditions ranging from epilepsy and chronic pain to schizophrenia. Consequently, augmentation of nucleoside function by inhibiting their metabolism appears to be a rational therapeutic strategy with distinct advantages: (i) in contrast to specific receptor modulation, the increase (or decrease) of the amount of a nucleoside will affect several signal transduction pathways simultaneously and therefore have the unique potential to modify complex neurochemical networks; (ii) by acting on the network level, inhibitors of nucleoside metabolism are highly suited to fine-tune, restore, or amplify physiological functions of nucleosides; (iii) therefore inhibitors of nucleoside metabolism have promise for the “soft and smart” therapy of neurological diseases with the added advantage of reduced systemic side effects. This review will first highlight the role of nucleoside function and dysfunction in physiological and pathophysiological situations with a particular emphasis on the anticonvulsant, neuroprotective, and antinociceptive roles of adenosine. The second part of this review will cover pharmacological approaches to use inhibitors of nucleoside metabolism, with a special emphasis on adenosine kinase, the key regulator of endogenous adenosine. Finally, novel gene-based therapeutic strategies to inhibit nucleoside metabolism and focal treatment approaches will be discussed. PMID:21401494

  5. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease.

    PubMed

    Han, Thang S; Lean, Mike Ej

    2016-01-01

    The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30-40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5-10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35-40 kg/m(2) with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists.

  6. A clinical perspective of obesity, metabolic syndrome and cardiovascular disease

    PubMed Central

    Lean, Mike EJ

    2016-01-01

    The metabolic syndrome is a condition characterized by a special constellation of reversible major risk factors for cardiovascular disease and type 2 diabetes. The main, diagnostic, components are reduced HDL-cholesterol, raised triglycerides, blood pressure and fasting plasma glucose, all of which are related to weight gain, specifically intra-abdominal/ectopic fat accumulation and a large waist circumference. Using internationally adopted arbitrary cut-off values for waist circumference, having metabolic syndrome doubles the risk of cardiovascular disease, but offers an effective treatment approach through weight management. Metabolic syndrome now affects 30–40% of people by age 65, driven mainly by adult weight gain, and by a genetic or epigenetic predisposition to intra-abdominal/ectopic fat accumulation related to poor intra-uterine growth. Metabolic syndrome is also promoted by a lack of subcutaneous adipose tissue, low skeletal muscle mass and anti-retroviral drugs. Reducing weight by 5–10%, by diet and exercise, with or without, anti-obesity drugs, substantially lowers all metabolic syndrome components, and risk of type 2 diabetes and cardiovascular disease. Other cardiovascular disease risk factors such as smoking should be corrected as a priority. Anti-diabetic agents which improve insulin resistance and reduce blood pressure, lipids and weight should be preferred for diabetic patients with metabolic syndrome. Bariatric surgery offers an alternative treatment for those with BMI ≥ 40 or 35–40 kg/m2 with other significant co-morbidity. The prevalence of the metabolic syndrome and cardiovascular disease is expected to rise along with the global obesity epidemic: greater emphasis should be given to effective early weight-management to reduce risk in pre-symptomatic individuals with large waists. PMID:26998259

  7. Mortality in patients with diabetes mellitus and Addison's disease: a nationwide, matched, observational cohort study.

    PubMed

    Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Bergthorsdottir, Ragnhildur; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Johannsson, Gudmundur

    2017-01-01

    Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD). Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model. Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes. Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed. © 2017 European Society of Endocrinology.

  8. Performance of the disease risk score in a cohort study with policy-induced selection bias.

    PubMed

    Tadrous, Mina; Mamdani, Muhammad M; Juurlink, David N; Krahn, Murray D; Lévesque, Linda E; Cadarette, Suzanne M

    2015-11-01

    To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

  9. Mesenchymal stem cells for bone repair and metabolic bone diseases.

    PubMed

    Undale, Anita H; Westendorf, Jennifer J; Yaszemski, Michael J; Khosla, Sundeep

    2009-10-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases.

  10. [Application of precision medicine in obesity and metabolic disease surgery].

    PubMed

    Wang, Cunchuan; Gao, Zhiguang

    2016-01-01

    The U. S. A. president Obama called for a new initiative to fund precision medicine during his State of Union Address on January 20th, 2015, which meant that the human medicine enters a new era. The meaning of "precision medicine" is significantly similar to the concept of precision obesity and metabolic disease surgery, which was proposed by the author in early August 2011. Nowadays, obesity and metabolic disease surgery has been transformed from open surgery to laparoscopic surgery, the extensive mode to the precision mode. The key value concept is to minimize postoperative complication, minimize postoperative hospital stay and obtain the best effect of weight loss by accurate preoperative assessment, delicate operation, excellent postoperative management and scientific follow-up. The precision obesity and metabolic disease surgery has more development space in the future.

  11. Mesenchymal Stem Cells for Bone Repair and Metabolic Bone Diseases

    PubMed Central

    Undale, Anita H.; Westendorf, Jennifer J.; Yaszemski, Michael J.; Khosla, Sundeep

    2009-01-01

    Human mesenchymal stem cells offer a potential alternative to embryonic stem cells in clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues, including bone, cartilage, fat, and other tissues of mesenchymal origin, makes them an attractive candidate for clinical applications. Patients who experience fracture nonunion and metabolic bone diseases, such as osteogenesis imperfecta and hypophosphatasia, have benefited from human mesenchymal stem cell therapy. Because of their ability to modulate immune responses, allogeneic transplant of these cells may be feasible without a substantial risk of immune rejection. The field of regenerative medicine is still facing considerable challenges; however, with the progress achieved thus far, the promise of stem cell therapy as a viable option for fracture nonunion and metabolic bone diseases is closer to reality. In this review, we update the biology and clinical applicability of human mesenchymal stem cells for bone repair and metabolic bone diseases. PMID:19797778

  12. Role of Autophagy in Metabolic Syndrome-Associated Heart Disease

    PubMed Central

    Ren, Sidney Y.; Xu, Xihui

    2014-01-01

    Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including abdominal obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Over the past decades, the prevalence of metabolic syndrome has increased dramatically, imposing a devastating, pandemic health threat. More importantly, individuals with metabolic syndrome are at an increased risk of diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of metabolic syndrome is heart anomalies leading to the loss of cardiomyocytes, cardiac dysfunction and ultimately heart failure. Up-to-date, a plethora cell signaling pathways have been postulated for the pathogenesis of cardiac complications in obesity including lipotoxicity, inflammation, oxidative stress, apoptosis and sympathetic overactivation although the precise mechanism of action underscoring obesity-associated heart dysfunction remains elusive. Recent evidence has indicated a potential role of protein quality control in components of metabolic syndrome. Within the protein quality control system, the autophagy-lysosome pathway is an evolutionarily conserved pathway responsible for bulk degradation of large intracellular organelles and protein aggregates. Autophagy has been demonstrated to play an indispensible role in the maintenance of cardiac geometry and function under both physiological and pathological conditions. Accumulating studies have demonstrated that autophagy plays a pivotal role in the etiology of cardiac anomalies under obesity and metabolic syndrome. In this mini review, we will discuss on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome. PMID:24810277

  13. Irregular eating of meals in adolescence and the metabolic syndrome in adulthood: results from a 27-year prospective cohort.

    PubMed

    Wennberg, Maria; Gustafsson, Per E; Wennberg, Patrik; Hammarström, Anne

    2016-03-01

    The objective was to investigate whether irregular eating of meals in adolescence predicts the metabolic syndrome and its components in adulthood, and if any specific meal is of particular importance. Prospective cohort study with 27 years of follow-up. Information on meals (breakfast, school lunch and dinner with family), lifestyle (alcohol consumption, smoking habits, physical activity, consumption of sweets and pastries) at age 16 years was assessed from questionnaires, and presence or not of the metabolic syndrome and its components were defined at age 43 years in 889 participants (82·1% of total cohort). Logistic regression was used to calculate odds ratios and confidence intervals. The Northern Swedish Cohort; all school-leavers of the 9th grade in the town Luleå in 1981. Adolescents (age 16 years). Irregular eating of meals at age 16 years was associated with higher prevalence of the metabolic syndrome at age 43 years (OR=1·74; 95% CI 1·12, 2·71), but this was explained by concurrent unhealthy lifestyle at age 16 years. Poor breakfast at age 16 years was the only meal associated with the metabolic syndrome at age 43 years, independent of other meals, BMI (kg/m2) and lifestyle at age 16 years (OR=1·67; 95% CI 1·00, 2·80). Irregular eating of meals in adolescence predicted the metabolic syndrome in adulthood, but not independently of BMI and lifestyle in adolescence. Poor breakfast in adolescence was the only specific meal associated with future metabolic syndrome, even after adjustments. Breakfast eating should be encouraged in adolescence.

  14. Potential of AAV vectors in the treatment of metabolic disease.

    PubMed

    Alexander, I E; Cunningham, S C; Logan, G J; Christodoulou, J

    2008-06-01

    Inborn errors of metabolism are collectively common, frequently severe and in many instances difficult or impossible to treat. Accordingly, there is a compelling need to explore novel therapeutic modalities, including gene therapy, and examine multiple phenotypes where the risks of experimental therapy are outweighed by potential benefits to trial participants. Among available gene delivery systems recombinant AAV shows special promise for the treatment of metabolic disease given the unprecedented efficiencies achieved in transducing key target tissues, such as liver and muscle, in small animal models. To date over 30 metabolic disease phenotypes have been investigated in small animal studies with complete phenotype correction being achieved in a substantial proportion. Achieving adequately widespread transduction within the central nervous system, however, remains a major challenge, and will be critical to realization of the therapeutic potential of gene therapy for many of the most clinically troubling metabolic disease phenotypes. Despite the relatively low immunogenicity of AAV vectors, immune responses are also emerging as a factor requiring special attention as efforts accelerate toward human clinical translation. Four metabolic disease phenotypes have reached phase I or I/II trials with one, targeting lipoprotein lipase deficiency, showing exciting early evidence of efficacy.

  15. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  16. NAD+ metabolism in health and disease.

    PubMed

    Belenky, Peter; Bogan, Katrina L; Brenner, Charles

    2007-01-01

    Nicotinamide adenine dinucleotide (NAD(+)) is both a coenzyme for hydride-transfer enzymes and a substrate for NAD(+)-consuming enzymes, which include ADP-ribose transferases, poly(ADP-ribose) polymerases, cADP-ribose synthases and sirtuins. Recent results establish protective roles for NAD(+) that might be applicable therapeutically to prevent neurodegenerative conditions and to fight Candida glabrata infection. In addition, the contribution that NAD(+) metabolism makes to lifespan extension in model systems indicates that therapies to boost NAD(+) might promote some of the beneficial effects of calorie restriction. Nicotinamide riboside, the recently discovered nucleoside precursor of NAD(+) in eukaryotic systems, might have advantages as a therapy to elevate NAD(+) without inhibiting sirtuins, which is associated with high-dose nicotinamide, or incurring the unpleasant side-effects of high-dose nicotinic acid.

  17. Cardiovascular disease in immune-mediated inflammatory diseases: A cross-sectional analysis of 6 cohorts.

    PubMed

    Fernández-Gutiérrez, Benjamín; Perrotti, Pedro P; Gisbert, Javier P; Domènech, Eugeni; Fernández-Nebro, Antonio; Cañete, Juan D; Ferrándiz, Carlos; Tornero, Jesús; García-Sánchez, Valle; Panés, Julián; Fonseca, Eduardo; Blanco, Francisco; Rodríguez-Moreno, Jesús; Carreira, Patricia; Julià, Antonio; Marsal, Sara; Rodriguez-Rodriguez, Luis

    2017-06-01

    To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID, traditional cardiovascular risk factors had a different contribution to CVD. Overall, older age, longer disease duration, presence of traditional cardiovascular risk factors, and male sex were independently associated with a higher CVD prevalence. After adjusting for demographic and traditional cardiovascular risk factors, systemic lupus erythematosus exhibited the highest CVD standardized prevalence, followed by rheumatoid arthritis, psoriasis, Crohn disease, psoriatic arthritis, and ulcerative colitis (4.5 [95% confidence interval (CI): 2.2, 6.8], 1.3 [95% CI: 0.8, 1.8], 0.9 [95% CI: 0.5, 1.2], 0.8 [95% CI: 0.2, 1.3], 0.6 [95% CI: 0.2, 1.0], and 0.5 [95% CI: 0.1, 0.8], respectively).Systemic lupus erythematosus, rheumatoid arthritis, and psoriasis are associated with higher prevalence of CVD compared with other IMIDs. Specific prevention programs should be established in subjects affected with these conditions to prevent CVD.

  18. Differential serum proteomic analysis in a model of metabolic disease.

    PubMed

    Matsumura, Takayoshi; Suzuki, Toru; Kada, Nanae; Aizawa, Kenichi; Munemasa, Yoshiko; Nagai, Ryozo

    2006-12-29

    Protein profiling would aid in better understanding the pathophysiology of metabolic disease. Here, we report on differential proteomic analysis using an animal model of diabetes mellitus and associated metabolic disorders (Otsuka Long-Evans Tokushima Fatty rat). Serum was analyzed by a new two-dimensional liquid chromatography system which separated proteins by chromatofocusing and subsequent reversed-phase chromatography. This is the first application of this approach to differential serum proteomics. Differentially expressed proteins, identified with MALDI-TOF mass spectrometry, included apolipoproteins and alpha2-HS-glycoprotein. These findings add to our understanding of the underlying pathophysiology. This new proteomic analysis is a promising tool to elucidate disease mechanisms.

  19. NF-κB, inflammation, and metabolic disease.

    PubMed

    Baker, Rebecca G; Hayden, Matthew S; Ghosh, Sankar

    2011-01-05

    Metabolic disorders including obesity, type 2 diabetes, and atherosclerosis have been viewed historically as lipid storage disorders brought about by overnutrition. It is now widely appreciated that chronic low-grade inflammation plays a key role in the initiation, propagation, and development of metabolic diseases. Consistent with its central role in coordinating inflammatory responses, numerous recent studies have implicated the transcription factor NF-κB in the development of such diseases, thereby further establishing inflammation as a critical factor in their etiology and offering hope for the development of new therapeutic approaches for their treatment.

  20. Metabolic syndrome and chronic kidney disease in Okinawa, Japan.

    PubMed

    Tanaka, H; Shiohira, Y; Uezu, Y; Higa, A; Iseki, K

    2006-01-01

    We assessed the prevalence of chronic kidney disease (CKD) in a hospital-based screening program in Okinawa, Japan. The significance of metabolic syndrome as a determinant of CKD was examined using multivariate logistic regression analysis. A total of 6980 participants, aged 30-79 years, participated in a screening program in Tomishiro Chuo Hospital. Metabolic syndrome was defined according to the criteria of the Adult Treatment Panel III (ATP III). Data were also analyzed according to the modified criteria of the National Cholesterol Education Program (NCEP) that defines abdominal obesity as a waist circumference of > oe =85 cm in men and > or =90 cm in women. CKD was defined as dipstick proteinuria (> or =1+) or a reduced glomerular filtration rate (GFR). GFR was estimated using the abbreviated Modification of Diet in Renal Disease (MDRD) formula. The prevalence of metabolic syndrome and CKD was 12.8 and 13.7%, respectively. Metabolic syndrome was a significant determinant of CKD (adjusted odds ratio (OR) 1.537 and 95% confidence interval (CI) 1.277-1.850, P<0.0001). The adjusted OR (95% CI) was 1.770 (1.215-2.579, P=0.0029) for those with four metabolic syndrome risk factors compared to those with no metabolic syndrome risk factors. Metabolic syndrome was a significant determinant for younger participants (<60 years; OR 1.686, 95% CI 1.348-2.107, P<0.0001), but not for older participants (> or =60 years; OR 1.254, 95% CI 0.906-1.735, NS). The relationship between the number of metabolic syndrome risk factors and the prevalence of CKD was linear using the modified criteria. The results suggest that metabolic syndrome is a significant determinant of CKD in men under 60 years of age, in Okinawa, Japan.

  1. Mineral metabolism and cardiovascular disease in CKD.

    PubMed

    Fujii, Hideki; Joki, Nobuhiko

    2017-03-01

    The mineral bone disorder of CKD, called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD), has a major role in the etiology and progression of cardiovascular disease in CKD patients. Since the main emphasis in CKD-MBD is on three categories (bone abnormalities, laboratory abnormalities, and vascular calcifications), we have routinely accepted ectopic cardiovascular calcifications as a central risk factor in the pathophysiology of CKD-MBD for cardiac events. However, recent compelling evidence suggests that some CKD-MBD-specific factors other than vascular calcification might contribute to the onset of cardiovascular disease. Most notable is fibroblast growth factor-23 (FGF23), which is thought to be independently associated with cardiac remodeling. Slow progression of cardiac disorders, such as vascular calcification and cardiac remodeling, characterizes cardiac disease due to CKD-MBD. In contrast, fatal arrhythmia may be induced when QT prolongation occurs with CKD-MBD treatment, such as with lower Ca dialysate or the use of calcimimetics. Sudden onset of fatal cardiac events, such as heart failure and sudden cardiac death, due to fatal arrhythmia would be another distinctive phenomenon of CKD-MBD. This may be defined as CKD-MBD-specific cardiac complex syndrome.

  2. Altered cholesterol and fatty acid metabolism in Huntington disease.

    PubMed

    Block, Robert C; Dorsey, E Ray; Beck, Christopher A; Brenna, J Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease.

  3. Altered Cholesterol and Fatty Acid Metabolism in Huntington Disease

    PubMed Central

    Block, Robert C.; Dorsey, E. Ray; Beck, Christopher A.; Brenna, J. Thomas; Shoulson, Ira

    2010-01-01

    Huntington disease is an autosomal dominant neurodegenerative disorder characterized by behavioral abnormalities, cognitive decline, and involuntary movements that lead to a progressive decline in functional capacity, independence, and ultimately death. The pathophysiology of Huntington disease is linked to an expanded trinucleotide repeat of cytosine-adenine-guanine (CAG) in the IT-15 gene on chromosome 4. There is no disease-modifying treatment for Huntington disease, and novel pathophysiological insights and therapeutic strategies are needed. Lipids are vital to the health of the central nervous system, and research in animals and humans has revealed that cholesterol metabolism is disrupted in Huntington disease. This lipid dysregulation has been linked to specific actions of the mutant huntingtin on sterol regulatory element binding proteins. This results in lower cholesterol levels in affected areas of the brain with evidence that this depletion is pathologic. Huntington disease is also associated with a pattern of insulin resistance characterized by a catabolic state resulting in weight loss and a lower body mass index than individuals without Huntington disease. Insulin resistance appears to act as a metabolic stressor attending disease progression. The fish-derived omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been examined in clinical trials of Huntington disease patients. Drugs that combat the dysregulated lipid milieu in Huntington disease may help treat this perplexing and catastrophic genetic disease. PMID:20802793

  4. Validation of metabolic syndrome using medical records in the SUN cohort

    PubMed Central

    2011-01-01

    Background The objective of this study was to evaluate the validity of self reported criteria of Metabolic Syndrome (MS) in the SUN (Seguimiento Universidad de Navarra) cohort using their medical records as the gold standard. Methods We selected 336 participants and we obtained MS related data according to Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF). Then we compared information on the self reported diagnosis of MS and MS diagnosed in their medical records. We calculated the proportion of confirmed MS, the proportion of confirmed non-MS and the intraclass correlation coefficients for each component of the MS. Results From those 336 selected participants, we obtained sufficient data in 172 participants to confirm or reject MS using ATP III criteria. The proportion of confirmed MS was 91.2% (95% CI: 80.7- 97.1) and the proportion of confirmed non-MS was 92.2% (95% CI: 85.7-96.4) using ATP III criteria. The proportion of confirmed MS using IDF criteria was 100% (95% CI: 87.2-100) and the proportion of confirmed non-MS was 97.1% (95% CI: 85.1-99.9). Kappa Index was 0.82 in the group diagnosed by ATP III criteria and 0.97 in the group diagnosed by IDF criteria. Intraclass correlation coefficients for the different component of MS were: 0.93 (IC 95%:0.91- 0.95) for BMI; 0.96 (IC 95%: 0.93-0.98) for waist circumference; 0.75 (IC 95%: 0.66-0.82) for fasting glucose; 0.50 (IC 95%:0.35-0.639) for HDL cholesterol; 0.78 (IC 95%: 0.70-0.84) for triglycerides; 0.49 (IC 95%:0.34-0.61) for systolic blood pressure and 0.55 (IC 95%: 0.41-0.65) for diastolic blood pressure. Conclusions Self-reported MS based on self reported components of the SM in a Spanish cohort of university graduates was sufficiently valid as to be used in epidemiological studies. PMID:22085407

  5. Heritability of the Severity of the Metabolic Syndrome in Whites and Blacks in 3 Large Cohorts.

    PubMed

    Musani, Solomon K; Martin, Lisa J; Woo, Jessica G; Olivier, Michael; Gurka, Matthew J; DeBoer, Mark D

    2017-04-01

    Although dichotomous criteria for the metabolic syndrome (MetS) appear heritable, it is not known whether MetS severity as assessed by a continuous MetS score is heritable and whether this varies by race. We used SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate heritability of Adult Treatment Panel-III MetS and a sex- and race-specific MetS severity Z score among 3 large familial cohorts: the JHS (Jackson Heart Study, 1404 black participants), TOPS (Take Off Pounds Sensibly, 1947 white participants), and PLRS (Princeton Lipid Research Study, 229 black and 527 white participants). Heritability estimates were larger for Adult Treatment Panel-III MetS among black compared with white cohort members (JHS 0.48; 95% confidence interval [CI], 0.28-0.68 and PLRS blacks 0.93 [95% CI, 0.73-1.13] versus TOPS 0.21 [95% CI, -0.18 to 0.60] and PLRS whites 0.27 [95% CI, -0.04 to 0.58]). The difference by race narrowed when assessing heritability of the MetS severity score (JHS 0.52 [95% CI, 0.38, 0.66] and PLRS blacks 0.64 [95% CI, 0.13-1.15] versus TOPS 0.23 [95% CI, 0.15-0.31] and PLRS whites 0.60 [95% CI, 0.33-0.87]). There was a high degree of genetic and phenotypic correlation between MetS severity and the individual components of MetS among all groups, although the genetic correlations failed to reach statistical significance among PLRS blacks. Meta-analyses revealed a combined heritability estimate for Adult Treatment Panel-III MetS of 0.24 (95% CI, 0.11-0.36) and for the MetS severity score of 0.50 (95% CI, -0.05 to 0.99). MetS severity seems highly heritable among whites and blacks. This continuous MetS severity Z score may provide a more useful means of characterizing phenotypic MetS in genetic studies by minimizing racial differences. © 2017 American Heart Association, Inc.

  6. Early growth and coronary heart disease and type 2 diabetes: findings from the Helsinki Birth Cohort Study (HBCS).

    PubMed

    Eriksson, Johan G

    2011-12-01

    A slow rate of intrauterine growth is a major risk factor for several common noncommunicable diseases, which include the following: coronary heart disease (CHD), hypertension, and type 2 diabetes. Likewise, growth patterns in infancy and childhood have been identified as important factors linked to the pathogenesis of these disorders. In this overview, patterns of growth associated with CHD, type 2 diabetes, and related metabolic traits in adult life are presented on the basis of findings from the Helsinki Birth Cohort Study (HBCS) 1934-1944. Later risk of CHD was associated with small body size at birth and during infancy, followed by an increase in body size later in childhood. This pattern of growth has been associated with dyslipidemia in later life, which offers an explanation for the observed findings. Type 2 diabetes and CHD share several risk factors. The early growth of persons who later develop type 2 diabetes includes a small body size at birth as well as a small body size during infancy. An early age at adiposity rebound was associated with a markedly increased risk of type 2 diabetes in adulthood. The patterns of growth associated with type 2 diabetes are also associated with alterations in body composition, which predisposes to insulin resistance and the metabolic syndrome. The presented findings suggest that to be able to understand the pathogenesis of several noncommunicable diseases, the diseases need to be studied from a life-course perspective, and prenatal and childhood growth as well as adult characteristics need to be taken into account.

  7. Metabolic biomarkers for predicting cardiovascular disease

    PubMed Central

    Montgomery, Jana E; Brown, Jeremiah R

    2013-01-01

    Cardiac and peripheral vascular biomarkers are increasingly becoming targets of both research and clinical practice. As of 2008, cardiovascular-related medical care accounts for greater than 20% of all the economic costs of illness in the United States. In the age of burgeoning financial pressures on the entire health care system, never has it been more important to try to understand who is at risk for cardiovascular disease in order to prevent new events. In this paper, we will discuss the cost of cardiovascular disease to society, clarify the definition of and need for biomarkers, offer an example of a current biomarker, namely high-sensitivity C-reactive protein, and finally examine the approval process for utilizing these in clinical practice. PMID:23386789

  8. Coeliac disease and invasive pneumococcal disease: a population-based cohort study.

    PubMed

    Röckert Tjernberg, A; Bonnedahl, J; Inghammar, M; Egesten, A; Kahlmeter, G; Nauclér, P; Henriques-Normark, B; Ludvigsson, J F

    2017-04-01

    Severe infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05-2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99-1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

  9. Mitochondria in metabolic disease: getting clues from proteomic studies.

    PubMed

    Peinado, Juan R; Diaz-Ruiz, Alberto; Frühbeck, Gema; Malagon, Maria M

    2014-03-01

    Mitochondria play a key role as major regulators of cellular energy homeostasis, but in the context of mitochondrial dysfunction, mitochondria may generate reactive oxidative species and induce cellular apoptosis. Indeed, altered mitochondrial status has been linked to the pathogenesis of several metabolic disorders and specially disorders related to insulin resistance, such as obesity, type 2 diabetes, and other comorbidities comprising the metabolic syndrome. In the present review, we summarize information from various mitochondrial proteomic studies of insulin-sensitive tissues under different metabolic states. To that end, we first focus our attention on the pancreas, as mitochondrial malfunction has been shown to contribute to beta cell failure and impaired insulin release. Furthermore, proteomic studies of mitochondria obtained from liver, muscle, and adipose tissue are summarized, as these tissues constitute the primary insulin target metabolic tissues. Since recent advances in proteomic techniques have exposed the importance of PTMs in the development of metabolic disease, we also present information on specific PTMs that may directly affect mitochondria during the pathogenesis of metabolic disease. Specifically, mitochondrial protein acetylation, phosphorylation, and other PTMs related to oxidative damage, such as nitrosylation and carbonylation, are discussed.

  10. Endoplasmic reticulum-mitochondria calcium signaling in hepatic metabolic diseases.

    PubMed

    Rieusset, Jennifer

    2017-06-01

    The liver plays a central role in glucose homeostasis, and both metabolic inflexibility and insulin resistance predispose to the development of hepatic metabolic diseases. Mitochondria and endoplasmic reticulum (ER), which play a key role in the control of hepatic metabolism, also interact at contact points defined as mitochondria-associated membranes (MAM), in order to exchange metabolites and calcium (Ca(2+)) and regulate cellular homeostasis and signaling. Here, we overview the role of the liver in the control of glucose homeostasis, mainly focusing on the independent involvement of mitochondria, ER and Ca(2+) signaling in both healthy and pathological contexts. Then we focus on recent data highlighting MAM as important hubs for hormone and nutrient signaling in the liver, thus adapting mitochondria physiology and cellular metabolism to energy availability. Lastly, we discuss how chronic ER-mitochondria miscommunication could participate to hepatic metabolic diseases, pointing MAM interface as a potential therapeutic target for metabolic disorders. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Metabolism

    MedlinePlus

    ... symptoms. Metabolic diseases and conditions include: Hyperthyroidism (pronounced: hi-per-THIGH-roy-dih-zum). Hyperthyroidism is caused ... or through surgery or radiation treatments. Hypothyroidism (pronounced: hi-po-THIGH-roy-dih-zum). Hypothyroidism is caused ...

  12. The Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases: Study Design and Baseline Characteristics

    PubMed Central

    Feng, Rennan; Li, Jie; Han, Tianshu; Lin, Liqun; Lan, Li; Yang, Chao; Li, Ying; Sun, Changhao

    2015-01-01

    Diet and nutrition have been reported to be associated with many common chronic diseases and blood-based assessment would be vital to investigate the association and mechanism, however, blood-based prospective studies are limited. The Harbin Cohort Study on Diet, Nutrition and Chronic Non-communicable Diseases was set up in 2010. From 2010 to 2012, 9,734 participants completed the baseline survey, including demographic characteristics, dietary intake, lifestyles and physical condition, and anthropometrics. A re-survey on 490 randomly selected participants was done by using the same methods which were employed in the baseline survey. For all participants, the mean age was 50 years and 36% of them were men. Approximately 99.4 % of cohort members donated blood samples. The mean total energy intake was 2671.7 kcal/day in men and 2245.9 kcal/day in women, the mean body mass index was 25.7 kg/m2 in men and 24.6 kg/m2 in women, with 18.4% being obese (≥28 kg/m2), 12.7% being diabetic, and 29.5% being hypertensive. A good agreement was obtained for the physical measurements between the baseline survey and re-survey. The resources from the cohort and its fasting and postprandial blood samples collected both at baseline and in each follow-up will be valuable and powerful in investigating relationship between diet, nutrition and chronic diseases and discovering novel blood biomarkers and the metabolism of these biomarkers related to chronic diseases. PMID:25856294

  13. Drug metabolism alterations in nonalcoholic fatty liver disease

    PubMed Central

    Merrell, Matthew D.; Cherrington, Nathan J.

    2013-01-01

    Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. PMID:21612324

  14. [Review on periodontal disease and metabolic control of diabetes mellitus].

    PubMed

    Steffens, João Paulo; Glaci Reinke, Stella Maria; Angel Muñoz, Miguel; Santos, Fábio André dos; Luiz Pilatti, Gibson

    2010-09-01

    There may be an interaction between periodontal disease and some systemic diseases such as diabetes mellitus. The objective of this review was to verify, by means of a review of clinical trials, if there is a positive association between periodontal disease and the glycemic control of type 2 diabetes mellitus (DM-2) patients. Eleven articles that fi t the study criteria were revised. It was concluded that periodontal disease may influence the metabolic control of DM-2. Additional studies with larger sample sizes and longer follow up are necessary for a better clarification of this issue.

  15. Sasang constitutional types for the risk prediction of metabolic syndrome: a 14-year longitudinal prospective cohort study.

    PubMed

    Lee, Sunghee; Lee, Seung Ku; Kim, Jong Yeol; Cho, Namhan; Shin, Chol

    2017-09-02

    To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.

  16. Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort.

    PubMed

    Dallal, Cher M; Lacey, James V; Pfeiffer, Ruth M; Bauer, Douglas C; Falk, Roni T; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea Z; Tice, Jeffrey A; Veenstra, Timothy D; Xu, Xia; Brinton, Louise A

    2016-02-01

    Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4

  17. Combined Effects of Smoking and Alcohol on Metabolic Syndrome: The LifeLines Cohort Study

    PubMed Central

    Slagter, Sandra N.; van Vliet-Ostaptchouk, Jana V.; Vonk, Judith M.; Boezen, H. Marieke; Dullaart, Robin P. F.; Kobold, Anneke C. Muller.; Feskens, Edith J. M.; van Beek, André P.; van der Klauw, Melanie M.; Wolffenbuttel, Bruce H.R.

    2014-01-01

    Introduction The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its individual components. Methods 64,046 participants aged 18–80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25–30, overweight; BMI≥30 kg/m2, obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis. Results Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7–71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks. Conclusion Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS. PMID:24781037

  18. Brain glucose metabolism: Role of Wnt signaling in the metabolic impairment in Alzheimer's disease.

    PubMed

    Cisternas, Pedro; Inestrosa, Nibaldo C

    2017-06-15

    The brain is an organ that has a high demand for glucose. In the brain, glucose is predominantly used in energy production, with almost 70% of the energy used by neurons. The importance of the energy requirement in neurons is clearly demonstrated by the fact that all neurodegenerative disorders exhibit a critical metabolic impairment that includes decreased glucose uptake/utilization and decreased mitochondrial activity, with a consequent diminution in ATP production. In fact, in Alzheimer's disease, the measurement of the general metabolic rate of the brain has been reported to be an accurate tool for diagnosis. Additionally, the administration of metabolic activators such as insulin/glucagon-like peptide 1 can improve memory/learning performance. Despite the importance of energy metabolism in the brain, little is known about the cellular pathways involved in the regulation of this process. Several reports postulate a role for Wnt signaling as a general metabolic regulator. Thus, in the present review, we discuss the antecedents that support the relationship between Wnt signaling and energy metabolism in the Alzheimer's disease. Copyright © 2017. Published by Elsevier Ltd.

  19. Endocrine and metabolic manifestations in inflammatory bowel disease.

    PubMed

    Tigas, Stelios; Tsatsoulis, Agathocles

    2012-01-01

    Extraintestinal manifestations from nearly every organ system are common in inflammatory bowel disease (IBD). This review article describes the epidemiology, pathogenesis, diagnosis and management of the main endocrine and metabolic manifestations in IBD, including metabolic bone disease, growth retardation, hypogonadism, pubertal delay, lipid abnormalities and insulin resistance. These clinical problems are commonly interrelated and they share a common basis, influenced by disease-related inflammation and nutritional status. In addition to nutritional support, every effort should be made to achieve and maintain disease remission, thus correcting the underlying chronic inflammation. The criteria for screening and diagnosing osteoporosis are described and treatment options are discussed (lifestyle advice, vitamin D and calcium supplementation, use of bisphosphonates or other specific antiosteoporotic agents, correction of hypogonadism). Chronic glucocorticoid therapy may affect growth as well as predispose to osteoporosis. The diagnosis and management of growth failure, pubertal delay and hypogonadism in IBD are discussed.

  20. High burden of metabolic comorbidities in a citywide cohort of HIV outpatients: evolving health care needs of people aging with HIV in Washington, DC.

    PubMed

    Levy, M E; Greenberg, A E; Hart, R; Powers Happ, L; Hadigan, C; Castel, A

    2017-05-15

    With the increasing impact of cardiovascular disease among populations aging with HIV, contemporary prevalence estimates for predisposing metabolic comorbidities will be important for guiding the provision of relevant lifestyle and pharmacological interventions. We estimated the citywide prevalence of hypertension, type 2 diabetes, dyslipidaemia, and obesity; examined differences by demographic subgroups; and assessed clinical correlates. Utilizing an electronic medical record (EMR) database from the DC Cohort study - a multicentre prospective cohort study of HIV-infected outpatients - we assessed the period prevalence of metabolic comorbidities between 2011 and 2015 using composite definitions that incorporated diagnoses, pharmacy records, and clinical/laboratory results. Of 7018 adult patients (median age 50 years; 77% black), 50% [95% confidence interval (CI) 49-51] had hypertension, 13% (95% CI: 12-14) had diabetes, 48% (95% CI: 47-49) had dyslipidaemia, and 35% (95% CI: 34-36) had obesity. Hypertension was more prevalent among black patients, diabetes and obesity were more prevalent among female and black patients, dyslipidaemia was more prevalent among male and white patients, and comorbidities were more prevalent among older patients (all P < 0.001). For many patients, evidence of treatment for these comorbidities was not available in the EMR. Longer time since HIV diagnosis, greater duration of antiretroviral treatment, and having controlled immunovirological parameters were associated with metabolic comorbidities. These findings underscore the pervasive burden of metabolic comorbidities among HIV-infected persons, serve as the basis for future analyses characterizing their impact on subsequent adverse cardiovascular outcomes, and highlight the need for an increased focus on the prevention and control of comorbid complications in this population. © 2017 British HIV Association.

  1. Cardiovascular disease risk of abdominal obesity vs. metabolic abnormalities.

    PubMed

    Wildman, Rachel P; McGinn, Aileen P; Lin, Juan; Wang, Dan; Muntner, Paul; Cohen, Hillel W; Reynolds, Kristi; Fonseca, Vivian; Sowers, MaryFran R

    2011-04-01

    It remains unclear whether abdominal obesity increases cardiovascular disease (CVD) risk independent of the metabolic abnormalities that often accompany it. Therefore, the objective of this study was to evaluate the independent effects of abdominal obesity vs. metabolic syndrome and diabetes on the risk for incident coronary heart disease (CHD) and stroke. The Framingham Offspring, Atherosclerosis Risk in Communities, and Cardiovascular Health studies were pooled to assess the independent effects of abdominal obesity (waist circumference >102 cm for men and >88 cm for women) vs. metabolic syndrome (excluding the waist circumference criterion) and diabetes on risk for incident CHD and stroke in 20,298 men and women aged ≥45 years. The average follow-up was 8.3 (s.d. 1.9) years. There were 1,766 CVD events. After adjustment for demographic factors, smoking, alcohol intake, number of metabolic syndrome components, and diabetes, abdominal obesity was not significantly associated with an increased risk of CVD (hazard ratio (HR) (95% confidence interval): 1.09 (0.98, 1.20)). However, after adjustment for demographics, smoking, alcohol intake, and abdominal obesity, having 1-2 metabolic syndrome components, the metabolic syndrome and diabetes were each associated with a significantly increased risk of CVD (2.12 (1.80, 2.50), 2.82 (1.92, 4.12), and 5.33 (3.37, 8.41), respectively). Although abdominal obesity is an important clinical tool for identification of individuals likely to possess metabolic abnormalities, these data suggest that the metabolic syndrome and diabetes are considerably more important prognostic indicators of CVD risk.

  2. Assessing the human gut microbiota in metabolic diseases.

    PubMed

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-10-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.

  3. Assessing the Human Gut Microbiota in Metabolic Diseases

    PubMed Central

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-01-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens–derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology. PMID:24065795

  4. Mitochondrial dysfunction and cellular metabolic deficiency in Alzheimer's disease.

    PubMed

    Gu, Xue-Mei; Huang, Han-Chang; Jiang, Zhao-Feng

    2012-10-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathology of AD includes amyloid-β (Aβ) deposits in neuritic plaques and neurofibrillary tangles composed of hyperphosphorylated tau, as well as neuronal loss in specific brain regions. Increasing epidemiological and functional neuroimaging evidence indicates that global and regional disruptions in brain metabolism are involved in the pathogenesis of this disease. Aβ precursor protein is cleaved to produce both extracellular and intracellular Aβ, accumulation of which might interfere with the homeostasis of cellular metabolism. Mitochondria are highly dynamic organelles that not only supply the main energy to the cell but also regulate apoptosis. Mitochondrial dysfunction might contribute to Aβ neurotoxicity. In this review, we summarize the pathways of Aβ generation and its potential neurotoxic effects on cellular metabolism and mitochondrial dysfunction.

  5. [Non-corticosteroid drug-induced metabolic bone disease].

    PubMed

    Briot, Karine

    2006-10-01

    After osteoporotic fracture or low bone mineral density measurements, it is necessary to look for secondary causes of osteoporosis, such as drugs. Corticosteroids are the most common cause of drug-induced metabolic bone disease. Other drugs responsible for bone disease include: aromatase inhibitors, GnRH agonists, anticonvulsants, heparin, and L thyroxin at TSH-suppressive doses. Confirmation is required of data about neuroleptics and antivitamin K.

  6. Optical diagnosis of a metabolic disease: cystinosis

    NASA Astrophysics Data System (ADS)

    Cinotti, Elisa; Perrot, Jean Luc; Labeille, Bruno; Espinasse, Marine; Ouerdane, Youcef; Boukenter, Aziz; Thuret, Gilles; Gain, Philippe; Campolmi, Nelly; Douchet, Catherine; Cambazard, Frédéric

    2013-04-01

    Nephropathic cystinosis (NC) is a rare autosomal recessive storage disease characterized by the lysosomal accumulation of cystine crystals throughout the body, particularly in blood cells, the cornea, skin, kidneys, the central nervous system, and the muscles. The skin and the cornea are the most accessible sites to explore, and in vivo reflectance confocal microscopy (IVCM) helps identify crystals in both but does not provide any information to help define their composition. Raman spectroscopy (RS) allows cystine to be easily recognized thanks to its characteristic signature with a band at 499 cm-1. Two dermatology confocal microscopes were used to visualize crystals in both the skin and the ocular surface of a cystinosis patient, and an ex vivo Raman examination of a skin biopsy and of the cornea was performed and removed during a corneal graft to confirm the cystine composition of the crystals. Recently, RS has been performed in vivo and coupled with IVCM. In the future, it is suggested that crystals in NC and other deposits in storage diseases could be identified with this noninvasive in vivo technique that combines IVCM to recognize the deposits and RS to confirm their chemical nature.

  7. Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality.

    PubMed

    Wulsin, Lawson R; Horn, Paul S; Perry, Jennifer L; Massaro, Joseph M; D'Agostino, Ralph B

    2015-06-01

    Identifying novel early predictors of metabolic disorders is essential to improving effective primary prevention. The objectives were to examine the contribution of two measures of autonomic imbalance, resting heart rate (RHR) and heart rate variability (HRV), on the development of five metabolic risk outcomes, and on cardiovascular disease, diabetes, and early mortality. This study was a secondary analysis of prospective data from Offspring Cohort participants (N = 1882) in the Framingham Heart Study (FHS). Participants at FHS Exam 3 (1983-1987) with 1) age years 18 or older, and 2) data on RHR, HRV, and five measures of metabolic risk (blood pressure, fasting glucose, triglycerides, high-density lipoprotein [HDL] cholesterol, and body mass index [BMI]) at three follow-up visits over 12 years. We conducted a backward elimination variable selection procedure on a logistic regression model, using baseline RHR, HRV, age, sex, and smoking status to predict the odds of developing a specific metabolic risk. Measures included hyperglycemia, high blood pressure, high triglycerides, low HDL cholesterol, and high BMI over 12 years; incident diabetes, cardiovascular disease, and early mortality over 20 years. RHR and HRV, along with sex, age, and smoking were significant predictors of high blood pressure, hyperglycemia, and a diagnosis of diabetes within 12 years. RHR and HRV also predicted the development of cardiovascular disease and early mortality for most of the sample. In this community sample two measures of autonomic imbalance predicted multiple poor metabolic outcomes and mortality, making autonomic imbalance a potentially worthy target for intervention studies to reduce risks for cardiovascular disorders, diabetes, and early death.

  8. Dietary Fiber, Microbiota and Obesity Related Metabolic Diseases

    USDA-ARS?s Scientific Manuscript database

    The presentation summarizes our research over the past 7 years on viscous soluble dietary fibers in animal models of obesity and metabolic diseases. We found that in addition to the well known cholesterol and glucose lowering ability of soluble fibers, viscous dietary fibers also prevent most of th...

  9. Frequency of metabolic syndrome in patients with ischaemic heart disease.

    PubMed

    Ashraf, Tariq; Memon, Muhammad Anis; Talpur, Muhammad Saeed; Panhwar, Ziauddin; Rasool, Syed Ishtiaq

    2011-08-01

    To evaluate the frequency of metabolic syndrome in patients with Ischaemic Heart Disease. This was a cross sectional observational study. Patients with a first time cardiac event arriving in emergency room during the period October 2009 to April 2010, were included. Five components of Metabolic syndrome were defined according to criteria set by International Diabetes Federation, American Heart Association & National Heart, Lung and Blood Institute which had abdominal obesity (waist circumference) as an integral part of the syndrome. Blood sugar, triglycerides, HDL-C were measured within 24 hrs of cardiac insult. Hypertension was defined as blood pressure > 130/85 mmHg. Variables were integrated for descriptive statistics. A total of 477 patients diagnosed with Ischaemic Heart Disease were inducted in the study. There were 355 (74%) males and 122 (26%) females. Frequency of metabolic syndrome in Ischaemic heart disease was seen in 195 (54.95%) males and 96 (78.7%) females (p < 0.001). According to recent criteria abdominal obesity was observed in 91 (81.1%) females as compared to males 219 (61.7%) (p < 0.001) Similarly, low HDL and Hypertension were high in frequency in females. No significant difference in triglycerides levels was found in either gender. Frequency of metabolic syndrome with Ischaemic heart disease was high in females as compared to males. This could be attributed to the increased prevalence of abdominal obesity.

  10. Metabolic disruption identified in the Huntington's disease transgenic sheep model.

    PubMed

    Handley, Renee R; Reid, Suzanne J; Patassini, Stefano; Rudiger, Skye R; Obolonkin, Vladimir; McLaughlan, Clive J; Jacobsen, Jessie C; Gusella, James F; MacDonald, Marcy E; Waldvogel, Henry J; Bawden, C Simon; Faull, Richard L M; Snell, Russell G

    2016-02-11

    Huntington's disease (HD) is a dominantly inherited, progressive neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of HTT, encoding huntingtin. There are no therapies that can delay the progression of this devastating disease. One feature of HD that may play a critical role in its pathogenesis is metabolic disruption. Consequently, we undertook a comparative study of metabolites in our transgenic sheep model of HD (OVT73). This model does not display overt symptoms of HD but has circadian rhythm alterations and molecular changes characteristic of the early phase disease. Quantitative metabolite profiles were generated from the motor cortex, hippocampus, cerebellum and liver tissue of 5 year old transgenic sheep and matched controls by gas chromatography-mass spectrometry. Differentially abundant metabolites were evident in the cerebellum and liver. There was striking tissue-specificity, with predominantly amino acids affected in the transgenic cerebellum and fatty acids in the transgenic liver, which together may indicate a hyper-metabolic state. Furthermore, there were more strong pair-wise correlations of metabolite abundance in transgenic than in wild-type cerebellum and liver, suggesting altered metabolic constraints. Together these differences indicate a metabolic disruption in the sheep model of HD and could provide insight into the presymptomatic human disease.

  11. Metabolic alterations to the mucosal microbiota in inflammatory bowel disease.

    PubMed

    Davenport, Michael; Poles, Jordan; Leung, Jacqueline M; Wolff, Martin J; Abidi, Wasif M; Ullman, Thomas; Mayer, Lloyd; Cho, Ilseung; Loke, P'ng

    2014-04-01

    Inflammation during inflammatory bowel disease may alter nutrient availability to adherent mucosal bacteria and impact their metabolic function. Microbial metabolites may regulate intestinal CD4 T-cell homeostasis. We investigated the relationship between inflammation and microbial function by inferred metagenomics of the mucosal microbiota from colonic pinch biopsies of patients with inflammatory bowel disease. Paired pinch biopsy samples of known inflammation states were analyzed from ulcerative colitis (UC) (23), Crohn's disease (CD) (21), and control (24) subjects by 16S ribosomal sequencing, histopathologic assessment, and flow cytometry. PICRUSt was used to generate metagenomic data and derive relative Kyoto Encyclopedia of Genes and Genomes Pathway abundance information. Leukocytes were isolated from paired biopsy samples and analyzed by multicolor flow cytometry. Active inflammation was defined by neutrophil infiltration into the epithelium. Carriage of metabolic pathways in the mucosal microbiota was relatively stable among patients with inflammatory bowel disease, despite large variations in individual bacterial community structures. However, microbial function was significantly altered in inflamed tissue of UC patients, with a reduction in carbohydrate and nucleotide metabolism in favor of increased lipid and amino acid metabolism. These differences were not observed in samples from CD patients. In CD, microbial lipid, carbohydrate, and amino acid metabolism tightly correlated with the frequency of CD4Foxp3 Tregs, whereas in UC, these pathways correlated with the frequency of CD4IL-22 (TH22) cells. Metabolic pathways of the mucosal microbiota in CD do not vary as much as UC with inflammation state, indicating a more systemic perturbation of host-bacteria interactions in CD compared with more localized dysfunction in UC.

  12. Fractures Related to Metabolic Bone Disease in Children with Congenital Heart Disease.

    PubMed

    Cheng, Henry H; Carmona, Fabio; McDavitt, Erica; Wigmore, Daniel; Perez-Rossello, Jeannette M; Gordon, Catherine M; Pigula, Frank A; Laussen, Peter C; Rajagopal, Satish K

    2016-01-01

    Critically ill children with congenital heart disease (CHD) are at risk for metabolic bone disease (MBD) and bone fractures. Our objective was to characterize a cohort of CHD patients with fractures and describe a Fragile Bone Protocol (FBP) developed to reduce fractures. Patients who developed fractures in the Cardiac Intensive Care Unit (CICU) of Boston Children's Hospital from 3/2008 to 6/2014 were identified via quality improvement and radiology databases. The FBP (initiated July 2011) systematically identifies patients at risk for MBD and prescribes special handling precautions. Twenty-three fractures were identified in 15 children. Median age at fracture identification was 6.2 months, with a median duration of hospitalization before fracture diagnosis of 2.7 months. Six patients (40%) had single ventricle CHD. Hyperparathyroidism and low 25-OH vitamin D levels were present in 77% and 40% of those tested, respectively. Compared with patients not diagnosed with fractures, fracture patients had increased exposure to possible risk factors for MBD and had elevated parathyroid and decreased calcitriol levels.Six patients (40%) did not survive to hospital discharge, compared with an overall CICU mortality rate of 2.6% (P < .01). The fracture case rate before implementation of the FBP was 2.6 cases/1000 admissions and was 0.7/1000 after implementation of the FBP (P = .04). Critically ill CHD patients are at risk for fractures. They represent a complex group who frequently has hyperparathyroidism and decreased calcitriol levels, and each may predispose to fractures. FBPs consisting of identification and careful patient handling should be considered in at-risk patients. © 2015 Wiley Periodicals, Inc.

  13. Analysis of cohort studies with multivariate and partially observed disease classification data.

    PubMed

    Chatterjee, Nilanjan; Sinha, Samiran; Diver, W Ryan; Feigelson, Heather Spencer

    2010-09-01

    Complex diseases like cancers can often be classified into subtypes using various pathological and molecular traits of the disease. In this article, we develop methods for analysis of disease incidence in cohort studies incorporating data on multiple disease traits using a two-stage semiparametric Cox proportional hazards regression model that allows one to examine the heterogeneity in the effect of the covariates by the levels of the different disease traits. For inference in the presence of missing disease traits, we propose a generalization of an estimating equation approach for handling missing cause of failure in competing-risk data. We prove asymptotic unbiasedness of the estimating equation method under a general missing-at-random assumption and propose a novel influence-function-based sandwich variance estimator. The methods are illustrated using simulation studies and a real data application involving the Cancer Prevention Study II nutrition cohort.

  14. Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease.

    PubMed

    Manco, Melania

    2011-10-01

    Compelling evidence supports the concept that nonalcoholic fatty liver disease (NAFLD) represents the hepatic component of metabolic syndrome (MetS). Intrahepatic fat seems to predict more strongly than does visceral adiposity an individual's cardiovascular risk and the likelihood that metabolic abnormalities are present in youth. Young individuals with fatty liver are more insulin resistant and present with a higher prevalence of metabolic abnormalities than do individuals without intrahepatic fat accumulation. They also present with a certain endothelial dysfunction and greater carotid intima-media thickness. Conversely, youth with MetS seem to have an increased risk of developing liver inflammation, a condition termed nonalcoholic steatohepatitis (NASH), and fibrosis. In the context of MetS, the liver is central in that it can drive both hepatic and systemic insulin resistance, trigger low-grade inflammation, and promote atherogenic processes. In the context of MetS, NAFLD and altered carbohydrate metabolism track from childhood to adulthood. Thus, prevention, recognition, and effective treatment of these two abnormalities may limit the burden of morbidity and mortality associated with obesity and may delay onset of cardiovascular disease in early adulthood. The present review aims at systematically presenting evidence of the critical interplay of fatty liver and altered glucose metabolism in youth. It attempts to provide pathogenetic explanations for such an association and the rationale for its treatment, with particular regard to nutritional interventions. Key teaching points: Overweight and obese youth should be screened for fatty liver disease once after puberty by liver function tests and ultrasonography. Screening for fatty liver should be accurately performed in young patients with features of metabolic syndrome. Obese patients with fatty liver are at increased risk for altered glucose metabolism, thus they should undergo an oral glucose tolerance test

  15. Quantifying prion disease penetrance using large population control cohorts.

    PubMed

    Minikel, Eric Vallabh; Vallabh, Sonia M; Lek, Monkol; Estrada, Karol; Samocha, Kaitlin E; Sathirapongsasuti, J Fah; McLean, Cory Y; Tung, Joyce Y; Yu, Linda P C; Gambetti, Pierluigi; Blevins, Janis; Zhang, Shulin; Cohen, Yvonne; Chen, Wei; Yamada, Masahito; Hamaguchi, Tsuyoshi; Sanjo, Nobuo; Mizusawa, Hidehiro; Nakamura, Yosikazu; Kitamoto, Tetsuyuki; Collins, Steven J; Boyd, Alison; Will, Robert G; Knight, Richard; Ponto, Claudia; Zerr, Inga; Kraus, Theo F J; Eigenbrod, Sabina; Giese, Armin; Calero, Miguel; de Pedro-Cuesta, Jesús; Haïk, Stéphane; Laplanche, Jean-Louis; Bouaziz-Amar, Elodie; Brandel, Jean-Philippe; Capellari, Sabina; Parchi, Piero; Poleggi, Anna; Ladogana, Anna; O'Donnell-Luria, Anne H; Karczewski, Konrad J; Marshall, Jamie L; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L; Kähler, Anna; Chambert, Kimberly; McCarroll, Steven; Sullivan, Patrick F; Hultman, Christina M; Purcell, Shaun M; Sklar, Pamela; van der Lee, Sven J; Rozemuller, Annemieke; Jansen, Casper; Hofman, Albert; Kraaij, Robert; van Rooij, Jeroen G J; Ikram, M Arfan; Uitterlinden, André G; van Duijn, Cornelia M; Daly, Mark J; MacArthur, Daniel G

    2016-01-20

    More than 100,000 genetic variants are reported to cause Mendelian disease in humans, but the penetrance-the probability that a carrier of the purported disease-causing genotype will indeed develop the disease-is generally unknown. We assess the impact of variants in the prion protein gene (PRNP) on the risk of prion disease by analyzing 16,025 prion disease cases, 60,706 population control exomes, and 531,575 individuals genotyped by 23andMe Inc. We show that missense variants in PRNP previously reported to be pathogenic are at least 30 times more common in the population than expected on the basis of genetic prion disease prevalence. Although some of this excess can be attributed to benign variants falsely assigned as pathogenic, other variants have genuine effects on disease susceptibility but confer lifetime risks ranging from <0.1 to ~100%. We also show that truncating variants in PRNP have position-dependent effects, with true loss-of-function alleles found in healthy older individuals, a finding that supports the safety of therapeutic suppression of prion protein expression.

  16. Parkinson’s Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort

    PubMed Central

    Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T.; Ben-Shlomo, Yoav; Hu, Michele T.M.

    2015-01-01

    Abstract Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s. PMID:26405788

  17. Parkinson's Disease Subtypes in the Oxford Parkinson Disease Centre (OPDC) Discovery Cohort.

    PubMed

    Lawton, Michael; Baig, Fahd; Rolinski, Michal; Ruffman, Claudio; Nithi, Kannan; May, Margaret T; Ben-Shlomo, Yoav; Hu, Michele T M

    2015-01-01

    Within Parkinson's there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Use a data-driven approach to unravel any heterogeneity in the Parkinson's phenotype in a well-characterised, population-based incidence cohort. 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Our approach identified several Parkinson's phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson's.

  18. [Metabolic disorders and nutritional status in autoimmune thyroid diseases].

    PubMed

    Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

    2015-01-02

    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

  19. Typical cerebral metabolic patterns in neurodegenerative brain diseases.

    PubMed

    Teune, Laura K; Bartels, Anna L; de Jong, Bauke M; Willemsen, Antoon T M; Eshuis, Silvia A; de Vries, Jeroen J; van Oostrom, Joost C H; Leenders, Klaus L

    2010-10-30

    The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [(18)F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting that this method can assist in early differential diagnosis of neurodegenerative brain diseases.We have studied patients who had an FDG-PET scan on clinical grounds at an early disease stage and included those with a retrospectively confirmed diagnosis according to strictly defined clinical research criteria. Ninety-six patients could be included of which 20 patients with Parkinson's disease (PD), 21 multiple system atrophy (MSA), 17 progressive supranuclear palsy (PSP), 10 corticobasal degeneration (CBD), 6 dementia with Lewy bodies (DLB), 15 Alzheimer's disease (AD), and 7 frontotemporal dementia (FTD). FDG PET images of each patient group were analyzed and compared to18 healthy controls using Statistical Parametric Mapping (SPM5).Disease-specific patterns of relatively decreased metabolic activity were found in PD (contralateral parietooccipital and frontal regions), MSA (bilateral putamen and cerebellar hemispheres), PSP (prefrontal cortex and caudate nucleus, thalamus, and mesencephalon), CBD (contralateral cortical regions), DLB (occipital and parietotemporal regions), AD (parietotemporal regions), and FTD (frontotemporal regions).The integrated method addressing a spectrum of various neurodegenerative brain diseases provided means to discriminate patient groups also at early disease stages. Clinical follow-up enabled appropriate patient inclusion. This implies that an early diagnosis in individual patients can be made by comparing each subject's metabolic findings with a complete database of specific disease related patterns.

  20. The impact of metabolic disease associated with metabolic syndrome on human pregnancy.

    PubMed

    Malek, Antoine

    2014-01-01

    Metabolic diseases induced by metabolic syndrome (MS) have been increased during the past two decades. During healthy pregnancy maternal organs and placenta are challenged to adapt to the increasingly physiological changes. In addition to the increasingly proatherogenic MS, pregnant woman develops a high cardiac output, hypercoagulability, increased inflammatory activity and insulin resistance with dyslipidemia. The MS describes a cluster of metabolic changes associated with an impact on the physiology of many organs. While the metabolic syndrome is directly responsible for the development of atherosclerotic cardiovascular disease, additional impact on human pregnancy like preterm delivery with low-birth-weight infants as well as the development of diseases such as diabetes, preeclampsia and hypertension. Recent evidence suggests that MS is originated in fetal life in association with maternal nutrition during pregnancy and fetal programming which apparently increases the susceptibility for MS in children and later life. This review will describe the MS in association with the origin of the emerging diseases during pregnancy such as diabetes, preeclampsia and others. The influence of perinatal environment and maternal diet and smoking on MS as well as the genetic biomarkers of MS will be described.

  1. [Updates on Lifestyle-Related Diseases and Bone Metabolism. The metabolic syndrome and bone metabolism].

    PubMed

    Yamaguchi, Toru

    2014-11-01

    The metabolic syndrome is featured by the combination of obesity induced by visceral fat accumulation, dyslipidemia, hyperglycemia, and hypertension. It is well documented that obesity and body weight increase are positively linked to increased bone mineral density (BMD) and reduced fracture risk of weight-bearing bones through mechanical stress. On the other hand, inflammatory cytokines secreted from visceral fat and advanced glycation products induced by hyperglycemia tend to reduce BMD and to increase fracture risk in contrast to obesity. Thus, BMD and fracture risk in patients with the metabolic syndrome may be determined by the balance between the beneficial effect of obesity and detrimental ones of inflammatory cytokines and hyperglycemia on bone.

  2. Relevance of cohort studies for the study of transplant infectious diseases.

    PubMed

    Berger, Christoph; Boggian, Katia; Cusini, Alexia; van Delden, Christian; Garzoni, Christian; Hirsch, Hans H; Khanna, Nina; Koller, Michael; Manuel, Oriol; Meylan, Pascal; Nadal, David; Weisser, Maja; Mueller, Nicolas J

    2012-12-01

    The debate on the merits of observational studies as compared with randomized trials is ongoing. We will briefly touch on this subject, and demonstrate the role of cohort studies for the description of infectious disease patterns after transplantation. The potential benefits of cohort studies for the clinical management of patients outside of the expected gain in epidemiological knowledge are reviewed. The newly established Swiss Transplantation Cohort Study and in particular the part focusing on infectious diseases will serve as an illustration. A neglected area of research is the indirect value of large, multicenter cohort studies. These benefits can range from a deepened collaboration to the development of common definitions and guidelines. Unfortunately, very few data exist on the role of such indirect effects on improving quality of patient management. This review postulates an important role for cohort studies, which should not be viewed as inferior but complementary to established research tools, in particular randomized trials. Randomized trials remain the least bias-prone method to establish knowledge regarding the significance of diagnostic or therapeutic measures. Cohort studies have the power to reflect a real-world situation and to pinpoint areas of knowledge as well as of uncertainty. Prerequisite is a prospective design requiring a set of inclusive data coupled with the meticulous insistence on data retrieval and quality.

  3. Periodontal Disease and Incident Lung Cancer Risk: A Meta-Analysis of Cohort Studies.

    PubMed

    Zeng, Xian-Tao; Xia, Ling-Yun; Zhang, Yong-Gang; Li, Sheng; Leng, Wei-Dong; Kwong, Joey S W

    2016-10-01

    Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta-analytic approach. PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case-control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed-effect inverse-variance model. Statistical heterogeneity was explored using the Q test as well as the I(2) statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger's test. Five cohort studies were included, involving 321,420 participants in this meta-analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I(2) = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population. Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.

  4. Adherence to Infliximab Treatment in a Pediatric Inflammatory Bowel Disease Cohort.

    PubMed

    Vitale, David S; Greenley, Rachel N; Lerner, Diana G; Mavis, Alisha M; Werlin, Steven L

    2015-10-01

    The aims of the study were to describe infliximab adherence in a pediatric inflammatory bowel disease cohort, to identify demographic and disease factors associated with adherence, and to examine differences in acute care use among adherent and nonadherent patients. Charts of patients who received infliximab at the Children's Hospital of Wisconsin (CHW) between October 2010 and October 2012 were retrospectively reviewed. A total of 151 patients met the inclusion criteria; 91.4% of the patients were adherent. Nonadherent patients had more emergency room visits and hospitalizations than adherent patients. The study is the first to show high adherence rates to infliximab in a pediatric cohort.

  5. Social circumstances and education: life course origins of social inequalities in metabolic risk in a prospective national birth cohort.

    PubMed

    Langenberg, Claudia; Kuh, Diana; Wadsworth, Michael E J; Brunner, Eric; Hardy, Rebecca

    2006-12-01

    We investigated the relative importance of education and childhood and adult social class in the risk of metabolic syndrome. We conducted a prospective birth cohort study of 1311 men and 1318 women aged 53 years in 1999, when metabolic syndrome components were measured. Logistic regression analyses were used to calculate relative index of inequality estimates. Relative to men and women at the highest education levels, men (odds ratio [OR]=2.0; 95% confidence interval [CI]=1.2, 3.2) and women (OR=2.7; 95% CI=1.5, 4.6) with the least education were at twice the risk or more of having the metabolic syndrome. Adjustment for childhood and adult social class strengthened this result among men and weakened it among women. Childhood social class was independently associated with the metabolic syndrome in women (OR=2.0; 95% CI=1.1, 3.6) but not in men (OR=1.1; 95% CI= 0.7, 1.8). Associations between adult social class and the metabolic syndrome or its components were largely accounted for by childhood socioeconomic measures. Educational differences should be considered in the design of interventions aimed at reducing the burden of the metabolic syndrome in socially disadvantaged groups.

  6. Metabolic syndrome and incidence of breast cancer in middle-aged Korean women: a nationwide cohort study.

    PubMed

    Lee, Jung Ah; Yoo, Jung Eun; Park, Hye Soon

    2017-04-01

    To evaluate the risk of breast cancer in middle-aged women with metabolic syndrome using the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We analyzed 23,820 women aged 50-64 years who participated in the NHIS-NCS in 2008 and 2009. We excluded subjects with any previous history of cancer or with inadequate information regarding metabolic syndrome. Participated subjects underwent anthropometric measurements and provided fasting blood samples for the assessment of glucose and lipid profiles, and answered a lifestyle questionnaire. Cox regression analysis was performed to evaluate relative risks (RRs) and 95% confidence intervals (CIs) for the association between metabolic syndrome and breast cancer. During the 5-year follow-up, 131 subjects were newly diagnosed with breast cancer (incidence, 10.86 per 10,000 person years). After adjusting for age and body mass index, the RR for incident breast cancer in participants with metabolic syndrome versus those without it was 1.47 (95% CI 1.01-2.13). For those individuals of metabolic syndrome, hyperglycemia was most primarily related with the incidence of breast cancer (RR 1.44, 95% CI 1.02-2.04). Among the study individuals who were middle-aged Korean women, metabolic syndrome is highly related with the risk of breast cancer. Therefore, it needs to be managed or prevented to reduce the incidence of breast cancer.

  7. Endothelial cell metabolism in normal and diseased vasculature

    PubMed Central

    Eelen, Guy; de Zeeuw, Pauline; Simons, Michael; Carmeliet, Peter

    2015-01-01

    Higher organisms rely on a closed cardiovascular circulatory system with blood vessels supplying vital nutrients and oxygen to distant tissues. Not surprisingly, vascular pathologies rank among the most life-threatening diseases. At the crux of most of these vascular pathologies are (dysfunctional) endothelial cells (ECs), the cells lining the blood vessel lumen. ECs display the remarkable capability to switch rapidly from a quiescent state to a highly migratory and proliferative state during vessel sprouting. This angiogenic switch has long been considered to be dictated by angiogenic growth factors (eg vascular endothelial growth factor; VEGF) and other signals (eg Notch) alone, but recent findings show that it is also driven by a metabolic switch in ECs. Furthermore, these changes in metabolism may even override signals inducing vessel sprouting. Here, we review how EC metabolism differs between the normal and dysfunctional/diseased vasculature and how it relates to or impacts the metabolism of other cell types contributing to the pathology. We focus on the biology of ECs in tumor blood vessel and diabetic ECs in atherosclerosis as examples of the role of endothelial metabolism in key pathological processes. Finally, current as well as unexplored ‘EC metabolism’-centric therapeutic avenues are discussed. PMID:25814684

  8. Metabolic syndrome and cardiovascular disease in South Asians.

    PubMed

    Eapen, Danny; Kalra, Girish L; Merchant, Nadya; Arora, Anjali; Khan, Bobby V

    2009-01-01

    This review discusses the prevalence of metabolic syndrome and cardiovascular disease in the South Asian population, evaluates conventional and emerging risk factors, and reinforces the need for ethnic-specific redefinition of guidelines used to diagnose metabolic syndrome. We reviewed recent and past literature using Ovid Medline and PubMed databases. South Asians represent one of the largest and fastest growing ethnic groups in the world. With this growth, a dramatic rise in the rates of acute myocardial infarction and diabetes is being seen in this population. Potential etiologies for this phenomenon include dietary westernization, poor lifestyle measures, adverse body fat patterning, and genetics. While traditional risk factors for diabetes and cardiovascular disease should not be overlooked, early metabolic syndrome has now been shown in the South Asian pediatric population, suggesting that "metabolic programming" and perinatal influences may likely play a substantial role. Health care practitioners must be aware that current guidelines used to identify individuals with metabolic syndrome are underestimating South Asian individuals at risk. New ethnic-specific guidelines and prevention strategies are discussed in this review and should be applied by clinicians to their South Asian patients.

  9. Dietary inorganic nitrate: From villain to hero in metabolic disease?

    PubMed

    McNally, Ben; Griffin, Julian L; Roberts, Lee D

    2016-01-01

    Historically, inorganic nitrate was believed to be an inert by-product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re-examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate-nitrite-NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti-obesity and anti-diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re-evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease.

  10. Dietary inorganic nitrate: From villain to hero in metabolic disease?

    PubMed Central

    McNally, Ben; Griffin, Julian L.

    2015-01-01

    Historically, inorganic nitrate was believed to be an inert by‐product of nitric oxide (NO) metabolism that was readily excreted by the body. Studies utilising doses of nitrate far in excess of dietary and physiological sources reported potentially toxic and carcinogenic effects of the anion. However, nitrate is a significant component of our diets, with the majority of the anion coming from green leafy vegetables, which have been consistently shown to offer protection against obesity, type 2 diabetes and metabolic diseases. The discovery of a metabolic pathway in mammals, in which nitrate is reduced to NO, via nitrite, has warranted a re‐examination of the physiological role of this small molecule. Obesity, type 2 diabetes and the metabolic syndrome are associated with a decrease in NO bioavailability. Recent research suggests that the nitrate‐nitrite‐NO pathway may be harnessed as a therapeutic to supplement circulating NO concentrations, with both anti‐obesity and anti‐diabetic effects, as well as improving vascular function. In this review, we examine the key studies that have led to the re‐evaluation of the physiological function of inorganic nitrate, from toxic and carcinogenic metabolite, to a potentially important and beneficial agent in the treatment of metabolic disease. PMID:26227946

  11. Associations between specific autoimmune diseases and subsequent dementia: retrospective record-linkage cohort study, UK.

    PubMed

    Wotton, Clare J; Goldacre, Michael J

    2017-06-01

    To determine whether hospital admission for autoimmune disease is associated with an elevated risk of future admission for dementia. Retrospective, record-linkage cohort study using national hospital care and mortality administrative data, 1999-2012. Cohorts of people admitted to hospital with a range of autoimmune diseases were constructed, along with a control cohort, and followed forward in time to see if they developed dementia. 1 833 827 people were admitted to hospital with an autoimmune disease; the number of people in cohorts for each autoimmune disease ranged from 1019 people in the Goodpasture's syndrome cohort, to 316 043 people in the rheumatoid arthritis cohort. The rate ratio for dementia after admission for an autoimmune disease, compared with the control cohort, was 1.20 (95% CI 1.19 to 1.21). Where dementia type was specified, the rate ratio was 1.06 (1.04 to 1.08) for Alzheimer's disease and 1.28 (1.26 to 1.31) for vascular dementia. Of 25 autoimmune diseases studied, 18 showed significant positive associations with dementia at p<0.05 (with 14 significant at p<0.001) including Addison's disease (1.48, 1.34 to 1.64), multiple sclerosis (1.97, 1.88 to 2.07), psoriasis (1.29, 1.25 to 1.34) and systemic lupus erythematosus (1.46, 1.32 to 1.61). The associations with vascular dementia may be one component of a broader association between autoimmune diseases and vascular damage. Though findings were significant, effect sizes were small. Clinicians should be aware of the possible coexistence of autoimmune disease and dementia in individuals. Further studies are needed to confirm or refute our findings and to explore possible mechanisms mediating any elevation of risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  12. Exosomes as the source of biomarkers of metabolic diseases

    PubMed Central

    Lee, Min-Jae; Park, Dong-Ho

    2016-01-01

    Exosomes are extracellular vesicles that contain molecules that regulate the metabolic functions of adjacent or remote cells. Recent in vitro, in vivo and clinical studies support the hypothesis that exosomes released from various cell types play roles in the progression of metabolic disorders including type 2 diabetes. Based on this concept and advances in other diseases, the proteins, mRNA, microRNA and lipids in exosomes isolated from biological fluids have been proposed as biomarkers in metabolic disorders. However, several problems with the development of clinically applicable biomarkers have not been resolved. In this review, the biologic functions of exosomes are briefly introduced, and we discuss the technical and practical pros and cons of different methods of exosome isolation for the identification of exosomal biomarkers of metabolic disorders. Standardization of preanalytical variables and isolation of high-purity exosomes from fully characterized biological fluids will be necessary for the identification of useful exosomal biomarkers that can provide insights into the pathogenic mechanisms of complications of metabolic syndrome and of whole-body metabolism. PMID:27777903

  13. B-Vitamin dependent methionine metabolism and alcoholic liver disease.

    PubMed

    Halsted, Charles H

    2013-03-01

    Convincing evidence links aberrant B-vitamin dependent hepatic methionine metabolism to the pathogenesis of alcoholic liver disease (ALD). This review focuses on the essential roles of folate and vitamins B6 and B12 in hepatic methionine metabolism, the causes of their deficiencies among chronic alcoholic persons, and how their deficiencies together with chronic alcohol exposure impact on aberrant methionine metabolism in the pathogenesis of ALD. Folate is the dietary transmethylation donor for the production of S-adenosylmethionine (SAM), which is the substrate for all methyltransferases that regulate gene expressions in pathways of liver injury, as well as a regulator of the transsulfuration pathway that is essential for production of glutathione (GSH), the principal antioxidant for defense against oxidative liver injury. Vitamin B12 regulates transmethylation reactions for SAM production and vitamin B6 regulates transsulfuration reactions for GSH production. Folate deficiency accelerates the experimental development of ALD in ethanol-fed animals while reducing liver SAM levels with resultant abnormal gene expression and decreased production of antioxidant GSH. Through its effects on folate metabolism, reduced SAM also impairs nucleotide balance with resultant increased DNA strand breaks, oxidation, hepatocellular apoptosis, and risk of carcinogenesis. The review encompasses referenced studies on mechanisms for perturbations of methionine metabolism in ALD, evidence for altered gene expressions and their epigenetic regulation in the pathogenesis of ALD, and clinical studies on potential prevention and treatment of ALD by correction of methionine metabolism with SAM.

  14. Cardiovascular Disease Risk in NASA Astronauts Across the Lifespan: Historical Cohort Studies

    NASA Technical Reports Server (NTRS)

    Charvat, Jacqueline M.; Lee, Stuart M. C.; Davenport, Eddie; Barlow, Carolyn E.; Radford, Nina B.; De Fina, Laura F.; Stenger, Michael B.; Van Baalen, Mary

    2017-01-01

    Acute effects of spaceflight on the cardiovascular system have been studied extensively, but the combined chronic effects of spaceflight and aging are not well understood. Preparation for and participation in space flight activities are potentially associated with cardiovascular disease risk factors (e.g., altered dietary and exercise habits, physical and emotional stress, circadian shifts, radiation). Further, astronauts who travel into space multiple times may be at an increased risk across their lifespan. However, comparing the risk of cardiovascular disease in astronauts to other large cohorts is difficult. For example, comparisons between astronauts and large national cohorts, such as the National Health and Nutrition Examination Survey and the National Health Information Survey, are hampered by significant differences in health status between astronauts and the general population, and most of these national studies fail to provide longitudinal data on population health. To address those limitations, NASA's Longitudinal Study of Astronaut Health previously sought to compare the astronauts to a cohort of civil servants employed at the Johnson Space Center. However, differences between the astronauts and civil servants at the beginning of the study, as well as differential follow up, limited the ability to interpret the results. To resolve some of these limitations, two unique cohorts of healthy workers, U.S. Air Force aviators and Cooper Center Longitudinal Study participants, have been identified as potential comparison populations for the astronaut corps. The Air Force cohort was chosen due to similarities in health at selection, screening, and some occupational exposures that Air Force aviators endure, many of which mirror that of the astronaut corps. The Cooper Clinic cohort, a generally healthy prevention cohort, was chosen for the vast array of clinical cardiovascular measures collected in a longitudinal manner complementary to those collected on

  15. Overlap in serum metabolic profiles between non-related diseases: Implications for LC-MS metabolomics biomarker discovery.

    PubMed

    Lindahl, Anna; Forshed, Jenny; Nordström, Anders

    2016-09-23

    Untargeted metabolic profiling has generated large activity in the field of clinical biomarker discovery. Yet, no clinically approved metabolite biomarkers have emerged with failure in validation phases often being a reason. To investigate why, we have applied untargeted metabolic profiling in a retrospective cohort of serum samples representing non-related diseases. Age and gender matched samples from patients diagnosed with pneumonia, congestive heart failure, lymphoma and healthy controls were subject to comprehensive metabolic profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The metabolic profile of each diagnosis was compared to the healthy control group and significant metabolites were filtered out using t-test with FDR correction. Metabolites found to be significant between each disease and healthy controls were compared and analyzed for overlap. Results show that despite differences in etiology and clinical disease presentation, the fraction of metabolites with an overlap between two or more diseases was 61%. A majority of these metabolites can be associated with immune responses thus representing non-disease specific events. We show that metabolic serum profiles from patients representing non-related diseases display very similar metabolic differences when compared to healthy controls. Many of the metabolites discovered as disease specific in this study have further been associated with other diseases in the literature. Based on our findings we suggest non-related disease controls in metabolomics biomarker discovery studies to increase the chances of a successful validation and future clinical applications. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

    PubMed Central

    Hsu, Tai-Yi; Shih, Hong-Mo; Wang, Yu-Chiao; Lin, Leng-Chieh; He, Guan-Yi; Chen, Chih-Yu; Kao, Chia-Hung; Chen, Chao-Hsien

    2016-01-01

    Purpose This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan. Methods This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI. Results The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001). Conclusion The risk of IBD was higher in patients with AI and increased with the length of hospital stay. PMID:27802288

  17. Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts

    PubMed Central

    Kelsen, Judith; Bittinger, Kyle; Pauly-Hubbard, Helen; Posivak, Leah; Grunberg, Stephanie; Baldassano, Robert; Lewis, James D; Wu, Gary D; Bushman, Frederic D

    2016-01-01

    Background Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric CD patients initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. Methods Pediatric CD patients were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodualtors, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). Results A majority of subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared to healthy controls after 8 weeks of therapy. Conclusions Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance. PMID:26288001

  18. Bisphenol A and Metabolic Diseases: Challenges for Occupational Medicine.

    PubMed

    Caporossi, Lidia; Papaleo, Bruno

    2017-08-25

    The prevalence of metabolic diseases has markedly increased worldwide during the last few decades. Lifestyle factors (physical activity, energy-dense diets), together with a genetic predisposition, are well known factors in the pathophysiology of health problems. Bisphenol A (BPA) is a chemical compound used for polycarbonate plastics, food containers, epoxy resins coating metallic cans for food and beverage conservation. The ability of BPA to act as an endocrine disruptor-xenoestrogen in particular-is largely documented in literature, with numerous publications of in vivo and in vitro studies as well as epidemiological data on humans. Recently, different researchers studied the involvement of BPA in the development of insulin resistance; evidences in this way showed a potential role in etiology of metabolic disease, both for children and for adults. We review the epidemiological literature in the relation between BPA exposure and the risk of metabolic diseases in adults, with a focus on occupational exposure. Considering published data and the role of occupational physicians in promoting Workers' Health, specific situations of exposure to BPA in workplace are described, and proposals for action to be taken are suggested. The comparison of the studies showed that exposure levels were higher in workers than in the general population, even if, sometimes, the measurement units used did not permit rapid comprehension. Nevertheless, occupational medicine focus on reproductive effects and not metabolic ones.

  19. [Carbohydrate: current role in diabetes mellitus and metabolic disease].

    PubMed

    Luna López, Victoria; López Medina, José Antonio; Vázquez Gutiérrez, Mercedes; Fernández Soto, M Luisa

    2014-11-01

    There is a prevalence of diabetes mellitus (DM), unknown DM and stress hyperglycemia among hospital patients, and the nutritional treatment is a key part of care, where carbohydrates (CH) intake is a controversial issue. There is also a discussion on the increase of prevalence for DM, obesity and metabolic disease with refined CH or sugar. This review examines the recommendations from different scientific societies about the percentage of CH in the total calorie intake of the diabetic patient, the CH value in the glycemic index and glycemic load, the new CH included in enteral formulae and the association of refined CH with the high prevalence of DM and metabolic disease. Systematic review of literature using the electronic scientific databases Pubmed, Science Direct, Scielo, Scopus and Medline. Scientific societies are flexible about the CH intake in the diet of diabetic patients, suggesting to customize it according to each metabolic profile. Using the glycemic index and glycemic load can provide an extra benefit in the postprandial glycemic control. The new diabetes-specific enteral formulae, with fructooligosaccharides, resistant maltodextrins and fructose-free show efficacy in improving the glycemic control, although more controlled and long-term studies are needed. There is still some controversy about the links between sugar intake and DM, obesity and metabolic disease, although this relationship would be more linked to an increase of the total calorie intake than to a specific nutrient. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  20. Diabetes mellitus related bone metabolism and periodontal disease

    PubMed Central

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-01-01

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts. PMID:25857702

  1. Diabetes mellitus related bone metabolism and periodontal disease.

    PubMed

    Wu, Ying-Ying; Xiao, E; Graves, Dana T

    2015-06-26

    Diabetes mellitus and periodontal disease are chronic diseases affecting a large number of populations worldwide. Changed bone metabolism is one of the important long-term complications associated with diabetes mellitus. Alveolar bone loss is one of the main outcomes of periodontitis, and diabetes is among the primary risk factors for periodontal disease. In this review, we summarise the adverse effects of diabetes on the periodontium in periodontitis subjects, focusing on alveolar bone loss. Bone remodelling begins with osteoclasts resorbing bone, followed by new bone formation by osteoblasts in the resorption lacunae. Therefore, we discuss the potential mechanism of diabetes-enhanced bone loss in relation to osteoblasts and osteoclasts.

  2. [Vitamin D deficiency in a Spanish cohort of patients with chronic kidney disease].

    PubMed

    Yuste, Claudia; García De Vinuesa, Soledad; Goicoechea, Marian; Barraca, Daniel; Panizo, Nayara; Quiroga, Borja; Luño, Jose

    2013-10-19

    Vitamin D (25-OH-D3) deficiency is an emerging global health problem. Chronic kidney disease (CKD) patients have a higher risk of this deficiency. We aimed to determine the prevalence of 25-OH-D3 deficiency in a cohort of CKD patients in an urban area of Spain and its relationship with cardiovascular disease (CVD). We evaluated the prevalence of 25-OH-D3 deficiency in 751 incident patients referred to our outpatient clinic (male gender 59.3%, mean age 67.2 [± 15] years, mean GFR (MDRD-4) 47.9 ± 25.5 ml/min/1.73 m(2)) with different stages of CKD. We excluded end stage renal disease patients and with kidney transplant. Clinical data and biochemical parameters related to bone and mineral metabolism were recorded. Levels of 25-OH-D3< 15 ng/ml were considered to be deficient. The mean 25-OH-D3 levels were 17.06 [± 12.93] ng/ml. Only 10% of our patients had adequate 25-OH-D3 levels (>30 ng/ml) and 51% showed deficient levels. 25-OH-D3 deficiency worsened with the progression of CKD (P<.05). Elderly people (P=.001), female gender (P=.02), and diabetes (P=.03) were closely associated with 25-OH-D3 deficiency. 25-OH-D3 deficiency was inversely associated with serum PTH (P=.02), and directly associated with serum calcium (P<.004). Patients with a history of CVD had lower 25-OH-D3 levels (P=.038). 25-OH-D3 deficiency has a high prevalence in CKD patients, and the severity increases with the progression of kidney disease. Elderly, women and diabetic patients have a higher risk of 25-OH-D3 deficiency. 25-OH-D3 deficiency was related to higher levels of PTH and lower serum calcium. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. Metabolic Dysfunction in Parkinson's Disease: Bioenergetics, Redox Homeostasis and Central Carbon Metabolism.

    PubMed

    Anandhan, Annadurai; Jacome, Maria S; Lei, Shulei; Hernandez-Franco, Pablo; Pappa, Aglaia; Panayiotidis, Mihalis I; Powers, Robert; Franco, Rodrigo

    2017-07-01

    The loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the accumulation of protein inclusions (Lewy bodies) are the pathological hallmarks of Parkinson's disease (PD). PD is triggered by genetic alterations, environmental/occupational exposures and aging. However, the exact molecular mechanisms linking these PD risk factors to neuronal dysfunction are still unclear. Alterations in redox homeostasis and bioenergetics (energy failure) are thought to be central components of neurodegeneration that contribute to the impairment of important homeostatic processes in dopaminergic cells such as protein quality control mechanisms, neurotransmitter release/metabolism, axonal transport of vesicles and cell survival. Importantly, both bioenergetics and redox homeostasis are coupled to neuro-glial central carbon metabolism. We and others have recently established a link between the alterations in central carbon metabolism induced by PD risk factors, redox homeostasis and bioenergetics and their contribution to the survival/death of dopaminergic cells. In this review, we focus on the link between metabolic dysfunction, energy failure and redox imbalance in PD, making an emphasis in the contribution of central carbon (glucose) metabolism. The evidence summarized here strongly supports the consideration of PD as a disorder of cell metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

    PubMed Central

    Nicholls, Andrew W.; Salek, Reza M.; Marques-Vidal, Pedro; Morya, Edgard; Sameshima, Koichi; Montoliu, Ivan; Da Silva, Laeticia; Collino, Sebastiano; Martin, François-Pierre; Rezzi, Serge; Steinbeck, Christoph; Waterworth, Dawn M.; Waeber, Gérard; Vollenweider, Peter; Beckmann, Jacques S.; Le Coutre, Johannes; Mooser, Vincent; Bergmann, Sven; Genick, Ulrich K.; Kutalik, Zoltán

    2014-01-01

    Metabolic traits are molecular phenotypes that can drive clinical phenotypes and may predict disease progression. Here, we report results from a metabolome- and genome-wide association study on 1H-NMR urine metabolic profiles. The study was conducted within an untargeted approach, employing a novel method for compound identification. From our discovery cohort of 835 Caucasian individuals who participated in the CoLaus study, we identified 139 suggestively significant (P<5×10−8) and independent associations between single nucleotide polymorphisms (SNP) and metabolome features. Fifty-six of these associations replicated in the TasteSensomics cohort, comprising 601 individuals from São Paulo of vastly diverse ethnic background. They correspond to eleven gene-metabolite associations, six of which had been previously identified in the urine metabolome and three in the serum metabolome. Our key novel findings are the associations of two SNPs with NMR spectral signatures pointing to fucose (rs492602, P = 6.9×10−44) and lysine (rs8101881, P = 1.2×10−33), respectively. Fine-mapping of the first locus pinpointed the FUT2 gene, which encodes a fucosyltransferase enzyme and has previously been associated with Crohn's disease. This implicates fucose as a potential prognostic disease marker, for which there is already published evidence from a mouse model. The second SNP lies within the SLC7A9 gene, rare mutations of which have been linked to severe kidney damage. The replication of previous associations and our new discoveries demonstrate the potential of untargeted metabolomics GWAS to robustly identify molecular disease markers. PMID:24586186

  5. Age, Period, and Cohort Effects on Mortality From Ischemic Heart Disease in Southern Spain.

    PubMed

    Ocaña-Riola, Ricardo; Mayoral-Cortés, José María; Fernández-Ajuria, Alberto; Sánchez-Cantalejo, Carmen; Martín-Olmedo, Piedad; Blanco-Reina, Encarnación

    2015-05-01

    Ischemic heart disease is the leading cause of death and one of the top 4 causes of burden of disease worldwide. The aim of this study was to evaluate age-period-cohort effects on mortality from ischemic heart disease in Andalusia (southern Spain) and in each of its 8 provinces during the period 1981-2008. A population-based ecological study was conducted. In all, 145 539 deaths from ischemic heart disease were analyzed for individuals aged between 30 and 84 years who died in Andalusia in the study period. A nonlinear regression model was estimated for each sex and geographical area using spline functions. There was an upward trend in male and female mortality rate by age from the age of 30 years. The risk of death for men and women showed a downward trend for cohorts born after 1920, decreasing after 1960 with a steep slope among men. Analysis of the period effect showed that male and female death risk first remained steady from 1981 to 1990 and then increased between 1990 and 2000, only to decrease again until 2008. There were similar age-period-cohort effects on mortality in all the provinces of Andalusia and for Andalusia as a whole. If the observed cohort and period effects persist, male and female mortality from ischemic heart disease will continue to decline. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  6. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome.

    PubMed

    Aguilar-Olivos, Nancy E; Almeda-Valdes, Paloma; Aguilar-Salinas, Carlos A; Uribe, Misael; Méndez-Sánchez, Nahum

    2016-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD is strongly associated with obesity and metabolic syndrome (MetS). Current treatment of NAFLD is based on weight reduction. Bariatric surgery is the most effective treatment for morbid obesity and its associated metabolic comorbidities. There is evidence indicating that bariatric surgery improves histological and biochemical parameters of NAFLD, but currently is not considered a treatment option for NAFLD. The aim of this work is to review the evidence for the effects of bariatric surgery on NAFLD and the MetS. We found that insulin resistance, alterations in glucose metabolism, hypertension, plasma lipids, transaminases, liver steatosis, steatohepatitis and fibrosis improve after bariatric surgery. Weight loss and improvement of NAFLD are greater after RYGB than after other interventions. These findings were obtained from retrospective or cohort studies. There are no studies designed to evaluate liver-specific mortality, liver transplantation, or quality of life. Patients with indications for bariatric surgery will benefit from the improvements in the MetS and NAFLD. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Increased risk of coronary heart disease in patients with hip fracture: a nationwide cohort study.

    PubMed

    Tsai, C-H; Lin, C-L; Hsu, H-C; Chung, W-S

    2015-06-01

    The study indicates that hip fracture is independently associated with increased risk of coronary heart disease. In addition, the highest risk of coronary heart disease following hip fracture appeared within the first year after hip fracture, indicating the need for multidisciplinary care for the patients. Bone and vasculature are modulated through numerous common pathways. However, data on the risk of coronary heart disease (CHD) after hip fracture are scarce. Therefore, we investigated whether hip fracture increased the risk of CHD by conducting a large nationwide cohort study. Using universal insurance claims data from 2000 to 2010, we identified a study cohort of 6013 participants newly diagnosed with hip fracture and a control cohort of 23,802 participants. Both cohorts were followed up to the end of 2011 to evaluate the risk of CHD. The overall incidence of CHD was 1.69-fold higher in the hip fracture cohort than it was in the control cohort (29.2 vs. 17.1 per 1000 person-years) with an adjusted hazard ratio of 1.51 (95 % confidence interval [CI] = 1.39-1.65). Sex-, age-, and comorbidity-specific analyses showed a higher relative risk of CHD for both women and men, all age groups, those with and without comorbidities, and patients with hip fracture compared with the control cohort. The highest risk of CHD was within the first year after hip fracture (adjusted HR = 1.72, 95 % CI = 1.45-2.04), and the risk remained high in the following years. Hip fracture was independently associated with a subsequent risk of CHD.

  8. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research.

    PubMed

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  9. metabolicMine: an integrated genomics, genetics and proteomics data warehouse for common metabolic disease research

    PubMed Central

    Lyne, Mike; Smith, Richard N; Lyne, Rachel; Aleksic, Jelena; Hu, Fengyuan; Kalderimis, Alex; Stepan, Radek; Micklem, Gos

    2013-01-01

    Common metabolic and endocrine diseases such as diabetes affect millions of people worldwide and have a major health impact, frequently leading to complications and mortality. In a search for better prevention and treatment, there is ongoing research into the underlying molecular and genetic bases of these complex human diseases, as well as into the links with risk factors such as obesity. Although an increasing number of relevant genomic and proteomic data sets have become available, the quantity and diversity of the data make their efficient exploitation challenging. Here, we present metabolicMine, a data warehouse with a specific focus on the genomics, genetics and proteomics of common metabolic diseases. Developed in collaboration with leading UK metabolic disease groups, metabolicMine integrates data sets from a range of experiments and model organisms alongside tools for exploring them. The current version brings together information covering genes, proteins, orthologues, interactions, gene expression, pathways, ontologies, diseases, genome-wide association studies and single nucleotide polymorphisms. Although the emphasis is on human data, key data sets from mouse and rat are included. These are complemented by interoperation with the RatMine rat genomics database, with a corresponding mouse version under development by the Mouse Genome Informatics (MGI) group. The web interface contains a number of features including keyword search, a library of Search Forms, the QueryBuilder and list analysis tools. This provides researchers with many different ways to analyse, view and flexibly export data. Programming interfaces and automatic code generation in several languages are supported, and many of the features of the web interface are available through web services. The combination of diverse data sets integrated with analysis tools and a powerful query system makes metabolicMine a valuable research resource. The web interface makes it accessible to first

  10. Plasma-parathyroid hormone is associated with subclinical and clinical atherosclerotic disease in 2 community-based cohorts.

    PubMed

    Hagström, Emil; Michaëlsson, Karl; Melhus, Håkan; Hansen, Thomas; Ahlström, Håkan; Johansson, Lars; Ingelsson, Erik; Sundström, Johan; Lind, Lars; Arnlöv, Johan

    2014-07-01

    Cardiovascular risk factors have different impact on different arterial territories. Diseases with elevated circulating parathyroid hormone (PTH) such as primary hyperparathyroidism and chronic renal failure have been shown to be associated with an increased risk of cardiovascular disease, predominantly heart or cerebrovascular diseases. However, data on the associations between circulating PTH and peripheral atherosclerosis are limited. Two prospective, community-based studies were used. In 306 men and women, who were 70 years old, from the Prospective investigation of the vasculature in Uppsala seniors (PIVUS) study, cross-sectional relations between PTH and atherosclerotic burden assessed by whole-body magnetic resonance angiography were investigated. In 998 men, who were 71 years old, from the Uppsala longitudinal study of adult men (ULSAM) study, the association between PTH concentration and risk of subsequent nonfatal atherosclerotic disease (excluding coronary or cerebrovascular disease) was investigated. Adjusting for established vascular risk factors, PTH was associated with burden of atherosclerosis (increase in total atherosclerotic score per SD PTH increase: 0.04, 0.003-0.08; P=0.03) in the PIVUS study. During follow-up in the ULSAM study (median 16.7 years), 89 men were diagnosed with nonfatal atherosclerotic disease. In Cox-regression analyses adjusting for established vascular risk factors and mineral metabolism, higher PTH was associated with an increased risk of nonfatal atherosclerotic disease (hazard ratio for 1 SD increase of PTH: 1.55, 1.33-1.88; P<0.0001). Results were similar when including fatal atherosclerotic disease in the outcome. In 2 independent community-based cohorts, PTH was associated to the degree of atherosclerosis and risk of clinically overt atherosclerotic disease, respectively. Our data confirm and extend previous studies supporting a role for PTH in the development of atherosclerotic disease. © 2014 American Heart

  11. The influence of carbohydrate quality on cardiovascular disease, the metabolic syndrome, type 2 diabetes, and obesity - an overview.

    PubMed

    Slyper, Arnold H

    2013-01-01

    There is compelling evidence that carbohydrate quality has important influences on cardiovascular disease, the metabolic syndrome, type 2 diabetes, and obesity. Cohort and interventional studies indicate that dietary fiber is an important determinant of satiation, satiety, and weight gain, and also protects against cardiovascular disease. Cohort studies have shown that vegetables and fruits protect against coronary heart disease, whereas whole grains provide protection against cardiovascular disease, type 2 diabetes, and weight gain. Dietary glycemia within the range eaten by most of the population seems not to have a significant influence on body weight, although it may influence waist circumference. There is strong evidence from interventional trials that dietary glycemia does influence insulin resistance and diabetes control. Moreover, replacing saturated fat with high-glycemic carbohydrate may increase cardiovascular risk. Soft drink consumption is a proven cause of weight gain, which may relate to the lack of satiation provided by these drinks. In large amounts, dietary fructose leads to greater adverse metabolic changes than equivalent amounts of glucose, although the extent to which fructose per se is contributing to many of the metabolic changes found in the obese, as distinct from the calories it provides, is still a matter of debate.

  12. Circadian Disruption and Metabolic Disease: Findings from Animal Models

    PubMed Central

    Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph

    2010-01-01

    Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease. PMID:21112026

  13. Circadian disruption and metabolic disease: findings from animal models.

    PubMed

    Arble, Deanna Marie; Ramsey, Kathryn Moynihan; Bass, Joseph; Turek, Fred W

    2010-10-01

    Social opportunities and work demands have caused humans to become increasingly active during the late evening hours, leading to a shift from the predominantly diurnal lifestyle of our ancestors to a more nocturnal one. This voluntarily decision to stay awake long into the evening hours leads to circadian disruption at the system, tissue, and cellular levels. These derangements are in turn associated with clinical impairments in metabolic processes and physiology. The use of animal models for circadian disruption provides an important opportunity to determine mechanisms by which disorganization in the circadian system can lead to metabolic dysfunction in response to genetic, environmental, and behavioral perturbations. Here we review recent key animal studies involving circadian disruption and discuss the possible translational implications of these studies for human health and particularly for the development of metabolic disease.

  14. The gut microbiota: a key regulator of metabolic diseases

    PubMed Central

    Yang, Jin-Young; Kweon, Mi-Na

    2016-01-01

    The prevalence of obesity and type 2 diabetes, two closely linked metabolic disorders, is increasing worldwide. Over the past decade, the connection between these disorders and the microbiota of the gut has become a major focus of biomedical research, with recent studies demonstrating the fundamental role of intestinal microbiota in the regulation and pathogenesis of metabolic disorders. Because of the complexity of the microbiota community, however, the underlying molecular mechanisms by which the gut microbiota is associated with metabolic disorders remain poorly understood. In this review, we summarize recent studies that investigate the role of the microbiota in both human subjects and animal models of disease and discuss relevant therapeutic targets for future research. [BMB Reports 2016; 49(10): 536-541] PMID:27530685

  15. The gut microbiota: a key regulator of metabolic diseases.

    PubMed

    Yang, Jin-Young; Kweon, Mi-Na

    2016-10-01

    The prevalence of obesity and type 2 diabetes, two closely linked metabolic disorders, is increasing worldwide. Over the past decade, the connection between these disorders and the microbiota of the gut has become a major focus of biomedical research, with recent studies demonstrating the fundamental role of intestinal microbiota in the regulation and pathogenesis of metabolic disorders. Because of the complexity of the microbiota community, however, the underlying molecular mechanisms by which the gut microbiota is associated with metabolic disorders remain poorly understood. In this review, we summarize recent studies that investigate the role of the microbiota in both human subjects and animal models of disease and discuss relevant therapeutic targets for future research. [BMB Reports 2016; 49(10): 536-541].

  16. The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease.

    PubMed

    Mazier, Wilfrid; Saucisse, Nicolas; Gatta-Cherifi, Blandine; Cota, Daniela

    2015-10-01

    The endocannabinoid system (ECS) functions to adjust behavior and metabolism according to environmental changes in food availability. Its actions range from the regulation of sensory responses to the development of preference for the consumption of calorically-rich food and control of its metabolic handling. ECS activity is beneficial when access to food is scarce or unpredictable. However, when food is plentiful, the ECS favors obesity and metabolic disease. We review recent advances in understanding the roles of the ECS in energy balance, and discuss newly identified mechanisms of action that, after the withdrawal of first generation cannabinoid type 1 (CB1) receptor antagonists for the treatment of obesity, have made the ECS once again an attractive target for therapy.

  17. Nutritional and metabolic modulation in chronic obstructive pulmonary disease management.

    PubMed

    Schols, A M W J

    2003-11-01

    In this paper the perspective for nutritional modulation of systemic impairment in patients with chronic obstructive pulmonary disease (COPD) is discussed. Progressive weight loss is characterised by disease-specific elevated energy requirements unbalanced by dietary intake. Weight gain per se can be achieved by caloric supplementation while future studies may prove efficacy of amino acid modulation to stimulate protein synthesis and enhance muscle anabolism. Disproportionate muscle wasting resembles the cachexia syndrome as described in other chronic wasting diseases (cancer, chronic heart failure, acquired immunodeficiency syndrome (AIDS)). There is yet no adequate nutritional strategy available to treat cachexia in COPD. Muscle substrate metabolism has hardly been investigated, but the few data available point towards a decreased fat oxidative capacity that may show similarities with the "metabolic syndrome" as described in type II diabetes and obesity and could theoretically benefit from polyunsaturated fatty acid modulation. To adequately target the different therapeutic options, clearly more clinical (intervention) studies are needed in chronic obstructive pulmonary disease patients that are adequately characterised by local and systemic impairment and in which molecular and metabolic markers are linked to functional outcome.

  18. Endocrine Manifestations in a Monocentric Cohort of 64 Patients With Erdheim-Chester Disease.

    PubMed

    Courtillot, C; Laugier Robiolle, S; Cohen Aubart, F; Leban, M; Renard-Penna, R; Drier, A; Charlotte, F; Amoura, Z; Touraine, P; Haroche, J

    2016-01-01

    Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, characterized by infiltration of foamy histiocytes in multiple organs. Endocrine involvement has mostly been described in case reports. We performed systematic endocrine evaluation in a large cohort of patients with ECD. This was a single-center observational study conducted between October 2007 and May 2013. The evaluation was conducted in Pitié-Salpêtrière Hospital (Paris, France), a tertiary care hospital. Sixty-four consecutive patients with ECD (sex ratio, 3.6; mean age, 57.6 years [range, 20-80 years]). Thirty-six patients had follow-up assessments. There were no interventions. Clinical, biological, and morphological evaluations of pituitary, gonadal, adrenal, and thyroid functions, as well as metabolic evaluation, were performed. Diabetes insipidus was found in 33.3% of patients, frequently as the first manifestation of ECD. Anterior pituitary dysfunction was found in 91.3% of patients with full anterior pituitary evaluation, including somatotropic deficiency (78.6%), hyperprolactinemia (44.1%), gonadotropic deficiency (22.2%), thyrotropic deficiency (9.5%), and corticotropic deficiency (3.1%). Thirty-five patients (54.7%) had ≥2 anterior pituitary dysfunctional axes, rising to 69.6% (16 of 23) when only patients with complete evaluations were considered. Two patients had panhypopituitarism. Infiltration of the pituitary and stalk was found with magnetic resonance imaging in 24.4% of patients. Testicular insufficiency was found in 53.1% of patients, with sonographic testicular infiltration in 29% of men, mostly bilateral. Computed tomography adrenal infiltration was found in 39.1% of patients, and 1 case of adrenal insufficiency was observed. No patient was free of endocrine hormonal or morphological involvement. Endocrine dysfunctions were most often permanent, and new deficits appeared during follow-up. Endocrine involvement is very frequent in ECD and should be evaluated

  19. Predictors of dementia in Parkinson disease: a prospective cohort study.

    PubMed

    Anang, Julius B M; Gagnon, Jean-Francois; Bertrand, Josie-Anne; Romenets, Silvia Rios; Latreille, Veronique; Panisset, Michel; Montplaisir, Jacques; Postuma, Ronald B

    2014-09-30

    We investigated an array of possible markers of early dementia in Parkinson disease. We performed a comprehensive assessment of autonomic, sleep, psychiatric, visual, olfactory, and motor manifestations in 80 patients with Parkinson disease who were dementia-free at baseline. After 4.4 years' follow-up, patients were evaluated for dementia. Predictive variables were assessed using logistic regression adjusting for disease duration, follow-up duration, age, and sex. Of 80 patients, 27 (34%) developed dementia. Patients destined to develop dementia were older and more often male (odds ratio [OR] = 3.64, p = 0.023). Those with baseline mild cognitive impairment had increased dementia risk (OR = 22.5, p < 0.001). REM sleep behavior disorder at baseline dramatically increased dementia risk (OR = 49.7, p = 0.001); however, neither daytime sleepiness nor insomnia predicted dementia. Higher baseline blood pressure increased dementia risk (OR = 1.37 per 10 mm Hg, p = 0.032). Orthostatic blood pressure drop was strongly associated with dementia risk (OR = 1.84 per 10 mm Hg, p < 0.001); having a systolic drop of >10 mm Hg increased dementia odds 7-fold (OR = 7.3, p = 0.002). Abnormal color vision increased dementia risk (OR = 3.3, p = 0.014), but olfactory dysfunction did not. Among baseline motor variables, proportion of gait involvement (OR = 1.12, p = 0.023), falls (OR = 3.02, p = 0.042), and freezing (OR = 2.63, p = 0.013), as well as the Purdue Pegboard Test (OR = 0.67, p = 0.049) and alternate tap test (OR = 0.97, p = 0.033) predicted dementia. Cardiovascular autonomic dysfunction, REM sleep behavior disorder, color discrimination ability, and gait dysfunction strongly predict development of dementia in Parkinson disease. © 2014 American Academy of Neurology.

  20. Synergistic Effects of Six Chronic Disease Pairs on Decreased Physical Activity: The SMILE Cohort Study

    PubMed Central

    Dörenkamp, Sarah; Mesters, Ilse; Vos, Rein; Schepers, Jan; van den Akker, Marjan; Teijink, Joep; de Bie, Rob

    2016-01-01

    Little is known about whether and how two chronic diseases interact with each other in modifying the risk of physical inactivity. The aim of the present study is to identify chronic disease pairs that are associated with compliance or noncompliance with the Dutch PA guideline recommendation and to study whether specific chronic disease pairs indicate an extra effect on top of the effects of the diseases individually. Cross-sectional data from 3,386 participants of cohort study SMILE were used and logistic regression analysis was performed to study the joint effect of the two diseases of each chronic disease pair for compliance with the Dutch PA guideline. For six chronic disease pairs, patients suffering from both diseases belonging to these disease pairs in question show a higher probability of noncompliance to the Dutch PA guideline, compared to what one would expect based on the effects of each of the two diseases alone. These six chronic disease pairs were chronic respiratory disease and severe back problems; migraine and inflammatory joint disease; chronic respiratory disease and severe kidney disease; chronic respiratory disease and inflammatory joint disease; inflammatory joint disease and rheumatoid arthritis; and rheumatoid arthritis and osteoarthritis of the knees, hips, and hands. PMID:27274994

  1. Microvesicles/exosomes as potential novel biomarkers of metabolic diseases

    PubMed Central

    Müller, Günter

    2012-01-01

    Biomarkers are of tremendous importance for the prediction, diagnosis, and observation of the therapeutic success of common complex multifactorial metabolic diseases, such as type II diabetes and obesity. However, the predictive power of the traditional biomarkers used (eg, plasma metabolites and cytokines, body parameters) is apparently not sufficient for reliable monitoring of stage-dependent pathogenesis starting with the healthy state via its initiation and development to the established disease and further progression to late clinical outcomes. Moreover, the elucidation of putative considerable differences in the underlying pathogenetic pathways (eg, related to cellular/tissue origin, epigenetic and environmental effects) within the patient population and, consequently, the differentiation between individual options for disease prevention and therapy – hallmarks of personalized medicine – plays only a minor role in the traditional biomarker concept of metabolic diseases. In contrast, multidimensional and interdependent patterns of genetic, epigenetic, and phenotypic markers presumably will add a novel quality to predictive values, provided they can be followed routinely along the complete individual disease pathway with sufficient precision. These requirements may be fulfilled by small membrane vesicles, which are so-called exosomes and microvesicles (EMVs) that are released via two distinct molecular mechanisms from a wide variety of tissue and blood cells into the circulation in response to normal and stress/pathogenic conditions and are equipped with a multitude of transmembrane, soluble and glycosylphosphatidylinositol-anchored proteins, mRNAs, and microRNAs. Based on the currently available data, EMVs seem to reflect the diverse functional and dysfunctional states of the releasing cells and tissues along the complete individual pathogenetic pathways underlying metabolic diseases. A critical step in further validation of EMVs as biomarkers will rely on

  2. POLYBROMINATED BIPHENYL EXPOSURE AND BENIGN BREAST DISEASE IN A COHORT OF US WOMEN. (R825300)

    EPA Science Inventory

    PURPOSE: We examined the relation between serum polybrominated biphenyl (PBB) levels and the risk of benign breast disease in a cohort of Michigan women unintentionally exposed to PBBs in 1973 and interviewed in 1997.

    METHODS: We used extend...

  3. Stargardt disease-associated mutation spectrum of a Russian Federation cohort.

    PubMed

    Zolnikova, Inna V; Strelnikov, Vladimir V; Skvortsova, Natalia A; Tanas, Alexander S; Barh, Debmalya; Rogatina, Elena V; Egorova, Irina V; Levina, Darja V; Demenkova, Olga N; Prikaziuk, Egor G; Ivanova, Marianna E

    2017-02-01

    ABCA4-associated mutation screening is extensively performed in European, African, American and several other populations for various retinopathies. However, it has not been well studied in a Russian cohort. Using next-generation (325 genes inherited disease panel) and Sanger sequencing technologies for the first time we documented the spectrum of genetic variations in a Russian retinopathy cohort of 51 patients from 10 ethnic groups. We found ABCA4 variations in 70.5% cases and one case with BEST1 variation. Multiple ABCA4 variations, ABCA4 + RDH12, and ABCA4 + BEST1 variations are also observed and the disease severity is found proportionate to the variation burden. Ten novel ABCA4 variations are detected of which 8 belongs to non-Slavonian population. Most of the detected known variations are found in European and American Stargardt disease populations. No retinopathy causing variation is detected in 14 (27%) cases suggesting that in this Russian retinopathies cohort the causal variants could be in genes that are not covered by our 325 gene panel. Therefore, whole genome/exome analysis is required to identify novel retinopathy associated genes and provide better disease management for this heterogeneous cohort.

  4. IQ in Childhood and the Metabolic Syndrome in Middle Age: Extended Follow-Up of the 1946 British Birth Cohort Study

    ERIC Educational Resources Information Center

    Richards, Marcus; Black, Stephanie; Mishra, Gita; Gale, Catharine R.; Deary, Ian J.; Batty, David G.

    2009-01-01

    IQ in early adulthood has been inversely associated with risk of the metabolic syndrome in midlife. We tested this association in the British 1946 birth cohort, which assessed IQ at age eight years and ascertained the metabolic syndrome at age 53 years based on modified (non-fasting blood) ATPIII criteria. Childhood IQ was inversely associated…

  5. IQ in Childhood and the Metabolic Syndrome in Middle Age: Extended Follow-Up of the 1946 British Birth Cohort Study

    ERIC Educational Resources Information Center

    Richards, Marcus; Black, Stephanie; Mishra, Gita; Gale, Catharine R.; Deary, Ian J.; Batty, David G.

    2009-01-01

    IQ in early adulthood has been inversely associated with risk of the metabolic syndrome in midlife. We tested this association in the British 1946 birth cohort, which assessed IQ at age eight years and ascertained the metabolic syndrome at age 53 years based on modified (non-fasting blood) ATPIII criteria. Childhood IQ was inversely associated…

  6. Influence of metabolic syndrome on upper gastrointestinal disease.

    PubMed

    Sogabe, Masahiro; Okahisa, Toshiya; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Takayama, Tetsuji

    2016-08-01

    A recent increase in the rate of obesity as a result of insufficient physical exercise and excess food consumption has been seen in both developed and developing countries throughout the world. Additionally, the recent increased number of obese individuals with lifestyle-related diseases associated with abnormalities in glucose metabolism, dyslipidemia, and hypertension, defined as metabolic syndrome (MS), has been problematic. Although MS has been highlighted as a risk factor for ischemic heart disease and arteriosclerotic diseases, it was also recently shown to be associated with digestive system disorders, including upper gastrointestinal diseases. Unlike high body weight and high body mass index, abdominal obesity with visceral fat accumulation is implicated in the onset of various digestive system diseases because excessive visceral fat accumulation may cause an increase in intra-abdominal pressure, inducing the release of various bioactive substances, known as adipocytokines, including tumor necrosis factor-α, interleukin-6, resistin, leptin, and adiponectin. This review article focuses on upper gastrointestinal disorders and their association with MS, including obesity, visceral fat accumulation, and the major upper gastrointestinal diseases.

  7. Abnormal erythrocyte metabolism in hepatic disease: effect of NADP repletion.

    PubMed

    Smith, J R; Kay, N E; Gottlieb, A J; Oski, F A

    1979-01-01

    Erythrocytes from ten patients with severe liver disease displayed low methylene blue-stimulated hexose monophosphate (HMP) shunt activity and glucose recycling despite elevated total glucose consumption when compared to controls. Heinz body formation was increased and reduced glutathione concentration significantly decreased. After hemolysis, no differences in methylene-blue estimulated HMP shunt activity or glucose recycling could be demonstrated between patients and controls. The addition of 2- and 4-mM NADP to the hemolysates produced significantly greater HMP shunt activity and glucose recycling in the patients' hemolysates. The addition of NADPH to the incubation mixture produced no significant stimulation of either HMP shunt activity or glucose recycling, unless methylene blue was also added. Omission of NAD or phosphate from the incubation mixture produced no change in shunt metabolism. The absence of supplemental ATP resulted in extremely low shunt metabolism and refractoriness to NADP stimulation in both patients and controls. In the absence of additional magnesium, a reduction of shunt metabolism was noted. These data suggest that the defect in stimulated shunt metabolism in the intact erythrocytes of patients with hepatic disease does not result from an absolute enzyme deficiency, but rather from an unavailability of NADP or other cofactor.

  8. Mechanistic modeling of aberrant energy metabolism in human disease

    PubMed Central

    Sangar, Vineet; Eddy, James A.; Simeonidis, Evangelos; Price, Nathan D.

    2012-01-01

    Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based (CB) models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell. PMID:23112774

  9. Peroxisome proliferator-activated receptors, metabolic syndrome and cardiovascular disease

    PubMed Central

    Azhar, Salman

    2011-01-01

    Metabolic syndrome (MetS) is a constellation of risk factors including insulin resistance, central obesity, dyslipidemia and hypertension that markedly increase the risk of Type 2 diabetes (T2DM) and cardiovascular disease (CVD). The peroxisome proliferators-activated receptor (PPAR) isotypes, PPARα, PPARδ/β and PPARγ are ligand-activated nuclear transcription factors, which modulate the expression of an array of genes that play a central role in regulating glucose, lipid and cholesterol metabolism, where imbalance can lead to obesity, T2DM and CVD. They are also drug targets, and currently, PPARα (fibrates) and PPARγ (thiazolodinediones) agonists are in clinical use for treating dyslipidemia and T2DM, respectively. These metabolic characteristics of the PPARs, coupled with their involvement in metabolic diseases, mean extensive efforts are underway worldwide to develop new and efficacious PPAR-based therapies for the treatment of additional maladies associated with the MetS. This article presents an overview of the functional characteristics of three PPAR isotypes, discusses recent advances in our understanding of the diverse biological actions of PPARs, particularly in the vascular system, and summarizes the developmental status of new single, dual, pan (multiple) and partial PPAR agonists for the clinical management of key components of MetS, T2DM and CVD. It also summarizes the clinical outcomes from various clinical trials aimed at evaluating the atheroprotective actions of currently used fibrates and thiazolodinediones. PMID:20932114

  10. BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

    PubMed Central

    Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

    2012-01-01

    Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

  11. Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

    PubMed Central

    Kumar, Surinder

    2015-01-01

    Abstract Significance: Maintenance of metabolic homeostasis is critical for cellular and organismal health. Proper regulation of mitochondrial functions represents a crucial element of overall metabolic homeostasis. Mitochondrial sirtuins (SIRT3, SIRT4, and SIRT5) play pivotal roles in promoting this homeostasis by regulating numerous aspects of mitochondrial metabolism in response to environmental stressors. Recent Advances: New work has illuminated multiple links between mitochondrial sirtuins and cancer. SIRT5 has been shown to regulate the recently described post-translational modifications succinyl-lysine, malonyl-lysine, and glutaryl-lysine. An understanding of these modifications is still in its infancy. Enumeration of SIRT3 and SIRT5 targets via advanced proteomic techniques promises to dramatically enhance insight into functions of these proteins. Critical Issues: In this review, we highlight the roles of mitochondrial sirtuins and their targets in cellular and organismal metabolic homeostasis. Furthermore, we discuss emerging roles for mitochondrial sirtuins in suppressing and/or promoting tumorigenesis, depending on the cellular and molecular context. Future Directions: Currently, hundreds of potential SIRT3 and SIRT5 molecular targets have been identified in proteomic experiments. Future studies will need to validate the major targets of these enzymes, and elucidate how acetylation and/or acylation modulate their functionality. A great deal of interest exists in targeting sirtuins pharmacologically; this endeavor will require development of sirtuin-specific modulators (activators and inhibitors) as potential treatments for cancer and metabolic disease. Antioxid. Redox Signal. 22, 1060–1077. PMID:25545135

  12. Resistant starches for the management of metabolic diseases.

    PubMed

    Bindels, Laure B; Walter, Jens; Ramer-Tait, Amanda E

    2015-11-01

    Recent clinical trials and animal studies indicate that resistant starches may be beneficial therapeutic tools for the management of metabolic diseases. The purpose of this review is to summarize these findings and discuss the established and proposed mechanisms by which resistant starches exert their benefits. We also examine open questions regarding how resistant starches improve metabolism and propose future research directions for the field. Data from both humans and animal models clearly support a role for resistant starches in improving a variety of metabolic features; however, discrepancies do exist regarding specific effects. Concomitant improvements in both insulin levels and body fat depots are often reported in rodents fed resistant starches, whereas resistant starch feeding in humans improves insulin sensitivity without having a major impact on fat mass. These differences could be explained by the coexistence of several mechanisms (both gut microbiota-dependent and gut microbiota-independent) underpinning the metabolic benefits of resistant starches. Together, the studies presented in this review offer new insights into the potential pathways by which resistant starches enhance metabolic health, including modulation of the gut microbiota, gut peptides, circulating inflammatory mediators, innate immune cells, and the bile acid cycle.

  13. Lipoprotein Metabolism, Dyslipidemia and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Cohen, David E.; Fisher, Edward A.

    2014-01-01

    Cardiovascular disease represents the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). NAFLD patients exhibit an atherogenic dyslipidemia that is characterized by an increased plasma concentration of triglycerides, reduced concentration of high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) particles that are smaller and more dense than normal. The pathogenesis of NAFLD-associated atherogenic dyslipidemia is multifaceted, but many aspects are attributable to manifestations of insulin resistance. Here we review the structure, function and metabolism of lipoproteins, which are macromolecular particles of lipids and proteins that transport otherwise insoluble triglyceride and cholesterol molecules within the plasma. We provide a current explanation of the metabolic perturbations that are observed in the setting of insulin resistance. An improved understanding of the pathophysiology of atherogenic dyslipidemia would be expected to guide therapies aimed at reducing morbidity and mortality in NAFLD patients. PMID:24222095

  14. Anthropometric parameters--predictive factors for cardio-metabolic diseases.

    PubMed

    Mihalache, Laura; Graur, Lidia Iuliana; Popescu, Dana Stefana; Niţă, Otilia; Graur, Mariana

    2012-01-01

    The aim of this study was to evaluate comparatively the predictive power of body mass index (BMI) and waist circumference (WC), two anthropometric parameters used in daily practice, for detecting cardio-metabolic diseases, in a rural community in north-east Romania. We evaluated 3248 persons, aged 19 or over, for whom we collected the following data: medical history, anthropometric parameters, blood pressure value and biochemical parameters. Both WC and BMI help correctly determine the presence of arterial hypertension, diabetes and dislipidemia. However, the cut-off value of each of these parameters differs for each pathology. The predictive value of WC for different cardio-metabolic diseases is maintained even at normal or borderline overweight values of BMI.

  15. Nonalcoholic fatty liver disease and metabolic syndrome in postmenopausal women.

    PubMed

    Rodrigues, Marcio H; Bruno, Anderson S; Nahas-Neto, Jorge; Santos, Maria Emilia S; Nahas, Eliana A P

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) is considered the most common cause of chronic liver disease in the Western countries. NAFLD includes a spectrum ranging from a simple steatosis to a nonalcoholic steatohepatitis (NASH) which is defined by the presence of inflammatory infiltrate, cellular necrosis, hepatocyte ballooning, and fibrosis and cirrhosis that can eventually develop into hepatocellular carcinoma. Studies emphasize the role of insulin resistance, oxidative stress, pro-inflammatory cytokines, adipokines in the development and progression of NAFLD. It seems to be independently associated with type II diabetes mellitus, increased triglycerides, decreased HDL-cholesterol, abdominal obesity and insulin resistance. These findings are in accordance with the criteria used in the diagnosis of metabolic syndrome (MetS). Here, we will discuss the current knowledge on the epidemiology, pathophysiology and diagnosis of NAFLD and the association of metabolic syndrome in postmenopausal women.

  16. [Gene transfer as treatment for metabolic inherited liver diseases

    PubMed

    Godoy, J L

    2000-01-01

    OBJECTIVE: To study gene transfer looking for its future clinical application in the treatment of metabolic inherited liver diseases. METHODS: Bibliographic review about the subject. RESULTS AND CONCLUSIONS: Gene transfer into the liver would be an alternative to liver transplantation to treat some inherited metabolic diseases. Various vectors have been employed for gene transfer, including retrovirus vectors, whose integration into the chromosomal DNA would allow stable long term expression of the transgene. The integration of retrovirus vectors into the genoma of the target cell is only possible during mitosis. Therefore, these vectors must be delivered during hepatic regeneration induced by partial hepatectomy, for example. Another obstacle to be overcome is the extra hepatic dissemination of retrovirus, in particular to the germinals cells, due to the risk of changing the genetical heritage of the progeniture.

  17. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states

    PubMed Central

    Naftalin, Richard J.

    2016-01-01

    A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD), non-alcoholic steatohepatitis, (NASH) and type 2 diabetes mellitus, (T2DM) demonstrates how when glucagon-like peptide-1, (GLP-1) is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA) blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU). When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic implications on GLP

  18. Disease activity, severity, and damage in the UK Juvenile-Onset Systemic Lupus Erythematosus Cohort.

    PubMed

    Watson, Louise; Leone, Valentina; Pilkington, Clarissa; Tullus, Kjell; Rangaraj, Satyapal; McDonagh, Janet E; Gardner-Medwin, Janet; Wilkinson, Nick; Riley, Phil; Tizard, Jane; Armon, Kate; Sinha, Manish D; Ioannou, Yiannis; Archer, Neil; Bailey, Kathryn; Davidson, Joyce; Baildam, Eileen M; Cleary, Gavin; McCann, Liza J; Beresford, Michael W

    2012-07-01

    The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease

  19. Alzheimer's Disease is an Important Risk Factor of Fractures: a Meta-analysis of Cohort Studies.

    PubMed

    Liang, Ying; Wang, Lei

    2016-04-12

    The risk of fracture in individuals with Alzheimer's disease had not been fully quantified. A systematic review and meta-analysis of cohort studies was performed to estimate the impact of Alzheimer's disease on risk of fractures. Pubmed and Embase were searched for eligible cohort studies assessing the association between Alzheimer's disease and risk of fractures. The overall relative risks (RRs) with 95% CIs were calculated using a random-effects model to evaluate the association. Six cohort studies with a total of 137,986 participants were included into the meta-analysis. Meta-analysis of a total of six studies showed that Alzheimer's disease was significantly associated with two-fold increased risk of fractures (RR = 2.18, 95 % CI 1.64-2.90, P < 0.001; I (2) = 91.4 %). Meta-regression analysis showed that type of fractures was a source of heterogeneity (P = 0.003). Meta-analysis of five studies on hip fracture showed that Alzheimer's disease was significantly associated with 2.5-fold increased risk of hip fracture (RR = 2.52, 95 % CI 2.26-2.81, P < 0.001; I (2) = 25.2 %). There was no risk of publication bias observed in the funnel plot. There is strong evidence that Alzheimer's disease is a risk factor of hip fracture.

  20. Risk of Periodontal Disease in Patients With Asthma: A Nationwide Population-Based Retrospective Cohort Study.

    PubMed

    Shen, Te-Chun; Chang, Pei-Ying; Lin, Cheng-Li; Wei, Chang-Ching; Tu, Chih-Yen; Hsia, Te-Chun; Shih, Chuen-Ming; Hsu, Wu-Huei; Sung, Fung-Chang; Kao, Chia-Hung

    2017-08-01

    Studies have reported an association between asthma and oral diseases, including periodontal diseases. The aim of this retrospective study is to investigate risk of periodontal diseases for patients with asthma. Using the claims data of National Health Insurance of Taiwan and patients without a history of periodontal diseases, 19,206 asthmatic patients, who were newly diagnosed from 2000 through 2010, were identified. For each case, four comparison individuals without history of asthma and periodontal disease were randomly selected from the general population and frequency matched (categorical matched) by sex, age, and year of diagnosis (n = 76,824). Both cohorts were followed to the end of 2011 to monitor occurrence of periodontal diseases. Adjusted hazard ratios (aHRs) of periodontal disease were estimated using Cox proportional hazards regression analysis. Overall incidence of periodontal diseases was 1.18-fold greater in the asthma cohort than in the comparison cohort (P <0.001). Patients with at least three emergency visits annually had an aHR of 55.9 (95% confidence interval [CI] = 50.6 to 61.7) for periodontal diseases compared with those with a mean of less than one visit. Patients with at least three admissions annually also had a similar aHR (51.8) for periodontal disease. In addition, asthmatic patients on inhaled corticosteroid (ICS) therapy had greater aHRs than non-users (aHR = 1.12; 95% CI = 1.03 to 1.23). In the studied population, asthmatic patients are at an elevated risk of developing periodontal diseases. The risk is much greater for those with emergency medical demands or hospital admissions and those on ICS treatment.

  1. Hematopoietic Gene Therapies for Metabolic and Neurologic Diseases.

    PubMed

    Biffi, Alessandra

    2017-10-01

    Increasingly, patients affected by metabolic diseases affecting the central nervous system and neuroinflammatory disorders receive hematopoietic cell transplantation (HCT) in the attempt to slow the course of their disease, delay or attenuate symptoms, and improve pathologic findings. The possible replacement of brain-resident myeloid cells by the transplanted cell progeny contributes to clinical benefit. Genetic engineering of the cells to be transplanted (hematopoietic stem cell) may endow the brain myeloid progeny of these cells with enhanced or novel functions, contributing to therapeutic effects. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Bone health and associated metabolic complications in neuromuscular diseases.

    PubMed

    Joyce, Nanette C; Hache, Lauren P; Clemens, Paula R

    2012-11-01

    This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed, focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future directions are discussed, including the urgent need for studies both to determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.

  3. The heart-liver metabolic axis: defective communication exacerbates disease

    PubMed Central

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-01-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state. PMID:24623378

  4. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    PubMed Central

    van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

    2015-01-01

    Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by “systems biology” approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework. PMID:26041981

  5. Chronic low-dose exposure in the Techa River Cohort: risk of mortality from circulatory diseases.

    PubMed

    Krestinina, Lyudmila Yurievna; Epifanova, Svetlana; Silkin, Stanislav; Mikryukova, Lyudmila; Degteva, Marina; Shagina, Natalia; Akleyev, Alexander

    2013-03-01

    The aim of the present study was to analyze the mortality from circulatory diseases for about 30,000 members of the Techa River cohort over the period 1950-2003, and to investigate how these rates depend on radiation doses. This population received both external and internal exposures from (90)Sr, (89)Sr, (137)Cs, and other uranium fission products as a result of waterborne releases from the Mayak nuclear facility in the Southern Urals region of the Russian Federation. The analysis included individualized estimates of the total (external plus internal) absorbed dose in muscle calculated based on the Techa River Dosimetry System 2009. The cohort-average dose to muscle tissue was 35 mGy, and the maximum dose was 510 mGy. Between 1950 and 2003, 7,595 deaths from circulatory diseases were registered among cohort members with 901,563 person years at risk. Mortality rates in the cohort were analyzed using a simple parametric excess relative risk (ERR) model. For all circulatory diseases, the estimated excess relative risk per 100 mGy with a 15-year lag period was 3.6 % with a 95 % confidence interval of 0.2-7.5 %, and for ischemic heart disease it was 5.6 % with a 95 % confidence interval of 0.1-11.9 %. A linear ERR model provided the best fit. Analyses with a lag period shorter than 15 years from the beginning of exposure did not reveal any significant risk of mortality from either all circulatory diseases or ischemic heart disease. There was no evidence of an increased mortality risk from cerebrovascular disease (p > 0.5). These results should be regarded as preliminary, since they will be updated after adjustment for smoking and alcohol consumption.

  6. Difference in celiac disease risk between Swedish birth cohorts suggests an opportunity for primary prevention.

    PubMed

    Olsson, Cecilia; Hernell, Olle; Hörnell, Agneta; Lönnberg, Göran; Ivarsson, Anneli

    2008-09-01

    Sweden experienced a unique epidemic of celiac disease in children <2 years of age. The epidemic was partly explained by changes in infant feeding over time and indicated a multifactorial pathogenesis. The main aim of this study was to analyze celiac disease risk in epidemic and postepidemic birth cohorts up to preschool age, to explore further the opportunity for primary prevention. A population-based incidence register of celiac disease in children covering the entire nation from 1998 to 2003 and part of the country back to 1973 was analyzed. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition diagnostic criteria for celiac disease were used. The annual incidence rate for each age group and the cumulative incidence according to age for each birth cohort were calculated. A considerable difference in cumulative incidences of celiac disease at comparable ages was demonstrated between birth cohorts from the epidemic and postepidemic periods. The difference persisted during the preschool years, although it decreased somewhat with age. During the last years of the follow-up period, there was again a successive increase in incidence rate among children <2 years of age. The difference in celiac disease risk between birth cohorts at comparable ages suggests an opportunity for primary prevention. This highlights the importance of further exploring the role of infant feeding and exogenous factors besides dietary gluten that might initiate or prevent disease development. Moreover, on the basis of postepidemic incidence trends, we speculate that the Swedish epidemic might not have been as unique as thought previously, although its magnitude was striking.

  7. Birth Weights in Sickle Cell Disease Pregnancies: A Cohort Study

    PubMed Central

    Robinson, Susan E.; Macleod, David

    2016-01-01

    Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There’s a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD (50 HbSS; 38 HbSC) and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight (P value = 0.004) and the mean birth weight centiles (P value = 0.016). We conclude that SCD is a risk factor for having a smaller baby. PMID:27776167

  8. Small molecules and Alzheimer's disease: misfolding, metabolism and imaging.

    PubMed

    Patel, Viharkumar; Zhang, Xueli; Tautiva, Nicolas A; Nyabera, Akwe N; Owa, Opeyemi O; Baidya, Melvin; Sung, Hee Chang; Taunk, Pardeep S; Abdollahi, Shahrzad; Charles, Stacey; Gonnella, Rachel A; Gadi, Nikhita; Duong, Karen T; Fawver, Janelle N; Ran, Chongzhao; Jalonen, Tuula O; Murray, Ian V J

    2015-01-01

    Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aβ), with

  9. The 2009 stock conference report: inflammation, obesity and metabolic disease.

    PubMed

    Hevener, A L; Febbraio, M A

    2010-09-01

    Obesity is linked with many deleterious health consequences and is associated with increased risk of chronic disease including type 2 diabetes, atherosclerosis and certain forms of cancer. Recent work has highlighted the impact of obesity to activate inflammatory gene networks and suggests a causal function of inflammation in the pathogenesis of the metabolic syndrome. Since 2005, when Dr Gokhan Hotamisligil chaired the fourth Stock Conference in Istanbul, Turkey, entitled 'Obesity and Inflammation', there has been an explosion of studies investigating the relationship between obesity, inflammation and substrate metabolism. The exuberance surrounding this field of research is exemplified by the body of work that has been published in these past 4 years, including over 1400 publications. During this time, several novel mechanisms relating to cellular inflammation have been uncovered including the role of the hematopoietic system, toll-like receptor activation, endoplasmic reticulum stress and very recently T-cell activation in obesity-induced insulin resistance. These discoveries have led us to rethink cellular nutrient sensing and its role in inflammation and metabolic disease. Despite burgeoning investigation in this field, there still remain a number of unanswered questions. This review that evolved from the 2009 Stock Conference summarizes current research and identifies the deficiencies in our understanding of this topic. The overall goal of this Stock Conference was to bring together leading investigators in the field of inflammation and obesity research in the hope of fostering new ideas, thus advancing the pursuit of novel therapeutic strategies to reduce disease risk and or better treat chronic disease including type 2 diabetes, cardiovascular disease and cancer.

  10. Respiratory diseases among union carpenters: cohort and case-control analyses.

    PubMed

    Lipscomb, H J; Dement, J M

    1998-02-01

    Lung diseases, defined by ICD-9 diagnoses on medical insurance claims, were studied through the combined use of administrative records, private health insurance, and workers' compensation claims for a cohort of 10,938 active union carpenters between 1989 and 1992. The cohort defined the study base for a nested case-control study, in which cases (n = 220) were initially identified by an ICD-9 code for asthma in private health insurance or workers' compensation files. A questionnaire was used to collect information on respiratory history and potential home and workplace exposures. Questions used by Burney et al. to define a discriminant function predictor (DFP) of a bronchial response to histamine were used to reclassify cases and controls for further exploratory analyses. Bronchitis accounted for over 50% of the lung disease cases among this cohort followed by asthma, chronic obstructive airway disease, and chronic bronchitis. Incidence density rates of asthma, chronic bronchitis, and chronic obstructive airway disease adjusted for age, sex, and time in the union increased with increasing age. Using Surveillance, Epidemiology, and End Results (SEER) Program data to estimate expected lung cancer cases in our cohort, an elevated standardized incidence rate (SIR) was seen among male carpenters between the ages of 45-54. Smoking history was not available for the entire cohort. Using the ICD-9 or Burney case definition of asthma, odds ratios were significantly elevated for exposure to hay, epoxy paints, enzymes, animals, and molds. Additional exposures associated with asthma using Burney's definition, are ones to which a majority of these carpenters were exposed including cement, drywall, and demolition dusts.

  11. Outcomes of borderline rheumatic heart disease: A prospective cohort study.

    PubMed

    Bertaina, Geneviève; Rouchon, Bernard; Huon, Bertrand; Guillot, Nina; Robillard, Corinne; Noël, Baptiste; Nadra, Marie; Tribouilloy, Christophe; Marijon, Eloi; Jouven, Xavier; Mirabel, Mariana

    2017-02-01

    The advent of systematic screening for rheumatic heart disease (RHD) by echocardiography in endemic regions has led to a new entity: borderline RHD. The pathogenicity and natural history of borderline RHD needs to be addressed. The aim of this study was to assess the outcomes of children detected by echocardiography as having borderline RHD. Schoolchildren in 4th grade (i.e., aged 9-10years) who were prospectively echo-screened for RHD (2012-2014) in Nouméa, New Caledonia, were asked to participate. Children with borderline RHD according to consistent independent review by two cardiologists were included and followed-up in 2015. Among the 8684 schoolchildren screened, 49 were diagnosed with borderline RHD according to the Cardiologist clinically involved in the child's management plan. After independent review by two cardiologists, 25 children were consistently diagnosed with borderline RHD and included in the follow-up study. Overall, inter-observer agreement was moderate with diagnostic kappa values of 0.63 (95% CI 0.45-0.78). After a median follow-up of 23months (IQR (20.5-33.0), 15 children (60.0%) had stability of valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria. Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no clinical events or audible pathological murmur during the study period. No factor could be identified as prognostic of either stability or progression. Borderline RHD diagnosed by systematic screening in high-risk populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline RHD may require two reviewers for consistency. Copyright © 2016. Published by Elsevier Ireland Ltd.

  12. From developmental origins of adult disease to life course research on adult disease and aging: insights from birth cohort studies.

    PubMed

    Power, Chris; Kuh, Diana; Morton, Susan

    2013-01-01

    Maturation of long-running birth cohort studies has fostered a life course approach to adult health, function, and disease and related to conceptual frameworks. Using broad concepts of human development including physical, cognitive, and emotional function, birth cohorts provide insights into the processes across the life course and between generations that link to adult outcomes. We discuss findings on the determinants and health consequences of lifetime trajectories of body size, cognitive and emotional function, and socioeconomic position. Findings from the studies suggest that, for some adult health outcomes, explanations will be incomplete unless exposures and processes from across the life course are taken into account. New birth cohort studies are poised to delineate further the nature and timing of life course relationships in contemporary generations of children.

  13. The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol.

    PubMed

    Durand, Madeleine; Chartrand-Lefebvre, Carl; Baril, Jean-Guy; Trottier, Sylvie; Trottier, Benoit; Harris, Marianne; Walmsley, Sharon; Conway, Brian; Wong, Alexander; Routy, Jean-Pierre; Kovacs, Colin; MacPherson, Paul A; Monteith, Kenneth Marc; Mansour, Samer; Thanassoulis, George; Abrahamowicz, Michal; Zhu, Zhitong; Tsoukas, Christos; Ancuta, Petronela; Bernard, Nicole; Tremblay, Cécile L

    2017-09-11

    With potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals. The Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the

  14. Obesity dependent metabolic signatures associated with nonalcoholic fatty liver disease progression

    PubMed Central

    Barr, J.; Caballería, J.; Martínez-Arranz, I.; Domínguez-Díez, A.; Alonso, C.; Muntané, J.; Pérez-Cormenzana, M.; García-Monzón, C.; Mayo, R.; Martín-Duce, A.; Romero-Gómez, M.; Iacono, O. Lo; Tordjman, J.; Andrade, R.J.; Pérez-Carreras, M.; Le Marchand-Brustel, Y.; Tran, A.; Fernández-Escalante, C.; Arévalo, E.; García–Unzueta, M.; Clement, K.; Crespo, J.; Gual, P.; Gómez-Fleitas, M.; Martínez-Chantar, M.L.; Castro, A.; Lu, S.C.; Vázquez-Chantada, M.; Mato, J.M.

    2012-01-01

    Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention. PMID:22364559

  15. Dry Eye Disease Incidence Associated with Chronic Graft-Host Disease: Nonconcurrent Cohort Study (An American Ophthalmological Society Thesis).

    PubMed

    Mian, Shahzad I; De la Parra-Colín, Paola; De Melo-Franco, Rafael; Johnson, Christopher; Barrientos-Gutierrez, Tonatiuh

    2015-09-01

    To determine if chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with stable or progressive dry eye disease and to determine the true incidence in patients with no prior history of dry eye disease. A nonconcurrent cohort study at a single institution with 136 patients who had no previous history of dry eye disease before HSCT. Survival analysis was used to estimate dry eye disease incidence. The incidence rate was calculated using life tables as the number of observed dry eye disease cases divided by the person-time at risk accumulated by the cohort. Transition probabilities were calculated from time of transplant to time of diagnosis, and then to last recorded visit. Incidence rate was 0.8 cases of dry eye disease per person-year, and half of the population at risk developed dry eye disease during the first 10 months post transplant. Time to develop dry eye disease was 2.5 months for mild dry eye disease, 9.6 months for moderate dry eye disease, and 13.2 months for severe dry eye disease. In terms of cumulative incidence, 73% of subjects developed dry eye disease (50% mild, 16% moderate, and 7% severe) at the time of diagnosis. Our findings suggest that dry eye disease associated with cGVHD is an extremely frequent event and shows a wide spectrum of severity, with a mild form presenting early and a moderate to severe form presenting later after HSCT. These findings need to be studied further to elucidate if these are two different pathophysiological entities or just different expressions of the same pathology.

  16. Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up.

    PubMed

    De Greef, Elisabeth; Hoffman, Ilse; Smets, Francoise; Van Biervliet, Stephanie; Bontems, Patrick; Hauser, Bruno; Paquot, Isabelle; Alliet, Philippe; Arts, Wim; Dewit, Olivier; De Vos, Martine; Baert, Filip; Bossuyt, Peter; Rahier, Jean-Francois; Franchimont, Denis; Vermeire, Severine; Fontaine, Fernand; Louis, Edouard; Coche, J C; Veereman, Gigi

    2016-08-01

    The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36.

  17. Hearing impairment and risk of Alzheimer's disease: a meta-analysis of prospective cohort studies.

    PubMed

    Zheng, Yuqiu; Fan, Shengnuo; Liao, Wang; Fang, Wenli; Xiao, Songhua; Liu, Jun

    2017-02-01

    Observational studies suggested an association between hearing impairment and cognitive disorders. However, whether hearing impairment is an independent risk factor or a harbinger of Alzheimer's disease remains controversial. Our goal was to assess the association between hearing impairment (HI) and the risk of Alzheimer's disease (AD) by conducting a meta-analysis of prospective cohort studies. We comprehensively searched the PubMed, Embase, Web of Science and Cochrane Library databases on January 19, 2016 to incorporate all the prospective cohort studies meeting the inclusion criteria to perform a systematic review and meta-analysis. Four prospective cohort studies with comparison between hearing impairment and normal hearing were incorporated, with 7461 participants. The outcomes of three studies were the incidence of Alzheimer's disease and the outcome of the fourth study was the incidence of mild cognitive impairment. The overall combined relative risk of people with hearing impairment to develop Alzheimer's disease was 4.87 (95% CI 0.90-26.35; p = 0.066), compared with the control group. Since both Alzheimer's disease and mild cognitive impairment are cognitive disorders, we incorporated all the four studies and the overall combined relative risk was 2.82 (95% CI 1.47-5.42; p = 0.002), indicating that the difference was significant. This meta-analysis suggests that hearing impairment significantly increases the risk of cognitive disorders and future well-designed prospective cohort studies are awaited to confirm the association between hearing impairment and risk of Alzheimer's disease.

  18. Metabolic syndrome after pregnancies complicated by pre-eclampsia or small-for-gestational-age: a retrospective cohort.

    PubMed

    Al-Nasiry, S; Ghossein-Doha, C; Polman, S E J; Lemmens, S; Scholten, R R; Heidema, W M; Spaan, J J; Spaanderman, M E A

    2015-12-01

    To study the prevalence of metabolic syndrome in women after a pregnancy complicated by pre-eclampsia or small-for-gestational-age (SGA), both epitomes of placental syndrome. A retrospective cohort study. Single tertiary centre for maternal medicine in the Netherlands. Women with a history of pre-eclampsia in absence of SGA (n = 742) or pregnancy complicated by normotensive SGA (n = 147) between 1996 and 2010. Women were routinely screened for underlying cardiometabolic and cardiovascular risk factors at least 6 months postpartum. Logistic regression analysis was used to calculate the odds ratio and adjusted odds ratio for each group. Adjustments were made for age, maternal height, smoking, parity, and interval between delivery and measurement. Prevalence of the metabolic syndrome. The prevalence of the metabolic syndrome in our population was two-fold higher for women with a history of pre-eclampsia (13.9%) compared with women with a history of SGA (7.6%). Calculated odds ratios for metabolic syndrome, fasting insulin, HOMA, and microalbuminuria were all higher for women with a history of pre-eclampsia compared with women with SGA. This difference persisted after adjustment for confounding factors: metabolic syndrome (adjusted odds ratio, aOR 2.11; 95% confidence interval, 95% CI 1.00-4.47) and hyperinsulinaemia (aOR 1.78; 95% CI 1.13-2.81) insulin resistance (HOMAIR ; aOR 1.80; 95% CI 1.14-2.86). Microalbuminuria (aOR 1.58; 95% CI 0.85-2.93) did not reach the level of significance after adjustment for confounding factors. A history of pre-eclampsia, rather than SGA, was associated with metabolic syndrome, suggesting that it relates to maternal rather than fetal etiology of placental syndrome. © 2014 Royal College of Obstetricians and Gynaecologists.

  19. [Alteration of biological rhythms causes metabolic diseases and obesity].

    PubMed

    Saderi, Nadia; Escobar, Carolina; Salgado-Delgado, Roberto

    2013-07-16

    The incidence of obesity worldwide has become a serious, constantly growing public health issue that reaches alarming proportions in some countries. To date none of the strategies developed to combat obesity have proved to be decisive, and hence there is an urgent need to address the problem with new approaches. Today, studies in the field of chronobiology have shown that our physiology continually adapts itself to the cyclical changes in the environment, regard-less of whether they are daily or seasonal. This is possible thanks to the existence of a biological clock in our hypothalamus which regulates the expression and/or activity of enzymes and hormones involved in regulating our metabolism, as well as all the homeostatic functions. It has been observed that this clock can be upset as a result of today's modern lifestyle, which involves a drop in physical activity during the day and the abundant ingestion of food during the night, among other factors, which together promote metabolic syndrome and obesity. Hence, the aim of this review is to summarise the recent findings that show the effect that altering the circadian rhythms has on the metabolism and how this can play a part in the development of metabolic diseases.

  20. Cortical Metabolic and Cognitive Correlates of Disorientation in Alzheimer's Disease.

    PubMed

    Weissberger, Gali H; Melrose, Rebecca J; Fanale, Candace M; Veliz, Joseph V; Sultzer, David L

    2017-01-01

    Orientation to time, date, and place is commonly utilized in clinical settings to aid in diagnosis, staging, and monitoring of Alzheimer's disease (AD). This study aimed to identify the cerebral metabolic correlates of orientation in patients with AD, and the degree to which regions associated with orientation overlap with memory-related structures. Eighty-five patients with a diagnosis of probable AD underwent fluorodeoxyglucose positron emission tomography (FDG-PET) and neuropsychological testing. Orientation items from the Dementia Rating Scale and recognition performance from the Consortium to Establish a Registry for AD (CERAD) Word List Learning test were correlated with cerebral glucose metabolism. Post-hoc analyses examined neuropsychological predictors of orientation. Better orientation performance related to greater cerebral metabolism in the bilateral middle-inferior temporal lobes, bilateral middle-posterior cingulate, left angular gyrus, and left middle occipital gyrus. In comparison, higher CERAD recognition discriminability score was associated with greater metabolic activity in left medial temporal lobe regions including the hippocampal and parahippocampal gyri, and the left fusiform gyrus. Post-hoc behavioral analyses revealed multiple cognitive functions to be related to orientation, including list learning, recognition memory, visuospatial functioning, attention, and language. Findings from the present study suggest that disorientation in AD results from dysfunction of a network of structures and cognitive abilities commonly found to be implicated in AD. The study supports the notion that memory is necessary but not sufficient for successful orientation.

  1. Disorders of Iron Metabolism and Anemia in Chronic Kidney Disease.

    PubMed

    Panwar, Bhupesh; Gutiérrez, Orlando M

    2016-07-01

    Dysregulated iron homeostasis plays a central role in the development of anemia of chronic kidney disease (CKD) and is a major contributor toward resistance to treatment with erythropoiesis-stimulating agents. Understanding the underlying pathophysiology requires an in-depth understanding of normal iron physiology and regulation. Recent discoveries in the field of iron biology have greatly improved our understanding of the hormonal regulation of iron trafficking in human beings and how its alterations lead to the development of anemia of CKD. In addition, emerging evidence has suggested that iron homeostasis interacts with bone and mineral metabolism on multiple levels, opening up new avenues of investigation into the genesis of disordered iron metabolism in CKD. Building on recent advances in our understanding of normal iron physiology and abnormalities in iron homeostasis in CKD, this review characterizes how anemia related to disordered iron metabolism develops in the setting of CKD. In addition, this review explores our emerging recognition of the connections between iron homeostasis and mineral metabolism and their implications for the management of altered iron status and anemia of CKD. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. The INSR rs2059806 single nucleotide polymorphism, a genetic risk factor for vascular and metabolic disease, associates with pre-eclampsia.

    PubMed

    Andraweera, Prabha H; Gatford, Kathryn L; Dekker, Gustaaf A; Leemaqz, Shalem; Jayasekara, Rohan W; Dissanayake, Vajira H W; McCowan, Lesley; Roberts, Claire T

    2017-04-01

    Pre-eclampsia is a risk factor for later life vascular and metabolic diseases. This study postulates that this reflects a common genetic cause, and investigates whether the INSR rs2059806 single nucleotide polymorphism (SNP) (a risk factor for essential hypertension, type 2 diabetes and metabolic syndrome) is also associated with pre-eclampsia. The association of INSR rs2059806 with pre-eclampsia was tested in two cohorts - a Caucasian case control group (123 pre-eclamptic mother-father-baby trios and 1185 mother-father-baby trios from uncomplicated pregnancies) and an independent cohort of Sinhalese women (175 women with pre-eclampsia and 171 women with uncomplicated pregnancies). In the Caucasian cohort, the prevalence of the INSR rs2059806 AA genotype was greater among pre-eclamptic women compared with the uncomplicated pregnancies (12.7% versus 4.7%, OR[95%CI] = 3.1[1.6-5.8], P = 0.0003). In the Sinhalese cohort, maternal INSR rs2059806 AA genotype was greater among pre-eclamptic women who delivered small for gestational age infants compared with the uncomplicated pregnancies (10.8% versus 4.2%, OR[95%CI] = 2.8[1.0-7.4], P = 0.03). Thus, it was found that the INSR rs2059806 SNP is also associated with pre-eclampsia phenotypes in two independent cohorts suggesting that genetic susceptibility may be implicated in the link between pre-eclampsia and subsequent vascular and metabolic diseases.

  3. Impact of DHA on Metabolic Diseases from Womb to Tomb

    PubMed Central

    Arnoldussen, Ilse A. C.; Kiliaan, Amanda J.

    2014-01-01

    Long chain polyunsaturated fatty acids (LC-PUFAs) are important mediators in improving and maintaining human health over the total lifespan. One topic we especially focus on in this review is omega-3 LC-PUFA docosahexaenoic acid (DHA). Adequate DHA levels are essential during neurodevelopment and, in addition, beneficial in cognitive processes throughout life. We review the impact of DHA on societal relevant metabolic diseases such as cardiovascular diseases, obesity, and diabetes mellitus type 2 (T2DM). All of these are risk factors for cognitive decline and dementia in later life. DHA supplementation is associated with a reduced incidence of both stroke and atherosclerosis, lower bodyweight and decreased T2DM prevalence. These findings are discussed in the light of different stages in the human life cycle: childhood, adolescence, adulthood and in later life. From this review, it can be concluded that DHA supplementation is able to inhibit pathologies like obesity and cardiovascular disease. DHA could be a dietary protector against these metabolic diseases during a person’s entire lifespan. However, supplementation of DHA in combination with other dietary factors is also effective. The efficacy of DHA depends on its dose as well as on the duration of supplementation, sex, and age. PMID:25528960

  4. Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can).

    PubMed

    Lindkvist, Björn; Almquist, Martin; Bjørge, Tone; Stocks, Tanja; Borena, Wegene; Johansen, Dorthe; Hallmans, Göran; Engeland, Anders; Nagel, Gabriele; Jonsson, Håkan; Selmer, Randi; Diem, Guenter; Häggström, Christel; Tretli, Steinar; Stattin, Pär; Manjer, Jonas

    2013-01-01

    Little is known about the association between the metabolic syndrome (MetS) and the risk of gastric adenocarcinoma. The aim of this study was to investigate whether metabolic risk factors, together or combined, were associated with the risk of gastric adenocarcinoma. The Metabolic Syndrome and Cancer Project (Me-Can) is a pooling of prospective cohorts in Austria, Norway, and Sweden with information on blood pressure, lipids, glucose, and BMI available in 578,700 individuals. Cox proportional hazards analysis was used to calculate hazard ratio (HR) of gastric adenocarcinoma using metabolic risk factors categorized into quintiles and transformed into z-scores (with mean = 0 and SD = 1). The standardized sum of all z-scores created a composite MetS score. In total, 1,210 incident cases of gastric adenocarcinoma were identified. Glucose was significantly associated with the risk of gastric adenocarcinoma [calibrated HR 1.58 (1.14-2.20) per one unit increment in z-score] in women. There was a statistically significant association between triglycerides and risk of gastric adenocarcinoma per mmol increment in triglycerides [HR 1.20 (1.06-1.36) per mmol] but not for the adjusted z-score in women. There were no significant association between any metabolic factors and gastric cancer among men. The composite MetS score was associated with the risk of gastric adenocarcinoma in women [HR 1.18 (1.00-1.38) per one unit increment in z-score] but not in men. Glucose and high levels of the composite MetS score were associated with an increased risk of gastric adenocarcinoma in women but not in men.

  5. Assessment of cardiometabolic risk in children in population studies: underpinning developmental origins of health and disease mother-offspring cohort studies.

    PubMed

    Huang, R-C; Prescott, Susan L; Godfrey, Keith M; Davis, Elizabeth A

    2015-01-01

    Pregnancy and birth cohorts have been utilised extensively to investigate the developmental origins of health and disease, particularly in relation to understanding the aetiology of obesity and related cardiometabolic disorders. Birth and pregnancy cohorts have been utilised extensively to investigate this area of research. The aim of the present review was twofold: first to outline the necessity of measuring cardiometabolic risk in children; and second to outline how it can be assessed. The major outcomes thought to have an important developmental component are CVD, insulin resistance and related metabolic outcomes. Conditions such as the metabolic syndrome, type 2 diabetes and CHD all tend to have peak prevalence in middle-aged and older individuals but assessments of cardiometabolic risk in childhood and adolescence are important to define early causal factors and characterise preventive measures. Typically, researchers investigating prospective cohort studies have relied on the thesis that cardiovascular risk factors, such as dyslipidaemia, hypertension and obesity, track from childhood into adult life. The present review summarises some of the evidence that these factors, when measured in childhood, may be of value in assessing the risk of adult cardiometabolic disease, and as such proceeds to describe some of the methods for assessing cardiometabolic risk in children.

  6. Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors.

    PubMed

    Koller, Tomas; Kollerova, Jana; Hlavaty, Tibor; Huorka, Martin; Payer, Juraj

    2012-02-01

    Cholelithiasis and nonalcoholic fatty liver disease (NAFLD) share the same risk factors. The aim of our study was to explore the relationship between these two conditions and to identify independent predictors of both diseases in a cohort of patients with metabolic risk factors. Consecutive patients with metabolic risk factors referred to the outpatient clinic during a one-year period were included. Cholelithiasis was defined by the presence of gallstones on abdominal ultrasound examination at inclusion or previously performed cholecystectomy. NAFLD was defined by the presence of at least one surrogate marker such as elevated alanine aminotransferase and/or gamma-glutamyl transpeptidase and/or ultrasound signs of fatty liver. Other common liver diseases were thoroughly excluded. The prevalence of cholelithiasis among patients with and without NAFLD was determined and clinical and laboratory parameters were identified as predictors of NAFLD by multivariate logistic regression. In total, 482 consecutive patients were included: mean age 61 years; 61% were women; 52% of patients had more than 2 metabolic risk factors (obesity, type 2 diabetes, hypertension, hypertriglyceridemia, or low HDL cholesterol). NAFLD and cholelithiasis were present in 41% and 34% of all patients, respectively. Significantly higher prevalence of cholelithiasis was found among patients with NAFLD compared with patients without NAFLD (47% vs. 26%, respectively; p < 0.0001). In multivariate logistic regression model, type 2 diabetes (odds ratio (OR) = 1.99), BMI above 25 kg/m(2) (OR = 1.78), and cholelithiasis (OR = 1.77) were identified as independent predictors of NAFLD. Fifty six percent of patients with cholelithiasis had NAFLD compared with 33% of patients without cholelithiasis (p < 0.0001). Multivariate logistic regression identified age above 50 years (OR = 3.46), NAFLD (OR = 1.92), triglycerides above 1.7 mmol/l (OR = 1.91), BMI above 25 kg/m(2) (OR = 1.84), and total cholesterol

  7. Probiotics and their Effects on Metabolic Diseases: An Update

    PubMed Central

    Aggarwal, Juhi; Swami, Gaurav; Kumar, Mayur

    2013-01-01

    Probiotics are lactic acid bacteria which are used extensively in therapeutic preparations and added to foods. There are many studies which have demonstrated the effects of probiotics on metabolic diseases. One study has shown the effect of fermented dairy products on the serum cholesterol, especially with selected strains of lactic acid bacteria. It has been found that a minute quantity of the dry culture of Lactobacillus fermentum KC4b, for example, can remove 14.8 mg of cholesterol from the culture medium. Lactobacilli also play an important role in deconjugating the bile salts in the intestine to form bile acids and thereby inhibiting the micelle formation. Probiotics reduce the lipid peroxidation and improve the lipid metabolism in vivo. The addition of probiotics to the diet for weeks improved the immune response without the release of inflammatory cytokines, thereby reducing the onset of systemic inflammatory induced diabetes. There are evidences that the differences in the composition of the gut microbiota may precede the development of obesity in children. This review has illustrated the potential of probiotics in mediating metabolic diseases via the positive modulation of several different physiological systems, apart from its conventional benefits for the gastrointestinal health. PMID:23449881

  8. Cardiorenal metabolic syndrome in the African diaspora: rationale for including chronic kidney disease in the metabolic syndrome definition.

    PubMed

    Lea, Janice P; Greene, Eddie L; Nicholas, Susanne B; Agodoa, Lawrence; Norris, Keith C

    2009-01-01

    Chronic kidney disease (CKD) is more likely to progress to end-stage renal disease (ESRD) in African Americans while the reasons for this are unclear. The metabolic syndrome is a risk factor for the development of diabetes, cardiovascular disease, and has been recently linked to incident CKD. Historically, fewer African Americans meet criteria for the definition of metabolic syndrome, despite having higher rates of cardiovascular mortality than Caucasians. The presence of microalbuminuria portends increased cardiovascular risks and has been shown to cluster with the metabolic syndrome. We recently reported that proteinuria is a predictor of CKD progression in African American hypertensives with metabolic syndrome. In this review we explore the potential value of including CKD markers--microalbuminuria/proteinuria or low glomerular filtration rate (GFR)-in refining the cluster of factors defined as metabolic syndrome, ie, "cardiorenal metabolic syndrome."

  9. Exposure to secondhand smoke and risk of peripheral arterial disease in southern Chinese non-smokers: The Guangzhou Biobank Cohort Study-Cardiovascular Disease Sub-cohort.

    PubMed

    Lu, Liya; Jiang, Chaoqiang; Mackay, Danny F; Pell, Jill P; Cheng, Kar Keung; Lam, Tai Hing; Thomas, G Neil

    2017-06-01

    Objectives We studied the association between secondhand smoke (SHS) exposure and peripheral arterial disease (PAD) in Chinese non-smokers. Methods We conducted a cross-sectional study using baseline data from the Guangzhou Biobank Cohort Study: Cardiovascular Disease Sub-cohort Study (GBCS-CVD). Guangzhou residents aged ≥ 50 years were recruited between 2003 and 2008. Baseline data included measurement of ankle brachial pressure index (ABPI) and self-reported smoking status and SHS exposure. Univariate and multivariate logistic regression analyses were used to analyze the association between SHS and PAD (defined as ABPI < 0.9). Results Of the 1507 non-smokers, 24 (1.6%) had PAD. Of these, 12 were men and 12 were women. Exposure to SHS at home of ≥25 h per week was reported by 16.7% of PAD cases compared with 3.8% of those without PAD (χ2 test, p = 0.003). After adjustment for potential confounders, exposure to ≥25 h per week at home was still associated with PAD (adjusted OR 7.86, 95% CI 2.00-30.95, p = 0.003), with suggestion of a dose-response relationship. Conclusions Our results extend the US Surgeon General's 2006 report that SHS exposure is an independent risk factor for PAD. National smoke-free legislation is needed to protect all people from exposure.

  10. Modelling disease progression in relapsing-remitting onset multiple sclerosis using multilevel models applied to longitudinal data from two natural history cohorts and one treated cohort.

    PubMed

    Tilling, Kate; Lawton, Michael; Robertson, Neil; Tremlett, Helen; Zhu, Feng; Harding, Katharine; Oger, Joel; Ben-Shlomo, Yoav

    2016-10-01

    The ability to better predict disease progression represents a major unmet need in multiple sclerosis (MS), and would help to inform therapeutic and management choices. To develop multilevel models using longitudinal data on disease progression in patients with relapsing-remitting MS (RRMS) or secondary-progressive MS (SPMS); and to use these models to estimate the association of disease-modifying therapy (DMT) with progression. Secondary analysis of three MS cohorts. Two natural history cohorts: University of Wales Multiple Sclerosis (UoWMS) cohort, UK, and British Columbia Multiple Sclerosis (BCMS) cohort, Canada. One observational DMT-treated cohort: UK MS risk-sharing scheme (RSS). The UoWMS database has > 2000 MS patients and the BCMS database (as of 2009) has > 5900 MS patients. All participants who had definite MS (RRMS/SPMS), who reached the criteria set out by the Association of British Neurologists (ABN) for eligibility for DMT [i.e. age ≥ 18 years, Expanded Disability Status Scale (EDSS) score of ≤ 6.5, occurrence of two or more relapses in the previous 2 years] and who had at least two repeated outcome measures were included: 404 patients for the UoWMS cohort and 978 patients for the BCMS cohort. Through the UK MS RSS scheme, 5583 DMT-treated patients were recruited, with the analysis sample being the 4137 who had RRMS and were eligible and treated at baseline, with at least one valid EDSS score post baseline. EDSS score observations post ABN eligibility. We used multilevel models in the development cohort (UoWMS) to develop a model for EDSS score with time since ABN eligibility, allowing for covariates and appropriate transformation of outcome and/or time. These methods were then applied to the BCMS cohort to obtain a 'natural history' model for changes in the EDSS score with time. We then used this natural history model to predict the trajectories of EDSS score in treated patients in the UK MS RSS database. Differences between the

  11. [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non- invasive assessment of bone turn over markers could define the cause of metabolic bone diseases].

    PubMed

    Suzuki, Atsushi

    2011-09-01

    Recent advances of the measurement of bone turn over markers contribute to non-invasive assessment of bone-metabolic disorders. We can detect the cause of the metabolic disorders with bone turn over markers and hormonal profiles more easily than before. Today, we can diagnose and treat metabolic bone diseases without invasive procedure such as bone biopsy.

  12. Bone Health and Associated Metabolic Complications in Neuromuscular Diseases

    PubMed Central

    Joyce, Nanette C.; Hache, Lauren P.; Clemens, Paula R.

    2014-01-01

    Synopsis This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Poor bone health with related morbidity is a significant problem for patients with NMD. Although the evidence addressing issues of bone health and osteoporosis have increased as a result of the Bone and Joint Decade, studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis and spinal muscular atrophy. These problems appear common. Osteomalacia often complicates disease-related baseline osteoporosis and may reduce fracture risk if treated. Future directions are discussed, including the urgent need for studies to both determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD. PMID:23137737

  13. Breast feeding and the risk of obesity and related metabolic diseases in the child.

    PubMed

    Plagemann, Andreas; Harder, Thomas

    2005-01-01

    Breast feeding is the best way to nurture healthy newborns of healthy mothers. A number of studies have shown that breast feeding may protect against the later development of obesity and related metabolic diseases. Using data from our own meta-analysis as well as studies by other groups, in this review we systematically examine the current state of evidence regarding this topic. Breast feeding, in general, is shown to be associated later in a child's life with decreased risk of overweight, decreased blood cholesterol and blood pressure, and a reduced risk of developing type 2 diabetes. Additionally, we review data of our Kaulsdorf Cohort Study (KCS) showing, however, that these effects might be reversed when the mother is affected by a non-communicable disease such as diabetes mellitus, which alters the composition of breast milk. In particular, exposure to breast milk from diabetic mothers during the first days of life (first week; early neonatal period) seems to increase rather than decrease risk of overweight and, consecutively, impaired glucose tolerance in childhood. Taken together, current findings show clearly that breast feeding is effective in lowering the risk of developing key features of the metabolic syndrome in later life, and should therefore be promoted. With increasing prevalence of overweight and diabetes in women, however, more research is urgently needed to clarify whether breast feeding might even have negative consequences for risk of overweight and diabetogenic disturbances when the mother suffers from a metabolic disorder. From a more general perspective, breast feeding and its long-term consequences are an important paradigm for "perinatal programming" of health and disease.

  14. Study Design and Outcomes of Korean Obstructive Lung Disease (KOLD) Cohort Study

    PubMed Central

    Park, Tai Sun; Lee, Jae Seung; Seo, Joon Beom; Hong, Yoonki; Yoo, Jung-Wan; Kang, Byung Ju; Lee, Sei Won; Oh, Yeon-Mok

    2014-01-01

    Background The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. Methods Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. Results From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. Conclusion The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD. PMID:24851130

  15. Epidemiological evidence of type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease in Japan.

    PubMed

    Saito, Isao

    2012-01-01

    Although epidemiological studies in the US and Europe have confirmed that type 2 diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD) events, evidence is limited in Japan. Earlier studies in Japan showed that hypertension has a major effect on atherosclerosis in relatively lean subjects, with type 2 DM contributing more to CVD events, because of a decline in blood pressure levels in both sexes and an increase in body mass index in men. Recent cohort studies in Japan using baseline assessments carried out during the 1990s have confirmed that type 2 DM is associated with an increased risk of coronary heart disease (CHD) and all types of stroke, except hemorrhagic stroke. In addition, the metabolic syndrome, a constellation of metabolic risk factors, was shown to predict CVD events in Japanese people, independent of the presence or absence of obesity. The strong association of type 2 DM with CHD (hazard ratio: 1.5-4) and ischemic stroke (hazard ratio: 2-4) events was confirmed in Japanese adults. Individuals with impaired glucose tolerance or impaired fasting glucose were also shown to have an increased risk of a CHD event, but not a stroke.

  16. Infectious, inflammatory, and metabolic diseases affecting the athlete's spine.

    PubMed

    Metz, Lionel N; Wustrack, Rosanna; Lovell, Alberto F; Sawyer, Aenor J

    2012-07-01

    Sports and weight-bearing activities can have a positive effect on bone health in the growing, mature, or aging athlete. However, certain athletic activities and training regimens may place the athlete at increased risk for stress fractures in the spine. In addition, some athletes have an underlying susceptibility to fracture due to either systemic or focal abnormalities. It is important to identify and treat these athletes in order to prevent stress fractures and reduce the risk of osteoporosis in late adulthood. Therefore, the pre-participation physical examination offers a unique opportunity to screen athletes for metabolic bone disease through the history and physical examination. Positive findings warrant a thorough workup including a metabolic bone laboratory panel, and possibly a DEXA scan, which includes a lateral spine view.

  17. Carotid body, insulin, and metabolic diseases: unraveling the links

    PubMed Central

    Conde, Sílvia V.; Sacramento, Joana F.; Guarino, Maria P.; Gonzalez, Constancio; Obeso, Ana; Diogo, Lucilia N.; Monteiro, Emilia C.; Ribeiro, Maria J.

    2014-01-01

    The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future. PMID:25400585

  18. Milk drinking, ischaemic heart disease and ischaemic stroke II. Evidence from cohort studies.

    PubMed

    Elwood, P C; Pickering, J E; Hughes, J; Fehily, A M; Ness, A R

    2004-05-01

    Milk consumption is considered a risk factor for vascular disease on the basis of relevant biological mechanisms and data from ecological studies. The aim was to identify published prospective studies of milk drinking and vascular disease, and conduct an overview. The literature was searched for cohort studies, in which an estimate of the consumption of milk, or the intake of calcium from dairy sources, has been related to incident vascular disease. Ischaemic heart disease and ischaemic stroke. In total, 10 studies were identified. Their results show a high degree of consistency in the reported risk for heart disease and stroke, all but one study suggesting a relative risk of less than one in subjects with the highest intakes of milk. A pooled estimate of relative odds in these subjects, relative to the risk in subjects with the lowest consumption, is 0.87 (95% CI 0.74-1.03) for ischaemic heart disease and 0.83 (0.77-0.90) for ischaemic stroke. The odds ratio for any vascular event is 0.84 (0.78-0.90). Cohort studies provide no convincing evidence that milk is harmful. While there still could be residual confounding from unidentified factors, the studies, taken together, suggest that milk drinking may be associated with a small but worthwhile reduction in heart disease and stroke risk. The University of Wales College of Medicine and Bristol University. Current support is from the Food Standards Agency.

  19. Characterisation of a Swedish cohort with orofacial granulomatosis with or without Crohn's disease.

    PubMed

    Gale, G; Östman, S; Rekabdar, E; Torinsson Naluai, Å; Högkil, K; Hasséus, B; Saalman, R; Jontell, M

    2015-01-01

    To compare oral manifestations in a Swedish cohort of patients with orofacial granulomatosis with or without Crohn's disease and to assess NOD2 polymorphisms in the two groups. Twenty-nine patients with orofacial granulomatosis were included. Demographics, disease history, clinical features and concurrent Crohn's disease were recorded. DNA was extracted from buccal swabs and examined for NOD2 variants Arg702Trp, Gly908Arg and Leu1007fsinsC, all previously linked to gastrointestinal Crohn's disease. Twelve of 29 patients were diagnosed with coexisting gastrointestinal Crohn's disease, and of whom 21 were males. Symptom duration was significantly longer for the orofacial granulomatosis group com-pared to the group with coexisting Crohn's disease (P < 0.0001). The orofacial granulomatosis patients also perceived their overall discomfort, aesthetic problems and social discomfort as more severe. No significant differences in the clinical presentation of oral lesions between the two groups were found. None of the patients with orofacial granulomatosis carried any of the NOD2 variations, whereas four of the 12 patients with coexisting Crohn's disease had a NOD2 variant (Arg702Trp). The two patient groups had similar phenotypic characteristics but seemed to have genotypic differences regarding NOD2. The Swedish cohort differed in their clinical characteristics from patients reported in other geographical regions. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Association of chronic obstructive pulmonary disease and hemorrhoids: A nationwide cohort study.

    PubMed

    Lin, Lih-Hwa; Siu, Justin Ji-Yuen; Liao, Po-Chi; Chiang, Jen-Huai; Chou, Pei-Chi; Chen, Huey-Yi; Ho, Tsung-Jung; Tsai, Ming-Yen; Chen, Yung-Hsiang; Chen, Wen-Chi

    2017-03-01

    According to traditional Chinese medicine (TCM) theory, a specific physiological and pathological relationship exists between the lungs and the large intestine. The aim of this study is to delineate the association of chronic obstructive pulmonary disease (COPD) and hemorrhoids in order to verify the "interior-exterior" relationship between the lungs and the large intestine. A retrospective cohort study is conceived from the National Health Insurance Research Database, Taiwan. The 2 samples (COPD cohort and non-COPD cohort) were selected from the 2000 to 2003 beneficiaries of the NHI, representing patients age 20 and older in Taiwan, with the follow-up ending on December 31, 2011. The COPD cohort (n = 51,506) includes every patient newly diagnosed as having Chronic Obstructive Pulmonary Disease (COPD, ICD-9-CM: 490-492, 494, 496), who have made at least 2 confirmed visits to the hospital/clinic. The non-COPD cohort (n = 103,012) includes patients without COPD and is selected via a 1:2 (COPD: non-COPD) matching by age group (per 5 years), gender, and index date (diagnosis date of COPD for the COPD cohort). Compared with non-COPD cohorts, patients with COPD have a higher likelihood of having hemorrhoids and the age-, gender- and comorbidies-adjusted hazard ratio (HR) for hemorrhoids is 1.56 (95% confidence intervals [CI]:1.50-1.62). The adjusted HR of hemorrhoids for females is 0.79 (95% CI: 0.77-0.83), which is significantly less than that for males. The elderly groups, 40 to 59 years and aged 60 or above, have higher adjusted HRs than younger age groups (20-39 years), 1.19 (95% CI: 1.14-1.26), and 1.18 (95% CI: 1.12-1.24), respectively. Patients with COPD may have a higher likelihood to have hemorrhoids in this retrospective cohort study. This study verifies the fundamental theorem of TCM that there is a definite pathogenic association between the lungs and large intestine.

  1. The Effect of Polymorphisms in DNA Repair Genes and Carcinogen Metabolizers on Leukocyte Telomere Length: A Cohort of Healthy Spanish Smokers.

    PubMed

    Verde, Zoraida; Reinoso-Barbero, Luis; Chicharro, Luis; Resano, Pilar; Sánchez-Hernández, Ignacio; Rodríguez González-Moro, Jose Miguel; Bandrés, Fernando; Gómez-Gallego, Félix; Santiago, Catalina

    2016-04-01

    Smoking implies exposure to carcinogenic agents that causes DNA damage, which could be suspected to enhance telomere attrition. To protect and deal with DNA damage, cells possess mechanisms that repair and neutralize harmful substances. Polymorphisms altering DNA repair capacity or carcinogen metabolism may lead to synergistic effects with tobacco carcinogen-induced shorter telomere length independently of cancer interaction. The aim of this study was to explore the association between leukocyte telomere length (LTL) and several genetic polymorphisms in DNA repair genes and carcinogen metabolizers in a cohort of healthy smokers. We evaluated the effect of six genetic polymorphisms in cytochrome P1A1 (Ile462Val), XRCC1 (Arg399Gln), APEX1 (Asp148Glu), XRCC3 (Thr241Met), and XPD (Asp312Asn; Lys751Gln) on LTL in a cohort of 145 healthy smokers in addition to smoking habits. Logistic regression analysis showed an association between XRCC1 399Gln allele and shorter telomere length (OR = 5.03, 95% CI = 1.08% to 23.36%). There were not association between the rest of polymorphisms analyzed and LTL. Continuous exposure to tobacco could overwhelm the DNA repair machinery, making the effect of the polymorphisms that reduce repair capacity more pronounced. Analyzing the function of smoking-induced DNA-repair genes and LTL is an important goal in order to identify therapeutic targets to treat smoking-induced diseases. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Prevalence of the metabolic syndrome and its components: findings from a Finnish general population sample and the Diabetes Prevention Study cohort.

    PubMed

    Ilanne-Parikka, Pirjo; Eriksson, Johan G; Lindström, Jaana; Hämäläinen, Helena; Keinänen-Kiukaanniemi, Sirkka; Laakso, Mauri; Louheranta, Anne; Mannelin, Marjo; Rastas, Merja; Salminen, Virpi; Aunola, Sirkka; Sundvall, Jouko; Valle, Timo; Lahtela, Jorma; Uusitupa, Matti; Tuomilehto, Jaakko

    2004-09-01

    To assess the prevalence of the metabolic syndrome (MetS) in two independent Finnish study cohorts. The prevalence of the MetS by modified World Health Organization criteria was analyzed in different categories of glucose tolerance in a cross-sectional, population-based sample of 2,049 individuals (FINRISK) aged 45-64 years and in 522 participants of the Finnish Diabetes Prevention Study (DPS) with impaired glucose tolerance (IGT). In the FINRISK cohort, the MetS was present in 38.8% of the men and 22.2% of the women. The prevalence was 14.4 and 10.1% in subjects with normal glucose tolerance, 74.0 and 52.2% in subjects with impaired fasting glucose, 84.8 and 65.4% in subjects with IGT, and 91.5 and 82.7% in subjects with type 2 diabetes in men and women, respectively. Among women, the prevalence of the MetS increased with increasing age. In the DPS cohort, the MetS was present in 78.4% of the men and 72.2% of the women with IGT. The MetS was extremely common in middle-aged subjects The high prevalence in men was mostly due to their high waist-to-hip ratio. The prevalence of the MetS increased in both sexes with deterioration in glucose regulation. Approximately 75% of the subjects with IGT had the MetS. Because the syndrome includes the major risk factors for atherosclerotic vascular diseases and is the major antecedent for type 2 diabetes, concerted preventive action should be targeted to control all the features of the MetS.

  3. DIETARY HYPERGLYCEMIA, GLYCEMIC INDEX AND METABOLIC RETINAL DISEASES

    PubMed Central

    Chiu, Chung-Jung; Taylor, Allen

    2014-01-01

    The glycemic index (GI) indicates how fast blood glucose is raised after consuming a carbohydrate-containing food. Human metabolic studies indicate that GI is related to patho-physiological responses after meals. Compared with a low-GI meal, a high-GI meal is characterized with hyperglycemia during the early postprandial stage (0~2 h) and a compensatory hyperlipidemia associated with counter-regulatory hormone responses during late postprandial stage (4~6 h). Over the past three decades, several human health disorders have been related to GI. The strongest relationship suggests that consuming low-GI foods prevents diabetic complications. Diabetic retinopathy (DR) is a complication of diabetes. In this aspect, GI appears to be useful as a practical guideline to help diabetic people choose foods. Abundant epidemiological evidence also indicates positive associations between GI and risk for type 2 diabetes, cardiovascular disease, and more recently, age-related macular degeneration (AMD) in people without diabetes. Although data from randomized controlled intervention trials are scanty, these observations are strongly supported by evolving molecular mechanisms which explain the pathogenesis of hyperglycemia. This wide range of evidence implies that dietary hyperglycemia is etiologically related to human aging and diseases, including DR and AMD. In this context, these diseases can be considered metabolic retinal diseases. Molecular theories that explain hyperglycemic pathogenesis involve a mitochondria-associated pathway and four glycolysis-associated pathways, including advanced glycation end products formation, protein kinase C activation, polyol pathway, and hexosamine pathway. While the four glycolysis-associated pathways appear to be universal for both normoxic and hypoxic conditions, the mitochondria-associated mechanism appears to be most relevant to the hyperglycemic, normoxic pathogenesis. For diseases that affect tissues with highly active metabolism and that

  4. Alterations in metabolic pathways and networks in Alzheimer's disease.

    PubMed

    Kaddurah-Daouk, R; Zhu, H; Sharma, S; Bogdanov, M; Rozen, S G; Matson, W; Oki, N O; Motsinger-Reif, A A; Churchill, E; Lei, Z; Appleby, D; Kling, M A; Trojanowski, J Q; Doraiswamy, P M; Arnold, S E

    2013-04-09

    The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We used targeted metabolomics platform to profile cerebrospinal fluid (CSF) from AD (n=40), mild cognitive impairment (MCI, n=36) and control (n=38) subjects; univariate and multivariate analyses to define between-group differences; and partial least square-discriminant analysis models to classify diagnostic groups using CSF metabolomic profiles. A partial correlation network was built to link metabolic markers, protein markers and disease severity. AD subjects had elevated methionine (MET), 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid, xanthosine and glutathione versus controls. MCI subjects had elevated 5-HIAA, MET, hypoxanthine and other metabolites versus controls. Metabolite ratios revealed changes within tryptophan, MET and purine pathways. Initial pathway analyses identified steps in several pathways that appear altered in AD and MCI. A partial correlation network showed total tau most directly related to norepinephrine and purine pathways; amyloid-β (Ab42) was related directly to an unidentified metabolite and indirectly to 5-HIAA and MET. These findings indicate that MCI and AD are associated with an overlapping pattern of perturbations in tryptophan, tyrosine, MET and purine pathways, and suggest that profound biochemical alterations are linked to abnormal Ab42 and tau metabolism. Metabolomics provides powerful tools to map interlinked biochemical pathway perturbations and study AD as a disease of network failure.

  5. Hepcidin: Homeostasis and Diseases Related to Iron Metabolism.

    PubMed

    Reichert, Cadiele Oliana; da Cunha, Joel; Levy, Débora; Maselli, Luciana Morganti Ferreira; Bydlowski, Sérgio Paulo; Spada, Celso

    2017-01-01

    Iron is an essential metal for cell survival that is regulated by the peptide hormone hepcidin. However, its influence on certain diseases is directly related to iron metabolism or secondary to underlying diseases. Genetic alterations influence the serum hepcidin concentration, which can lead to an iron overload in tissues, as observed in haemochromatosis, in which serum hepcidin or defective hepcidin synthesis is observed. Another genetic imbalance of iron is iron-refractory anaemia, in which serum concentrations of hepcidin are increased, precluding the flow and efflux of extra- and intracellular iron. During the pathogenesis of certain diseases, the resulting oxidative stress, as well as the increase in inflammatory cytokines, influences the transcription of the HAMP gene to generate a secondary anaemia due to the increase in the serum concentration of hepcidin. To date, there is no available drug to inhibit or enhance hepcidin transcription, mostly due to the cytotoxicity described in the in vitro models. The proposed therapeutic targets are still in the early stages of clinical trials. Some candidates are promising, such as heparin derivatives and minihepcidins. This review describes the main pathways of systemic and genetic regulation of hepcidin, as well as its influence on the disorders related to iron metabolism. © 2017 S. Karger AG, Basel.

  6. Endocrine manifestations related to inherited metabolic diseases in adults

    PubMed Central

    2012-01-01

    Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

  7. Prevalence of Comorbidity in Patients With Young-Onset Alzheimer Disease Compared With Late-Onset: A Comparative Cohort Study.

    PubMed

    Gerritsen, Adrie A J; Bakker, Christian; Verhey, Frans R J; de Vugt, Marjolein E; Melis, René J F; Koopmans, Raymond T C M

    2016-04-01

    With the lack of a cure for Alzheimer disease (AD), the identification of comorbidity is important to reduce the possibility of excess disability. Although comorbidity in patients with late-onset AD (LO-AD) is common, for people with young-onset AD (YO-AD), it is unclear how often comorbidity occurs. Furthermore, it is uncertain whether comorbidity in patients with YO-AD differs from that in patients with LO-AD. The aim of this study was to explore the prevalence, types of morbidity, and morbidity profiles in patients with YO-AD compared with those of patients with LO-AD. Explorative cohort study from 2 separate Dutch cohorts (Needs in Young-onset Dementia [NeedYD] and the Clinical Course of Cognition and Comorbidity-Dementia Study [4C-Dementia study]). Participants were recruited in 2007 and 2008 from (1) the memory clinics of 3 Dutch Alzheimer centers, (2) the memory clinics of general hospitals, (3) mental health services in the southern part of the Netherlands, and (4) young-onset dementia specialized day care facilities. A comparison group of community-dwelling, elderly patients with AD was selected from the 4C-Dementia study. Patients in this study were recruited in 2010 and 2011 from the aforementioned Alzheimer centers. The prevalence rates of comorbidity were compared between 177 patients with YO-AD and 155 patients with LO-AD. Comorbidity was classified using the International Classification of Diseases, 10th Revision (ICD-10). The total amount of comorbidity was established by counting the number of existing diseases (ICD categories or chapters) and comorbidity was also dichotomized as present or absent. Furthermore, a hierarchical cluster analysis was performed to study clusters of comorbidity. Compared with LO-AD, patients with YO-AD showed less (P < .001) overall comorbidity (58.2% vs 86.5%) and had lower prevalence rates of diabetes, obesity, and circulatory diseases; however, the prevalence rates of diseases of the nervous system in YO-AD (6

  8. Comparison of the clinical profile of Parkinson's disease between Spanish and Cameroonian cohorts.

    PubMed

    Cubo, Esther; Doumbe, Jacques; Martinez-Martin, Pablo; Rodriguez-Blazquez, Carmen; Kuate, Callixte; Mariscal, Natividad; Lopez, Irene; Noubissi, Gustave; Mapoure, Yacouba Njankouo; Jon, Jean Louis; Mbahe, Salomon; Tchaleu, Benjamin; Catalan, Maria-Jose

    2014-01-15

    There are limited data in terms of the clinical profile of Parkinson's disease in sub-Saharan African patients. To compare the clinical profile and access to standard antiparkinsonian therapies of a Cameroonian cohort of patients with an age, sex, and disease duration-matched Spanish cohort (Longitudinal Study of Parkinson's disease, ELEP). Observational, cross-sectional design. Demographic data were collected and the following ELEP assessments were applied: Scales for Outcomes in Parkinson's disease (SCOPA) Motor, Autonomic, Cognition, Sleep and Psychosocial; Hoehn and Yahr staging; modified Parkinson Psychosis Rating Scale; Cumulative Illness Rating Scale-Geriatrics; Hospital Anxiety and Depression Scale; pain and fatigue visual analog scales; Zarit, and EuroQoL. 74 patients with idiopathic Parkinson's disease were included (37 from each country) with a mean age of 64.4±10.5 years old, 70.3% males, and mean disease duration of 5.6±5.9 years. Compared to the Spanish cohort, Cameroonians were intermittently treated, less frequently received dopaminergic agonists (p<0.001), had a trend for taking lower doses of levodopa (p=0.06), and were more frequently on anticholinergics (p<0.0005). Cameroonians were more severely impaired in terms of motor (Hoehn Yahr stage, p=0.03; SCOPA-Motor, p<0.001), cognitive status (p<0.001), anxiety and depression (p<0.001), psychosis (p=0.008), somnolence, fatigue and pain (p<0.001, respectively), caregiver burden (p<0.0001), and quality of life (p=0.002). Instead, autonomic, comorbidity, and nocturnal sleep problems were similarly found. Limited and intermittent access to dopaminergic drugs has a negative impact on motor symptoms, nonmotor symptoms and quality of life in patients with Parkinson's disease and their caregivers. © 2013.

  9. X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients.

    PubMed

    Shahrizaila, Nortina; Samulong, Sarimah; Tey, Shelisa; Suan, Liaw Chiew; Meng, Lao Kah; Goh, Khean Jin; Ahmad-Annuar, Azlina

    2014-02-01

    Data regarding Charcot-Marie-Tooth disease is lacking in Southeast Asian populations. We investigated the frequency of the common genetic mutations in a multiethnic Malaysian cohort. Patients with features of Charcot-Marie-Tooth disease or hereditary liability to pressure palsies were investigated for PMP22 duplication, deletion, and point mutations and GJB1, MPZ, and MFN2 point mutations. Over a period of 3 years, we identified 25 index patients. A genetic diagnosis was reached in 60%. The most common were point mutations in GJB1, accounting for X-linked Charcot-Marie-Tooth disease (24% of the total patient population), followed by PMP22 duplication causing Charcot-Marie-Tooth disease type 1A (20%). We also discovered 2 novel GJB1 mutations, c.521C>T (Proline174Leucine) and c.220G>A (Valine74Methionine). X-linked Charcot-Marie-Tooth disease was found to predominate in our patient cohort. We also found a better phenotype/genotype correlation when applying a more recently recommended genetic approach to Charcot-Marie-Tooth disease. Copyright © 2013 Wiley Periodicals, Inc.

  10. Associations between Sugar Intake from Different Food Sources and Adiposity or Cardio-Metabolic Risk in Childhood and Adolescence: The Korean Child–Adolescent Cohort Study

    PubMed Central

    Hur, Yang-Im; Park, Hyesook; Kang, Jae-Heon; Lee, Hye-Ah; Song, Hong Ji; Lee, Hae-Jeung; Kim, Ok-Hyun

    2015-01-01

    The increasing prevalence of childhood obesity is a serious public health problem associated with co-morbidities in adulthood, as well as childhood. This study was conducted to identify associations between total sugar intake and sugar intake from different foods (fruit, milk, and sugar-sweetened beverages (SSBs)), and adiposity and continuous metabolic syndrome scores (cMetS) among Korean children and adolescents using cohort data. The study subjects were children (n = 770) who participated in the 4th year (2008) of the Korean Child–Adolescent Cohort Study (KoCAS). Dietary intake data were collected via three-day 24-h food records, and sugar intake was calculated for the total sugar content of foods using our database compiled from various sources. Anthropometric measurements, assessments of body composition, and blood sample analysis were performed at baseline and at follow-up four years later. The cMetS was calculated based on waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and mean arterial blood pressure. According to multiple linear regression analysis, there were no significant associations between total sugar intake and adiposity and cMetS. However, higher intake of fruit sugar at baseline was significantly associated with lower body mass index (BMI) z-scores and body fat percentages at baseline (β = −0.10, p = 0.02 and β = −0.78, p < 0.01, respectively). At follow-up, sugar intake from fruit at baseline was still negatively associated with the above outcomes, but only the relationship with BMI z-scores retained statistical significance (β = −0.08, p < 0.05). There was a significant positive relationship between consumption of sugar from SSBs and cMetS at baseline (β = 0.04, p = 0.02), but that relationship was not observed at follow-up (p = 0.83). Differences in consumption sugars from fruit and SSBs might play an important role in the risk of adiposity and metabolic disease in children and adolescents. Our

  11. Associations between Sugar Intake from Different Food Sources and Adiposity or Cardio-Metabolic Risk in Childhood and Adolescence: The Korean Child-Adolescent Cohort Study.

    PubMed

    Hur, Yang-Im; Park, Hyesook; Kang, Jae-Heon; Lee, Hye-Ah; Song, Hong Ji; Lee, Hae-Jeung; Kim, Ok-Hyun

    2015-12-31

    The increasing prevalence of childhood obesity is a serious public health problem associated with co-morbidities in adulthood, as well as childhood. This study was conducted to identify associations between total sugar intake and sugar intake from different foods (fruit, milk, and sugar-sweetened beverages (SSBs)), and adiposity and continuous metabolic syndrome scores (cMetS) among Korean children and adolescents using cohort data. The study subjects were children (n = 770) who participated in the 4th year (2008) of the Korean Child-Adolescent Cohort Study (KoCAS). Dietary intake data were collected via three-day 24-h food records, and sugar intake was calculated for the total sugar content of foods using our database compiled from various sources. Anthropometric measurements, assessments of body composition, and blood sample analysis were performed at baseline and at follow-up four years later. The cMetS was calculated based on waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and mean arterial blood pressure. According to multiple linear regression analysis, there were no significant associations between total sugar intake and adiposity and cMetS. However, higher intake of fruit sugar at baseline was significantly associated with lower body mass index (BMI) z-scores and body fat percentages at baseline (β = -0.10, p = 0.02 and β = -0.78, p < 0.01, respectively). At follow-up, sugar intake from fruit at baseline was still negatively associated with the above outcomes, but only the relationship with BMI z-scores retained statistical significance (β = -0.08, p < 0.05). There was a significant positive relationship between consumption of sugar from SSBs and cMetS at baseline (β = 0.04, p = 0.02), but that relationship was not observed at follow-up (p = 0.83). Differences in consumption sugars from fruit and SSBs might play an important role in the risk of adiposity and metabolic disease in children and adolescents. Our results

  12. Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study.

    PubMed

    Hong, Chien Tai; Huang, Yao Hsien; Liu, Hung Yi; Chiou, Hung-Yi; Chan, Lung; Chien, Li-Nien

    2016-07-14

    Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.

  13. DIVAS: a centralized genetic variant repository representing 150,000 individuals from multiple disease cohorts.

    PubMed

    Cheng, Wei-Yi; Hakenberg, Jörg; Li, Shuyu Dan; Chen, Rong

    2016-01-01

    A plethora of sequenced and genotyped disease cohorts is available to the biomedical research community, spread across many portals and represented in various formats. We have gathered several large studies, including GERA and GRU, and computed population- and disease-specific genetic variant frequencies. In total, our portal provides fast access to genetic variants observed in 84,928 individuals from 39 disease populations. We also include 66,335 controls, such as the 1000 Genomes and Scripps Wellderly. Combining multiple studies helps validate disease-associated variants in each underlying data set, detect potential false positives using frequencies of control populations, and identify novel candidate disease-causing alterations in known or suspected genes. https://rvs.u.hpc.mssm.edu/divas rong.chen@mssm.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  14. DIVAS: a centralized genetic variant repository representing 150 000 individuals from multiple disease cohorts

    PubMed Central

    Cheng, Wei-Yi; Hakenberg, Jörg; Li, Shuyu Dan; Chen, Rong

    2016-01-01

    Motivation: A plethora of sequenced and genotyped disease cohorts is available to the biomedical research community, spread across many portals and represented in various formats. Results: We have gathered several large studies, including GERA and GRU, and computed population- and disease-specific genetic variant frequencies. In total, our portal provides fast access to genetic variants observed in 84 928 individuals from 39 disease populations. We also include 66 335 controls, such as the 1000 Genomes and Scripps Wellderly. Conclusion: Combining multiple studies helps validate disease-associated variants in each underlying data set, detect potential false positives using frequencies of control populations, and identify novel candidate disease-causing alterations in known or suspected genes. Availability and implementation: https://rvs.u.hpc.mssm.edu/divas Contact: rong.chen@mssm.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26363178

  15. Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease.

    PubMed

    Bras, Jose; Singleton, Andrew; Cookson, Mark R; Hardy, John

    2008-12-01

    Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis.

  16. Prevalence of metabolic syndrome and its relationship with clinically prevalent cardiovascular disease in the Veneto region, northeastern Italy.

    PubMed

    Novelletto, Bruno Franco; Guzzinati, Stefano; Avogaro, Angelo

    2012-02-01

    Cardiovascular disease (CVD) is more frequent in adults with metabolic syndrome than in those without. We wished to assess the prevalence of the metabolic syndrome and the role of its specific components on prevalent CVD in a large cohort of subjects from the general population. Seventy-eight general practitioners among 3,542 were identified and participated in this study. Personal, anthropometric, and lifestyle data were obtained as was data relevant to CVD [coronary heart disease (CHD) or stroke or both]. A stratified random sample of 6,347 subjects taken from the population of the Veneto region in northeastern Italy was analyzed. The prevalence [and its 95% confidence limits (CL)] of metabolic syndrome by gender and age classes was higher in men than women (21.9% vs. 16.8) and it increased with age (29.8% in ages 60-69 vs. 8.0 in ages 30-39). The most frequent triad of metabolic syndrome was waist circumference (WC)-blood pressure (BP)-hyperglycemia (GLYC) (33%). Metabolic syndrome was significantly associated with CVD [odds ratio (OR)=1.53, 95% CL, 1.02-2.29] and gender (men have about six times the risk of women), and the risk of CVD increases with age (11% per additional year of age). High-density lipoprotein (HDL) is the only component of metabolic syndrome associated with CVD: The OR was 2.12 (95% CL, 1.32-3.43) and remains significant in sex-specific models only in men. The prevalence of metabolic syndrome in the Veneto region among subjects ages 30-69 is high. There is a significant association between prevalent CVD and metabolic syndrome, but the biological basis of association is strongly influenced by gender.

  17. Degeneration of Dopaminergic Neurons Due to Metabolic Alterations and Parkinson’s Disease

    PubMed Central

    Song, Juhyun; Kim, Jongpil

    2016-01-01

    The rates of metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, and cardiovascular disease (CVD), markedly increase with age. In recent years, studies have reported an association between metabolic changes and various pathophysiological mechanisms in the central nervous system (CNS) in patients with metabolic diseases. Oxidative stress and hyperglycemia in metabolic diseases lead to adverse neurophysiological phenomena, including neuronal loss, synaptic dysfunction, and improper insulin signaling, resulting in Parkinson’s disease (PD). In addition, several lines of evidence suggest that alterations of CNS environments by metabolic changes influence the dopamine neuronal loss, eventually affecting the pathogenesis of PD. Thus, we reviewed recent findings relating to degeneration of dopaminergic neurons during metabolic diseases. We highlight the fact that using a metabolic approach to manipulate degeneration of dopaminergic neurons can serve as a therapeutic strategy to attenuate pathology of PD. PMID:27065205

  18. Metabolic abnormalities in patients with inflammatory rheumatic diseases.

    PubMed

    Dessein, Patrick H; Solomon, Ahmed; Hollan, Ivana

    2016-10-01

    Patients with rheumatoid arthritis (RA) experience an increased cardiometabolic risk factor burden that is substantially driven by systemic inflammation. This occurs less consistently in patients with ankylosing spondylitis (AS). Psoriatic arthritis most strongly associates with excess adiposity and metabolic risk. RA patients also often have systemic inflammation-induced proinflammatory high-density lipoprotein (HDL) cholesterol particles and lean/muscle mass loss in association with increased adiposity, a condition termed rheumatoid cachexia, which further enhances cardiovascular risk. The presence of proinflammatory HDL and lean mass loss was also reported in patients with AS. Individualized aerobic and resistance exercise programs can improve body composition and metabolic risk factor profiles in RA and AS. Future studies should assess how long-term lifestyle changes can be effectuated and if these can influence cardiovascular events in inflammatory rheumatic diseases. Herein, we review the current evidence on metabolic abnormalities in inflammatory arthritis. We propose management strategies and a research agenda. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Relationship Between Prehypertension/Hypertension and Periodontal Disease: A Prospective Cohort Study.

    PubMed

    Kawabata, Yuya; Ekuni, Daisuke; Miyai, Hisataka; Kataoka, Kota; Yamane, Mayu; Mizutani, Shinsuke; Irie, Koichiro; Azuma, Tetsuji; Tomofuji, Takaaki; Iwasaki, Yoshiaki; Morita, Manabu

    2016-03-01

    Most cross-sectional studies have found a significant positive relationship between periodontal disease and prehypertension/hypertension. However, these studies had limitations and there are few prospective cohort studies in young adults. The purpose of this prospective cohort study was to investigate whether periodontal disease was related to prehypertension/hypertension in Japanese university students. Students (n = 2,588), who underwent health examinations before entering university and before graduation, were included in the analysis. The association between periodontal disease such as the percentage of bleeding on probing (BOP) and community periodontal index (CPI) scores, and change in blood pressure status was determined. At the reexamination, the numbers of participants with prehypertension (systolic blood pressure 120-139mm Hg or diastolic blood pressure 80-89mm Hg) and hypertension (≥140/90mm Hg) were 882 (34.1%) and 109 (4.2%), respectively. In a logistic regression model, the risk of hypertension was significantly associated with male (odds ratio (OR): 6.31; 95% confidence interval (CI): 2.63-15.13; P < 0.001), no habitual physical activity at baseline (OR: 2.90; 95% CI: 1.56-5.38; P < 0.01) and periodontal disease defined as the presence of both probing pocket depth (PPD) ≥ 4mm and BOP ≥ 30% at baseline (OR: 2.74; 95% CI: 1.19-6.29; P = 0.02) in participants with prehypertension at baseline. On the other hand, the risk of prehypertension was not associated with presence of periodontal disease (OR: 0.93; 95% CI: 0.51-1.70; P = 0.82). In the short-term prospective cohort study, a significant association between presence of periodontal disease and hypertension was observed in Japanese university students. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Mortality from cardiovascular diseases in the German uranium miners cohort study, 1946-1998.

    PubMed

    Kreuzer, M; Kreisheimer, M; Kandel, M; Schnelzer, M; Tschense, A; Grosche, B

    2006-09-01

    An increased risk of cardiovascular diseases after exposure to low doses of ionizing radiation has been suggested among the atomic bomb survivors. Few and inconclusive results on this issue are available from miner studies. A positive correlation between coronary heart disease mortality and radon exposure has been reported in the Newfoundland fluorspar miners study, yet low statistical power due to small sample size was of concern. To get further insight into this controversial issue, data from the German uranium miners cohort study were used, which is by far the largest miner study up to date. The cohort includes 59,001 male subjects who were employed for at least six months between 1946 and 1989 at the former Wismut uranium company in Eastern Germany. Exposure to radon, long-lived radionuclides and external gamma radiation was estimated by using a detailed job-exposure matrix. About 16,598 cohort members were deceased until 31 December 1998, including 5,417 deaths from cardiovascular diseases. Linear Poisson regression models were used to estimate the excess relative risk (ERR) per unit of cumulative radiation exposure after adjusting for attained age and calendar period. No trend in risk of circulatory diseases with increasing cumulative exposure to either radon [ERR per 100 working level month: 0.0006; 95% confidence limit (CI): -0.004 to 0.006], external gamma radiation (ERR per Sv: -0.26, 95% CI: -0.6 to 0.05) or long-lived radionuclides (ERR per 100 kBqh/m3: -0.2, 95% CI: -0.5 to 0.06), respectively, was observed. This was also true for the sub-group heart disease and stroke. Our findings do not support an association between cardiovascular disease mortality and exposure to radiation among miners, yet low doses and uncontrolled confounding hamper interpretation.

  1. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients

    PubMed Central

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-01-01

    Abstract Background: Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Methods: Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. Results: The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. Conclusions: For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Translational Impacts: Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions. PMID:28445256

  2. Cost-effectiveness analysis of ultrasonography screening for nonalcoholic fatty liver disease in metabolic syndrome patients.

    PubMed

    Phisalprapa, Pochamana; Supakankunti, Siripen; Charatcharoenwitthaya, Phunchai; Apisarnthanarak, Piyaporn; Charoensak, Aphinya; Washirasaksiri, Chaiwat; Srivanichakorn, Weerachai; Chaiyakunapruk, Nathorn

    2017-04-01

    Nonalcoholic fatty liver disease (NAFLD) can be diagnosed early by noninvasive ultrasonography; however, the cost-effectiveness of ultrasonography screening with intensive weight reduction program in metabolic syndrome patients is not clear. This study aims to estimate economic and clinical outcomes of ultrasonography in Thailand. Cost-effectiveness analysis used decision tree and Markov models to estimate lifetime costs and health benefits from societal perspective, based on a cohort of 509 metabolic syndrome patients in Thailand. Data were obtained from published literatures and Thai database. Results were reported as incremental cost-effectiveness ratios (ICERs) in 2014 US dollars (USD) per quality-adjusted life year (QALY) gained with discount rate of 3%. Sensitivity analyses were performed to assess the influence of parameter uncertainty on the results. The ICER of ultrasonography screening of 50-year-old metabolic syndrome patients with intensive weight reduction program was 958 USD/QALY gained when compared with no screening. The probability of being cost-effective was 67% using willingness-to-pay threshold in Thailand (4848 USD/QALY gained). Screening before 45 years was cost saving while screening at 45 to 64 years was cost-effective. For patients with metabolic syndromes, ultrasonography screening for NAFLD with intensive weight reduction program is a cost-effective program in Thailand. Study can be used as part of evidence-informed decision making. Findings could contribute to changes of NAFLD diagnosis practice in settings where economic evidence is used as part of decision-making process. Furthermore, study design, model structure, and input parameters could also be used for future research addressing similar questions.

  3. Disordered energy and protein metabolism in liver disease.

    PubMed

    McCullough, A J; Tavill, A S

    1991-11-01

    Although progress has been made, more information is needed on the role of nutritional therapy in liver disease. Because considerable heterogeneity exists among patients regarding both nutritional needs and the pathophysiology of malnutrition, their nutritional status must be monitored to permit careful selection and individualization of therapy. It is important to remember that the factors controlling nutritional status and overall survival in cirrhosis are multifactorial and the pathophysiologic mechanisms influencing outcome remained to be further defined. Consequently, it seems unlikely that any single therapy will be effective alone. In this regard, it should be emphasized that nutritional management should not be aimed solely at restoring normal metabolic homeostasis but should maximize anabolic regenerative processes in addition and minimize abnormal liver function so as to promote the effectiveness of other interventional therapies in patients with chronic liver disease.

  4. Ornithine and its role in metabolic diseases: An appraisal.

    PubMed

    Sivashanmugam, Muthukumaran; J, Jaidev; V, Umashankar; K N, Sulochana

    2017-02-01

    Ornithine is a non-essential amino acid produced as an intermediate molecule in urea cycle. It is a key substrate for the synthesis of proline, polyamines and citrulline. Ornithine also plays an important role in the regulation of several metabolic processes leading to diseases like hyperorithinemia, hyperammonemia, gyrate atrophy and cancer in humans. However, the mechanism of action behind the multi-faceted roles of ornithine is yet to be unraveled completely. Several types of cancers are also characterized by excessive polyamine synthesis from ornithine by different rate limiting enzymes. Hence, in this review we aim to provide extensive insights on potential roles of ornithine in many of the disease related cellular processes and also on the structural features of ornithine interacting proteins, enabling development of therapeutic modalities.

  5. Dyslipidemia and Cardiovascular Disease Risk Factor Management in HIV-1-Infected Subjects Treated with HAART in the Spanish VACH Cohort

    PubMed Central

    Domingo, Pere; Suarez-Lozano, Ignacio; Teira, Ramón; Lozano, Fernando; Terrón, Alberto; Viciana, Pompeyo; González, Juan; Galindo, Mª José; Geijo, Paloma; Vergara, Antonio; Cosín, Jaime; Ribera, Esteban; Roca, Bernardino; Garcia-Alcalde, Mª Luisa; Sánchez, Trinitario; Torres, Ferran; Lacalle, Juan Ramón; Garrido, Myriam

    2008-01-01

    Background: There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients. Objectives: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies. Methods: Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy. Results: The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77–6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12–7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24–43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients. Conclusion: Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication. PMID:18923695

  6. NAD+ metabolism, a therapeutic target for age-related metabolic disease

    PubMed Central

    Auwerx, Johan

    2013-01-01

    Nicotinamide adenine dinucleotide (NAD) is a central metabolic cofactor by virtue of its redox capacity, and as such regulates a wealth of metabolic transformations. However, the identification of the longevity protein Sir2, the founding member of the sirtuin protein family, as being NAD+-dependent reignited interest in this metabolite. The sirtuins (SIRT1-7 in mammals) utilize NAD+ to deacetylate proteins in different subcellular compartments with a variety of functions, but with a strong convergence on optimizing mitochondrial function. Since cellular NAD+ levels are limiting for sirtuin activity, boosting its levels is a powerful means to activate sirtuins as a potential therapy for mitochondrial, often age-related, diseases. Indeed, supplying excess precursors, or blocking its utilization by PARP enzymes or CD38/CD157, boosts NAD+ levels, activates sirtuins and promotes healthy aging. Here, we discuss the current state of knowledge of NAD+ metabolism, primarily in relation to sirtuin function. We highlight how NAD+ levels change in diverse physiological conditions, and how this can be employed as a pharmacological strategy. PMID:23742622

  7. The Effects of Age, Period, and Cohort on Mortality from Ischemic Heart Disease in China

    PubMed Central

    Chang, Jie; Li, Boyang; Li, Jingjing; Sun, Yang

    2017-01-01

    In contrast with most developed countries, mortality due to ischemic heart disease (IHD) continues to rise in China. We examined the effects of age, period, and cohort on IHD mortality in urban and rural populations from 1987 to 2013 to identify the drivers of this trend. Region-specific data on annual IHD mortality among adults aged 20 to 84 years and corresponding population statistics were collected. We then tested for age, period, and cohort effects using the Intrinsic Estimator approach. Our results indicated that IHD mortality in China increased significantly over the three decades studied. There was a log-linear increase in the age effect on IHD mortality as those aged 80–84 showed 277 and 161 times greater IHD mortality risk than those aged 20–24 in urban and rural populations, respectively. While there was an upward trend in the period effect in both populations, the influence of the cohort effect on mortality decreased over time for those born from 1904 to 1993. The age, period, and cohort effects on mortality in China were generally comparable between urban and rural populations. The results suggest that population aging is a major driver behind the rapid rise in IHD mortality. Increased exposure to air pollution may also have played a role in driving the period effect PMID:28067846

  8. Benign Prostatic Hyperplasia, Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease: Is Metaflammation the Link?

    PubMed

    Russo, Giorgio Ivan; Cimino, Sebastiano; Castelli, Tommaso; Favilla, Vincenzo; Gacci, Mauro; Carini, Marco; Condorelli, Rosita A; La Vignera, Sandro; Calogero, Aldo E; Motta, Fabio; Puzzo, Lidia; Caltabiano, Rosario; Morgia, Giuseppe

    2016-12-01

    The prevalence of prostatic inflammation (PI) is very frequent in patients affected by benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). To investigate the relationship between prostatic inflammation (PI) and the presence of MetS and non-alcoholic fatty liver disease (NAFLD) in a cohort of patients affected by BPH/LUTS. We conducted a prospective study from January 2012 to June 2014 on 264 consecutive patients, who underwent transurethral resection of the prostate for bladder outlet obstruction. Metabolic syndrome (MetS) has been defined according to the International Diabetes Federation (IDF). Prior to surgery, each patient has been evaluated for the presence of MetS and NAFLD. All surgical specimens were investigated for the presence of an inflammatory infiltrate, according to the Irani score. The prevalence of patients affected by MetS alone was 13.8% (32/232), 13.8% (32/232) by NAFLD alone, and 42.7% (99/232) by both diseases. The rate of subjects affected by MetS + NAFLD and severe PI was significantly greater than those with only one metabolic alteration (75.8% vs. 24.2%, P < 0.01). The multivariate logistic regression analysis revealed that FLI was independently associated with high PI (Irani score ≥ 4) (odds ratio [OR]: 1.04; P < 0.01). Further, the combination between MetS and NAFLD was associated severe PI (OR: 4.5; P < 0.01) while not MetS as a single alteration. Patients with BPH/LUTS and metabolic aberration exhibited grater PI. The coexistence of MetS and NAFLD exerted a greater detrimental effect on prostate gland by increasing severity of inflammation. Prostate 76:1528-1535, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. [Updates on Lifestyle-Related Diseases and Bone Metabolism. Bisphosphonates for lifestyle-related disease].

    PubMed

    Okada, Yosuke; Tanaka, Yoshiya

    2014-11-01

    A lifestyle-related disease and osteoporosis are diseases to increase with aging and a lifestyle-related disease has an influence on the bone metabolism. Because the number of patients with lifestyle-related disease is getting larger, it is necessary to prevent fracture in those. Unfortunately, substantial randomized control studies are yet to be done in patients with lifestyle-related disease to clarify if anti-osteoporotic drugs are effective to prevent fractures. It is suggested by the subanalysis in the existing clinical study with usefulness of bisphosphonates with evidence as an osteoporotic therapeutic drug in life-related disease. Here I will review about the effective and problem with bisphosphonate for the lifestyle-related disease with arteriosclerosis.

  10. Adult asthma and risk of coronary heart disease, cerebrovascular disease, and heart failure: a prospective study of 2 matched cohorts.

    PubMed

    Iribarren, Carlos; Tolstykh, Irina V; Miller, Mary K; Sobel, Erica; Eisner, Mark D

    2012-12-01

    Asthma has been associated with increased cardiovascular disease (CVD) risk. The authors ascertained the association of asthma with CVD and the roles that sex, concurrent allergy, and asthma medications may play in this association. They assembled a cohort of 203,595 Northern California adults with asthma and a parallel asthma-free referent cohort (matched 1:1 on age, sex, and race/ethnicity); both cohorts were followed for incident nonfatal or fatal CVD and all-cause mortality from January 1, 1996, through December 31, 2008. Each cohort was 66% female and 47% white. After adjustment for age, sex, race/ethnicity, cardiac risk factors, and comorbid allergy, asthma was associated with a 1.40-fold (95% confidence interval (CI): 1.35, 1.45) increased hazard of coronary heart disease, a 1.20-fold (95% CI: 1.15, 1.25) hazard of cerebrovascular disease, a 2.14-fold (95% CI: 2.06, 2.22) hazard of heart failure, and a 3.28-fold (95% CI: 3.15, 3.41) hazard of all-cause mortality. Stronger associations were noted among women. Comorbid allergy predicted CVD but did not synergistically increase the CVD risk associated with asthma. Only asthma patients using asthma medications (particularly those on oral corticosteroids alone or in combination) were at enhanced risk of CVD. In conclusion, asthma was prospectively associated with increased risk of major CVD. Modifying effects were noted for sex and asthma medication use but not for comorbid allergy.

  11. Childhood-Onset Disease Predicts Mortality in an Adult Cohort of Patients with Systemic Lupus Erythematosus

    PubMed Central

    Hersh, Aimee O.; Trupin, Laura; Yazdany, Jinoos; Panopalis, Peter; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

    2013-01-01

    Objective To examine childhood-onset disease as a predictor of mortality in a cohort of adult patients with systemic lupus erythematosus (SLE). Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 957 adult subjects with SLE that includes 98 subjects with childhood-onset SLE. Baseline and follow-up data were obtained via telephone interviews conducted between 2002-2007. The number of deaths during 5 years of follow-up was determined and standardized mortality ratios (SMRs) for the cohort, and across age groups, were calculated. Kaplan-Meier life table analysis was used to compare mortality rates between childhood (defined as SLE diagnosis <18 years) and adult-onset SLE. Multivariate Cox proportional hazard models were used to determine predictors of mortality. Results During the median follow-up period of 48 months, 72 deaths (7.5% of subjects) occurred, including 9 (12.5%) among those with childhood-onset SLE. The overall SMR was 2.5 (CI 2.0-3.2). In Kaplan-Meier survival analysis, after adjusting for age, childhood-onset subjects were at increased risk for mortality throughout the follow-up period (p<0.0001). In a multivariate model adjusting for age, disease duration and other covariates, childhood-onset SLE was independently associated with an increased mortality risk (hazard ratio [HR]: 3.1; 95% confidence interval [CI]: 1.3-7.3), as was low socioeconomic status measured by education (HR: 1.9; 95% CI 1.1-3.2) and end stage renal disease (HR: 2.1; 95% CI 1.1-4.0). Conclusion Childhood-onset SLE was a strong predictor of mortality in this cohort. Interventions are needed to prevent early mortality in this population. PMID:20235215

  12. Understanding the role of gut microbiome in metabolic disease risk.

    PubMed

    Sanz, Yolanda; Olivares, Marta; Moya-Pérez, Ángela; Agostoni, Carlo

    2015-01-01

    The gut microbiota structure, dynamics, and function result from interactions with environmental and host factors, which jointly influence the communication between the gut and peripheral tissues, thereby contributing to health programming and disease risk. Incidence of both type-1 and type-2 diabetes has increased during the past decades, suggesting that there have been changes in the interactions between predisposing genetic and environmental factors. Animal studies show that gut microbiota and its genome (microbiome) influence alterations in energy balance (increased energy harvest) and immunity (inflammation and autoimmunity), leading to metabolic dysfunction (e.g., insulin resistance and deficiency). Thus, although they have different origins, both disorders are linked by the association of the gut microbiota with the immune-metabolic axis. Human studies have also revealed shifts in microbiome signatures in diseased subjects as compared with controls, and a few of them precede the development of these disorders. These studies contribute to pinpointing specific microbiome components and functions (e.g., butyrate-producing bacteria) that can protect against both disorders. These could exert protective roles by strengthening gut barrier function and regulating inflammation, as alterations in these are a pathophysiological feature of both disorders, constituting common targets for future preventive approaches.

  13. Roles of leptin in bone metabolism and bone diseases.

    PubMed

    Chen, Xu Xu; Yang, Tianfu

    2015-09-01

    Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

  14. Adipokines in Healthy Skeletal Muscle and Metabolic Disease.

    PubMed

    Coles, C A

    2016-01-01

    Adipose tissue not only functions as a reserve to store energy but has become of major interest as an endocrine organ, releasing signalling molecules termed adipokines which impact on other tissues, such as skeletal muscle. Adipocytes, within skeletal muscle and adipose tissue, secrete adipokines to finely maintain the balance between feed intake and energy expenditure. This book chapter focuses on the three adipokines, adiponectin, leptin and IL-6, which have potent effects on skeletal muscle during rest and exercise. Similarly, adiponectin, leptin and IL-6 enhance glucose uptake and increase fatty acid oxidation in skeletal muscle. Fatty acid oxidation is increased through activation of AMPK (adenosine monophosphate-activated protein kinase signalling) causing phosphorylation and inhibition of ACC (acetyl-coenzyme A carboxylase), decreasing availability of malonyl CoA. Leptin and adiponectin also control feed intake via AMPK signalling in the hypothalamus. Adipokines function to maintain energy homeostasis, however, when feed intake exceeds energy expenditure adipokines can become dysregulated causing lipotoxicity in skeletal muscle and metabolic disease can prevail. Cross-talk between adipocytes and skeletal muscle via correct control by adipokines is important in controlling energy homeostasis during rest and exercise and can help prevent metabolic disease.

  15. Epicardial adipose tissue in endocrine and metabolic diseases.

    PubMed

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  16. Lipoprotein metabolism differs between Marek's disease susceptible and resistant chickens.

    PubMed

    Yuan, P; Yu, Y; Luo, J; Tian, F; Zhang, H; Chang, S; Ramachandran, R; Zhang, L; Song, J

    2012-10-01

    Marek's disease (MD) is a lymphoproliferative disease of chickens caused by MD virus and has an important impact on the poultry industry worldwide. There have been reports showing different physiological characteristics between MD susceptible and resistant chickens. However, little is known about whether there are differences in lipid metabolism between MD susceptible and resistant lines of chickens. In this study, we examined the BW and the weight of tissues (abdominal fat, breast muscle with bone, leg muscle with bone, liver, and heart), the lipoprotein-cholesterol concentrations and distributions, and the plasma and tissue levels of adiponectin and its receptors in the highly resistant and susceptible lines during chicken growth. Our data showed that the increase in total cholesterol during growth was mainly due to the elevation of cholesterol in the low-density/very low-density lipoprotein fraction in MD susceptible chickens, whereas the increase of total cholesterol was mainly attributable to the increase in high-density lipoprotein-cholesterol in MD resistant chickens. Meanwhile, the MD resistant line appeared to have increased plasma adiponectin levels compared with MD susceptible chickens during growth. Taken together, our data suggested that lipoprotein-cholesterol and adiponectin metabolism are different between MD susceptible and resistant chickens.

  17. Determinants of increased cardiovascular disease in obesity and metabolic syndrome.

    PubMed

    Vazzana, N; Santilli, F; Sestili, S; Cuccurullo, C; Davi, G

    2011-01-01

    Obesity is associated with an increased mortality and morbidity for cardiovascular disease (CV