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Title:
Dietary medium chain fatty acid supplementation leads to reduced VLDL lipolysis and uptake rates in comparison to linoleic acid supplementation
Authors:
van Schalkwijk, Daniel B.; Pasman, Wilrike J.; Hendriks, Henk F. J.; Verheij, Elwin R.; Rubingh, Carina M.; van Bochove, Kees; Vaes, Wouter H. J.; Adiels, Martin; Freidig, Andreas P.; de Graaf, Albert A.
Abstract:
Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51+/-7 years; BMI 28.5+/-0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.
Published:
2014
Title:
Dietary polyamine intake and polyamines measured in urine
Authors:
Vargas, A.J.; Ashbeck, E.L.; Thomson, C.A.; Gerner, E.W.; Thompson, P.A.
Abstract:
Dietary polyamines have recently been associated with increased risk of pre-malignant colorectal lesions. Because polyamines are synthesized in cells and taken up from dietary sources, development of a biomarker of exposure is challenging. Excess polyamines are primarily excreted in the urine. This pilot study seeks to identify dietary correlates of excreted urinary polyamines as putative biomarkers of exposure. Dietary polyamines/other nutrients were estimated from a food frequency questionnaire (FFQ) and correlated with urinary levels of acetylated polyamines in 36 men using 24-h urine samples. Polyamines, abundant in cheese and citrus, were highly positively correlated with urinary N8-acetylspermidine (correlation coefficient; r = 0.37, P = 0.03), but this correlation was attenuated after adjustment for total energy intake (r = 0.07, P = 0.68). Dietary energy intake itself was positively correlated with urinary total acetylated polyamine output (r =.40, P = 0.02). In energy-adjusted analyses, folic acid and folate from food were associated with urinary N1,N12-diacetylspermine (r = 0.34, P = 0.05 and r =-0.39, P = 0.02, respectively). Red meat negatively correlated with total urinary acetylated polyamines (r =-0.42, P = 0.01). Our findings suggest that energy, folate, folic acid, saturated fat, and red meat intake, as opposed to FFQ-estimated dietary polyamines, are correlated with urinary polyamines. © 2014 Taylor and Francis Group, LLC.
Published:
2014
Title:
Dietary sources and health implications of arachidonic acid
Authors:
Martins, S.V.; Alfaia, C.M.; Lopes, P.A.; Prates, J.M.
Abstract:
Dietary habits in Western societies, in particular the amount and type of fat consumed, play an important role in human health condition. The present chapter reviews the biosynthesis, dietary sources and health implications of the arachidonic acid (20:4n-6, AA), a long-chain polyunsaturated fatty acid (PUFA) from the n-6 family found in mammalian cells, especially in membrane phospholipids. Systemic and tissue levels of AA may result from two origins, the endogenous synthesis from linoleic acid (18:2n-6, LA) elongation and the exogenous dietary source. LA elongation involves desaturation and chain elongation enzymes, which are also common to the n-3 PUFA α-linolenic acid (18:3n-3, ALA) elongation pathway. As dietary intake of ALA is low, the production of AA from LA is little restrained. Humans consume AA from animal-derived foods (e.g., eggs and meat) as it does not occur in plants. The major biological functions of AA are as cell signaling molecule and as precursor to an extensive group of compounds, called eicosanoids. Different eicosanoids, namely prostaglandins, thromboxanes, leukotrienes, and other bioactive metabolites, are produced by different types of cells via distinct enzymatic pathways. These AA mediators act like potent chemical messengers on immunity regulation. The overproduction of prothrombotic and pro-inflammatory eicosanoids, thromboxanes and leukotrienes derived from AA, has been associated with numerous diseases, such as cancer, heart disease, rheumatoid arthritis or asthma. In addition, AA and its end-products are involved in physiological processes in the central nervous system and have been implicated in neurological, neurodegenerative, and psychiatric disorders. During several decades, AA and its metabolites have been considered nothing but pro-inflammatory with recommendations to lower its intake from the diet. However, the discovery of anti-inflammatory mediators produced from AA is changing the long-held misunderstandings about this fatty acid. Unlike the pro-inflammatory prostaglandins and leukotrienes, AA-derived lipoxins display counter-regulatory actions by promoting the resolution of acute inflammatory responses. In conclusion, AA has been the focus of new investigations in the recent years and, rather than being detrimental, moderate AA intake seems to be a key dietary component for cardiovascular and cognitive health, with harmless effects in healthy subjects. © 2014 Nova Science Publishers, Inc.
Published:
2014
Title:
Dopamine and glucose, obesity and reward deficiency syndrome
Authors:
Blum, Kenneth; Thanos, Panayotis K.; Gold, Mark S.
Abstract:
Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain's production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization of powerful dopamine D2 agonists have failed due to chronic down regulation of D2 receptors newer targets based on novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of reward deficiency.
Published:
2014
Title:
Dynamic changes in metabolic profiles of rats subchronically exposed to mequindox
Authors:
Jiang, L.; Zhao, X.; Huang, C.; Lei, H.; Tang, H.; Wang, Y.
Abstract:
Mequindox is widely used as an antibacterial veterinary drug and a feeding additive for farm animals in China. Although its toxicity has been widely studied, little is known regarding the metabolic effects of subchronic exposure to mequindox, which is vital for the health of meat producing livestock. Here, we characterized the dose- and time-dependent metabolic alterations in female Wistar rats subchronically exposed to mequindox through dietary supplementation at the level of 40, 110 and 280 mg kg-1 for 13 weeks, employing a NMR based metabonomics approach with supplementary information from serum clinical chemistry. We found that urinary metabolic profiles were significantly affected in all dosed groups during the supplementation period; plasma and hepatic metabolic profiles were significantly affected only in rats dosed with moderate and high levels of mequindox. We also observed a return to control levels, for the profiles of urine and liver, at all dose levels after a two weeks washout period. However, this was not the case for the metabolic profiles of plasma from rats dosed at high levels. At the molecular level, we showed that subchronic exposure to mequindox resulted in tricarboxylic acid cycle (TCA cycle) stimulation, suppression of glycolysis, and promotion of gluconeogenesis and lipid oxidation in rats. In addition, subchronic exposure to mequindox induced oxidative stress in rats. Furthermore, a disturbance of gut microbiota, manifested by alterations in the urinary excretion of hippurate, phenylacetylglycine, 3-(3-hydroxyphenyl)propionate, p-cresol glucuronide, methylamine, dimethylamine, and formate, was associated with mequindox exposure. The present study provided important holistic metabolic information on the effects of subchronic dosage of mequindox on rats, which is useful for evaluating the safety of mequindox usage in meat producing animals. © the Partner Organisations 2014.
Published:
2014
Title:
Effects of low-carbohydrate and low-fat diets: A randomized trial
Authors:
Bazzano, Lydia A.; Hu, Tian; Reynolds, Kristi; Yao, Lu; Bunol, Calynn; Liu, Yanxi; Chen, Chung Shiuan; Klag, Michael J.; Whelton, Paul K.; He, Jiang
Abstract:
BACKGROUND Low-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations. OBJECTIVE To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors. DESIGN A randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271). SETTING A large academic medical center. PARTICIPANTS 148 men and women without clinical cardiovascular disease and diabetes. INTERVENTION A low-carbohydrate (\textless40 g/d) or low-fat (\textless30% of daily energy intake from total fat [\textless7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial. MEASUREMENTS Data on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months. RESULTS Sixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P \textless 0.001) than those on the low-fat diet. LIMITATION Lack of clinical cardiovascular disease end points. CONCLUSION The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors. PRIMARY FUNDING SOURCE National Institutes of Health.
Published:
2014
Title:
Effects of whole grain, fish and bilberries on serum metabolic profile and lipid transfer protein activities: a randomized trial (Sysdimet)
Authors:
Lankinen, Maria; Kolehmainen, Marjukka; Jääskeläinen, Tiina; Paananen, Jussi; Joukamo, Laura; Kangas, Antti J.; Soininen, Pasi; Poutanen, Kaisa; Mykkänen, Hannu; Gylling, Helena; Orešič, Matej; Jauhiainen, Matti; Ala-Korpela, Mika; Uusitupa, Matti; Schwab, Ursula
Abstract:
OBJECTIVE: We studied the combined effects of wholegrain, fish and bilberries on serum metabolic profile and lipid transfer protein activities in subjects with the metabolic syndrome. METHODS: Altogether 131 subjects (40-70 y, BMI 26-39 kg/m(2)) with impaired glucose metabolism and features of the metabolic syndrome were randomized into three groups with 12-week periods according to a parallel study design. They consumed either: a) wholegrain and low postprandial insulin response grain products, fatty fish 3 times a week, and bilberries 3 portions per day (HealthyDiet), b) wholegrain and low postprandial insulin response grain products (WGED), or c) refined wheat breads as cereal products (Control). Altogether 106 subjects completed the study. Serum metabolic profile was studied using an NMR-based platform providing information on lipoprotein subclasses and lipids as well as low-molecular-weight metabolites. RESULTS: There were no significant differences in clinical characteristics between the groups at baseline or at the end of the intervention. Mixed model analyses revealed significant changes in lipid metabolites in the HealthyDiet group during the intervention compared to the Control group. All changes reflected increased polyunsaturation in plasma fatty acids, especially in n-3 PUFAs, while n-6 and n-7 fatty acids decreased. According to tertiles of changes in fish intake, a greater increase of fish intake was associated with increased concentration of large HDL particles, larger average diameter of HDL particles, and increased concentrations of large HDL lipid components, even though total levels of HDL cholesterol remained stable. CONCLUSIONS: The results suggest that consumption of diet rich in whole grain, bilberries and especially fatty fish causes changes in HDL particles shifting their subclass distribution toward larger particles. These changes may be related to known protective functions of HDL such as reverse cholesterol transport and could partly explain the known protective effects of fish consumption against atherosclerosis. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov NCT00573781.
Published:
2014
Title:
Ethnoelephantology and The Multispeces Turn- New Approaches to Human-Elephant Relations
Authors:
P, Locke
Abstract:
Humans and elephants have lived together and shared space together in diverse ways for millennia. The intersections between these thinking and feeling species have been differently explored, for different reasons, by disciplines across the sciences, humanities, and social sciences. Such disciplinary divisions, predicated on oppositions of human/animal and nature/culture, are integral to the configuration of modernist thought. However, posthumanist and biocultural thinking questions the underlying epistemological conventions, thereby opening up interdisciplinary possibilities for human-animal studies. In relation to issues of conflict and coexistence, this paper charts the emergence of an interdisciplinary research programme and discursive space for human-elephant intersections under the rubric of ethnoelephantology. Recognizing continuities between the sentient and affective lifeworlds of humans and elephants, the mutual entanglements of their social, historical, and ecological relations, and the relevance of combining social and natural science methodologies, it surveys recent research from anthropology, history, and geography that exemplifies this new approach.
Published:
2014
Title:
Expression differences between African American and Caucasian prostate cancer tissue reveals that stroma is the site of aggressive changes
Authors:
Kinseth, Matthew A.; Jia, Zhenyu; Rahmatpanah, Farahnaz; Sawyers, Anne; Sutton, Manuel; Wang‐Rodriguez, Jessica; Mercola, Dan; McGuire, Kathleen L.
Abstract:
In prostate cancer, race/ethnicity is the highest risk factor after adjusting for age. African Americans have more aggressive tumors at every clinical stage of the disease, resulting in poorer prognosis and increased mortality. A major barrier to identifying crucial gene activity differences is heterogeneity, including tissue composition variation intrinsic to the histology of prostate cancer. We hypothesized that differences in gene expression in specific tissue types would reveal mechanisms involved in the racial disparities of prostate cancer. We examined 17 pairs of arrays for AAs and Caucasians that were formed by closely matching the samples based on the known tissue type composition of the tumors. Using pair-wise t-test we found significantly altered gene expression between AAs and CAs. Independently, we performed multiple linear regression analyses to associate gene expression with race considering variation in percent tumor and stroma tissue. The majority of differentially expressed genes were associated with tumor-adjacent stroma rather than tumor tissue. Extracellular matrix, integrin family and signaling mediators of the epithelial-to-mesenchymal transition (EMT) pathways were all downregulated in stroma of AAs. Using MetaCore (GeneGo) analysis, we observed that 35% of significant (p
Published:
2014
Title:
Fasting Guidelines
Authors:
Christie, Megan
Abstract:
Published:
2014
Title:
Feeding France: new sciences of food, 1760-1815
Authors:
Spary, E. C
Abstract:
"Feeding France is the first comprehensive study of the French food industry in the decades surrounding the French Revolution of 1789. Though the history of gastronomy and the restaurant have been explored by scholars, few are aware that France was also one of the first nations to produce industrial foods. In this time of political and social upheaval, chemists managed to succeed both as public food experts and as industrial food manufacturers. This book explores the intersection between knowledge, practice and commerce which made this new food expertise possible, and the institutional and experimental culture which housed it. Ranging from the exigencies of Old Regime bread-making to the industrial showcasing of gelatine manufacture, Emma Spary rewrites the history of the French relationship with food to show that industrialisation and patrimonialism were intimately intertwined"--
Published:
2014
Title:
Fish consumption, sleep, daily functioning, and heart rate variability
Authors:
Hansen, A.L.; Dahl, L.; Olson, G.; Thornton, D.; Graff, I.E.; Frøyland, L.; Thayer, J.F.; Pallesen, S.
Abstract:
Study Objectives: This study investigated the effects of fatty fish on sleep, daily functioning and biomarkers such as heart rate variability (HRV), vitamin D status (serum 25-hydroxyvitamin D (25OHD), and eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) in red blood cells. Moreover the relationship among sleep, daily functioning, HRV, vitamin D status, and levels of EPA+DHA was investigated. Methods: Ninety-five male forensic patients from a secure forensic inpatient facility in the USA were randomly assigned into a Fish or a Control group. The Fish group received Atlantic salmon three times per week from September to February, and the Control group was provided an alternative meal (e.g., chicken, pork, beef), but with the same nutritional value as their habitual diet, three times per week during the same period. Sleep (sleep latency, sleep efficiency, actual sleep time, and actual wake time), self-perceived sleep quality and daily functioning, as well as vitamin D status, EPA+DHA, and HRV, were assessed pre- and post-intervention period. Results: There was a significant increase in sleep latency from pre- to post-test in the Control group. The Fish group reported better daily functioning than the Control group during post-test. Fish consumption throughout the wintertime had also an effect on resting HRV and EPA+DHA, but not on vitamin D status. However, at post-test, the vitamin D status in the Fish group was still closer to the level regarded as optimal compared to the Control group. Vitamin D status correlated negatively with actual wake time and positively with sleep efficiency during pre-test, as well as positively with daily functioning and sleep quality during post-test. Finally, HRV correlated negatively with sleep latency and positively with daily functioning. Conclusions: Fish consumption seemed to have a positive impact on sleep in general and also on daily functioning, which may be related to vitamin D status and HRV.
Published:
2014
Title:
Flow Cytometry Analyses of Adipose Tissue Macrophages
Authors:
Cho, Kae Won; Morris, David L.; Lumeng, Carey N.
Abstract:
Within adipose tissue, multiple leukocyte interactions contribute to metabolic homeostasis in health as well as to the pathogenesis of insulin resistance with obesity. Adipose tissue macrophages (ATMs) are the predominant leukocyte population in fat and contribute to obesityinduced inflammation. Characterization of ATMs and other leukocytes in the stromal vascular fraction from fat has benefited from the use of flow cytometry and flow-assisted cell sorting techniques. These methods permit the immunophenotyping, quantification, and purification of these unique cell populations from multiple adipose tissue depots in rodents and humans. Proper isolation, quantification, and characterization of ATM phenotypes are critical for understanding their role in adipose tissue function and obesity-induced metabolic diseases. Here, we present the flow cytometry protocols for phenotyping ATMs in lean and obese mice employed by our laboratory.
Published:
2014
Title:
Food as a Drug
Authors:
Poston, Walker SC; Haddock, C. Keith
Abstract:
Published:
2014
Title:
Food, eating and identity in early Medieval England
Authors:
Frantzen, Allen J
Abstract:
Food in the Middle Ages usually evokes images of feasting, speeches, and special occasions, even though most evidence of food culture consists of fragments of ordinary things such as knives, cooking pots, and grinding stones, which are rarely mentioned by contemporary writers. This book puts daily life and its objects at the centre of the food world. It brings together archaeological and textual evidence to show how words and implements associated with food contributed to social identity at all levels of Anglo-Saxon society. It also looks at the networks which connected fields to kitchens and linked rural centres to trading sites. Fasting, redesigned field systems, and the place of fish in the diet are examined in a wide-ranging, interdisciplinary inquiry into the power of food to reveal social complexity.
Published:
2014
Title:
High-resolution mass spectrometry applied to the study of metabolome modifications in various chicken tissues after amoxicillin administration
Authors:
Hermo, M.P.; Saurina, J.; Barbosa, J.; Barrón, D.
Abstract:
The performance of high resolution accurate mass spectrometry (HRMS) operating in full scan MS mode was investigated for the quantitative determination of amoxicillin (AMX) as well as qualitative analysis of metabolomic profiles in tissues of medicated chickens. The metabolomic approach was exploited to compile analytical information on changes in the metabolome of muscle, kidney and liver from chickens subjected to a pharmacological program with AMX. Data consisting of m/z features taken throughout the entire chromatogram were extracted and filtered to be treated by Principal Component Analysis. As a result, it was found that medicated and non-treated animals were clearly clustered in distinct groups. Besides, the multivariate analysis revealed some relevant mass features contributing to this separation. In this context, recognizing those potential markers of each chicken class was a priority research for both metabolite identification and, obviously, evaluation of food quality and health effects associated to food consumption. © 2013 Elsevier Ltd. All rights reserved.
Published:
2014
Title:
Hypertonic saline with furosemide for the treatment of acute congestive heart failure: A systematic review and meta-analysis
Authors:
Gandhi, Sumeet; Mosleh, Wassim; Myers, Robert B.H.
Abstract:
Background Advanced congestive heart failure (CHF) therapies include intravenous inotropic agents, change in class of diuretics, and venous ultrafiltration or hemodialysis. These modalities have not been associated with improved prognosis and are limited by availability and cost. Compared to high-dose furosemide alone, concomitant hypertonic saline solution (HSS) administration has demonstrated improved clinical outcomes with good safety profile. Methods A literature search was conducted for randomized controlled trials that investigated the use of HSS in patients admitted to hospital with acute CHF. Results 1032 patients treated with HSS and 1032 controls, demonstrated decreased all-cause mortality in patients treat with HSS with RR of 0.56 (95% CI 0.41-0.76,p = 0.0003). 1012 patients treated with HSS and 1020 controls, demonstrated decreased heart failure hospital readmission with RR of 0.50 (95% CI 0.33-0.76,p = 0.001). Patients treated with HSS also demonstrated decreased hospital length of stay (p = 0.0002), greater weight loss (p \textless 0.00001), and preservation of renal function (p \textless 0.00001). Conclusion The results of this meta-analysis demonstrate that in patients with advanced CHF concomitant hypertonic saline administration improved weight loss, preserved renal function, and decreased length of hospitalization, mortality and heart failure rehospitalization. A future adequately powered, multi-centre, placebo controlled, randomized, double dummy, blinded trial is needed to assess the benefit of hypertonic saline in patients with renal dysfunction, in diverse patient populations, as well using a patient population on optimal current heart failure treatment. Pending further validation, there is promise for hypertonic saline as an advanced therapy for the management of acute advanced CHF. © 2014 Elsevier Ireland Ltd.
Published:
2014
Title:
Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz
Authors:
Naidoo, Panjasaram; Chetty, Vasudevan V.; Chetty, Manoranjenni
Abstract:
Abstract PurposeDifferences in drug metabolism due to cytochrome P450 (CYP) polymorphisms may be significant enough to warrant different dosing strategies in carriers of specific cytochrome P450 (CYP) polymorphisms, especially for drugs with a narrow therapeutic index. The impact of such polymorphisms on drug plasma concentrations and the resulting dosing strategies are presented in this review, using the example of efavirenz (EFV). MethodsA structured literature search was performed to extract information pertaining to EFV metabolism and the influence of polymorphisms of CYP2B6, ethnicity, sex and drug interactions on plasma concentrations of EFV. The corresponding dosing strategies developed for carriers of specific CYP2B6 genotypes were also reviewed. ResultsThe polymorphic CYP2B6 enzyme, which is the major enzyme in the EFVmetabolic pathway, is a key determinant for the significant inter-individual differences seen in EFV pharmacokinetics and pharmacodynamics (PKPD). Ethnic differences and the associated prevalence of CYP2B6 polymorphisms result in significant differences in the PKPD associated with a standard 600 mg per day dose of EFV, warranting dosage reduction in carriers of specific CYP2B6 polymorphisms. Drug interactions and auto-induction also influence EFV PKPD significantly. ConclusionUsing EFV as an example of a drug with a narrow therapeutic index and a high inter-patient variability in plasma concentrations corresponding to a standard dose of the drug, this review demonstrates how genotyping of the primary metabolising enzyme can be useful for appropriate dosage adjustments in individuals. However, other variables such as drug interactions and auto-induction may necessitate plasma concentration measurements as well, prior to personalising the dose.
Published:
2014
Title:
Including food 25-hydroxyvitamin D in intake estimates may reduce the discrepancy between dietary and serum measures of vitamin D status
Authors:
Taylor, Christine L; Patterson, Kristine Y; Roseland, Janet M; Wise, Stephen A; Merkel, Joyce M; Pehrsson, Pamela R; Yetley, Elizabeth A
Abstract:
The discrepancy between the commonly used vitamin D status measures-intake and serum 25-hydroxyvitamin D [25(OH)D] concentrations--has been perplexing. Sun exposure increases serum 25(OH)D concentrations and is often used as an explanation for the higher population-based serum concentrations in the face of apparently low vitamin D intake. However, sun exposure may not be the total explanation. 25(OH)D, a metabolite of vitamin D, is known to be present in animal-based foods. It has been measured and reported only sporadically and is not currently factored into U.S. estimates of vitamin D intake. Previously unavailable preliminary USDA data specifying the 25(OH)D content of a subset of foods allowed exploration of the potential change in the reported overall vitamin D content of foods when the presence of 25(OH)D was included. The issue of 25(OH)D potency was addressed, and available commodity intake estimates were used to outline trends in projected vitamin D intake when 25(OH)D in foods was taken into account. Given the data available, there were notable increases in the total vitamin D content of a number of animal-based foods when potency-adjusted 25(OH)D was included, and in turn there was a potentially meaningful increase (1.7-2.9 μg or 15-30% of average requirement) in vitamin D intake estimates. The apparent increase could reduce discrepancies between intake estimates and serum 25(OH)D concentrations. The relevance to dietary interventions is discussed, and the need for continued exploration regarding 25(OH)D measurement is highlighted.
Published:
2014
Title:
Influences on adherence to diet and physical activity recommendations in women and children: insights from six European studies
Authors:
Inskip, Hazel; Baird, Janis; Barker, Mary; Briley, Annette L.; D'Angelo, Stefania; Grote, Veit; Koletzko, Berthold; Lawrence, Wendy; Manios, Yannis; Moschonis, George; Chrousos, George P.; Poston, Lucilla; Godfrey, Keith
Abstract:
BACKGROUND: Across Europe, poor health behaviours are associated with increased risks of non-communicable diseases. There is particular concern about young women, children and families, not least as health behaviours operating before and during pregnancy and in early postnatal life may have profound long-term consequences for children's health. Using findings drawn from 7 European countries, we aimed to identify barriers to the implementation and uptake of dietary and physical activity recommendations, and to consider how best to achieve changes in mothers' behaviours and thereby improve the adoption of health recommendations. Six studies across the 7 countries were used for this narrative synthesis of findings. KEY MESSAGES: A woman's education has a strong influence on her own and her children's health behaviours. Women's diets vary across ethnic groups and according to number of children, but psychological factors, such as self-efficacy and sense of control, which may be amenable to modification, are powerful, too, particularly in women with lower educational attainment. Maternal influences on children's behaviours are strong. Differences exist in infant feeding across countries, and there are apparent urban/rural differences in children's diets and physical activity. CONCLUSIONS: Interventions are needed before, as well as during, pregnancy to improve the diets of families with young children. Interventions to address psychological barriers to eating well and being more active are indicated.
Published:
2014
Title:
Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: A review of human findings
Authors:
Barnosky, Adrienne R.; Hoddy, Kristin K.; Unterman, Terry G.; Varady, Krista A.
Abstract:
Intermittent fasting (IF) regimens have gained considerable popularity in recent years, as some people find these diets easier to follow than traditional calorie restriction (CR) approaches. IF involves restricting energy intake on 1-3 d/wk, and eating freely on the nonrestriction days. Alternate day fasting (ADF) is a subclass of IF, which consists of a "fast day" (75% energy restriction) alternating with a "feed day" (ad libitum food consumption). Recent findings suggest that IF and ADF are equally as effective as CR for weight loss and cardioprotection. What remains unclear, however, is whether IF/ADF elicits comparable improvements in diabetes risk indicators, when compared with CR. Accordingly, the goal of this review was to compare the effects of IF and ADF with daily CR on body weight, fasting glucose, fasting insulin, and insulin sensitivity in overweight and obese adults. Results reveal superior decreases in body weight by CR vs IF/ADF regimens, yet comparable reductions in visceral fat mass, fasting insulin, and insulin resistance. None of the interventions produced clinically meaningful reductions in glucose concentrations. Taken together, these preliminary findings show promise for the use of IF and ADF as alternatives to CR for weight loss and type 2 diabetes risk reduction in overweight and obese populations, but more research is required before solid conclusions can be reached.
Published:
2014
Title:
Intestinal epithelial cells: regulators of barrier function and immune homeostasis
Authors:
Peterson, Lance W; Artis, David
Abstract:
The abundance of innate and adaptive immune cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host–microbial interactions and tissue homeostasis. This homeostasis depends on the diverse functions of intestinal epithelial cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediators of intestinal homeostasis that enable the establishment of an immunological environment permissive to colonization by commensal bacteria. In this Review, we provide a comprehensive overview of how IECs maintain host–commensal microbial relationships and immune cell homeostasis in the intestine.
Published:
2014
Title:
Investigation of the effects of a high fish diet on inflammatory cytokines, blood pressure, and lipids in healthy older Australians
Authors:
Grieger, J.A.; Miller, M.D.; Cobiac, L.
Abstract:
Background: Aging is a condition of chronic inflammation. In healthy Australians ≥64 years, the primary aim was to determine whether four servings/week of mixed fish (FISH) improves serum cytokines (i.e. C-reactive protein (CRP), IL-1, IL-6, TNF-α) compared to a diet low in fish (<1 serving/week, CONTROL); the secondary aims were to assess the effect of the diet on blood pressure and serum lipids (TC, HDL-C, TG, calculated LDL-C). Methods: An 8-week randomized, parallel study, stratified by CRP (<3 mg/L vs. ≥3 mg/L) on entry to the study. Compliance was measured using 3-day weighed food records in weeks 1 and 7 of the study. A 12-h fasting blood sample was taken at baseline and 8-weeks for erythrocyte fatty acids as confirmation of compliance, and measurement of serum cytokines and lipids. Blood pressure was measured at both time points. Results: Eighty participants completed the study (mean (SD) age: 69.6 (5.8) years). During week 1 of the study, mean±SEM daily dietary intake of very long chain omega-3 polyunsaturated fatty acids (VLCN n-3 PUFA) in FISH vs. CONTROL was 1,676±129 mg vs. 27±5 mg (p
Published:
2014
Title:
Ketosis onset type 2 diabetes had better islet β-cell function and more serious insulin resistance
Authors:
Lu, Hongyun; Hu, Fang; Zeng, Yingjuan; Zou, Lingling; Luo, Shunkui; Sun, Ying; Liu, Hong; Sun, Liao
Abstract:
Diabetic ketosis had been identified as a characteristic of type 1 diabetes mellitus (T1DM), but now emerging evidence has identified that they were diagnosed as T2DM after long time follow up. This case control study was aimed at comparing the clinical characteristic, β-cell function, and insulin resistance of ketosis and nonketotic onset T2DM and providing evidence for treatment selection. 140 cases of newly diagnosed T2DM patients were divided into ketosis (62 cases) and nonketotic onset group (78 cases). After correction of hyperglycemia and ketosis with insulin therapy, plasma C-peptide concentrations were measured at 0, 0.5, 1, 2, and 3 hours after 75 g glucose oral administration. Area under the curve (AUC) of C-peptide was calculated. Homoeostasis model assessment was used to estimate basal β-cell function (HOMA-β) and insulin resistance (HOMA-IR). Our results showed that ketosis onset group had higher prevalence of nonalcoholic fatty liver disease (NAFLD) than nonketotic group (P = 0.04). Ketosis onset group had increased plasma C-peptide levels at 0 h, 0.5 h, and 3 h and higher AUC(0-0.5), AUC₀₋₁, AUC₀₋₃ (P < 0.05). Moreover, this group also had higher HOMA-β and HOMA-IR than nonketotic group (P
Published:
2014
Title:
Key elements of plant-based diets associated with reduced risk of metabolic syndrome
Authors:
Turner-McGrievy, Gabrielle; Harris, Metria
Abstract:
Approximately 20 %-25 % of adults worldwide have metabolic syndrome. Vegetarian and vegan diets have demonstrated effectiveness in improving body weight, glycemic control, and cardiovascular risk factors, as compared with conventional therapeutic approaches, and are potentially useful in the prevention of metabolic syndrome. This article consists of two steps: (1) a review of the literature on studies examining vegetarian and vegan diets and metabolic syndrome and (2) a review of foods and nutrients that are protective against or associated with metabolic syndromes that may help to explain the beneficial effects of plant-based dietary approaches for metabolic syndrome. The present review found eight observational research studies, and no intervention studies, examining the association of plant-based dietary approaches with metabolic syndrome. These studies, conducted mostly in Asian populations, yielded varying results. The majority, however, found better metabolic risk factors and lowered risk of metabolic syndrome among individuals following plant-based diets, as compared with omnivores. Some dietary components that are lower in the diets of vegetarians, such as energy intake, saturated fat, heme iron, and red and processed meat, may influence metabolic syndrome risk. In addition, plant-based diets are higher in fruits, vegetables, and fiber, which are protective against the development of metabolic syndrome.
Published:
2014
Title:
Lipoprotein Insulin Resistance Index: A Lipoprotein Particle–Derived Measure of Insulin Resistance
Authors:
Shalaurova, Irina; Connelly, Margery A.; Garvey, W. Timothy; Otvos, James D.
Abstract:
Abstract Background: Lipoprotein particle sizes and concentrations are characteristically altered in patients with insulin resistance (IR) or type 2 diabetes mellitus (T2DM). This study assessed the ability of an IR score, based on nuclear magnetic resonance (NMR)-derived lipoprotein information, to detect IR in otherwise healthy individuals. Methods: Lipoprotein subclass and size information were evaluated for strength of association with IR, as measured by homeostasis model assessment of insulin resistance (HOMA-IR) in the Multi-Ethnic Study of Atherosclerosis (MESA). To increase the likelihood of identifying subjects with IR, six lipoprotein measures were combined into a single algorithm. The resulting assay [Lipoprotein Insulin Resistance Index (LP-IR)] was developed using HOMA-IR in 4972 nondiabetic subjects from MESA and verified independently using glucose disposal rates (GDRs) measured during hyperinsulinemic-euglycemic clamps in 56 insulin-sensitive, 46 insulin-resistant, and 46 untreated subjects with T2DM. Results: LP-IR exhibited stronger associations with HOMA-IR (r=0.51) and GDR (r=-0.53) than each of the individual lipoprotein parameters as well as the triglycerides/high-density lipoprotein cholesterol (TGs/HDL-C) ratio (r=0.41 and -0.44, respectively). In MESA, associations between the LP-IR score and HOMA-IR were strong in men (r=0.51), women (r=0.52), European Americans (r=0.58), African Americans (r=0.48), Chinese Americans (r=0.49), and Hispanic Americans (r=0.45). When LP-IR was categorized by HOMA-IR and either body mass index (BMI) or fasting plasma glucose (FPG), subgroups were revealed whose LP-IR scores were high (≥50), despite having normal BMIs (\textless24 kg/m(2)) or FPG (\textless100 mg/dL). Conclusions: LP-IR scores had strong associations with multiple measures, HOMA-IR, and GDR, the former being more reflective of hepatic and the latter of peripheral insulin sensitivity, and may represent a simple means to identify individuals with IR.
Published:
2014
Title:
Long term weight maintenance after advice to consume low carbohydrate, higher protein diets - A systematic review and meta analysis
Authors:
Clifton, P. M.; Condo, D.; Keogh, J. B.
Abstract:
Background: Meta analysis of short term trials indicates that a higher protein, lower carbohydrate weight loss diet enhances fat mass loss and limits lean mass loss compared with a normal protein weight loss diet. Whether this benefit persists long term is not clear. Methods and results: We selected weight loss studies in adults with at least a 12 month follow up in which a higher percentage protein/lower carbohydrate diet was either planned or would be expected for either weight loss or weight maintenance. Studies were selected regardless of the success of the advice but difference in absolute and percentage protein intake at 12 months was used as a moderator in the analysis. Data was analysed using Comprehensive Meta analysis V2 using a random effects analysis. As many as 32 studies with 3492 individuals were analysed with data on fat and lean mass, glucose and insulin from 18 to 22 studies and lipids from 28 studies. A recommendation to consume a lower carbohydrate, higher protein diet in mostly short term intensive interventions with long term follow up was associated with better weight and fat loss but the effect size was small-standardised means of 0.14 and 0.22, p = 0.008 and p \textless 0.001 respectively (equivalent to 0.4 kg for both). A difference of 5% or greater in percentage protein between diets at 12mo was associated with a 3 fold greater effect size compared with \textless5% (p = 0.038) in fat mass (0.9 vs. 0.3 kg). Fasting triglyceride and insulin were also lower with high protein diets with effect sizes of 0.17 and 0.22, p = 0.003 and p = 0.042 respectively. Other lipids and glucose were not different. Conclusion: The short term benefit of higher protein diets appears to persist to a small degree long term. Benefits are greater with better compliance to the diet. © 2013 Elsevier B.V.
Published:
2014
Title:
Low Levels of Low-Density Lipoprotein Cholesterol: A Negative Predictor of Survival in Elderly Patients with Advanced Heart Failure
Authors:
Charach, Gideon; Rabinovich, Alexander; Ori, Argov; Weksler, Dov; Sheps, David; Charach, Lior; Weintraub, Moshe; George, Jacob
Abstract:
Objectives: There are conflicting reports on the role of cholesterol as an adverse prognostic predictor in patients with heart failure (HF). This study aimed to examine the impact of low levels of low-density lipoprotein cholesterol (LDL-c) on cardiac mortality in a cohort of elderly patients with moderate and severe HF. Methods: Chronic HF patients from the HF Unit at the Tel-Aviv Medical Center (n = 212, 77% males) with an average NYHA classification of 2.8, a mean age of 76.9 ± 7.3 years (range 66-91) and a mean follow-up of 3.7 years were consecutively enrolled. The cohort was divided into tertiles according to LDL-c levels: LDL 115 mg/dl (group 3). Results: The Cox regression analysis revealed that group 3 patients had the best outcome (p = 0.01 vs. groups 2 and 3), with 58% of them surviving longer than 50 months compared to 34% in group 1. The same trend was seen in the group of patients suffering from ischemic cardiomyopathy and in patients who were treated by statins (p = 0.04). Conclusion: Low LDL-c levels are associated with a reduced survival in elderly patients with clinically controlled moderate and severe HF.
Published:
2014
Title:
Low-carbohydrate/high-protein diet improves diastolic cardiac function and the metabolic syndrome in overweight-obese patients with type 2 diabetes
Authors:
Von Bibra, H.; Wulf, G.; St John Sutton, M.; Pfützner, A.; Schuster, T.; Heilmeyer, P.
Abstract:
Background: Diastolic dysfunction/heart failure in the metabolic syndrome and type 2 diabetes (T2D) is an epidemic without evidence-based treatment strategies. While improved glycemic control/insulin sensitivity has been associated with augmented cardiac function in pharmacologic studies, studies on dietary intervention are scarce. Low-carbohydrate nutrition (LC) improves postprandial glucose control and insulin resistance more than standard low-fat diet (LF). We tested the hypothesis, that LC improves cardiac function in overweight-obese patients with T2D more than LF. Methods: Two matched groups of 16 T2D patients without overt heart disease (52±7years, BMI 34±6kg/m2) were studied in a parallel and partial cross-over design during a 3-week rehabilitation programme with either LC or LF followed by 2weeks LC. Cardiac function was assessed as myocardial velocity during systole and early diastole (E') using Doppler tissue imaging and metabolic control before and after a standardised breakfast. Results: In the parallel groups, both diets induced similar and significant reductions of weight, HbA1c and cholesterol. LC considerably improved insulin resistance, fasting and postmeal triglycerides, blood pressure and diastolic cardiac function E' (by 0.9. ±. 1.4. cm/s, p. = 0.023). None of these variables changed on LF, but all of them improved significantly after subsequent LC (E' by 0.9. ±. 1.1. cm/s, p. = 0.023). Postprandial intact proinsulin was unchanged on LF but decreased with subsequent LC (p. = 0.032). Conclusions: These data indicate, that a low-glycaemic/high-protein but not a low-fat/high-carbohydrate nutrition modulates diastolic dysfunction in overweight T2D patients, improves insulin resistance and may prevent or delay the onset of diabetic cardiomyopathy and the metabolic syndrome. © 2013 The Authors.
Published:
2014
Title:
Lymphedema Prevalence and Treatment
Authors:
Km, Brayton; At, Hirsch; Pj, Brien
Abstract:
Background: Lymphedema is a common complication of cancer therapeutics; its prevalence, treatment outcomes, and costs have been poorly defined. The objective of this study was to examine lymphedema prevalence among cancer survivors and to characterize changes in clinical outcomes and costs associated with a defined therapeutic intervention (use of a pneumatic compression devices [PCD]) in a representative, privately insured population.
Published:
2014
Title:
Mammalian MYC Proteins and Cancer
Authors:
Tansey, William P.
Abstract:
The MYC family of proteins is a group of basic-helix-loop-helix-leucine zipper transcription factors that feature prominently in cancer. Overexpression of MYC is observed in the vast majority of human malignancies and promotes an extraordinary set of changes that impact cell proliferation, growth, metabolism, DNA replication, cell cycle progression, cell adhesion, differentiation, and metastasis. The purpose of this review is to introduce the reader to the mammalian family of MYC proteins, highlight important functional properties that endow them with their potent oncogenic potential, describe their mechanisms of action and of deregulation in cancer cells, and discuss efforts to target the unique properties of MYC, and of MYC-driven tumors, to treat cancer.
Published:
2014
Title:
Meditation can produce beneficial effects to prevent cardiovascular disease
Authors:
Koike, Marcia Kiyomi; Cardoso, Roberto
Abstract:
Coronary heart disease is the major cause of global cardiovascular mortality and morbidity. Lifestyle behaviour contributes as a risk factor: unhealthy diet, sedentary lifestyle, tobacco, alcohol, hypertension, diabetes, dyslipidemia and psychosocial stress. Atherosclerosis pathologic mechanisms involving oxidative stress, dyslipidemia, inflammation and senescence are associated with arterial wall damage and plaque formation. Stress reduction was observed in several types of meditation. After meditation, hormonal orchestration modulates effects in the central nervous system and in the body. All types of meditation are associated with blood pressure control, enhancement in insulin resistance, reduction of lipid peroxidation and cellular senescence, independent of type of meditation. This review presents scientific evidence to explain how meditation can produce beneficial effects on the cardiovascular system, and particularly regarding vascular aspects.
Published:
2014
Title:
Meditation programs for psychological stress and well-being: A systematic review and meta-analysis
Authors:
Goyal, Madhav; Singh, Sonal; Sibinga, Erica M.S.; Gould, Neda F.; Rowland-Seymour, Anastasia; Sharma, Ritu; Berger, Zackary; Sleicher, Dana; Maron, David D.; Shihab, Hasan M.; Ranasinghe, Padmini D.; Linn, Shauna; Saha, Shonali; Bass, Eric B.; Haythornthwaite, Jennifer A.
Abstract:
IMPORTANCE Many people meditate to reduce psychological stress and stress-related health problems. To counsel people appropriately, clinicians need to know what the evidence says about the health benefits of meditation. OBJECTIVE To determine the efficacy of meditation programs in improving stress-related outcomes (anxiety, depression, stress/distress, positive mood, mental health-related quality of life, attention, substance use, eating habits, sleep, pain, and weight) in diverse adult clinical populations. EVIDENCE REVIEW We identified randomized clinical trials with active controls for placebo effects through November 2012 from MEDLINE, PsycINFO, EMBASE, PsycArticles, Scopus, CINAHL, AMED, the Cochrane Library, and hand searches. Two independent reviewers screened citations and extracted data. We graded the strength of evidence using 4 domains (risk of bias, precision, directness, and consistency) and determined the magnitude and direction of effect by calculating the relative difference between groups in change from baseline. When possible, we conducted meta-analyses using standardized mean differences to obtain aggregate estimates of effect size with 95% confidence intervals. FINDINGS After reviewing 18 753 citations, we included 47 trials with 3515 participants. Mindfulness meditation programs had moderate evidence of improved anxiety (effect size, 0.38 [95% CI, 0.12-0.64] at 8 weeks and 0.22 [0.02-0.43] at 3-6 months), depression (0.30 [0.00-0.59] at 8 weeks and 0.23 [0.05-0.42] at 3-6 months), and pain (0.33 [0.03- 0.62]) and low evidence of improved stress/distress and mental health-related quality of life. We found low evidence of no effect or insufficient evidence of any effect of meditation programs on positive mood, attention, substance use, eating habits, sleep, and weight. We found no evidence that meditation programs were better than any active treatment (ie, drugs, exercise, and other behavioral therapies). CONCLUSIONS AND RELEVANCE Clinicians should be aware that meditation programs can result in small to moderate reductions of multiple negative dimensions of psychological stress. Thus, clinicians should be prepared to talk with their patients about the role that a meditation program could have in addressing psychological stress. Stronger study designs are needed to determine the effects of meditation programs in improving the positive dimensions of mental health and stress-related behavior.
Published:
2014
Title:
Metabolic features of the cell danger response
Authors:
Naviaux, Robert K.
Abstract:
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis. © 2013 The Authors.
Published:
2014
Title:
Metabolic reprogramming induced by ketone bodies diminishes pancreatic cancer cachexia
Authors:
Shukla, Surendra K; Gebregiworgis, Teklab; Purohit, Vinee; Chaika, Nina V; Gunda, Venugopal; Radhakrishnan, Prakash; Mehla, Kamiya; Pipinos, Iraklis I; Powers, Robert; Yu, Fang; Singh, Pankaj K
Abstract:
Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in view the significant role of metabolic alterations in cancer, we hypothesized that a ketogenic diet may diminish glycolytic flux in tumor cells to alleviate cachexia syndrome and, hence, may provide an efficient therapeutic strategy. Results: We observed reduced glycolytic flux in tumor cells upon treatment with ketone bodies. Ketone bodies also diminished glutamine uptake, overall ATP content, and survival in multiple pancreatic cancer cell lines, while inducing apoptosis. A decrease in levels of c-Myc, a metabolic master regulator, and its recruitment on glycolytic gene promoters, was in part responsible for the metabolic phenotype in tumor cells. Ketone body-induced intracellular metabolomic reprogramming in pancreatic cancer cells also leads to a significantly diminished cachexia in cell line models. Our mouse orthotopic xenograft models further confirmed the effect of a ketogenic diet in diminishing tumor growth and cachexia. Conclusions: Thus, our studies demonstrate that the cachectic phenotype is in part due to metabolic alterations in tumor cells, which can be reverted by a ketogenic diet, causing reduced tumor growth and inhibition of muscle and body weight loss.
Published:
2014
Title:
Mistimed sleep disrupts circadian regulation of the human transcriptome
Authors:
Archer, Simon N.; Laing, Emma E.; Möller-Levet, Carla S.; Van Der Veen, Daan R.; Bucca, Giselda; Lazar, Alpar S.; Santhi, Nayantara; Slak, Ana; Kabiljo, Renata; Von Schantz, Malcolm; Smith, Colin P.; Dijk, Derk Jan
Abstract:
Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep-wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep-wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep-wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.
Published:
2014
Title:
Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations
Authors:
Gammage, Payam A.; Rorbach, Joanna; Vincent, Anna I.; Rebar, Edward J.; Minczuk, Michal
Abstract:
We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site-specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T\textgreaterG point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the "common deletion" (CD), a 4977-bp repeat-flanked deletion associated with adult-onset chronic progressive external ophthalmoplegia and, less frequently, Kearns-Sayre and Pearson's marrow pancreas syndromes. Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and subsequent repopulation of wild-type mtDNA restored mitochondrial respiratory function in a CD cybrid cell model. This study constitutes proof-of-principle that, through heteroplasmy manipulation, delivery of site-specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species. © 2014 The Authors.
Published:
2014
Title:
Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes
Authors:
Ariel, Danit; Reaven, Gerald
Abstract:
AIMS This study was based on the hypothesis that: (1) coronary heart disease (CHD) risk is accentuated in the insulin-resistant subset of persons with normal glucose tolerance (NGT) or prediabetes (PreDM); (2) the prevalence of insulin resistance, and associated abnormalities, is greater in subjects with PreDM; and (3) insulin resistance is the major contributor to increased CHD risk in these individuals. METHODS A 75 g oral glucose challenge was used to classify volunteers as having NGT or PreDM. Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test subdivided both groups into insulin sensitive (IS = SSPG \textless 8.4 mmol/L) or resistant (IR = SSPG ≥ 8.4 mmol/L). Measurements were made of demographic characteristics, blood pressure, and lipid and lipoprotein concentrations, and comparisons made between the subgroups. RESULTS Subjects with PreDM (n = 127) were somewhat older, more likely to be non-Hispanic men, with increased adiposity than those with NGT (n = 315). In addition, they had higher FPG concentrations, were insulin resistant (SSPG concentration; 11.4 vs. 7.2 mmol/L), with higher blood pressures, and a significantly more adverse CHD risk lipid profile (p \textless 0.001). Twice as many subjects with PreDM were IR (72 vs. 35 %), and the CHD risk profile was significantly worse in the IR subgroups in those with either NGT or PreDM. CONCLUSIONS Coronary heart disease risk profile is significantly more adverse in subjects with PreDM as compared to individuals with NGT. However, glucose tolerance status is not the only determinant of CHD risk in nondiabetic individuals, and differences in degree of insulin resistance significantly modulate CHD risk in subjects with NGT or PreDM.
Published:
2014
Title:
More Evidence on Meat's Negative Health Effects
Authors:
Levin, Susan
Abstract:
Published:
2014
Title:
Nutrition and economic development in the eighteenth-century Habsburg monarchy: An anthropometric history
Authors:
Komlos, John
Abstract:
Published:
2014
Title:
Nutritional modulation of the metabonome: Applications of metabolic phenotyping in translational nutritional research
Authors:
Kinross, J.; Li, J.V.; Muirhead, L.J.; Nicholson, J.
Abstract:
PURPOSE OF REVIEW: Metabolic profiling technologies provide a global overview of complex dietary processes. Metabonomic analytical approaches have now been translated into multiple areas of clinical nutritional research based on the widespread adoption of high-throughput mass spectrometry and proton nuclear magnetic resonance spectroscopy. This has generated novel insights into the molecular mechanisms that shape the microbiome-dietary-chronic disease axis. RECENT FINDINGS: Metabolome-wide association studies have created a new paradigm in nutritional molecular epidemiology and they have highlighted the importance of gut microbial cometabolic processes in the development of cardiovascular disease and diabetes. Targeted analyses are helping to explain the mechanisms by which high-risk diets (such as red meat) modulate disease risk and they are generating novel biomarkers that will serve to re-define how the efficacy of nutritional interventions is assessed. Nutritional metabonome-microbiome interactions have also been defined in extreme dietary states such as obesity and starvation, and they also serve as important models for understanding how the gut microbiome modifies disease risk. Finally, nutritional systems medicine approaches are creating novel insights into the functional components of our diet, and the mechanisms by which they cause disease. SUMMARY: Diet is an important modulator of the human metabolic phenotype and the analysis of the nutritional metabolome will drive future development of personalized nutritional interventions. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Published:
2014
Title:
Nutritional status and eating habits of bus drivers during the day and night
Authors:
Balieiro, L.C.T.; Rossato, L.T.; Waterhouse, J.; Paim, S.L.; Mota, M.C.; Crispim, C.A.
Abstract:
The aim of this study was to compare anthropometry and food intake patterns in bus drivers working during the day and night. One hundred and fifty males (81 night workers and 69 day workers) participated in the study. Dietary intake was assessed using a validated semi-quantitative food frequency questionnaire. Measurements of height, weight, waist circumference (WC), systolic and diastolic blood pressure, blood glucose, and lipid profile were obtained. A significant difference between groups was observed for mean WC (98.5 ± 10.7 cm in day workers versus 103.2 ± 9.7 cm in night workers; p = 0.005). Night workers had higher prevalence of being overweight and obese (BMI ≥ 25 kg/m2) than day workers (78.2% day workers versus 90.2% night workers; p = 0.004) and increased WC (>94 cm) (72.4% day workers versus 86.4% night workers; p = 0.03). Significant differences were found for meat consumption (2.3 servings ±0.9 for night workers versus 2.0 servings ±0.7 day workers, p = 0.04) and fruit intake (0.9 servings ±0.4 for night workers versus 0.7 servings for day workers ±0.5; p = 0.006). Night workers had a lower intake of vegetables than recommended compared to day workers (100 versus 92.7%, respectively, p = 0.01) and higher intake of oil (40.7 versus 24.6%, p = 0.03). Multivariate logistic regression analysis indicated that night work was associated with being overweight (OR = 2.94, 95% IC: 1.14-7.66, p = 0.03) and abnormal values of WC (OR = 2.82, 95% IC: 1.20-6.69, p = 0.009) after adjusting for potential confounders. It is concluded that night workers had a higher prevalence and risk of being overweight/obese and increased WC compared with day workers. Night workers also presented a higher proportion of inappropriate intakes of food groups when compared to day workers, even though both groups were eating poor diets. These results demonstrate the need of lifestyle-intervention programs in these workers. © 2014 Informa Healthcare USA, Inc.
Published:
2014
Title:
Oxidized low-density lipoprotein, OXPAPC, corrects defects in maturation and cytokine secretion of peripheral blood dendritic cells from sepsis patients
Authors:
Tan, Yun; Li, Jin-Xiu; Xiang, Xu-Dong; Lü, Jian-Lei
Abstract:
OBJECTIVE: To investigate the expression differences in maturation and cytokine production of dendritic cells (DCs) from sepsis patients and the effect of oxidized phospholipid 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) on DCs phenotypes. METHODS: Peripheral blood mononuclear cells from 50 sepsis patients and 50 controls were cultured in the presence of GM-CSF, IL-4 and TNF-α to induce DCs maturation. DCs from sepsis patients were also treated with three different concentrations of OXPAPC. Cells were characterized with optical and electron microscopy, FACS analysis for CD1α, HLA-DR and CD86 on cell surface and ELISA analysis of IL-12p70 in the supernatant. RESULTS: DCs from sepsis patients had smaller cell bodies and nucleus and had almost no surface projection. DCs had similar CD1α expression in sepsis patients (86.37 ± 17.24) and controls (88.58 ± 10.05). HLA-DR expression was dramatically reduced in sepsis patients (2.74 ± 5.15) compared to controls (198.35 ± 12.04). Similarly, CD86 expression was also drastically lower in sepsis patients (14.72 ± 4.83) than controls (154.56 ± 11.56). Furthermore, OXPAPC treatment of DCs from sepsis patients increased cell surface projection, HLA-DR and CD86 surface expression and IL-12p70 secretion in a dose-dependent manner. With 40 μg/ml of OXPAPC, DCs of sepsis patients have similar phenotypes observed in healthy controls. CONCLUSION: DCs from sepsis patients are defective in maturation and cytokine secretion and these defects can be corrected by OXPAPC treatment.
Published:
2014
Title:
Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: Rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives
Authors:
Sparks, J.A.; Iversen, M.D.; Miller Kroouze, R.; Mahmoud, T.G.; Triedman, N.A.; Kalia, S.S.; Atkinson, M.L.; Lu, B.; Deane, K.D.; Costenbader, K.H.; Green, R.C.; Karlson, E.W.
Abstract:
We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6. weeks, 6. months, and 12. months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention. © 2014 Elsevier Inc.
Published:
2014
Title:
Possible metabolic impact of Ramadan fasting in healthy men
Authors:
Vardarli, Mustafa Cumhur; Hammes, Hans-Peter; Vardarli, İrfan
Abstract:
BACKGROUND/AIM: Insulin sensitivity and β-cell function during Ramadan fasting in healthy male subjects have not been investigated so far. We assessed the changes of these and other metabolic parameters to judge the potential metabolic benefits of Ramadan fasting. MATERIALS AND METHODS: Twenty-four healthy males of Turkish origin living in Germany, with normal glucose tolerance, participated in this study during Ramadan of 2009; 19 who completed fasting were analyzed. Blood was drawn at sunset after a period of fasting lasting approximately 15 h on days 0, 16, and 30 of Ramadan, as well as 7 and 28 days later. Insulin sensitivity (Homeostasis Model Assessment, HOMA), β-cell function, and other parameters were assessed. RESULTS: Ramadan fasting was associated with a significant reduction (-) or increment (+) for the following variables: insulin sensitivity (-20%; P = 0.04), β-cell function (+10%; P = 0.049), high-density lipoprotein cholesterol (-23%; P = 0.0003), low-density lipoprotein cholesterol (+14%; P = 0.007), nonesterified fatty acids (-62%; P
Published:
2014
Title:
Provocative Issues in Heart Disease Prevention
Authors:
Juneau, M.; Hayami, D.; Gayda, M.; Lacroix, S.; Nigam, A.
Abstract:
In this article, new areas of cardiovascular (CV) prevention and rehabilitation research are discussed: high-intensity interval training (HIIT) and new concepts in nutrition. HIIT consists of brief periods of high-intensity exercise interspersed by periods of low-intensity exercise or rest. The optimal mode according our work (15-second exercise intervals at peak power with passive recovery intervals of the same duration) is associated with longer total exercise time, similar time spent near peak oxygen uptake (VO2 peak) VO2 peak, and lesser perceived exertion relative to other protocols that use longer intervals and active recovery periods. Evidence also suggests that compared with moderate-intensity continuous exercise training, HIIT has superior effects on cardiorespiratory function and on the attenuation of multiple cardiac and peripheral abnormalities. With respect to nutrition, a growing body of evidence suggests that the gut microbiota is influenced by lifestyle choices and might play a pivotal role in modulating CV disease development. For example, recent evidence linking processed (but not unprocessed) meats to increased CV risk pointed to the gut microbial metabolite trimethylamine N-oxide as apotential culprit. In addition, altered gutmicrobiota could also mediate the proinflammatory and cardiometabolic abnormalities associated with excess added free sugar consumption, and in particular high-fructose corn syrup. Substantially more research is required, however, to fully understand how and which alterations in gut flora can prevent or lead to CV disease and other chronic illnesses. We conclude with thoughts about the appropriate role for HIIT in CV training and future research in the role of gut flora-directed interventions in CV prevention. Dans cet article, nous examinerons les nouveaux axes de recherche en réadaptation cardiaque et en prévention des maladies cardiovasculaires (CV) : l'entraînement par intervalles à haute intensité (EIHE) et les nouveaux concepts en nutrition. L'EIHE consiste en de brèves périodes d'effort de haute intensité entrecoupées de périodes d'effort de faible intensité ou de repos. Le mode optimal selon notre travail (intervalles d'effort de 15 secondes à la puissance maximale suivis d'intervalles de récupération active de la même durée) est associé à une durée totale d'effort plus longue, une durée similaire près de la consommation maximale d'oxygène (VO2 max) et une perception de l'effort moindre par rapport à d'autres protocoles qui utilisent des intervalles et des périodes de récupération active plus longs. Les données scientifiques indiquent également que comparativement à l'entraînement continu à intensité modérée, l'EIHE a des effets supérieurs sur le fonctionnement cardiorespiratoire et sur l'atténuation de multiples anomalies cardiaques et périphériques. En ce qui concerne la nutrition, des données de plus en plus nombreuses indiquent que le microbiote intestinal est influencé par les choix relatifs au mode de vie et qu'il pourrait jouer un rÔle pivot dans la modulation du développement de la maladie CV. Par exemple, des données récentes liant les viandes transformées (mais non les viandes non transformées) à l'augmentation du risque CV ont désigné la triméthylamine N-oxyde produite par le microbiote intestinal comme étant un responsable potentiel. De plus, la modification du microbiote intestinal pourrait également intervenir dans les anomalies pro-inflammatoires et cardiométaboliques associées à l'excès de consommation de sucres ajoutés et en particulier le sirop de maïs à haute teneur en fructose. Cependant, davantage de recherches sont nécessaires pour bien comprendre quelles modifications dans la flore intestinale et de quelle manière elles peuvent prévenir ou mener à la maladie CV et à d'autres maladies chroniques. Nous concluons par des réflexions sur le rÔle approprié de l'EIHE dans l'entraînement CV et sur la recherche future concernant le rÔle des interventions orientées sur la flore intestinale dans la prévention des maladies CV. © 2014 Canadian Cardiovascular Society.
Published:
2014
Title:
Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus
Authors:
Guldbrand, H.; Lindström, T.; Dizdar, B.; Bunjaku, B.; Östgren, C. J.; Nystrom, F. H.; Bachrach-Lindström, M.
Abstract:
Aims: To compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD. Methods: Prospective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55-60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention. Results: Mean body-mass-index was 32.7±5.4kg/m2 at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: -3.99±4.1kg, LCD: -4.31±3.6kg (p\textless0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p\textless0.009) while no change occurred in the LFD group (p\textless0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042-0.009) while there was no change within the LFD group. Conclusions: Weight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.
Published:
2014
Title:
Relationship between disease severity, hyperinsulinemia, and impaired insulin clearance in patients with nonalcoholic steatohepatitis
Authors:
Bril, Fernando; Lomonaco, Romina; Orsak, Beverly; Ortiz-Lopez, Carolina; Webb, Amy; Tio, Fermin; Hecht, Joan; Cusi, Kenneth
Abstract:
Hyperinsulinemia is believed to play a key role in the pathogenesis of nonalcoholic steatohepatitis (NASH) and associated cardiovascular risk. However, the relative contribution of insulin clearance to hyperinsulinemia and its relationship to liver histology have not been carefully evaluated before. To examine this, we enrolled 190 patients (32 without nonalcoholic fatty liver disease [NAFLD], 36 with simple steatosis [SS], and 122 with biopsy-proven NASH). Insulin secretion and hepatic insulin clearance were estimated by means of an oral glucose tolerance test, whereas peripheral insulin sensitivity and whole-body insulin clearance were measured during a euglycemic insulin clamp. A liver biopsy was performed to assess histology (grade/stage). Patients with NASH had similar hepatic insulin sensitivity, compared to patients with SS, but more severe adipose tissue insulin resistance and worse hyperinsulinemia. Patients with SS and NASH had a similar ∼30% reduction (P\textless0.01) in hepatic insulin clearance, when compared to patients without NAFLD. Reduced hepatic insulin clearance was not associated with severity of inflammation, ballooning, and fibrosis. In contrast, worse histological inflammation and ballooning (but not steatosis or fibrosis) were associated with a progressive reduction in whole-body insulin clearance (P\textless0.001 for trend). There was no significant difference in insulin secretion between patients with SS versus NASH. CONCLUSION Decreased hepatic insulin clearance develops with a mild increase in liver fat (LFAT) accumulation. It appears to be largely driven by hepatic steatosis, whereas steatohepatitis is more closely associated with reduced whole-body insulin clearance. Hyperinsulinemia in NAFLD correlated strongly with impaired insulin clearance, but not with insulin secretion. Strategies that reduce LFAT and improve insulin clearance hold the potential to revert the unfavorable effects of hyperinsulinemia in these patients.
Published:
2014
Title:
Resistance to thyroid hormone
Authors:
Onigata, Kazumichi; Szinnai, Gabor
Abstract:
Resistance to thyroid hormone (RTH) or thyroid hormone action defect (THAD) is the most frequent form of syndromes of reduced sensitivity to thyroid hormone. It is characterized by variable tissue hyposensitivity to thyroid hormone. RTHβ (formerly only RTH) is caused by mutations in the thyroid hormone receptor β gene (THRB). The clinical phenotype reflects the dysbalance between resistance of tissues predominantly expressing the thyroid hormone receptor β-isoforms 1 and 2 and the overstimulation of tissues mainly expressing the thyroid hormone receptor α-isoform to thyroid hormones. The hallmark of RTHβ is goiter, sinus tachycardia, attention deficit hyperactivity disorder in the context of increased levels of triiodothyronine/free thyroxine and nonsuppressed thyroid-stimulating hormone. Only recently have mutations in the thyroid hormone receptor α gene (THRA) been identified causing a new form of RTH, RTHα. The few patients described so far suffered from mental retardation of variable degree, short stature with decreased subischial leg length, chronic constipation and bradycardia. This review provides an overview of clinical, biochemical and genetic aspects of RTHα and RTHβ relevant for diagnosis, treatment and counseling of affected patients and families.
Published:
2014
Title:
Retrospective study on the efficacy of a low-carbohydrate diet for impaired glucose tolerance
Authors:
Maekawa, Satoshi; Kawahara, Tetsuya; Nomura, Ryosuke; Murase, Takayuki; Ann, Yasuyoshi; Oeholm, Masayuki; Harada, Masaru
Abstract:
BACKGROUND: In recent years, the number of people with impaired glucose tolerance (IGT) has increased steadily worldwide. It is clear that the prevention of diabetes is important from the perspective of public health, medical care, and economics. It was recently reported that a low-carbohydrate diet (LCD) is useful for achieving weight loss and glycemic control, but there is no information about the effects of the LCD on IGT. We designed a 7-day in-hospital educational program focused on the LCD for IGT. METHODS: The subjects were 72 patients with IGT (36 in the LCD group and 36 in the control group) who were enrolled from April 2007-March 2012 and followed for 12 months. We retrospectively compared the LCD group with the control group. RESULTS: In 69.4% of the LCD group, blood glucose was normalized at 12 months and the 2-hour plasma glucose level in the oral glucose tolerance test (OGTT) was reduced by 33 mg/dL. In addition, the incidence of diabetes was significantly lower in the LCD group than in the control group at 12 months (0% versus 13.9%, P=0.02). The LCD group showed a significant decrease in fasting plasma glucose, hemoglobin A1c, the homeostasis model of assessment of insulin resistance value, body weight and serum triglycerides (TGs) at 12 months, while there was a significant increase of the serum high-density lipoprotein (HDL) cholesterol level. CONCLUSION: The LCD is effective for normalizing blood glucose and preventing progression to type 2 diabetes in patients with IGT.
Published:
2014
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