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Title:
Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4·4 million participants
Authors:
Zhou, B; Lu, Y; Hajifathalian, K; Bentham, J; Di Cesare, M; Danaei, G; Bixby, H; Cowan, MJ; Ali, MK; Taddei, C; Lo, WC; Reis-Santos, B; Stevens, GA; Riley, LM; Miranda, JJ; Bjerregaard, P; Rivera, JA; Fouad, HM; Ma, G; Mbanya, JC; McGarvey, ST; Mohan, V; Onat, A; Pilav, A; Ramachandran, A; Romdhane, HB; Paciorek, CJ; Bennett, JE; Ezzati, M; Abdeen, ZA; Abdul Kadir, K; Abu-Rmeileh, NM; Acosta-Cazares, B; Adams, R; Aekplakorn, W; Aguilar-Salinas, CA; Agyemang, C; Ahmadvand, A; Al-Othman, AR; Alkerwi, A; Amouyel, P; Amuzu, A; Andersen, LB; Anderssen, SA; Anjana, RM; Aounallah-Skhiri, H; Aris, T; Arlappa, N; Arveiler, D; Assah, FK; Avdicová, M; Azizi, F; Balakrishna, N; Bandosz, P; Barbagallo, CM; Barceló, A; Batieha, AM; Baur, LA; Romdhane, HB; Benet, M; Bernabe-Ortiz, A; Bharadwaj, S; Bhargava, SK; Bi, Y; Bjerregaard, P; Bjertness, E; Bjertness, MB; Björkelund, C; Blokstra, A; Bo, S; Boehm, BO; Boissonnet, CP; Bovet, P; Brajkovich, I; Breckenkamp, J; Brenner, H; Brewster, LM; Brian, GR; Bruno, G; Bugge, A; Cabrera de León, A; Can, G; Cândido, AP; Capuano, V; Carlsson, AC; Carvalho, MJ; Casanueva, FF; Casas, JP; Caserta, CA; Castetbon, K; Chamukuttan, S; Chaturvedi, N; Chen, CJ; Chen, F; Chen, S; Cheng, CY; Chetrit, A; Chiou, ST; Cho, Y; Chudek, J; Cifkova, R; Claessens, F; Concin, H; Cooper, C; Cooper, R; Costanzo, S; Cottel, D; Cowell, C; Crujeiras, AB; D'Arrigo, G; Dallongeville, J; Dankner, R; Dauchet, L; de Gaetano, G; De Henauw, S; Deepa, M; Dehghan, A; Deschamps, V; Dhana, K; Di Castelnuovo, AF; Djalalinia, S; Doua, K; Drygas, W; Du, Y; Dzerve, V; Egbagbe, EE; Eggertsen, R; El Ati, J; Elosua, R; Erasmus, RT; Erem, C; Ergor, G; Eriksen, L; Escobedo-de la Peña, J; Fall, CH; Farzadfar, F; Felix-Redondo, FJ; Ferguson, TS; Fernández-Bergés, D; Ferrari, M; Ferreccio, C; Feskens, EJ; Finn, JD; Föger, B; Foo, LH; Forslund, AS; Fouad, HM; Francis, DK; Franco Mdo, C; Franco, OH; Frontera, G; Furusawa, T; Gaciong, Z; Garnett, SP; Gaspoz, JM; Gasull, M; Gates, L; Geleijnse, JM; Ghasemian, A; Ghimire, A; Giampaoli, S; Gianfagna, F; Giovannelli, J; Giwercman, A; Gross, MG; González Rivas, JP; Gorbea, MB; Gottrand, F; Grafnetter, D; Grodzicki, T; Grøntved, A; Gruden, G; Gu, D; Guan, OP; Guerrero, R; Guessous, I; Guimaraes, AL; Gutierrez, L; Hambleton, IR; Hardy, R; Hari Kumar, R; Hata, J; He, J; Heidemann, C; Herrala, S; Hihtaniemi, IT; Ho, SY; Ho, SC; Hofman, A; Hormiga, CM; Horta, BL; Houti, L; Howitt, C; Htay, TT; Htet, AS; Htike, MM; Hu, Y; Hussieni, AS; Huybrechts, I; Hwalla, N; Iacoviello, L; Iannone, AG; Ibrahim, MM; Ikeda, N; Ikram, MA; Irazola, VE; Islam, M; Iwasaki, M; Jacobs, JM; Jafar, T; Jamil, KM; Jasienska, G; Jiang, CQ; Jonas, JB; Joshi, P; Kafatos, A; Kalter-Leibovici, O; Kasaeian, A; Katz, J; Kaur, P; Kavousi, M; Keinänen-Kiukaanniemi, S; Kelishadi, R; Kengne, AP; Kersting, M; Khader, YS; Khalili, D; Khang, YH; Kiechl, S; Kim, J; Kolsteren, P; Korrovits, P; Kratzer, W; Kromhout, D; Kujala, UM; Kula, K; Kyobutungi, C; Laatikainen, T; Lachat, C; Laid, Y; Lam, TH; Landrove, O; Lanska, V; Lappas, G; Laxmaiah, A; Leclercq, C; Lee, J; Lee, J; Lehtimäki, T; Lekhraj, R; León-Muñoz, LM; Li, Y; Lim, WY; Lima-Costa, MF; Lin, HH; Lin, X; Lissner, L; Lorbeer, R; Lozano, JE; Luksiene, D; Lundqvist, A; Lytsy, P; Ma, G; Machado-Coelho, GL; Machi, S; Maggi, S; Magliano, DJ; Makdisse, M; Mallikharjuna Rao, K; Manios, Y; Manzato, E; Margozzini, P; Marques-Vidal, P; Martorell, R; Masoodi, SR; Mathiesen, EB; Matsha, TE; Mbanya, JC; McFarlane, SR; McGarvey, ST; McLachlan, S; McNulty, BA; Mediene-Benchekor, S; Meirhaeghe, A; Menezes, AM; Merat, S; Meshram, II; Mi, J; Miquel, JF; Miranda, JJ; Mohamed, MK; Mohammad, K; Mohammadifard, N; Mohan, V; Mohd Yusoff, MF; Møller, NC; Molnár, D; Mondo, CK; Morejon, A; Moreno, LA; Morgan, K; Moschonis, G; Mossakowska, M; Mostafa, A; Mota, J; Motta, J; Mu, TT; Muiesan, ML; Müller-Nurasyid, M; Mursu, J; Nagel, G; Námešná, J; Nang, EE; NangThetia, VB; Navarrete-Muñoz, EM; Ndiaye, NC; Nenko, I; Nervi, F; Nguyen, ND; Nguyen, QN; Nieto-Martínez, RE; Ning, G; Ninomiya, T; Noale, M; Noto, D; Nsour, MA; Ochoa-Avilés, AM; Oh, K; Onat, A; Ordunez, P; Osmond, C; Otero, JA; Owusu-Dabo, E; Pahomova, E; Palmieri, L; Panda-Jonas, S; Panza, F; Parsaeian, M; Peixoto, SV; Pelletier, C; Peltonen, M; Peters, A; Peykari, N; Pham, ST; Pilav, A; Pitakaka, F; Piwonska, A; Piwonski, J; Plans-Rubió, P; Porta, M; Portegies, ML; Poustchi, H; Pradeepa, R; Price, JF; Punab, M; Qasrawi, RF; Qorbani, M; Radisauskas, R; Rahman, M; Raitakari, O; Rao, SR; Ramachandran, A; Ramke, J; Ramos, R; Rampal, S; Rathmann, W; Redon, J; Reganit, PF; Rigo, F; Robinson, SM; Robitaille, C; Rodríguez-Artalejo, F; Rodriguez-Perez Mdel, C; Rodríguez-Villamizar, LA; Rojas-Martinez, R; Ronkainen, K; Rosengren, A; Rubinstein, A; Rui, O; Ruiz-Betancourt, BS; Russo Horimoto, RV; Rutkowski, M; Sabanayagam, C; Sachdev, HS; Saidi, O; Sakarya, S; Salanave, B; Salonen, JT; Salvetti, M; Sánchez-Abanto, J; Santos, D; dos Santos, RN; Santos, R; Saramies, JL; Sardinha, LB; Sarrafzadegan, N; Saum, KU; Scazufca, M; Schargrodsky, H; Scheidt-Nave, C; Sein, AA; Sharma, SK; Shaw, JE; Shibuya, K; Shin, Y; Shiri, R; Siantar, R; Sibai, AM; Simon, M; Simons, J; Simons, LA; Sjostrom, M; Slowikowska-Hilczer, J; Slusarczyk, P; Smeeth, L; Snijder, MB; So, HK; Sobngwi, E; Söderberg, S; Solfrizzi, V; Sonestedt, E; Soumare, A; Staessen, JA; Stathopoulou, MG; Steene-Johannessen, J; Stehle, P; Stein, AD; Stessman, J; Stöckl, D; Stokwiszewski, J; Stronks, K; Strufaldi, MW; Sun, CA; Sundström, J; Sung, YT; Suriyawongpaisal, P; Sy, RG; Tai, ES; Tamosiunas, A; Tang, L; Tarawneh, M; Tarqui-Mamani, CB; Taylor, A; Theobald, H; Thijs, L; Thuesen, BH; Tolonen, HK; Tolstrup, JS; Topbas, M; Torrent, M; Traissac, P; Trinh, OT; Tulloch-Reid, MK; Tuomainen, TP; Turley, ML; Tzourio, C; Ueda, P; Ukoli, FA; Ulmer, H; Uusitalo, HM; Valdivia, G; Valvi, D; van Rossem, L; van Valkengoed, IG; Vanderschueren, D; Vanuzzo, D; Vega, T; Velasquez-Melendez, G; Veronesi, G; Verschuren, WM; Verstraeten, R; Viet, L; Vioque, J; Virtanen, JK; Visvikis-Siest, S; Viswanathan, B; Vollenweider, P; Voutilainen, S; Vrijheid, M; Wade, AN; Wagner, A; Walton, J; Wan Mohamud, WN; Wang, F; Wang, MD; Wang, Q; Wang, YX; Wannamethee, SG; Weerasekera, D; Whincup, PH; Widhalm, K; Wiecek, A; Wijga, AH; Wilks, RJ; Willeit, J; Wilsgaard, T; Wojtyniak, B; Wong, TY; Woo, J; Woodward, M; Wu, FC; Wu, SL; Xu, H; Yan, W; Yang, X; Ye, X; Yoshihara, A; Younger-Coleman, NO; Zambon, S; Zargar, AH; Zdrojewski, T; Zhao, W; Zheng, Y; Zuñiga Cisneros, J
Abstract:
FINDINGS: We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (\textgreater30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. INTERPRETATION: Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. FUNDING: Wellcome Trust. BACKGROUND: One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. METHODS: We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue.
Published:
2016-04
Title:
AMPK: An Energy-Sensing Pathway with Multiple Inputs and Outputs
Authors:
Hardie, D. Grahame; Schaffer, Bethany E.; Brunet, Anne
Abstract:
AMP-activated protein kinase (AMPK) is a key regulator of energy balance expressed ubiquitously in eukaryotic cells. Here we review the canonical adenine nucleotide-dependent mechanism that activates AMPK when cellular energy status is compromised, as well as other, noncanonical activation mechanisms. Once activated, AMPK acts to restore energy homeostasis by promoting catabolic pathways, resulting in ATP generation, and inhibiting anabolic pathways that consume ATP. We also review the various hypothesis-driven and unbiased approaches that have been used to identify AMPK substrates and have revealed substrates involved in both metabolic and non-metabolic processes. We particularly focus on methods for identifying the AMPK target recognition motif and how it can be used to predict new substrates.
Published:
2016-03
Title:
Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: A systematic review and meta-analysis
Authors:
Lally, John; Tully, John; Robertson, Dene; Stubbs, Brendon; Gaughran, Fiona; MacCabe, James H.
Abstract:
The primary aim of this systematic review and meta-analysis was to assess the proportion of patients with Treatment Resistant Schizophrenia (TRS) that respond to ECT augmentation of clozapine (C + ECT). We searched major electronic databases from 1980 to July 2015. We conducted a random effects meta-analysis reporting the proportion of responders to C + ECT in RCTs and open-label trials. Five clinical trials met our eligibility criteria, allowing us to pool data from 71 people with TRS who underwent C+ ECT across 4 open label trials (n = 32) and 1 RCT (n = 39). The overall pooled proportion of response to C + ECT was 54%, (95% CI: 21.8–83.6%) with some heterogeneity evident (I2 = 69%). With data from retrospective chart reviews, case series and case reports, 192 people treated with C + ECT were included. All studies together demonstrated an overall response to C + ECT of 66% (95% CI: 57.5–74.3%) (83 out of 126 patients responded to C + ECT). The mean number of ECT treatments used to augment clozapine was 11.3. 32% of cases (20 out of 62 patients) with follow up data (range of follow up: 3–468 weeks) relapsed following cessation of ECT. Adverse events were reported in 14% of identified cases (24 out of 166 patients). There is a paucity of controlled studies in the literature, with only one single blinded randomised controlled study located, and the predominance of open label trials used in the meta-analysis is a limitation. The data suggests that ECT may be an effective and safe clozapine augmentation strategy in TRS. A higher number of ECT treatments may be required than is standard for other clinical indications. Further research is needed before ECT can be included in standard TRS treatment algorithms.
Published:
2016-03
Title:
Diagnostic Accuracy of Rating Scales for Attention-Deficit/Hyperactivity Disorder: A Meta-analysis
Authors:
Chang, Ling-Yin; Wang, Mei-Yeh; Tsai, Pei-Shan
Abstract:
CONTEXT: The Child Behavior Checklist-Attention Problem (CBCL-AP) scale and Conners Rating Scale-Revised (CRS-R) are commonly used behavioral rating scales for diagnosing attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. OBJECTIVE: To evaluate and compare the diagnostic performance of CBCL-AP and CRS-R in diagnosing ADHD in children and adolescents. DATA SOURCES: PubMed, Ovid Medline, and other relevant electronic databases were searched for articles published up to May 2015. STUDY SELECTION: We included studies evaluating the diagnostic performance of either CBCL-AP scale or CRS-R for diagnosing ADHD in pediatric populations in comparison with a defined reference standard. DATA EXTRACTION: Bivariate random effects models were used for pooling and comparing diagnostic performance. RESULTS: We identified and evaluated 14 and 11 articles on CBCL-AP and CRS-R, respectively. The results revealed pooled sensitivities of 0.77, 0.75, 0.72, and 0.83 and pooled specificities of 0.73, 0.75, 0.84, and 0.84 for CBCL-AP, Conners Parent Rating Scale-Revised, Conners Teacher Rating Scale-Revised, and Conners Abbreviated Symptom Questionnaire (ASQ), respectively. No difference was observed in the diagnostic performance of the various scales. Study location, age of participants, and percentage of female participants explained the heterogeneity in the specificity of the CBCL-AP. CONCLUSIONS: CBCL-AP and CRS-R both yielded moderate sensitivity and specificity in diagnosing ADHD. According to the comparable diagnostic performance of all examined scales, ASQ may be the most effective diagnostic tool in assessing ADHD because of its brevity and high diagnostic accuracy. CBCL is recommended for more comprehensive assessments.
Published:
2016-03
Title:
Distance learning strategies for weight management utilizing social media: A comparison of phone conference call versus social media platform. Rationale and design for a randomized study
Authors:
Willis, Erik A.; Szabo-Reed, Amanda N.; Ptomey, Lauren T.; Steger, Felicia L.; Honas, Jeffery J.; Al-Hihi, Eyad M.; Lee, Robert; Vansaghi, Lisa; Washburn, Richard A.; Donnelly, Joseph E.
Abstract:
Management of obesity in the context of the primary care physician visit is of limited efficacy in part because of limited ability to engage participants in sustained behavior change between physician visits. Therefore, healthcare systems must find methods to address obesity that reach beyond the walls of clinics and hospitals and address the issues of lifestyle modification in a cost-conscious way. The dramatic increase in technology and online social networks may present healthcare providers with innovative ways to deliver weight management programs that could have an impact on health care at the population level. A randomized study will be conducted on 70 obese adults (BMI 30.0–45.0 kg/m2) to determine if weight loss (6 months) is equivalent between weight management interventions utilizing behavioral strategies by either a conference call or social media approach. The primary outcome, body weight, will be assessed at baseline and 6 months. Secondary outcomes including waist circumference, energy and macronutrient intake, and physical activity will be assessed on the same schedule. In addition, a cost analysis and process evaluation will be completed.
Published:
2016-03
Title:
Effects of nutrition education on weight gain prevention: a randomized controlled trial
Authors:
Metzgar, Catherine J.; Nickols-Richardson, Sharon M.
Abstract:
CONCLUSIONS: A majority of all participants maintained BW over one year and were able to do so regardless of whether they received nutrition education. Additional studies that include a variety of clinical outcomes are needed to evaluate further aspects of nutrition education on weight gain prevention and health status over the long term.
Published:
2016-03
Title:
Estimating the Ages of Selection Signals from Different Epochs in Human History
Authors:
Nakagome, Shigeki; Alkorta-Aranburu, Gorka; Amato, Roberto; Howie, Bryan; Peter, Benjamin M.; Hudson, Richard R.; Di Rienzo, Anna
Abstract:
Genetic variation harbors signatures of natural selection driven by selective pressures that are often unknown. Estimating the ages of selection signals may allow reconstructing the history of environmental changes that shaped human phenotypes and diseases. We have developed an approximate Bayesian computation (ABC) approach to estimate allele ages under a model of selection on new mutations and under demographic models appropriate for human populations. We have applied it to two resequencing data sets: An ultra-high depth data set from a relatively small sample of unrelated individuals and a lower depth data set in a larger sample with transmission information. In addition to evaluating the accuracy of our method based on simulations, for each SNP, we assessed the consistency between the posterior probabilities estimated by the ABC approach and the ancient DNA record, finding good agreement between the two types of data and methods. Applying this ABC approach to data for eight single nucleotide polymorphisms (SNPs), we were able to rule out an onset of selection prior to the dispersal out-of-Africa for three of them and more recent than the spread of agriculture for an additional three SNPs.
Published:
2016-03
Title:
Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial
Authors:
Longland, Thomas M.; Oikawa, Sara Y.; Mitchell, Cameron J.; Devries, Michaela C.; Phillips, Stuart M.
Abstract:
BACKGROUND: A dietary protein intake higher than the Recommended Dietary Allowance during an energy deficit helps to preserve lean body mass (LBM), particularly when combined with exercise. OBJECTIVE: The purpose of this study was to conduct a proof-of-principle trial to test whether manipulation of dietary protein intake during a marked energy deficit in addition to intense exercise training would affect changes in body composition. DESIGN: We used a single-blind, randomized, parallel-group prospective trial. During a 4-wk period, we provided hypoenergetic (~40% reduction compared with requirements) diets providing 33 ± 1 kcal/kg LBM to young men who were randomly assigned (n = 20/group) to consume either a lower-protein (1.2 g · kg(-1) · d(-1)) control diet (CON) or a higher-protein (2.4 g · kg(-1) · d(-1)) diet (PRO). All subjects performed resistance exercise training combined with high-intensity interval training for 6 d/wk. A 4-compartment model assessment of body composition was made pre- and postintervention. RESULTS: As a result of the intervention, LBM increased (P < 0.05) in the PRO group (1.2 ± 1.0 kg) and to a greater extent (P < 0.05) compared with the CON group (0.1 ± 1.0 kg). The PRO group had a greater loss of fat mass than did the CON group (PRO: -4.8 ± 1.6 kg; CON: -3.5 ± 1.4kg; P
Published:
2016-03
Title:
Meal sequence and glucose excursion, gastric emptying and incretin secretion in type 2 diabetes: a randomised, controlled crossover, exploratory trial
Authors:
Kuwata, Hitoshi; Iwasaki, Masahiro; Shimizu, Shinobu; Minami, Kohtaro; Maeda, Haruyo; Seino, Susumu; Nakada, Koji; Nosaka, Chihiro; Murotani, Kenta; Kurose, Takeshi; Seino, Yutaka; Yabe, Daisuke
Abstract:
AIMS/HYPOTHESIS: Investigation of dietary therapy for diabetes has focused on meal size and composition; examination of the effects of meal sequence on postprandial glucose management is limited. The effects of fish or meat before rice on postprandial glucose excursion, gastric emptying and incretin secretions were investigated. METHODS: The experiment was a single centre, randomised controlled crossover, exploratory trial conducted in an outpatient ward of a private hospital in Osaka, Japan. Patients with type 2 diabetes (n = 12) and healthy volunteers (n = 10), with age 30-75 years, HbA1c 9.0% (75 mmol/mol) or less, and BMI 35 kg/m(2) or less, were randomised evenly to two groups by use of stratified randomisation, and subjected to meal sequence tests on three separate mornings; days 1 and 2, rice before fish (RF) or fish before rice (FR) in a crossover fashion; and day 3, meat before rice (MR). Pre- and postprandial levels of glucose, insulin, C-peptide and glucagon as well as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide were evaluated. Gastric emptying rate was determined by (13)C-acetate breath test involving measurement of (13)CO2 in breath samples collected before and after ingestion of rice steamed with (13)C-labelled sodium acetate. Participants, people doing measurements or examinations, and people assessing the outcomes were not blinded to group assignment. RESULTS: FR and MR in comparison with RF ameliorated postprandial glucose excursion (AUC-15-240 min-glucose: type 2 diabetes, FR 2,326.6 ± 114.7 mmol/l × min, MR 2,257.0 ± 82.3 mmol/l × min, RF 2,475.6 ± 87.2 mmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 1,419.8 ± 72.3 mmol/l × min, MR 1,389.7 ± 69.4 mmol/l × min, RF 1,483.9 ± 72.8 mmol/l × min) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, FR 1.94 ± 0.22 mmol/l, MR 1.68 ± 0.18 mmol/l, RF 2.77 ± 0.24 mmol/l [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 0.95 ± 0.21 mmol/l, MR 0.83 ± 0.16 mmol/l, RF 1.18 ± 0.27 mmol/l). FR and MR also enhanced GLP-1 secretion, MR more strongly than FR or RF (AUC-15-240 min-GLP-1: type 2 diabetes, FR 7,123.4 ± 376.3 pmol/l × min, MR 7,743.6 ± 801.4 pmol/l × min, RF 6,189.9 ± 581.3 pmol/l × min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 3,977.3 ± 324.6 pmol/l × min, MR 4,897.7 ± 330.7 pmol/l × min, RF 3,747.5 ± 572.6 pmol/l × min [p < 0.05 for MR vs RF and MR vs FR]). FR and MR delayed gastric emptying (Time50%: type 2 diabetes, FR 83.2 ± 7.2 min, MR 82.3 ± 6.4 min, RF 29.8 ± 3.9 min [p < 0.05 for FR vs RF and MR vs RF]; healthy, FR 66.3 ± 5.5 min, MR 74.4 ± 7.6 min, RF 32.4 ± 4.5 min [p < 0.05 for FR vs RF and MR vs RF]), which is associated with amelioration of postprandial glucose excursion (AUC-15-120 min-glucose: type 2 diabetes, r = -0.746, p < 0.05; healthy, r = -0.433, p < 0.05) and glucose variability (SD-15-240 min-glucose: type 2 diabetes, r = -0.578, p < 0.05; healthy, r = -0.526, p < 0.05), as well as with increasing GLP-1 (AUC-15-120 min-GLP-1: type 2 diabetes, r = 0.437, p < 0.05; healthy, r = 0.300, p = 0.107) and glucagon (AUC-15-120 min-glucagon: type 2 diabetes, r = 0.399, p < 0.05; healthy, r = 0.471, p
Published:
2016-03
Title:
Metabolic Effects of a 24-Week Energy-Restricted Intervention Combined with Low or High Dairy Intake in OverweightWomen: An NMR-Based Metabolomics Investigation
Authors:
Yde, Christian C.; Clausen, Morten R.; Bertram, Hanne Christine; Hong Zheng; Lorenzen, Janne K.; Astrup, Arne; Larsen, Lesli H.
Abstract:
We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD) on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA). A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO) and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study.
Published:
2016-03
Title:
Metabolic characteristics of keto-adapted ultra-endurance runners
Authors:
Volek, Jeff S.; Freidenreich, Daniel J.; Saenz, Catherine; Kunces, Laura J.; Creighton, Brent C.; Bartley, Jenna M.; Davitt, Patrick M.; Munoz, Colleen X.; Anderson, Jeffrey M.; Maresh, Carl M.; Lee, Elaine C.; Schuenke, Mark D.; Aerni, Giselle; Kraemer, William J.; Phinney, Stephen D.
Abstract:
BACKGROUND: Many successful ultra-endurance athletes have switched from a high-carbohydrate to a low-carbohydrate diet, but they have not previously been studied to determine the extent of metabolic adaptations. METHODS: Twenty elite ultra-marathoners and ironman distance triathletes performed a maximal graded exercise test and a 180 min submaximal run at 64% VO2max on a treadmill to determine metabolic responses. One group habitually consumed a traditional high-carbohydrate (HC: n=10, %carbohydrate:protein:fat=59:14:25) diet, and the other a low-carbohydrate (LC; n=10, 10:19:70) diet for an average of 20 months (range 9 to 36 months). RESULTS: Peak fat oxidation was 2.3-fold higher in the LC group (1.54±0.18 vs 0.67±0.14 g/min; P=0.000) and it occurred at a higher percentage of VO2max (70.3±6.3 vs 54.9±7.8%; P=0.000). Mean fat oxidation during submaximal exercise was 59% higher in the LC group (1.21±0.02 vs 0.76±0.11 g/min; P=0.000) corresponding to a greater relative contribution of fat (88±2 vs 56±8%; P=0.000). Despite these marked differences in fuel use between LC and HC athletes, there were no significant differences in resting muscle glycogen and the level of depletion after 180 min of running (-64% from pre-exercise) and 120 min of recovery (-36% from pre-exercise). CONCLUSION: Compared to highly trained ultra-endurance athletes consuming an HC diet, long-term keto-adaptation results in extraordinarily high rates of fat oxidation, whereas muscle glycogen utilization and repletion patterns during and after a 3 hour run are similar.
Published:
2016-03
Title:
Red meat metabolite levels high in acute heart failure patients, research shows
Authors:
Abstract:
Published:
2016-03
Title:
Repeated evolution of carnivory among Indo-Australian rodents
Authors:
Rowe, Kevin C.; Achmadi, Anang S.; Esselstyn, Jacob A.
Abstract:
Convergent evolution, often observed in island archipelagos, provides compelling evidence for the importance of natural selection as a generator of species and ecological diversity. The Indo-Australian Archipelago (IAA) is the world's largest island system and encompasses distinct biogeographic units, including the Asian (Sunda) and Australian (Sahul) continental shelves, which together bracket the oceanic archipelagos of the Philippines and Wallacea. Each of these biogeographic units houses numerous endemic rodents in the family Muridae. Carnivorous murids, that is those that feed on animals, have evolved independently in Sunda, Sulawesi (part of Wallacea), the Philippines, and Sahul, but the number of origins of carnivory among IAA murids is unknown. We conducted a comprehensive phylogenetic analysis of carnivorous murids of the IAA, combined with estimates of ancestral states for broad diet categories (herbivore, omnivore, and carnivore) and geographic ranges. These analyses demonstrate that carnivory evolved independently four times after overwater colonization, including in situ origins on the Philippines, Sulawesi, and Sahul. In each biogeographic unit the origin of carnivory was followed by evolution of more specialized carnivorous ecomorphs such as vermivores, insectivores, and amphibious rats.
Published:
2016-03
Title:
The Warburg Effect: How Does it Benefit Cancer Cells?
Authors:
Liberti, Maria V.; Locasale, Jason W.
Abstract:
Cancer cells rewire their metabolism to promote growth, survival, proliferation, and long-term maintenance. The common feature of this altered metabolism is the increased glucose uptake and fermentation of glucose to lactate. This phenomenon is observed even in the presence of completely functioning mitochondria and, together, is known as the 'Warburg Effect'. The Warburg Effect has been documented for over 90 years and extensively studied over the past 10 years, with thousands of papers reporting to have established either its causes or its functions. Despite this intense interest, the function of the Warburg Effect remains unclear. Here, we analyze several proposed explanations for the function of Warburg Effect, emphasize their rationale, and discuss their controversies.
Published:
2016-03
Title:
The diverse nature of saturated fats and the case of medium-chain triglycerides: how one recommendation may not fit all. [Review]
Authors:
Bhavsar, Nilam; St-Onge, Marie-Pierre
Abstract:
SUMMARY: It is clinically relevant to distinguish between sources of saturated fats for cardiovascular health. Medium, and possibly shorter chain, saturated fats behave differently than long-chain saturated fats and should not be judged similarly when it comes to their cardio-metabolic health effects. Given their neutral, and potentially beneficial cardiovascular health effects, they should not be categorized together.
Published:
2016-03
Title:
An eHealth Platform to Manage Chronic Disease in Primary Care: An Innovative Approach
Authors:
Talboom-Kamp, Esther PWA; Verdijk, Noortje A; Harmans, Lara M; Numans, Mattijs E; Chavannes, Niels H
Abstract:
The number of individuals with chronic illness and multimorbidity is growing due to the rapid ageing of the population and the greater longevity of individuals. This causes an increasing workload in care, which results in a growing need for structural changes of the health care system. In recent years this led to a strong focus on promoting "self-management" in chronically ill patients. Research showed that patients who understand more about their disease, health, and lifestyle have better experiences and health outcomes, and often use less health care resources; the effect is even more when these patients are empowered to and responsible for managing their health and disease. In addition to the skills of patients, health care professionals need to shift to a role of teacher, partner, and professional supervisor of their patients. One way of supervising patients is by the use of electronic health (eHealth), which helps patients manage and control their disease. The application of eHealth solutions can provide chronically ill patients high-quality care, to the satisfaction of both patients and health care professionals, alongside a reduction in health care consumption and costs.
Published:
2016-02
Title:
Associations between Vitamin B-12 Status and Oxidative Stress and Inflammation in Diabetic Vegetarians and Omnivores
Authors:
Lee, Yau-Jiunn; Wang, Ming-Yang; Lin, Mon-Chiou; Lin, Ping-Ting
Abstract:
Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (<= 250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p
Published:
2016-02
Title:
Changes in the human plasma and urinary metabolome associated with acute dietary exposure to sucrose and the identification of potential biomarkers of sucrose intake
Authors:
Beckmann, Manfred; Joosen, Annemiek M.; Clarke, Michelle M.; Mugridge, Owen; Frost, Gary; Engel, Barbara; Taillart, Kathleen; Lloyd, Amanda J.; Draper, John; Lodge, John K.
Abstract:
SCOPE: The intake of sucrose is of public health concern but limited information is available on the metabolic effects of short-term exposure. Our aim was to use metabolomics to investigate the metabolic impact of acute sucrose exposure. METHODS AND RESULTS: We performed a randomized, parallel, single-dose feeding study on healthy females (n = 90, aged 29.9 ± 4.7 years, BMI 23.3 ± 2.5 kg/m(2) ) consuming either 0, 50, or 100 g sucrose in 500 mL water. Blood and urine samples were taken before and 24 h post sucrose intake. Urine and plasma samples underwent detailed metabolite profiling analysis using established protocols. Flow-injection electrospray MS fingerprinting analysis showed that 3 h after intake was the most informative time point in urine and plasma and out of 120 explanatory signals, highlighted 16 major metabolite signals in urine and 25 metabolite signals in plasma that were discriminatory and correlated with sucrose intake over time. The main confirmed metabolites positively correlated with intake were sucrose, fructose, and erythronic acid, while those negatively correlating with intake included fatty acids and derivatives, acyl-carnitines, and ketone bodies. GC-TOF-MS profiling analysis confirmed the fingerprinting data. CONCLUSION: Acute exposure to sucrose identified a number of metabolites correlated with sucrose intake and several compounds attributed to metabolic fasting.
Published:
2016-02
Title:
Curcumin inhibits advanced glycation end product-induced oxidative stress and inflammatory responses in endothelial cell damage via trapping methylglyoxal
Authors:
SUN, YAN PING; GU, JUN FEI; TAN, XIAO BIN; WANG, CHUN FEI; JIA, XIAO BIN; FENG, LIANG; LIU, JI PING
Abstract:
Methylglyoxal (MGO)-induced carbonyl stress and pro-inflammatory responses have been suggested to contribute to endothelial dysfunction. Curcumin (Cur), a polyphenolic compound from Curcuma longa L., may protect endothelial cells against carbonyl stress-induced damage by trapping dicarbonyl compounds such as MGO. However, Cur-MGO adducts have not been studied in depth to date and it remains to be known whether Cur-MGO adducts are able to attenuate endothelial damage by trapping MGO. In the present study, 1,2-diaminobenzene was reacted with MGO to ensure the reliability of the reaction system. Cur was demonstrated to trap MGO at a 1:1 ratio to form adducts 1, 2 and 3 within 720 min. The structures of these adducts were identified by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry. The kinetic curves of Cur (10−7, 10−6 and 10−5 M) were measured from 0–168 h by fluorescent intensity. Cur significantly inhibited the formation of advanced glycation end products (AGEs). The differences in oxidative damage and the levels of pro-inflammatory cytokines following MGO + HSA or Cur-MGO treatment were investigated in human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs to the Cur-MGO reaction adducts significantly reduced the intracellular ROS levels and improved cell viability compared with MGO alone. Furthermore, there was a significant reduction in the expression levels of transforming growth factor-β1 and intercellular adhesion molecule-1 following treatment with Cur-MGO adducts compared with MGO alone. These results provide further evidence that the trapping of MGO by Cur inhibits the formation of AGEs. The current study indicates that the protective effect of Cur on carbonyl stress and pro-inflammatory responses in endothelial damage occurs via the trapping of MGO.
Published:
2016-02
Title:
Effect of Fat Intake on the Inflammatory Process and Cardiometabolic Risk in Obesity After Interdisciplinary Therapy
Authors:
Jamar, G.; Pisani, L. P.; Medeiros, A.; Oyama, L. M.; Masquio, D. C. L.; Colantonio, E.; Garcia, S.; Sanches, R. B.; dos Santos Moraes, A.; Belote, C.; Caranti, D. A.
Abstract:
Changes in diet and eating behavior along with excessive consumption of sugar or fat and a sedentary lifestyle are related to increased obesity and its associated comorbidities. The aim of this study was to investigate the role of the type of macronutrients on specific health benefits associated with the weight loss in treating obesity. A total of 30 obese women (34.89+/-3.04 kg/m(2) and 43.3+/-5.34 years) participated in an interdisciplinary therapy approach to lifestyle change, which consisted of nutritional counseling, exercise, and psychological therapy for over a period of 26 weeks. The profile was obtained by anthropometric measurements and body composition by bioelectrical impedance analysis (BIA). Usual food intake was assessed with 3-day food record diaries and blood tests were used to determine metabolic and adipokines parameters. After therapy, there was significant reduction in all anthropometric and body composition variables. Food consumption also decreased while still providing adequate nutrient intake. There was significant improvement in LDL-cholesterol, PAI-1, leptin, CRP, ICAM-1, and VCAM-1. Lower dietary carbohydrate and fat intake led to weight loss. The effect of lower carbohydrate intake on weight loss is related to changes in body composition and leptin levels. Weight loss by reducing fat intake modified the inflammatory process and cardiovascular risk, indicating dietary fat as an independent predictor factor of cell adhesion molecules. Therefore, decreasing dietary fat consumption had greater impact on the inflammatory process on obese individuals. Our results show that the type of macronutrient influences the health benefits associated with weight loss. Copyright © Georg Thieme Verlag KG Stuttgart . New York.
Published:
2016-02
Title:
Effect of extended morning fasting upon ad libitum lunch intake and associated metabolic and hormonal responses in obese adults
Authors:
Chowdhury, E. A.; Richardson, J. D.; Tsintzas, K.; Thompson, D.; Betts, J. A.
Abstract:
BACKGROUND/OBJECTIVES: Breakfast omission is positively associated with obesity and increased risk of disease. However, little is known about the acute effects of extended morning fasting upon subsequent energy intake and associated metabolic/regulatory factors in obese adults. SUBJECTS/METHODS: In a randomised cross-over design, 24 obese men (n=8) and women (n=16) extended their overnight fast by omitting breakfast consumption or ingesting a typical carbohydrate-rich breakfast of 2183±393 kJ (521±94 kcal), before an ad libitum pasta lunch 3 h later. Blood samples were obtained throughout the day until 3 h post lunch and analysed for hormones implicated in appetite regulation, along with metabolic outcomes and subjective appetite measures. RESULTS: Lunch intake was unaffected by extended morning fasting (difference=218 kJ, 95% confidence interval -54 kJ, 490 kJ; P=0.1) resulting in lower total intake in the fasting trial (difference=-1964 kJ, 95% confidence interval -1645 kJ, -2281 kJ; P<0.01). Systemic concentrations of peptide tyrosine-tyrosine and leptin were lower during the afternoon following morning fasting (P⩽0.06). Plasma-acylated ghrelin concentrations were also lower following the ad libitum lunch in the fasting trial (P<0.05) but this effect was not apparent for total ghrelin (P⩾0.1). Serum insulin concentrations were greater throughout the afternoon in the fasting trial (P=0.05), with plasma glucose also greater 1 h after lunch (P
Published:
2016-02
Title:
Effects of Arsenite Exposure during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Disease in Male Mice
Authors:
Ditzel, Eric J.; Nguyen, Thu; Parker, Patricia; Camenisch, Todd D.
Abstract:
BACKGROUND: Chronic exposure to arsenicals at various life stages and across a range of exposures has been implicated in cardiometabolic and liver disease, but disease predisposition from developmental exposures remains unclear. OBJECTIVES: In utero and post-weaning exposure to trivalent arsenic (AsIII) was examined on the background of a Western-style diet to determine whether AsIII exposure affects metabolic disease. METHODS: Male Swiss Webster mice were exposed to 100 ppb AsIII in utero, after weaning, or both. Ad libitum access to a Western-style diet was provided after weaning, and the plasma metabolome, liver histopathology, liver enzyme activity, and gene expression were analyzed. RESULTS: Hepatic lipid composition and histopathology revealed that developmental AsIII exposure exacerbated Western-style diet--induced fatty liver disease. Continuous AsIII exposure increased cardiometabolic risk factors including increased body weight, insulin resistance, hyperglycemia, and plasma triglycerides. AsIII exposure produced a decrease in the intermediates of glycolysis and the TCA cycle while increasing ketones. Hepatic isocitrate dehydrogenase activity was also decreased, which confirmed disruption of the TCA cycle. Developmental AsIII exposure increased the expression of genes involved in fatty acid synthesis, lipogenesis, inflammation, and packaging of triglycerides, suggesting an increased acetyl coenzyme A (acetyl-CoA) load. CONCLUSIONS: In utero and continuous early-life exposure to AsIII disrupted normal metabolism and elevated the risk for fatty liver disease in mice maintained on a high-fat diet. Our findings suggest that individuals exposed to AsIII during key developmental periods and who remain exposed to AsIII on the background of a Western-style diet may be at increased risk for metabolic disease later in life.
Published:
2016-02
Title:
Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice
Authors:
Gotthardt, Juliet D.; Verpeut, Jessica L.; Yeomans, Bryn L.; Yang, Jennifer A.; Yasrebi, Ali; Roepke, Troy A.; Bello, Nicholas T.
Abstract:
Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%-52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%-13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%-42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%-60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%-32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%-75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.
Published:
2016-02
Title:
Intestinal lymphangiectasia in children
Authors:
Isa, Hasan M.; Al-Arayedh, Ghadeer G.; Mohamed, Afaf M.
Abstract:
Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification.
Published:
2016-02
Title:
Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane
Authors:
Xiao, Hongyan; Liu, Bing; Chen, Yali; Zhang, Jun
Abstract:
PURPOSE: Developmental exposure to volatile anesthetics has been associated with cognitive deficits at adulthood. Rodent studies have revealed impairments in performance in learning tasks involving the hippocampus. However, how the duration of anesthesia exposure impact on hippocampal synaptic plasticity, learning, and memory is as yet not fully elucidated. METHODS: On postnatal day 7(P7), rat pups were divided into 3 groups: control group (n=30), 3% sevoflurane treatment for 1h (Sev 1h group, n=30) and 3% sevoflurane treatment for 6h (Sev 6h group, n=28). Following anesthesia, synaptic vesicle-associated proteins and dendrite spine density and synapse ultrastructure were measured using western blotting, Golgi staining, and transmission electron microscopy (TEM) on P21. In addition, the effects of sevoflurane treatment on long-term potentiation (LTP) and long-term depression (LTD), two molecular correlates of memory, were studied in CA1 subfields of the hippocampus, using electrophysiological recordings of field potentials in hippocampal slices on P35-42. Rats' neurocognitive performance was assessed at 2 months of age, using the Morris water maze and novel-object recognition tasks. RESULTS: Our results showed that neonatal exposure to 3% sevoflurane for 6h results in reduced spine density of apical dendrites along with elevated expression of synaptic vesicle-associated proteins (SNAP-25 and syntaxin), and synaptic ultrastructure damage in the hippocampus. The electrophysiological evidence indicated that hippocampal LTP, but not LTD, was inhibited and that learning and memory performance were impaired in two behavioral tasks in the Sev 6h group. In contrast, lesser structural and functional damage in the hippocampus was observed in the Sev 1h group. CONCLUSION: Our data showed that 6-h exposure of the developing brain to 3% sevoflurane could result in synaptic plasticity impairment in the hippocampus and spatial and nonspatial hippocampal-dependent learning and memory deficits. In contrast, shorter-duration exposure (1h) results in less damage. These results provide further evidences that duration of anesthesia exposure could have differential effects on neuronal plasticity and neurocognitive performance.
Published:
2016-02
Title:
Longitudinal study of low serum LDL cholesterol and depressive symptom onset in postmenopause
Authors:
Persons, Jane E.; Robinson, Jennifer G.; Coryell, William H.; Payne, Martha E.; Fiedorowicz, Jess G.
Abstract:
OBJECTIVE: The aim of this study was to characterize the relationship between serum low-density lipoprotein cholesterol (LDL-c) and subsequent depressive symptoms onset in postmenopausal women. We secondarily assessed serum high-density lipoprotein (HDL-c), total cholesterol, and triglycerides. METHOD: This population-based prospective cohort study utilizes data from 24,216 women between 50 and 79 years of age who were participants of the Women's Health Initiative, which originally ran from 1993 to 2005 and has since incorporated 2 extension studies, with the most recent culminating in 2015. Fasting lipids were measured for all participants at baseline and for a subset through 6 years of follow-up. Depressive symptoms were characterized using the Burnam 8-item scale for depressive disorders (Center for Epidemiologic Studies-Depression/Diagnostic Interview Schedule short form) at baseline and during follow-up, using a cut point of 0.06 to indicate presence of depressive symptoms. RESULTS: The lowest quintile of LDL-c was associated with an increased risk of subsequent depressive symptoms (hazard ratio [HR] = 1.25, 95% CI = 1.05-1.49, P = .01), and follow-up analyses demonstrated that the elevated risk appeared to be confined to the lowest decile (LDL-c < 100 mg/dL). Further, this elevated risk was moderated by lipid-lowering drug treatment. Elevated risk was demonstrated among those who reported no lipid-lowering medication use (HR = 1.23, 95% CI = 1.03-1.47, P = .02), but not among those reporting use (HR = 0.65, 95% CI = 0.18-2.29, P = .50). CONCLUSIONS: Among postmenopausal women, untreated serum LDL-c below 100 mg/dL was associated with an increased risk of developing depressive symptoms. No excess risk was observed in those attaining LDL-c
Published:
2016-02
Title:
Organoid culture systems for prostate epithelial tissue and prostate cancer tissue
Authors:
Drost, Jarno; Karthaus, Wouter R.; Gao, Dong; Driehuis, Else; Sawyers, Charles L.; Chen, Yu; Clevers, Hans
Abstract:
This protocol describes a recently developed strategy to generate 3D prostate organoid cultures from healthy mouse and human prostate (either bulk or FAC-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumour cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumour. The stepwise establishment of these cultures and the fully defined serum-free conditioned medium that is required to sustain organoid growth are outlined. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.
Published:
2016-02
Title:
Plasma Concentrations of Trimethylamine-N-oxide Are Directly Associated with Dairy Food Consumption and Low-Grade Inflammation in a German Adult Population
Authors:
Rohrmann, Sabine; Linseisen, Jakob; Allenspach, Martina; von Eckardstein, Arnold; Müller, Daniel
Abstract:
Background: Trimethylamine-N-oxide (TMAO) is a metabolite of carnitine, choline, and phosphatidylcholine, which is inversely associated with survival of cardiovascular disease (CVD) patients.Objective: We examined the associations of diet with plasma concentrations of TMAO, choline, and betaine and the associations of TMAO with plasma concentrations of various cytokines.Methods: Plasma TMAO, choline, and betaine concentrations were measured using LC-high resolution mass spectrometry in 271 participants, ≥18 y old, of the Second Bavarian Food Consumption Survey, conducted in 2002 and 2003. Food consumption was assessed using at least two 24-h dietary recalls. Cytokines were measured in plasma with enzyme-linked immunosorbent assays. Geometric mean concentrations of TMAO, choline, and betaine by categories of meat, dairy food, egg, and fish consumption were computed, adjusted for sex, age, and BMI. Multivariable-adjusted geometric mean concentrations of cytokines [tumor necrosis factor-α (TNF-α), soluble TNF receptors (sTNF-R) p55, sTNF-R p75, interleukin-6 (IL-6), and C-reactive protein (CRP)] were computed by quartiles of TMAO concentration using general linear models.Results: Meat, egg, or fish consumption was not associated with TMAO, choline, or betaine concentrations (all P-trend ≥ 0.05). With increases in milk and other dairy food consumption, the plasma TMAO concentration increased [geometric mean bottom quartile of milk consumption: 2.08 μM (95% CI: 1.69, 2.57 μM); compared with top quartile: 3.13 μM (95% CI: 2.56, 3.84 μM); P-trend = 0.008]. Participants in the top TMAO quartile had higher plasma concentrations of TNF-α, sTNF-R p55, and sTNF-R p75 than participants in the bottom quartile (percentage difference ranging between 14.4% and 17.3%; all P-trend
Published:
2016-02
Title:
Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?
Authors:
Nugent, S.; Castellano, C. A.; Bocti, C.; Dionne, I.; Fulop, T.; Cunnane, S. C.
Abstract:
Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.
Published:
2016-02
Title:
The mouse prostate: a basic anatomical and histological guideline
Authors:
Oliveira, Daniel S. M.; Dzinic, Sijana; Bonfil, Alan I.; Saliganan, Allen D.; Sheng, Shijie; Bonfil, R. Daniel
Abstract:
Despite substantial similarities in embryological, cellular and molecular biology features, human and mouse prostates differ in organ morphology and tissue architecture. Thus, a clear understanding of the anatomy and histology of the mouse prostate is essential for the identification of urogenital phenotypes in genetically engineered mice, as well as for the study of the etiology, development, and treatment of human prostatic diseases for which mouse models are used. The purpose of this manuscript is to provide a brief guide for the dissection of the mouse prostate and the identification of its different lobes and histology, to both basic researchers and medical pathologists who are unfamiliar with mouse tissues.
Published:
2016-02
Title:
A Review of Cutoffs for Nutritional Biomarkers
Authors:
Raghavan, Ramkripa; Ashour, Fayrouz Sakr; Bailey, Regan
Abstract:
The nutritional status of an individual or population needs to be assessed through valid and reliable biomarkers. Cutoffs generally have an underlying relation to health status and are one of the important quantitative criteria against which biomarker outputs are compared. For this reason, cutoffs are integral for surveys, surveillance, screening, interventions, monitoring, and evaluation. Despite their importance, nutritional biomarker cutoffs have not been adequately addressed in the literature. Furthermore, the field has not reached a consensus on which cutoff to use for each biomarker, and different cutoffs are often used for the same biomarkers in published studies. This review provides a comprehensive overview of cutoffs related to nutritional biomarkers and highlights some of the high-priority research gaps and challenges of using micronutrient case studies.
Published:
2016-01
Title:
Effects of dry-aging on meat quality attributes and metabolite profiles of beef loins
Authors:
Kim, Yuan H. Brad; Kemp, Robert; Samuelsson, Linda M.
Abstract:
The objectives of this study were to evaluate different dry-aging regimes and their impacts on quality attributes and metabolite profiles of beef loins. Thirty loins (M. longissimus lumborum) from 15 beef carcasses at 2 days post-mortem were obtained. Each loin was cut in half yielding 60 sections, which were randomly assigned to six treatments including 4 dry-aging (2 temperatures (1 or 3degreeC) x 2 air-velocities (0.2 or 0.5 m/s)) and 2 wet-aging regimes for 3 weeks; n=10/treatment. The sensory panel found that dry-aged loins had better flavour and overall liking (P
Published:
2016-01
Title:
Examining the association between posttraumatic stress disorder and attention-deficit/hyperactivity disorder: a systematic review and meta-analysis
Authors:
Spencer, Andrea E.; Faraone, Stephen V.; Bogucki, Olivia E.; Pope, Amanda L.; Uchida, Mai; Milad, Mohammed R.; Spencer, Thomas J.; Woodworth, K. Yvonne; Biederman, Joseph
Abstract:
OBJECTIVE: To conduct a systematic review and meta-analysis examining the relationship between attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD). DATA SOURCES: We reviewed literature through PubMed and PsycINFO without a specified date range, utilizing the search (posttraumatic stress disorder OR PTSD) AND (ADHD OR attention deficit hyperactivity disorder OR ADD OR attention deficit disorder OR hyperkinetic syndrome OR minimal brain dysfunction). References from relevant articles were reviewed. STUDY SELECTION: We identified 402 articles; 28 met criteria. We included original human research in English that operationalized diagnoses of ADHD and PTSD, evaluated the relationship between the disorders, and included controls. We excluded articles that failed to differentiate ADHD or PTSD from nonspecific or subsyndromal deficits or failed to compare their relationship. DATA EXTRACTION: We extracted sample size, age, diagnostic methods, design, referral status, control type, and number of subjects with and without ADHD and PTSD alone and combined. We computed meta-analyses for 22 studies examining ADHD in PTSD and PTSD in ADHD using a random effects model and meta-analytic regression. We assessed for heterogeneity and publication bias and adjusted for intrastudy clustering. RESULTS: The relative risk (RR) for PTSD in ADHD was 2.9 (P < .0005); in samples using healthy controls, the RR was 3.7 (P = .001); and in samples using traumatized controls, the RR was 1.6 (P = .003). The RR for ADHD in PTSD was 1.7 (P < .0005); in samples using traumatized controls, the RR was 2.1 (P
Published:
2016-01
Title:
Glucagon increases energy expenditure independently of brown adipose tissue activation in humans
Authors:
Salem, V.; Izzi‐Engbeaya, C.; Coello, C.; Thomas, D. B.; Chambers, E. S.; Comninos, A. N.; Buckley, A.; Win, Z.; Al‐Nahhas, A.; Rabiner, E. A.; Gunn, R. N.; Budge, H.; Symonds, M. E.; Bloom, S. R.; Tan, T. M.; Dhillo, W. S.
Abstract:
Published:
2016-01
Title:
Hyperfunctional Voice Disorder in Children With Attention Deficit Hyperactivity Disorder (ADHD). A Phenotypic Characteristic?
Authors:
Barona-Lleo, Luz; Fernandez, Secundino
Abstract:
OBJECTIVE: The purpose of this study was to detect specific vocal aerodynamic patterns in attention deficit hyperactivity disorder (ADHD) patients and to define a possible new phenotypic feature of this disorder that must be diagnosed and treated. STUDY DESIGN: This is a prospective study. METHODS: Seventy-nine children aged 5-13 years were recruited: 44 children with ADHD diagnosis and 35 children, as a control group, matched according to age and gender. All children were evaluated in the voice laboratory. Each subject repeated sustained vowels, syllables, words, and sentences several times. Intraoral pressure, transglottal airflow, microphone, and electroglottograph results were recorded and analyzed. Children affected by ADHD, with adequate tolerance, were evaluated endoscopically and by the speech therapist. RESULTS: The aerodynamic analysis shows that the subglottal pressure is higher and transglottal airflow is lower in ADHD children compared with the children of the control group. Those differences are statistically significant. The endoscopic physical examination showed vocal nodules in 25 children (78.125%) and hyperfunctional vocal behavior in all ADHD children studied. CONCLUSIONS: We proposed that every child with ADHD disorder must be evaluated from a laryngeal point of view (otolaryngologist and speech therapist) as an important part of the diagnosis and global treatment. It could be considered as a new phenotypic characteristic of this disorder.
Published:
2016-01
Title:
Insulin Pumps in Type 1 Diabetes with Mental Disorders: Real-Life Clinical Data Indicate Discrepancies to Recommendations
Authors:
Prinz, Nicole; Bächle, Christina; Becker, Marianne; Berger, Gabriele; Galler, Angela; Haberland, Holger; Meusers, Michael; Mirza, Joaquina; Plener, Paul L.; von Sengbusch, Simone; Thienelt, Michaela; Holl, Reinhard W.; DPV Initiative
Abstract:
BACKGROUND: The latest American Association of Clinical Endocrinologists/American College of Endocrinologists consensus statement published in 2014 does not recommend continuous subcutaneous insulin infusion (CSII) in patients with mental health problems. This study investigated the use and discontinuation of CSII in daily routine care of type 1 diabetes (T1D) patients with or without comorbid mental disorders. MATERIALS AND METHODS: Insulin-treated T1D patients (n = 48,700) between 5 and 30 years of age (median [interquartile range], 15.6 [12.0-17.7] years) from the German/Austrian diabetes patient follow-up registry (DPV) were studied. A comorbid diagnosis and/or specific treatment of mental disorder was documented in 3,158 (6.5%) patients: attention-deficit hyperactivity disorder (ADHD), n = 1,352; depression, n = 692; eating disorders, n = 395; needle phobia, n = 319; anxiety/obsessive compulsive disorder (OCD), n = 231; and psychosis and/or neuroleptic medication, n = 169. Multivariable logistic regression with age, sex, diabetes duration, and migration background as independent variables was used to compare groups. RESULTS: After adjustment for confounders, use of CSII was more common in patients with depression (41.5%), anxiety/OCD (41.4%), or needle phobia (75.8%) compared with patients without mental disorders (34.6%) (each P < 0.05). By contrast, psychotic patients (26.2%, P < 0.05) used CSII less often, and patients with ADHD (36.3%) or eating disorders (33.9%) used it with a similar frequency. Compared with patients without mental disorders (5.1%), the rate of CSII discontinuation was higher in patients with ADHD (9.7%), depression (8.2%), or eating disorders (10.0%) (P
Published:
2016-01
Title:
Mitochondrial quality control as a therapeutic target
Authors:
Suliman, Hagir B.; Piantadosi, Claude A.
Abstract:
In addition to oxidative phosphorylation (OXPHOS), mitochondria perform other functions such as heme biosynthesis and oxygen sensing and mediate calcium homeostasis, cell growth, and cell death. They participate in cell communication and regulation of inflammation and are important considerations in aging, drug toxicity, and pathogenesis. The cell's capacity to maintain its mitochondria involves intramitochondrial processes, such as heme and protein turnover, and those involving entire organelles, such as fusion, fission, selective mitochondrial macroautophagy (mitophagy), and mitochondrial biogenesis. The integration of these processes exemplifies mitochondrial quality control (QC), which is also important in cellular disorders ranging from primary mitochondrial genetic diseases to those that involve mitochondria secondarily, such as neurodegenerative, cardiovascular, inflammatory, and metabolic syndromes. Consequently, mitochondrial biology represents a potentially useful, but relatively unexploited area of therapeutic innovation. In patients with genetic OXPHOS disorders, the largest group of inborn errors of metabolism, effective therapies, apart from symptomatic and nutritional measures, are largely lacking. Moreover, the genetic and biochemical heterogeneity of these states is remarkably similar to those of certain acquired diseases characterized by metabolic and oxidative stress and displaying wide variability. This biologic variability reflects cell-specific and repair processes that complicate rational pharmacological approaches to both primary and secondary mitochondrial disorders. However, emerging concepts of mitochondrial turnover and dynamics along with new mitochondrial disease models are providing opportunities to develop and evaluate mitochondrial QC-based therapies. The goals of such therapies extend beyond amelioration of energy insufficiency and tissue loss and entail cell repair, cell replacement, and the prevention of fibrosis. This review summarizes current concepts of mitochondria as disease elements and outlines novel strategies to address mitochondrial dysfunction through the stimulation of mitochondrial biogenesis and quality control.
Published:
2016-01
Title:
Nerve growth factor (NGF) and pro-NGF increase low-density lipoprotein (LDL) receptors in neuronal cells partly by different mechanisms: role of LDL in neurite outgrowth
Authors:
Do, Hai Thi; Bruelle, Céline; Pham, Dan Duc; Jauhiainen, Matti; Eriksson, Ove; Korhonen, Laura T.; Lindholm, Dan
Abstract:
Published:
2016-01
Title:
Notch signaling dynamics in the adult healthy prostate and in prostatic tumor development
Authors:
Pedrosa, Ana-Rita; Graça, José L.; Carvalho, Sandra; Peleteiro, Maria C.; Duarte, António; Trindade, Alexandre
Abstract:
BACKGROUND: The Notch signaling pathway has been implicated in prostate development, maintenance and tumorigenesis by its key role in cell-fate determination, differentiation and proliferation. Therefore, we proposed to analyze Notch family members transcription and expression, including ligands (Dll1, 3, 4 and Jagged1 and 2), receptors (Notch1-4) and effectors (Hes1, 2, 5 and Hey1, 2, L), in both normal and tumor bearing mouse prostates to better understand the dynamics of Notch signaling in prostate tumorigenesis. METHODS: Wild type mice and transgenic adenocarcinoma of the mouse prostate model (TRAMP) mice were sacrificed at 18, 24 or 30 weeks of age and the prostates collected and processed for either whole prostate or prostate cell specific populations mRNA analysis and for protein expression analysis by immunohistochemistry and immunofluorescence. RESULTS: We observed that Dll1 and Dll4 are expressed in the luminal compartment of the mouse healthy prostate, whereas Jagged2 expression is restricted to the basal and stromal compartment. Additionally, Notch2 and Notch4 are normally expressed in the prostate luminal compartment while Notch2 and Notch3 are also expressed in the stromal layer of the healthy prostate. As prostate tumor development takes place, there is up-regulation of Notch components. Particularly, the prostate tumor lesions have increased expression of Jagged1 and 2, of Notch3 and of Hey1. We have also detected the presence of activated Notch3 in prostatic tumors that co-express Jagged1 and ultimately the Hey1 effector. CONCLUSIONS: Taken together our results point out the Notch axis Jagged1-2/Notch3/Hey1 to be important for prostate tumor development and worthy of additional functional studies and validation in human clinical disease.
Published:
2016-01
Title:
Reduced dietary intake of simple sugars alters perceived sweet taste intensity but not perceived pleasantness
Authors:
Wise, Paul M.; Nattress, Laura; Flammer, Linda J.; Beauchamp, Gary K.
Abstract:
BACKGROUND: Individuals who adhere to reduced-sodium diets come to prefer less salt over time, but it is unclear whether sweet taste perception is modulated by reduced sugar intake. OBJECTIVE: The objective was to determine how a substantial reduction in dietary intake of simple sugars affects sweetness intensity and pleasantness of sweet foods and beverages. DESIGN: Healthy men and women aged 21-54 y participated for 5 mo. After the baseline month, 2 subject groups were matched for demographic characteristics, body mass index, and intake of simple sugars. One group (n = 16; 13 of whom completed key experimental manipulations) was randomly assigned to receive a low-sugar diet during the subsequent 3 mo, with instructions to replace 40% of calories from simple sugars with fats, proteins, and complex carbohydrates. The other (control) group (n = 17; 16 of whom completed the study) did not change their sugar intake. During the final month, both groups chose any diet they wished. Each month subjects rated the sweetness intensity and pleasantness of vanilla puddings and raspberry beverages that varied in sucrose concentration. RESULTS: ANOVA showed no systematic differences between groups in rated sweetness during the baseline or first diet month. During the second diet month, the low-sugar group rated low-sucrose pudding samples as more intense than did the control group (significant group-by-concentration interaction, P = 0.002). During the third diet month, the low-sugar subjects rated both low and high concentrations in puddings as ∼40% sweeter than did the control group (significant effect of group, P = 0.01). A weaker effect on rated sweetness was obtained for the beverages. Rated pleasantness was not affected for either of the stimuli. CONCLUSIONS: This experiment provides empirical evidence that changes in consumption of simple sugars influence perceived sweet taste intensity. More work is needed to determine whether sugar intake ultimately shifts preferences for sweet foods and beverages. This trial was registered at clinicaltrials.gov as NCT02090478.
Published:
2016-01
Title:
The gut microbial community in metabolic syndrome patients is modified by diet
Authors:
Haro, Carmen; Garcia-Carpintero, Sonia; Alcala-Diaz, Juan F.; Gomez-Delgado, Francisco; Delgado-Lista, Javier; Perez-Martinez, Pablo; Rangel Zuñiga, Oriol A.; Quintana-Navarro, Gracia M.; Landa, Blanca B.; Clemente, Jose C.; Lopez-Miranda, Jose; Camargo, Antonio; Perez-Jimenez, Francisco
Abstract:
Published:
2016-01
Title:
Vegetarian Diets and Weight Reduction: a Meta-Analysis of Randomized Controlled Trials
Authors:
Huang, Ru-Yi; Huang, Chuan-Chin; Hu, Frank B.; Chavarro, Jorge E.
Abstract:
BACKGROUND: Vegetarian diets may promote weight loss, but evidence remains inconclusive. METHODS: PubMed, EMBASE and UpToDate databases were searched through September 22, 2014, and investigators extracted data regarding study characteristics and assessed study quality among selected randomized clinical trials. Population size, demographic (i.e., gender and age) and anthropometric (i.e., body mass index) characteristics, types of interventions, follow-up periods, and trial quality (Jadad score) were recorded. The net changes in body weight of subjects were analyzed and pooled after assessing heterogeneity with a random effects model. Subgroup analysis was performed based on type of vegetarian diet, type of energy restriction, study population, and follow-up period. RESULTS: Twelve randomized controlled trials were included, involving a total of 1151 subjects who received the intervention over a median duration of 18 weeks. Overall, individuals assigned to the vegetarian diet groups lost significantly more weight than those assigned to the non-vegetarian diet groups (weighted mean difference, -2.02 kg; 95 % confidence interval [CI]: -2.80 to -1.23). Subgroup analysis detected significant weight reduction in subjects consuming a vegan diet (-2.52 kg; 95 % CI: -3.02 to -1.98) and, to a lesser extent, in those given lacto-ovo-vegetarian diets (-1.48 kg; 95 % CI: -3.43 to 0.47). Studies on subjects consuming vegetarian diets with energy restriction (ER) revealed a significantly greater weight reduction (-2.21 kg; 95 % CI: -3.31 to -1.12) than those without ER (-1.66 kg; 95 % CI: -2.85 to -0.48). The weight loss for subjects with follow-up of
Published:
2016-01
Title:
Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial: Weight Loss-Diet and Insulin Resistance
Authors:
Gardner, Christopher D.; Offringa, Lisa C.; Hartle, Jennifer C.; Kapphahn, Kris; Cherin, Rise
Abstract:
Published:
2016-01
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