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1.  Cardiovascular risk factors as determinants of retinal and skin microvascular function: The Maastricht Study 
PLoS ONE  2017;12(10):e0187324.
Objective
Microvascular dysfunction is an important underlying mechanism of microvascular diseases. Determinants (age, sex, hypertension, dyslipidemia, hyperglycemia, obesity, and smoking) of macrovascular diseases affect large-artery endothelial function. These risk factors also associate with microvascular diseases. We hypothesized that they are also determinants of microvascular (endothelial) function.
Methods
In The Maastricht Study, a type 2 diabetes-enriched population-based cohort study (n = 1991, 51% men, aged 59.7±8.2 years), we determined microvascular function as flicker light-induced retinal arteriolar %-dilation and heat-induced skin %-hyperemia. Multiple linear regression analyses were used to assess the associations of cardiovascular risk factors (age, sex, waist circumference, total-to-high-density lipoprotein (HDL) cholesterol ratio, fasting plasma glucose (FPG), 24-h systolic blood pressure, and cigarette smoking) with retinal and skin microvascular function.
Results
In multivariate analyses, age and FPG were inversely associated with retinal and skin microvascular function (regression coefficients per standard deviation (SD) were -0.11SD (95%CI: -0.15;-0.06) and -0.12SD (-0.17;-0.07) for retinal arteriolar %-dilation and -0.10SD (-0.16;-0.05) and -0.11SD (-0.17;-0.06) for skin %-hyperemia, respectively. Men and current smokers had -0.43SD (-0.58;-0.27) and -0.32SD (-0.49;-0.15) lower skin %-hyperemia, respectively. 24-h systolic blood pressure, waist circumference, and total-to-HDL cholesterol ratio were not statistically significantly associated with these microvascular functions.
Conclusions
Associations between cardiovascular risk factors and retinal and skin microvascular function show a pattern that is partly similar to the associations between cardiovascular risk factors and macrovascular function. Impairment of microvascular function may constitute a pathway through which an adverse cardiovascular risk factor pattern may increase risk of diseases that are partly or wholly of microvascular origin.
doi:10.1371/journal.pone.0187324
PMCID: PMC5659678  PMID: 29077770
2.  Differences in biopsychosocial profiles of diabetes patients by level of glycaemic control and health-related quality of life: The Maastricht Study 
PLoS ONE  2017;12(7):e0182053.
Aims
Tailored, patient-centred innovations are needed in the care for persons with type 2 diabetes mellitus (T2DM), in particular those with insufficient glycaemic control. Therefore, this study sought to assess their biopsychosocial characteristics and explore whether distinct biopsychosocial profiles exist within this subpopulation, which differ in health-related quality of life (HRQoL).
Methods
Cross-sectional study based on data from The Maastricht Study, a population-based cohort study focused on the aetiology, pathophysiology, complications, and comorbidities of T2DM. We analysed associations and clustering of glycaemic control and HRQoL with 38 independent variables (i.e. biopsychosocial characteristics) in different subgroups and using descriptive analyses, latent class analysis (LCA), and logistic regressions.
Results
Included were 840 persons with T2DM, mostly men (68.6%) and with a mean age of 62.6 (±7.7) years. Mean HbA1c was 7.1% (±3.2%); 308 patients (36.7%) had insufficient glycaemic control (HbA1c>7.0% [53 mmol/mol]). Compared to those with sufficient control, these patients had a significantly worse-off status on multiple biopsychosocial factors, including self-efficacy, income, education and several health-related characteristics. Two ‘latent classes’ were identified in the insufficient glycaemic control subgroup: with low respectively high HRQoL. Of the two, the low HRQoL class comprised about one-fourth of patients and had a significantly worse biopsychosocial profile.
Conclusions
Insufficient glycaemic control, particularly in combination with low HRQoL, is associated with a generally worse biopsychosocial profile. Further research is needed into the complex and multidimensional causal pathways explored in this study, so as to increase our understanding of the heterogeneous care needs and preferences of persons with T2DM, and translate this knowledge into tailored care and support arrangements.
doi:10.1371/journal.pone.0182053
PMCID: PMC5531491  PMID: 28750026
3.  Troponin I and T in relation to cardiac injury detected with electrocardiography in a population-based cohort - The Maastricht Study 
Scientific Reports  2017;7:6610.
Interest in high-sensitivity cardiac troponin I(hs-cTnI) and T(hs-cTnT) has expanded from acute cardiac care to cardiovascular disease(CVD) risk stratification. Whether hs-cTnI and hs-cTnT are interchangeable in the ambulant setting is largely unexplored. Cardiac injury is a mechanism that may underlie the associations between troponin levels and mortality in the general population. In the population-based Maastricht Study, we assessed the correlation and concordance between hs-cTnI and hs-cTnT. Multiple regression analyses were conducted to assess the association of hs-cTnI and hs-cTnT with electrocardiographic (ECG) changes indicative of cardiac abnormalities. In 3016 eligible individuals(mean age,60 ± 8years;50.6%,men) we found a modest correlation between hs-cTnI and hs-cTnT(r = 0.585). After multiple adjustment, the association with ECG changes indicative of cardiac abnormalities was similar for both hs-cTn assays(OR,hs-cTnI:1.72,95%CI:1.40-2.10;OR,hs-cTnT:1.60,95%CI:1.22–2.11). The concordance of dichotomized hs-cTnI and hs-cTnT was κ = 0.397(≥sex-specific 75th percentile). Isolated high levels of hs-cTnI were associated with ECG changes indicative of cardiac abnormalities(OR:1.93,95%CI:1.01–3.68), whereas isolated high levels of hs-cTnT were not(OR:1.07,95%CI:0.49–2.31). In conclusion, there is a moderate correlation and limited concordance between hs-cTnI and hs-cTnT under non-acute conditions. These data suggest that associations of hs-cTnI and hs-cTnT with cardiac injury detected by ECG are driven by different mechanisms. This information may benefit future development of CVD risk stratification algorithms.
doi:10.1038/s41598-017-06978-3
PMCID: PMC5529453  PMID: 28747765
4.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
5.  World Congress Integrative Medicine & Health 2017: part three 
Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Parvizi, Mohammad M. | Handjani, Farhad | Zarshenas, Mohammad M. | Moein, Mahmood R. | Nimrouzi, Majid | Hatam, Gholamreza | Hasanzadeh, Jafar | Hamidizadeh, Nasrin | Parvizi, Mohammad M. | Heydari, Mojtaba | Namazi, Mohammad R. | Parvizi, Zahra | Pasalar, Mehdi | Mosaffa-Jahromi, Maryam | Bagheri-Lankarani, Kamran | Afsharypuor, Suleiman | Tamaddon, Ali M. | Ostovar, Mohadeseh | Peloni, Giuseppe | Bolliger, Ingo | Faria, Rui M. Da Cunha | Quadri, Pierluigi | Sanzeni, Wilma | Zemp, Damiano | Risvoll, Hilde | Giverhaug, Trude | Halvorsen, Kjell H. | Waaseth, Marit | Musial, Frauke | Rossi, Elio | Baccetti, Sonia | Picchi, Marco | Conti, Tommaso | Firenzuoli, Fabio | Guido, Carmelo | Bosco, Filippo | Guido, Carmelo | Rossi, Elio | Panozzo, Marialessandra | Picchi, Marco | Cervino, Chiara | Nurra, Linda | Rossi, Elio | Picchi, Marco | Firenzuoli, Fabio | Traversi, Antonella | Vuono, Katia | Sabatini, Federica | Bellandi, Tommaso | Rutert, Britta | Eggert, Angelika | Seifert, Georg | Stritter, Wiebke | Holmberg, Christine | Längler, Alfred | Salamonsen, Anita | Wiesener, Solveig | Schad, Friedemann | Steele, Megan | Kröz, Matthias | Matthes, Harald | Herbstreit, Cornelia | Thronicke, Anja | Schlingensiepen, Irene | von Schoen-Angerer, Tido | Schneider, Romy | Waeber, Livia | Vagedes, Jan | Kaczala, Gregor | Pharisa, Cosette | Wildhaber, Johannes | Huber, Benedikt | Sidorov, Pavel | Sovershaeva, Evgeniya | Simões-Wüst, Ana P. | Nietlispach, Anna | Mennet, Mónica | Schnelle, Martin | von Mandach, Ursula | Wang, Xia | Woo, Hye L. | Lee, Jin M. | Wu, Yuhao | Cho, Yumin | Yun, Younghee | Kim, Hyunho | Jung, Wonmo | Jang, Bo-Hyung | Ziea, Eric | Hui, Henny | Li, Mia | Tsui, Dora | Lam, Christine | Hsieh, Joyce | Chan, Edith | Balneaves, Lynda | Burnside, Sandra | Doyle, Ethel | Dorazio, Shelley | Chan, Pak K. | Bhagra, Anjali | Chen, Po-Hsu | Chung, Vincent C. H. | Wu, Justin C. Y. | Lin, Zhi X. | Wong, Wendy | Wu, Xin Y. | Ho, Robin S. T. | Wong, Charlene H. L. | Chan, Lily | Ziea, Eric T. C. | Elder, William | Cardarelli, Roberto | Kaspar, Cornelia | Kempenich, Robert | Kopferschmitt, Jacques | Marinko, Zulj | Damir, Sebo | Vcev, Aleksandar | Monezi, Ricardo | Ruggerini, Eny Márcia | Fuchigami, Ivna M. | Mazini, Ana C. Moreno | Monezi, Ricardo | Oliveira, Maria Waldenez | Papuga, Petar | Schloss, Janet | Steel, Amie | Jacobsen, Márcia da Silva | Monezi, Ricardo | Jacobsen, Miranda Rodrigo | Mangini, Maria T. | Trapani, Gianfranco | Di Giampietro, Tiziana | Zanino, Luisella | Ciullo, Luigi | Lanaro, Diego | Cerritelli, Francesco | Macrì, Francesco | Tsai, Andre | Lin, Chin | Wu, Tu-Hsing | D’Alessandro, Eduardo | Watts, Sam | Zhang, Ying | Wu, Xufang | Li, Xun | Fei, Yutong | Liu, Jianping | Zhao, Nanqi | Jia, Liyan | Yan, Xiaoyi | Zhen, Fei | Liu, Zhaolan | Liu, Jianping | Ahn, Jinhyang | Yun, Younghee | AlEidi, Sulaiman | Mohamed, Ashry Gad | Al-Beda, Abdullah M. | Abutalib, Raid A. | Khalil, Mohemmed K. M. | Amri, Hakima | Badekila, Sathyanarayana | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Shirooye, Pantea | Meybodi, Razie N. | Mokaberinejad, Roshanak | Tansaz, Mojgan | Mozaffarpour, Seyyedali | Chung, Vincent C. H. | Wu, Xin Y. | Wu, Justin C. Y. | Daneshfard, Babak | Hosseinkhani, Ayda | Tafazoli, Vahid | Jaladat, Amir M. | Jaladat, Amir M. | Sadeghi, Hasan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Larsen, Anette L. | Salamonsen, Anita | Kristoffersen, Agnete E. | Hamran, Torunn | Evjen, Bjørg | Stub, Trine | Li, Meiling | Cai, Jianxiong | Lu, Taoying | Yin, Lingjia | Wu, Darong | Wang, Lixin | Liew, Siaw M. | Liu, Tiegang | Bai, Chen | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Liu, Zhaolan | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Yang, Guoyan | Liu, Jianping | Mozaffarpour, Seyyedali | Behmanesh, Elham | Nimrouzi, Majid | Tafazoli, Vahid | Daneshfard, Babak | Ostrowski, Deja | Fox, Kealoha | Pasalar, Mehdi | Tabatabei, Fatemeh | Amini, Fatemeh | Sathasivampillai, Saravanan | Rajamanoharan, Pholtan | Munday, Michael | Heinrich, Michael | Scherrer, Yvonne M. | Heinrich, Michael | Szuter, Carolyn | Amini, Fatemeh | Tabatabaei, Fatemeh | Tavakoli, Ali | Tavakoli, Fatemeh | Pasalar, Mehdi | rostami, Mahsa | Torri, Maria C. | Szuter, Carolyn | Walach, Harald | Warner, Faith | Majumdar, Anne | Serasingh, Palitha | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Liu, Zhaolan | Liu, Jianping | Zhao, Nanqi | Zhen, Fei | Jia, Liyan | Yan, Xiaoyi | Liu, Zhaolan | Liu, Jianping | Abbing, Annemarie | Ponstein, Anne | Baars, Erik | Croke, Sarah | Hanser, Suzanne | Heckel, Viola | Krüerke, Daniel | Simões-Wüst, Ana P. | Weiss, Sebastian | Metzner, Susanne | Lee, Jang W. | Hyun, Min K. | Masetti, Morgana | Oepen, Renate | Gruber, Harald | Heusser, Peter | Pelz, Holger | Perlitz, Volker | Ponstein, Anne | Abbing, Annemarie | Baars, Erik | Robinson, Nicola | Ronan, Patricia | Mian, Awais | Madge, Su | Lorenc, Ava | Agent, Penny | Carr, Siobhan | Ronan, Patricia | Robinson, Nicola | Carr, Siobhan | Mian, Awais | Lorenc, Ava | Agent, Penny | Madge, Su | Winnubst, Monica E. | Monezi, Ricardo | Abolghasemi, Jafar | Heydari, Mojtaba | Baccetti, Sonia | Rossi, Elio | Fedi, Paolo | Di Stefano, Mariella | Belvedere, Katia | Baccetti, Sonia | Rossi, Elio | Firenzuoli, Fabio | Di Stefano, Mariella | Belvedere, Katia | Beaven, Katherine | Rose, Anita | Florschutz, Gerhard | Phil, Nicola Brough | Parsons, Helen | Stewart-Brown, Sarah | Burke, Katherine | Busch, Martine | Heyning, Fenna | Smit, Jan | Jeekel, Hans | de Goeij, Hans | Guido, Paulo Caceres | Barraza, Norma | Balbarrey, Ziomara | Ribas, Alejandra | Jimenez, Beatriz | Iachino, Claudia | Quattrone, Fabiana | Gaioli, Marisa | Dell’Orso, Marta | Villanueva, Silvia | Rocha, Carmen | Macchi, Adriana | Cai, Jianxiong | Chen, Lina | Wu, Darong | Wang, Sicheng | Choi, Eunji | Go, Namgyeong | Lee, Yongho | Dahal, Gokarna | Frauenknecht, Xaver | Gerhardt, Heike | Galanti, Mónica | Cerda, Carmen J. | Galanti, Mónica | Galanti, Mónica | Heckersdorf, Daniela Navarrete | Jorquera, Héctor | Saldivia, María L. Alcázar | Jakubonienė, Daiva | McEwen, Bradley | Melo, Francislete | Fontana, Fernanda Mulinari | Valle, Ana C. Viana | Neres, Maria T. Borges | Mohagheghzadeh, Abolali | Zohalinezhad, Mohammad E. | Njaradi, Olja | Dunjic, Momir | Njaradi, Olja | Dunjic, Momir | Ostrowski, Deja | Fox, Kealoha | Pokladnikova, Jitka | Selke-Krulichova, Iva | Seo, Jinsoon | Jang, Hyunchul | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | Tihanyi, Eva | Hegyi, Gabriella | Zhang, Ying | Li, Xun | Fei, Yutong | Liu, Jianping | Zhang, Ying | Liu, Jianping | Tong, Xiaolin
doi:10.1186/s12906-017-1784-2
PMCID: PMC5499100
6.  Sedentary Behavior Is Only Marginally Associated with Physical Function in Adults Aged 40–75 Years—the Maastricht Study 
Background: In an aging population, regular physical activity (PA) and exercise have been recognized as important factors in maintaining physical function and thereby preventing loss of independence and disability. However, (older) adults spent the majority of their day sedentary and therefore insight into the consequences of sedentary behavior on physical function, independent of PA, is warranted.
Objective: To examine the associations of objectively measured sedentary time (ST), patterns of sedentary behavior, overall PA, and higher intensity PA (HPA) with objective measures of physical function.
Methods: This is a cross-sectional study in 1,932 men and women (aged 40–75 years) participating in The Maastricht Study. The activPAL3 was used to assess daily sedentary behavior: ST (h), sedentary breaks (n), prolonged (≥30 min) sedentary bouts (n), and to assess time spent in (H)PA (h). Measures of physical function included: covered distance during a 6 min walk test [6MWD (meters)], timed chair rise stand test performance [TCSTtime (seconds)], grip strength (kg kg−1), and elbow flexion and knee extension strength (Nm kg−1). Linear regression analyses were used to examine associations between daily sedentary behavior and PA with physical function.
Results: Every additional hour ST was associated with shorter 6MWD [B = −2.69 m (95% CI = −4.69; −0.69)] and lower relative elbow extension strength (B = −0.01 Nm kg−1 (−0.02; 0.00). More sedentary breaks were associated with faster TCSTtime: B = −0.55 s (−0.85; −0.26). Longer average sedentary bout duration was associated with slower TCSTtime [B = 0.17 s (0.09; 0.25)] and lower knee extension strength [B = −0.01 Nm kg−1 (−0.02; 0.00)]. Every hour of PA and HPA were associated with greater 6MWD [BPA = 15.88 m (9.87; 21.89), BHPA = 40.72 m (30.18; 51.25)], faster TCSTtime [BPA = −0.55 s (−1.03; −0.07), BHPA = −2.25 s (−3.09; −1.41)], greater elbow flexion strength [BPA = 0.03 Nm kg−1 (0.01; 0.07)], [BHPA = 0.05 Nm kg−1 (0.01; 0.08)], and greater knee extension strength [BPA = 0.04 Nm kg−1 (0.01; 0.07)], [BHPA = 0.13 Nm kg−1 (0.06; 0.20)].
Conclusion: In adults aged 40–75 years, sedentary behavior appeared to be marginally associated with lower physical function, independent of HPA. This suggests that merely reducing sedentary behavior is insufficient to improve/maintain physical function. In contrast, engaging regularly in PA, in particular HPA, is important for physical function.
doi:10.3389/fphys.2017.00242
PMCID: PMC5403943
accelerometry; muscle strength; sedentary lifestyle; pattern; physical fitness
7.  The association of early life socioeconomic conditions with prediabetes and type 2 diabetes: results from the Maastricht study 
Background
Using cross-sectional data from The Maastricht Study, we examined the association of socioeconomic conditions in early life with prediabetes and T2DM in adulthood. We also examined potential mediating pathways via both adulthood socioeconomic conditions and adult BMI and health behaviours.
Methods
Of the 3263 participants (aged 40–75 years), 493 had prediabetes and 906 were diagnosed with T2DM. By using logistic regression analyses, the associations and possible mediating pathways were examined.
Results
Participants with low early life socioeconomic conditions had a 1.56 times higher odds of prediabetes (95% confidence interval (CI) = 1.21-2.02) and a 1.61 times higher odds of T2DM (95% CI = 1.31-1.99). The relation between low early life socioeconomic conditions and prediabetes was independent of current socioeconomic conditions (OR = 1.38, 95% CI = 1.05-1.80), whereas the relation with T2DM was not independent of current socioeconomic conditions (OR = 1.10, 95% CI = 0.87-1.37). BMI party mediated the association between early life socioeconomic conditions and prediabetes.
Conclusions
Socioeconomic inequalities starting in early life were associated with diabetes-related outcomes in adulthood and suggest the usefulness of early life interventions aimed at tackling these inequalities.
Electronic supplementary material
The online version of this article (doi:10.1186/s12939-017-0553-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s12939-017-0553-7
PMCID: PMC5382485  PMID: 28381297
Type 2 diabetes; Prediabetes; Childhood socioeconomic conditions; Adulthood socioeconomic conditions; Health behaviour; Obesity
8.  Associations of Dietary Glucose, Fructose, and Sucrose with β-Cell Function, Insulin Sensitivity, and Type 2 Diabetes in the Maastricht Study 
Nutrients  2017;9(4):380.
The associations of glucose, fructose, and sucrose intake with type 2 diabetes mellitus (T2DM) have been inconsistent. Furthermore, there is a lack of studies focusing on early markers of T2DM that provide insight into the process of T2DM progression: impaired pancreatic β-cell function (BCF) and insulin sensitivity. This study evaluated associations cross-sectionally in a population-based cohort consisting of 2818 individuals (mean ± SD age 59.7 ± 8.18, 49.5% male, n = 120 newly diagnosed T2DM). Glucose, fructose, and sucrose intake were assessed by a food frequency questionnaire. Glucose metabolism status, insulin sensitivity, and BCF were measured by a seven-points oral glucose tolerance test. Linear regression analysis revealed a positive association of glucose intake with insulin sensitivity in the fully adjusted model (standardized beta (95% CI) 0.07 (0.05, 0.14) SD for ≥23 g vs. <10 g of glucose). Fructose and sucrose intake were not associated with insulin sensitivity after full adjustments. In addition, no associations of dietary glucose, fructose, and sucrose with BCF were detected. In conclusion, higher intake of glucose, not fructose and sucrose, was associated with higher insulin sensitivity, independent of dietary fibre. No convincing evidence was found for associations of dietary glucose, fructose, and sucrose with BCF in this middle-aged population.
doi:10.3390/nu9040380
PMCID: PMC5409719  PMID: 28406435
beta-cell function; diet; fructose; glucose; insulin sensitivity; prediabetes; sucrose; type 2 diabetes
9.  Use of thiazolidinediones and the risk of elective hip or knee replacement: a population based case–control study 
Aims
Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs.
Methods
A population based case–control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 94 609) were defined as patients >18 years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use.
Results
There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR.
Conclusion
Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs.
doi:10.1111/bcp.12786
PMCID: PMC4833153  PMID: 26374732
arthroplasty; diabetes mellitus; glitazones; osteoarthritis; thiazolidinediones
10.  Severity of Diabetes Mellitus and Total Hip or Knee Replacement 
Medicine  2016;95(20):e3739.
Supplemental Digital Content is available in the text
Abstract
It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.
To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.
A population-based case–control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.
Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78–0.94)) and THR (OR = 0.90 (95% CI = 0.82–0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.
This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes.
doi:10.1097/MD.0000000000003739
PMCID: PMC4902440  PMID: 27196498
11.  Physical Activity and Sedentary Behavior in Metabolically Healthy versus Unhealthy Obese and Non-Obese Individuals – The Maastricht Study 
PLoS ONE  2016;11(5):e0154358.
Background
Both obesity and the metabolic syndrome are associated with increased risk of cardiovascular diseases and type 2 diabetes. Although both frequently occur together in the same individual, obesity and the metabolic syndrome can also develop independently from each other. The (patho)physiology of “metabolically healthy obese” (i.e. obese without metabolic syndrome) and “metabolically unhealthy non-obese” phenotypes (i.e. non-obese with metabolic syndrome) is not fully understood, but physical activity and sedentary behavior may play a role.
Objective
To examine objectively measured physical activity and sedentary behavior across four groups: I) “metabolically healthy obese” (MHO); II) “metabolically unhealthy obese” (MUO); III)”metabolically healthy non-obese” (MHNO); and IV) “metabolically unhealthy non-obese” (MUNO).
Methods
Data were available from 2,449 men and women aged 40–75 years who participated in The Maastricht Study from 2010 to 2013. Participants were classified into the four groups according to obesity (BMI≥30kg/m2) and metabolic syndrome (ATPIII definition). Daily activity was measured for 7 days with the activPAL physical activity monitor and classified as time spent sitting, standing, and stepping.
Results
In our study population, 562 individuals were obese. 19.4% of the obese individuals and 72.7% of the non-obese individuals was metabolically healthy. After adjustments for age, sex, educational level, smoking, alcohol use, waking time, T2DM, history of CVD and mobility limitation, MHO (n = 107) spent, per day, more time stepping (118.2 versus 105.2 min; p<0.01) and less time sedentary (563.5 versus 593.0 min., p = 0.02) than MUO (n = 440). In parallel, MHNO (n = 1384) spent more time stepping (125.0 versus 115.4 min; p<0.01) and less time sedentary (553.3 versus 576.6 min., p<0.01) than MUNO (n = 518).
Conclusion
Overall, the metabolically healthy groups were less sedentary and more physically active than the metabolically unhealthy groups. Therefore, physical activity and sedentary time may partly explain the presence of the metabolic syndrome in obese as well as non-obese individuals.
doi:10.1371/journal.pone.0154358
PMCID: PMC4854448  PMID: 27138596
12.  Associations of total amount and patterns of sedentary behaviour with type 2 diabetes and the metabolic syndrome: The Maastricht Study 
Diabetologia  2016;59:709-718.
Aims/hypothesis
The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome.
Methods
We included 2,497 participants (mean age 60.0 ± 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (≥30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses.
Results
Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome.
Conclusions/interpretation
An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings.
doi:10.1007/s00125-015-3861-8
PMCID: PMC4779127  PMID: 26831300
Accelerometry; Diabetes mellitus type 2; Metabolic syndrome; Sedentary bouts; Sedentary breaks; Sedentary lifestyle; Sedentary time
13.  Psychological and personality factors in type 2 diabetes mellitus, presenting the rationale and exploratory results from The Maastricht Study, a population-based cohort study 
BMC Psychiatry  2016;16:17.
Background
Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice.
Methods
We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level.
Results
Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83–3.60), 1.50 (0.72–3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23–3.10), 1.35 (0.93–1.94) and 1.70 (1.14–2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small.
Conclusions
Individuals with type 2 diabetes experience more psychological distress and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes.
doi:10.1186/s12888-016-0722-z
PMCID: PMC4728860  PMID: 26817600
Type 2 diabetes; Cohort; Design; Exploratory results; Depression; Anxiety; Personality
14.  Identification of antithrombotic drugs related to total joint replacement using anonymised free-text notes: a search strategy in the Clinical Practice Research Datalink 
BMJ Open  2015;5(11):e009017.
Objectives
We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD).
Setting
General practice database representative of the UK.
Participants
All patients undergoing total hip replacement (THR, n=25 898) or total knee replacement (TKR, n=22 231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data.
Primary and secondary outcome measures
Internal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics.
Results
PPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use.
Conclusions
We have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery.
doi:10.1136/bmjopen-2015-009017
PMCID: PMC4679841  PMID: 26621515
STATISTICS & RESEARCH METHODS; ORTHOPAEDIC & TRAUMA SURGERY; EPIDEMIOLOGY
15.  Vegetarianism, low meat consumption and the risk of colorectal cancer in a population based cohort study 
Scientific Reports  2015;5:13484.
To study how a vegetarian or low meat diet influences the risk of colorectal cancer compared to a high meat diet, and to assess the explanatory role of factors associated with these diets. In the Netherlands Cohort Study – Meat Investigation Cohort (NLCS-MIC) (cohort of 10,210 individuals including 1040 self-defined vegetarians), subjects completed a baseline questionnaire in 1986, based on which they were classified into vegetarians (n = 635), pescetarians (n = 360), 1 day/week- (n = 1259), 2–5 day/week- (n = 2703), and 6-7 day/week meat consumers (n = 5253). After 20.3 years of follow-up, 437 colorectal cancer cases (307 colon, 92 rectal) were available. A non-significantly decreased risk of CRC for vegetarians, pescetarians, and 1 day/week compared to 6-7 day/week meat consumers was observed (age/sex adjusted Hazard Ratios (HR): 0.73(0.47–1.13), 0.80(0.47–1.39), and 0.72(0.52–1.00), respectively). Most of the differences in HR between these groups could be explained by intake of dietary fiber and soy products. Other (non-)dietary factors characteristic for a vegetarian or low meat diet had negligible individual effects, but attenuated the HRs towards the null when combined. Vegetarians, pescetarians, and 1 day/week meat eaters showed a non-significantly decreased risk of colorectal cancer compared to 6-7 day/week meat consumers, mainly due to differences in dietary pattern other than meat intake.
doi:10.1038/srep13484
PMCID: PMC4551995  PMID: 26316135
16.  The Effectiveness of Lifestyle Triple P in the Netherlands: A Randomized Controlled Trial 
PLoS ONE  2015;10(4):e0122240.
Introduction
Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands.
Method
We used a parallel randomized controlled design to test the effectiveness of the intervention. In total, 86 child-parent triads (children 4–8 years old, overweight or obese) were recruited and randomly assigned (allocation ratio 1:1) to the Lifestyle Triple P intervention or the control condition. Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions. Primary outcome measure was the children’s body composition (BMI z-scores, waist circumference and skinfolds). The research assistant who performed the measurements was blinded for group assignment. Secondary outcome measures were the children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, and parental self-efficacy. Outcome measures were assessed at baseline and 4 months (short-term) and 12 months (long-term) after baseline. Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures.
Results
No intervention effects were found on children’s body composition. Analyses of secondary outcomes showed positive short-term intervention effects on children’s soft-drink consumption and parental responsibility regarding physical activity, encouragement to eat, psychological control, and efficacy and satisfaction with parenting. Longer-term intervention effects were found on parent’s report of children’s time spent on sedentary behavior and playing outside, parental monitoring food intake, and responsibility regarding nutrition.
Conclusion
Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures, no effects were visible on children’s body composition or objectively measured physical activity. Several adjustments of the intervention content are recommended, for example including a booster session.
Trial Registration
Nederlands Trial Register NTR 2555
doi:10.1371/journal.pone.0122240
PMCID: PMC4388496  PMID: 25849523
17.  Parental perception of child’s weight status and subsequent BMIz change: the KOALA birth cohort study 
BMC Public Health  2014;14:291.
Background
Parents often fail to correctly perceive their children’s weight status, but no studies have examined the association between parental weight status perception and longitudinal BMIz change (BMI standardized to a reference population) at various ages. We investigated whether parents are able to accurately perceive their child’s weight status at age 5. We also investigated predictors of accurate weight status perception. Finally, we investigated the predictive value of accurate weight status perception in explaining children’s longitudinal weight development up to the age of 9, in children who were overweight at the age of 5.
Methods
We used longitudinal data from the KOALA Birth Cohort Study. At the child’s age of 5 years, parents filled out a questionnaire regarding child and parent characteristics and their perception of their child’s weight status. We calculated the children’s actual weight status from parental reports of weight and height at ages 2, 5, 6, 7, 8, and 9 years. Regression analyses were used to identify factors predicting which parents accurately perceived their child’s weight status. Finally, regression analyses were used to predict subsequent longitudinal BMIz change in overweight children.
Results
Eighty-five percent of the parents of overweight children underestimated their child’s weight status at age 5. The child’s BMIz at age 2 and 5 were significant positive predictors of accurate weight status perception (vs. underestimation) in normal weight and overweight children. Accurate weight status perception was a predictor of higher future BMI in overweight children, corrected for actual BMI at baseline.
Conclusions
Children of parents who accurately perceived their child’s weight status had a higher BMI over time, probably making it easier for parents to correctly perceive their child’s overweight. Parental awareness of the child’s overweight as such may not be sufficient for subsequent weight management by the parents, implying that parents who recognize their child’s overweight may not be able or willing to adequately manage the overweight.
doi:10.1186/1471-2458-14-291
PMCID: PMC3983903  PMID: 24678601
Body Mass Index; Children; Overweight; Parents; Weight Perception
18.  The Netherlands Cohort Study – Meat Investigation Cohort; a population-based cohort over-represented with vegetarians, pescetarians and low meat consumers 
Nutrition Journal  2013;12:156.
Background
Vegetarian diets have been associated with lower risk of chronic disease, but little is known about the health effects of low meat diets and the reliability of self-reported vegetarian status. We aimed to establish an analytical cohort over-represented with vegetarians, pescetarians and 1 day/week meat consumers, and to describe their lifestyle and dietary characteristics. In addition, we were able to compare self-reported vegetarians with vegetarians whose status has been confirmed by their response on the extensive food frequency questionnaire (FFQ).
Study methods
Embedded within the Netherlands Cohort Study (n = 120,852; including 1150 self-reported vegetarians), the NLCS-Meat Investigation Cohort (NLCS-MIC) was defined by combining all FFQ-confirmed-vegetarians (n = 702), pescetarians (n = 394), and 1 day/week meat consumers (n = 1,396) from the total cohort with a random sample of 2–5 days/week- and 6–7 days/week meat consumers (n = 2,965 and 5,648, respectively).
Results
Vegetarians, pescetarians, and 1 day/week meat consumers had more favorable dietary intakes (e.g. higher fiber/vegetables) and lifestyle characteristics (e.g. lower smoking rates) compared to regular meat consumers in both sexes. Vegetarians adhered to their diet longer than pescetarians and 1 day/week meat consumers. 75% of vegetarians with a prevalent cancer at baseline had changed to this diet after diagnosis. 50% of self-reported vegetarians reported meat or fish consumption on the FFQ. Although the misclassification that occurred in terms of diet and lifestyle when merely relying on self-reporting was relatively small, the impact on associations with disease risk remains to be studied.
Conclusion
We established an analytical cohort over-represented with persons at the lower end of the meat consumption spectrum which should facilitate prospective studies of major cancers and causes of death using ≥20.3 years of follow-up.
doi:10.1186/1475-2891-12-156
PMCID: PMC4220685  PMID: 24289207
Vegetarian; Low meat diet; Cohort; Self-report; FFQ
19.  Parental self-efficacy in childhood overweight: validation of the Lifestyle Behavior Checklist in the Netherlands 
Background
Evaluating whether parental challenges and self-efficacy toward managing children’s lifestyle behaviors are successfully addressed by interventions requires valid instruments. The Lifestyle Behavior Checklist (LBC) has recently been developed in the Australian context. It consists of two subscales: the Problem scale, which measures parental perceptions of children’s behavioral problems related to overweight and obesity, and the Confidence scale, measuring parental self-efficacy in dealing with these problems. The aim of the current study was to systematically translate the questionnaire into Dutch and to evaluate its internal consistency, construct validity and test-retest reliability.
Methods
The LBC was systematically translated by four experts at Maastricht University. In total, 392 parents of 3-to13-year-old children were invited to fill out two successive online questionnaires with a two-week interval. Of these, 273 parents responded to the first questionnaire (test, response rate = 69.6%), and of the 202 who could be invited for the second questionnaire (retest), 100 responded (response rate = 49.5%). We assessed the questionnaire’s internal consistency (Cronbach’s α), construct validity (Spearman’s Rho correlation tests, using the criterion measures: restrictiveness, nurturance, and psychological control), and test-retest reliability (Spearman’s Rho correlation tests).
Results
Both scales had high internal consistency (Cronbach’s α ≥ 0.90). Spearman correlation coefficients indicated acceptable test-retest reliability for both the Problem scale (rs = 0.74) and the Confidence scale (rs = 0.70). The LBC Problem scale was significantly correlated to all criterion scales (nurturance, restrictiveness, psychological control) in the hypothesized direction, and the LBC Confidence scale was significantly correlated with nurturance and psychological control in the hypothesized direction, but not with restrictiveness.
Conclusions
The Dutch translation of the LBC was found to be a reliable and reasonably valid questionnaire to measure parental perceptions of children’s weight-related problem behavior and the extent to which parents feel confident to manage these problems.
doi:10.1186/1479-5868-10-7
PMCID: PMC3626773  PMID: 23331330
Childhood obesity; Parenting; Self-efficacy; Validation
20.  The P2X7 loss-of-function Glu496Ala polymorphism affects ex vivo cytokine release and protects against the cytotoxic effects of high ATP-levels 
BMC Immunology  2012;13:64.
Background
The P2X7 receptor plays an important role in cytokine release during the inflammatory response in vivo. Polymorphisms within the P2X7 receptor gene that lead to loss of receptor function may contribute to impaired cytokine release by immune cells. Therefore, we investigated whether a known loss-of-function polymorphism (Glu496Ala) in the P2X7 receptor gene leads to alterations in cytokine release in response to ATP.
Results
An ex vivo whole blood model was used to induce an inflammatory reaction with the pro-inflammatory stimuli LPS and PHA (phytohemagglutinin). Blood from n=9 subjects with the Glu496Ala P2X7 SNP (P2X7MUT) and n=7 ‘wild-type’ subjects (no P2X7 SNP; P2X7WT) was used.
Addition of ATP (0.9-3 mM) to LPS/PHA-stimulated whole blood induced an increase in IL-1β release in P2X7MUT subjects, whereas decreased release was observed in P2X7WT subjects. Decreased levels of IL-6 and TNF-α in response to ATP were shown in both P2X7MUT and P2X7WT subjects, which was less pronounced in P2X7MUT subjects. ATP at 3 mM also significantly decreased levels of lactate dehydrogenase (LDH) in P2X7MUT subjects compared to P2X7WT subjects.
Conclusions
The presence of the non-synonymous Glu496Ala loss-of-function polymorphism within the P2X7 receptor gene is likely to be of importance in the release of cytokines during inflammation. Furthermore, this study suggests that carriers of the Glu496Ala loss-of-function polymorphism are protected against the cytotoxic effects of high ATP-levels.
doi:10.1186/1471-2172-13-64
PMCID: PMC3526505  PMID: 23210974
ATP; P2X7; Polymorphism; Inflammation
21.  Association of P2Y2 receptor SNPs with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients 
Purinergic Signalling  2012;9(1):41-49.
The P2Y2 receptor is a G-protein-coupled receptor with adenosine 5′-triphosphate (and UTP) as natural ligands. It is thought to be involved in bone physiology in an anti-osteogenic manner. As several non-synonymous single nucleotide polymorphisms (SNPs) have been identified within the P2Y2 receptor gene in humans, we examined associations between genetic variations in the P2Y2 receptor gene and bone mineral density (BMD) (i.e., osteoporosis risk), in a cohort of fracture patients. Six hundred and ninety women and 231 men aged ≥50 years, visiting an osteoporosis outpatient clinic at Maastricht University Medical Centre for standard medical follow-up after a recent fracture, were genotyped for three non-synonymous P2Y2 receptor gene SNPs. BMD was measured at three locations (total hip, lumbar spine, and femoral neck) using dual-energy X-ray absorptiometry. Differences in BMD between different genotypes were tested using analysis of covariance. In women, BMD values at all sites were significantly different between the genotypes for the Leu46Pro polymorphism, with women homozygous for the variant allele showing the highest BMD values (0.05 > p > 0.01). The Arg312Ser and Arg334Cys polymorphisms showed no differences in BMD values between the different genotypes. This is the first report that describes the association between the Leu46Pro polymorphism of the human P2Y2 receptor and the risk of osteoporosis.
doi:10.1007/s11302-012-9326-3
PMCID: PMC3568433  PMID: 22773251
P2Y2 receptor; Osteoporosis; Bone mineral density; Polymorphisms
22.  Transoral incisionless fundoplication for treatment of gastroesophageal reflux disease in clinical practice 
Surgical Endoscopy  2012;26(11):3307-3315.
Background
Transoral incisionless fundoplication is a recently introduced endoluminal technique for the treatment of gastroesophageal reflux disease (GERD). The objective of this study was to determine outcomes in chronic GERD patients who were referred for surgical management.
Methods
A cohort of 38 patients underwent transoral incisionless fundoplication (TIF) in a tertiary care setting. Pre- and post-procedure assessment included GERD-related quality of life questionnaires, proton pump inhibitor (PPI) usage, 24-h pH measurements, upper gastrointestinal endoscopy, esophageal manometry, and registration of adverse events. Duration of follow-up was 36 months.
Results
Gastroesophageal valves were constructed of 4 cm (range, 4–6) in length and 220° (range, 180–240) in circumference. One serious adverse event occurred, consisting of intraluminal bleeding at a fastener site. Hiatal hernia was completely reduced in 56 % and esophagitis was cured in 47 % of patients. Postprocedure esophageal acid exposure did not significantly improve (p > 0.05). At 36 (range, 29–41) months follow-up 14 patients (36 %) had undergone revisional laparoscopic fundoplication. Quality of life scores of the remaining cohort showed significant improvement (p < 0.0001) and daily use of antisecretory medication was discontinued by 74 %.
Conclusions
Endoluminal fundoplication improved quality of life and reduced the need for PPIs in only a subgroup of patients at 3 years follow-up. The amount of patients requiring additional medication and revisional surgery was high.
doi:10.1007/s00464-012-2324-2
PMCID: PMC3472060  PMID: 22648098
Endoscopy; Fundoplication; GERD
23.  Barriers to successful recruitment of parents of overweight children for an obesity prevention intervention: a qualitative study among youth health care professionals 
BMC Family Practice  2012;13:37.
Background
The recruitment of participants for childhood overweight and obesity prevention interventions can be challenging. The goal of this study was to identify barriers that Dutch youth health care (YHC) professionals perceive when referring parents of overweight children to an obesity prevention intervention.
Methods
Sixteen YHC professionals (nurses, physicians and management staff) from eleven child health clinics participated in semi-structured interviews. An intervention implementation model was used as the framework for conducting, analyzing and interpreting the interviews.
Results
All YHC professionals were concerned about childhood obesity and perceived prevention of overweight and obesity as an important task of the YHC organization. In terms of frequency and perceived impact, the most important impeding factors for referring parents of overweight children to an intervention were denial of the overweight problem by parents and their resistance towards discussing weight issues. A few YHC professionals indicated that their communication skills in discussing weight issues could be improved, and some professionals mentioned that they had low self-efficacy in raising this topic.
Conclusions
We consider it important that YHC professionals receive more training to increase their self-efficacy and skills in motivating parents of overweight children to participate in obesity prevention interventions. Furthermore, parental awareness towards their child’s overweight should be addressed in future studies.
doi:10.1186/1471-2296-13-37
PMCID: PMC3403855  PMID: 22591134
24.  Adenosine 5′-triphosphate (ATP) supplements are not orally bioavailable: a randomized, placebo-controlled cross-over trial in healthy humans 
Background
Nutritional supplements designed to increase adenosine 5′-triphosphate (ATP) concentrations are commonly used by athletes as ergogenic aids. ATP is the primary source of energy for the cells, and supplementation may enhance the ability to maintain high ATP turnover during high-intensity exercise. Oral ATP supplements have beneficial effects in some but not all studies examining physical performance. One of the remaining questions is whether orally administered ATP is bioavailable. We investigated whether acute supplementation with oral ATP administered as enteric-coated pellets led to increased concentrations of ATP or its metabolites in the circulation.
Methods
Eight healthy volunteers participated in a cross-over study. Participants were given in random order single doses of 5000 mg ATP or placebo. To prevent degradation of ATP in the acidic environment of the stomach, the supplement was administered via two types of pH-sensitive, enteric-coated pellets (targeted at release in the proximal or distal small intestine), or via a naso-duodenal tube. Blood ATP and metabolite concentrations were monitored by HPLC for 4.5 h (naso-duodenal tube) or 7 h (pellets) post-administration. Areas under the concentration vs. time curve were calculated and compared by paired-samples t-tests.
Results
ATP concentrations in blood did not increase after ATP supplementation via enteric-coated pellets or naso-duodenal tube. In contrast, concentrations of the final catabolic product of ATP, uric acid, were significantly increased compared to placebo by ~50% after administration via proximal-release pellets (P = 0.003) and naso-duodenal tube (P = 0.001), but not after administration via distal-release pellets.
Conclusions
A single dose of orally administered ATP is not bioavailable, and this may explain why several studies did not find ergogenic effects of oral ATP supplementation. On the other hand, increases in uric acid after release of ATP in the proximal part of the small intestine suggest that ATP or one of its metabolites is absorbed and metabolized. Uric acid itself may have ergogenic effects, but this needs further study. Also, more studies are needed to determine whether chronic administration of ATP will enhance its oral bioavailability.
doi:10.1186/1550-2783-9-16
PMCID: PMC3441280  PMID: 22510240
ATP; Metabolism; Nutritional supplement; Bioavailability; Gastrointestinal transit; Multi-particulate supplement
25.  Lifestyle Triple P: a parenting intervention for childhood obesity 
BMC Public Health  2012;12:267.
Background
Reversing the obesity epidemic requires the development and evaluation of childhood obesity intervention programs. Lifestyle Triple P is a parent-focused group program that addresses three topics: nutrition, physical activity, and positive parenting. Australian research has established the efficacy of Lifestyle Triple P, which aims to prevent excessive weight gain in overweight and obese children. The aim of the current randomized controlled trial is to assess the effectiveness of the Lifestyle Triple P intervention when applied to Dutch parents of overweight and obese children aged 4–8 years. This effectiveness study is called GO4fit.
Methods/Design
Parents of overweight and obese children are being randomized to either the intervention or the control group. Those assigned to the intervention condition receive the 14-week Lifestyle Triple P intervention, in which they learn a range of nutritional, physical activity and positive parenting strategies. Parents in the control group receive two brochures, web-based tailored advice, and suggestions for exercises to increase active playing at home. Measurements are taken at baseline, directly after the intervention, and at one year follow-up. Primary outcome measure is the children’s body composition, operationalized as BMI z-score, waist circumference, and fat mass (biceps and triceps skinfolds). Secondary outcome measures are children’s dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, parental self-efficacy, and body composition of family members (parents and siblings).
Discussion
Our intervention is characterized by a focus on changing general parenting styles, in addition to focusing on changing specific parenting practices, as obesity interventions typically do. Strengths of the current study are the randomized design, the long-term follow-up, and the broad range of both self-reported and objectively measured outcomes.
Trial Registration
Current Controlled Trials NTR 2555
MEC AzM/UM
NL 31988.068.10 / MEC 10-3-052
doi:10.1186/1471-2458-12-267
PMCID: PMC3408381  PMID: 22471971

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