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1. Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study.

Author

Beran, Magdalena, van Gennip, April, Stehouwer, Coen, Jansen, Jacobus, Gupta, Monideepa, Houben, Alfons, Berendschot, Tos, Webers, Carroll, Wesselius, Anke, Schalkwijk, Casper, Backes, Walter, de Jong, Joost, van der Kallen, Carla, van Greevenbroek, Marleen, Köhler, Sebastian, Vonk, Jet, Geerlings, Mirjam, Schram, Miranda, and van Sloten, Thomas

Subjects
cerebral microcirculation, cohort, diffusion tensor imaging, microvascular dysfunction, white matter connectivity, Humans, Female, Middle Aged, Aged, Male, White Matter, Cross-Sectional Studies, Brain, Diffusion Magnetic Resonance Imaging, Biomarkers
Abstract

BACKGROUND: Microvascular dysfunction is involved in the development of various cerebral disorders. It may contribute to these disorders by disrupting white matter tracts and altering brain connectivity, but evidence is scarce. We investigated the association between multiple biomarkers of microvascular function and whole-brain white matter connectivity. METHODS AND RESULTS: Cross-sectional data from The Maastricht Study, a Dutch population-based cohort (n=4326; age, 59.4±8.6 years; 49.7% women). Measures of microvascular function included urinary albumin excretion, central retinal arteriolar and venular calibers, composite scores of flicker light-induced retinal arteriolar and venular dilation, and plasma biomarkers of endothelial dysfunction (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and von Willebrand factor). White matter connectivity was calculated from 3T diffusion magnetic resonance imaging to quantify the number (average node degree) and organization (characteristic path length, global efficiency, clustering coefficient, and local efficiency) of white matter connections. A higher plasma biomarkers of endothelial dysfunction composite score was associated with a longer characteristic path length (β per SD, 0.066 [95% CI, 0.017-0.114]) after adjustment for sociodemographic, lifestyle, and cardiovascular factors but not with any of the other white matter connectivity measures. After multiple comparison correction, this association was nonsignificant. None of the other microvascular function measures were associated with any of the connectivity measures. CONCLUSIONS: These findings suggest that microvascular dysfunction as measured by indirect markers is not associated with whole-brain white matter connectivity.

Published
2024

2. Disease severity-based subgrouping of type 2 diabetes does not parallel differences in quality of life: the Maastricht Study

Author

Werkman, Nikki C. C., García-Sáez, Gema, Nielen, Johannes T. H., Tapia-Galisteo, Jose, Somolinos-Simón, Francisco J., Hernando, Maria E., Wang, Junfeng, Jiu, Li, Goettsch, Wim G., van der Kallen, Carla J. H., Koster, Annemarie, Schalkwijk, Casper G., de Vries, Hein, de Vries, Nanne K., Eussen, Simone J. P. M., Driessen, Johanna H. M., and Stehouwer, Coen D. A.

Published
2024
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3. (Pre)diabetes and a higher level of glycaemic measures are continuously associated with corneal neurodegeneration assessed by corneal confocal microscopy: the Maastricht Study

Author

Mokhtar, Sara B. A., van der Heide, Frank C. T., Oyaert, Karel A. M., van der Kallen, Carla J. H., Berendschot, Tos T. J. M., Scarpa, Fabio, Colonna, Alessia, de Galan, Bastiaan E., van Greevenbroek, Marleen M. J., Dagnelie, Pieter C., Schalkwijk, Casper G., Nuijts, Rudy M. M. A., Schaper, Nicolaas C., Kroon, Abraham A., Schram, Miranda T., Webers, Carroll A. B., and Stehouwer, Coen D. A.

Published
2023
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6. Alcohol consumption and microvascular dysfunction: a J-shaped association: The Maastricht Study

Author

van der Heide, Frank C. T., Eussen, Simone J. P. M., Houben, Alfons J. H. M., Henry, Ronald M. A., Kroon, Abraham A., van der Kallen, Carla J. H., Dagnelie, Pieter C., van Dongen, Martien C. J. M., Berendschot, Tos T. J. M., Schouten, Jan S. A. G., Webers, Carroll A. B., van Greevenbroek, Marleen M. J., Wesselius, Anke, Schalkwijk, Casper G., Koster, Annemarie, Jansen, Jacobus F. A., Backes, Walter H., Beulens, Joline W. J., and Stehouwer, Coen D. A.

Published
2023
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7. Lower heart rate variability, an index of worse autonomic function, is associated with worse beta cell response to a glycemic load in vivo—The Maastricht Study

Author

Rinaldi, Elisabetta, van der Heide, Frank CT, Bonora, Enzo, Trombetta, Maddalena, Zusi, Chiara, Kroon, Abraham A, Schram, Miranda T, van der Kallen, Carla JH, Wesselius, Anke, Bonadonna, Riccardo, Mari, Andrea, Schalkwijk, Casper G, van Greevenbroek, Marleen MJ, and Stehouwer, Coen DA

Published
2023
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8. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Heijmans, Bastiaan, ’t Hoen, Peter, van Meurs, Joyce, Jansen, Rick, Franke, Lude, Boomsma, Dorret, Pool, René, van Dongen, Jenny, Hottenga, Jouke, van Greevenbroek, Marleen, Stehouwer, Coen, van der Kallen, Carla, Schalkwijk, Casper, Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje, Slagboom, P. Eline, Beekman, Marian, Deelen, Joris, Van Heemst, Diana, Veldink, Jan, van den Berg, Leonard, van Duijn, Cornelia, Hofman, Bert, Isaacs, Aaron, Uitterlinden, André, Jhamai, P. Mila, Verbiest, Michael, Suchiman, H. Eka, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, Zhernakova, Dasha, van ‘t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Luijk, René, Bonder, Marc, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon, Swertz, Morris, van Zwet, Erik, Hoang, Thanh T., Lee, Yunsung, McCartney, Daniel L., Kersten, Elin T.G., Page, Christian M., Hulls, Paige M., Lee, Mikyeong, Walker, Rosie M., Breeze, Charles E., Bennett, Brian D., Burkholder, Adam B., Ward, James, Brantsæter, Anne Lise, Caspersen, Ida H., Motsinger-Reif, Alison A., Richards, Marie, White, Julie D., Zhao, Shanshan, Richmond, Rebecca C., Magnus, Maria C., Koppelman, Gerard H., Evans, Kathryn L., Marioni, Riccardo E., Håberg, Siri E., and London, Stephanie J.

Published
2024
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9. Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

Author

Tore, Elena C., Elshorbagy, Amany K., Bakers, Frans C. H., Brouwers, Martijn C. G. J., Dagnelie, Pieter C., Eussen, Simone J. P. M., Jansen, Jacobus F. A., Kooi, M. Eline, Kusters, Yvo H. A. M., Meex, Steven J. R., Olsen, Thomas, Refsum, Helga, Retterstøl, Kjetil, Schalkwijk, Casper G., Stehouwer, Coen D. A., Vinknes, Kathrine J., and van Greevenbroek, Marleen M. J.

Published
2023
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12. Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation

Author

Wölfel, Eva M, Schmidt, Felix N, vom Scheidt, Annika, Siebels, Anna K, Wulff, Birgit, Mushumba, Herbert, Ondruschka, Benjamin, Püschel, Klaus, Scheijen, Jean, Schalkwijk, Casper G, Vettorazzi, Eik, Jähn‐Rickert, Katharina, Gludovatz, Bernd, Schaible, Eric, Amling, Michael, Rauner, Martina, Hofbauer, Lorenz C, Zimmermann, Elizabeth A, and Busse, Björn

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Autoimmune Disease, Women's Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Male, Humans, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Glycation End Products, Advanced, Bone and Bones, Collagen, advanced glycation end-products, bone quality, collagen deformation, cortical bone, diabetes mellitus, Biological Sciences, Engineering, Medical and Health Sciences, Anatomy & Morphology, Biological sciences, Biomedical and clinical sciences
Abstract

Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case-control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic controls (n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2020

17. Sedentary behaviour and physical activity are associated with biomarkers of endothelial dysfunction and low-grade inflammation—relevance for (pre)diabetes: The Maastricht Study

Author

Vandercappellen, Evelien J., Koster, Annemarie, Savelberg, Hans H. C. M., Eussen, Simone J. P. M., Dagnelie, Pieter C., Schaper, Nicolaas C., Schram, Miranda T., van der Kallen, Carla J. H., van Greevenbroek, Marleen M. J., Wesselius, Anke, Schalkwijk, Casper G., Kroon, Abraham A., Henry, Ronald M. A., and Stehouwer, Coen D. A.

Published
2022
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23. (Pre)diabetes, glycemia, and daily glucose variability are associated with retinal nerve fiber layer thickness in The Maastricht Study

Author

van der Heide, Frank C. T., Foreman, Yuri D., Franken, Iris W. M., Henry, Ronald M. A., Kroon, Abraham A., Dagnelie, Pieter C., Eussen, Simone J. P. M., Berendschot, Tos T. J. M., Schouten, Jan S. A. G., Webers, Carroll A. B., Schram, Miranda T., van der Kallen, Carla J. H., van Greevenbroek, Marleen M. J., Wesselius, Anke, Schalkwijk, Casper G., Schaper, Nicolaas C., Brouwers, Martijn C. G. J., and Stehouwer, Coen D. A.

Published
2022
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24. Pyridoxamine Alleviates Cardiac Fibrosis and Oxidative Stress in Western Diet-Induced Prediabetic Rats.

Author

D'Haese, Sarah, Claes, Lisa, Jaeken, Eva, Deluyker, Dorien, Evens, Lize, Heeren, Ellen, Haesen, Sibren, Vastmans, Lotte, Lambrichts, Ivo, Wouters, Kristiaan, Schalkwijk, Casper G., Hansen, Dominique, Eijnde, BO, and Bito, Virginie

Subjects
TYPE 2 diabetes, GLUCOSE tolerance tests, BLOOD sugar, HEART fibrosis, HEART failure
Abstract

Individuals with type 2 diabetes mellitus (T2DM) are at an increased risk for heart failure, yet preventive cardiac care is suboptimal in this population. Pyridoxamine (PM), a vitamin B6 analog, has been shown to exert protective effects in metabolic and cardiovascular diseases. In this study, we aimed to investigate whether PM limits adverse cardiac remodeling and dysfunction in rats who develop T2DM. Male rats received a standard chow diet or Western diet (WD) for 18 weeks to induce prediabetes. One WD group received additional PM (1 g/L) via drinking water. Glucose tolerance was assessed with a 1 h oral glucose tolerance test. Cardiac function was evaluated using echocardiography and hemodynamic measurements. Histology on left ventricular (LV) tissue was performed. Treatment with PM prevented the increase in fasting plasma glucose levels compared to WD-fed rats (p < 0.05). LV cardiac dilation tended to be prevented using PM supplementation. In LV tissue, PM limited an increase in interstitial collagen deposition (p < 0.05) seen in WD-fed rats. PM tended to decrease 3-nitrotyrosine and significantly lowered 4-hydroxynonenal content compared to WD-fed rats. We conclude that PM alleviates interstitial fibrosis and oxidative stress in the hearts of WD-induced prediabetic rats. [ABSTRACT FROM AUTHOR]

Published
2024
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25. Phenotype prediction using biologically interpretable neural networks on multi-cohort multi-omics data.

Author

van Hilten, Arno, van Rooij, Jeroen, Heijmans, Bastiaan T., 't Hoen, Peter A. C., Meurs, Joyce van, Jansen, Rick, Franke, Lude, Boomsma, Dorret I., Pool, René, van Dongen, Jenny, Hottenga, Jouke J., van Greevenbroek, Marleen M. J., Stehouwer, Coen D. A., van der Kallen, Carla J. H., Schalkwijk, Casper G., Wijmenga, Cisca, Zhernakova, Sasha, Tigchelaar, Ettje F., Slagboom, P. Eline, and Beekman, Marian

Subjects
GENE expression, MULTIOMICS, PREDICTION models, NETWORK performance, INDIVIDUALIZED medicine
Abstract

Integrating multi-omics data into predictive models has the potential to enhance accuracy, which is essential for precision medicine. In this study, we developed interpretable predictive models for multi-omics data by employing neural networks informed by prior biological knowledge, referred to as visible networks. These neural networks offer insights into the decision-making process and can unveil novel perspectives on the underlying biological mechanisms associated with traits and complex diseases. We tested the performance, interpretability and generalizability for inferring smoking status, subject age and LDL levels using genome-wide RNA expression and CpG methylation data from the blood of the BIOS consortium (four population cohorts, Ntotal = 2940). In a cohort-wise cross-validation setting, the consistency of the diagnostic performance and interpretation was assessed. Performance was consistently high for predicting smoking status with an overall mean AUC of 0.95 (95% CI: 0.90–1.00) and interpretation revealed the involvement of well-replicated genes such as AHRR, GPR15 and LRRN3. LDL-level predictions were only generalized in a single cohort with an R2 of 0.07 (95% CI: 0.05–0.08). Age was inferred with a mean error of 5.16 (95% CI: 3.97–6.35) years with the genes COL11A2, AFAP1, OTUD7A, PTPRN2, ADARB2 and CD34 consistently predictive. For both regression tasks, we found that using multi-omics networks improved performance, stability and generalizability compared to interpretable single omic networks. We believe that visible neural networks have great potential for multi-omics analysis; they combine multi-omic data elegantly, are interpretable, and generalize well to data from different cohorts. [ABSTRACT FROM AUTHOR]

Published
2024
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26. DNA Methylation Analysis Identifies Loci for Blood Pressure Regulation

Author

Richard, Melissa A, Huan, Tianxiao, Ligthart, Symen, Gondalia, Rahul, Jhun, Min A, Brody, Jennifer A, Irvin, Marguerite R, Marioni, Riccardo, Shen, Jincheng, Tsai, Pei-Chien, Montasser, May E, Jia, Yucheng, Syme, Catriona, Salfati, Elias L, Boerwinkle, Eric, Guan, Weihua, Mosley, Thomas H, Bressler, Jan, Morrison, Alanna C, Liu, Chunyu, Mendelson, Michael M, Uitterlinden, André G, van Meurs, Joyce B, Consortium, BIOS, Heijmans, Bastiaan T, Hoen, Peter AC ’t, van Meurs, Joyce, Isaacs, Aaron, Jansen, Rick, Franke, Lude, Boomsma, Dorret I, Pool, René, van Dongen, Jenny, Hottenga, Jouke J, van Greevenbroek, Marleen MJ, Stehouwer, Coen DA, van der Kallen, Carla JH, Schalkwijk, Casper G, Wijmenga, Cisca, Zhernakova, Alexandra, Tigchelaar, Ettje F, Slagboom, P Eline, Beekman, Marian, Deelen, Joris, van Heemst, Diana, Veldink, Jan H, van den Berg, Leonard H, van Duijn, Cornelia M, Hofman, Albert, Jhamai, P Mila, Verbiest, Michael, Suchiman, H Eka D, Verkerk, Marijn, van der Breggen, Ruud, van Rooij, Jeroen, Lakenberg, Nico, Mei, Hailiang, van Iterson, Maarten, van Galen, Michiel, Bot, Jan, van ’t Hof, Peter, Deelen, Patrick, Nooren, Irene, Moed, Matthijs, Vermaat, Martijn, Zhernakova, Dasha V, Luijk, René, Bonder, Marc Jan, van Dijk, Freerk, Arindrarto, Wibowo, Kielbasa, Szymon M, Swertz, Morris A, van Zwet, Erik W, Franco, Oscar H, Zhang, Guosheng, Li, Yun, Stewart, James D, Bis, Joshua C, Psaty, Bruce M, Chen, Yii-Der Ida, Kardia, Sharon LR, Zhao, Wei, Turner, Stephen T, Absher, Devin, Aslibekyan, Stella, Starr, John M, McRae, Allan F, Hou, Lifang, Just, Allan C, Schwartz, Joel D, Vokonas, Pantel S, Menni, Cristina, Spector, Tim D, Shuldiner, Alan, Damcott, Coleen M, Rotter, Jerome I, Palmas, Walter, Liu, Yongmei, and Paus, Tomáš

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Aetiology, 2.1 Biological and endogenous factors, Aged, Blood Pressure, CpG Islands, Cross-Sectional Studies, DNA Methylation, Epigenesis, Genetic, Genetic Variation, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Middle Aged, Nerve Tissue Proteins, Quantitative Trait Loci, Tetraspanins, BIOS Consortium, DNA methylation, Mendelian randomization, blood pressure, epigenome-wide association study, gene expression, sequence variation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry. Of 31 discovery-stage cytosine-phosphate-guanine (CpG) dinucleotides, 13 replicated after Bonferroni correction (discovery: N = 9,828, p < 1.0 × 10-7; replication: N = 7,182, p  30%) and independent of known BP genetic variants, explaining an additional 1.4% and 2.0% of the interindividual variation in systolic and diastolic BP, respectively. Bidirectional Mendelian randomization among up to 4,513 individuals of European ancestry from 4 cohorts suggested that methylation at cg08035323 (TAF1B-YWHAQ) influences BP, while BP influences methylation at cg00533891 (ZMIZ1), cg00574958 (CPT1A), and cg02711608 (SLC1A5). Gene expression analyses further identified six genes (TSPAN2, SLC7A11, UNC93B1, CPT1A, PTMS, and LPCAT3) with evidence of triangular associations between methylation, gene expression, and BP. Additional integrative Mendelian randomization analyses of gene expression and DNA methylation suggested that the expression of TSPAN2 is a putative mediator of association between DNA methylation at cg23999170 and BP. These findings suggest that heritable DNA methylation plays a role in regulating BP independently of previously known genetic variants.

Published
2017

27. Retinal microvascular function and incidence and trajectories of clinically relevant depressive symptoms: the Maastricht Study

Author

van Gennip, April C. E., primary, Gupta, Monideepa D., additional, Houben, Alfons J. H. M., additional, Berendschot, Tos T. J. M., additional, Webers, Carroll A. B., additional, van Greevenbroek, Marleen M. J., additional, van der Kallen, Carla J. H., additional, Koster, Annemarie, additional, Wesselius, Anke, additional, Eussen, Simone J. P. M., additional, Schalkwijk, Casper G., additional, de Galan, Bastiaan E., additional, Köhler, Sebastian, additional, Schram, Miranda T., additional, Stehouwer, Coen D. A., additional, and van Sloten, Thomas T., additional

Published
2024
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28. Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults

Author

Debras, Charlotte, primary, Cordova, Reynalda, additional, Mayén, Ana-Lucia, additional, Maasen, Kim, additional, Knaze, Viktoria, additional, Eussen, Simone J. P. M., additional, Schalkwijk, Casper G., additional, Huybrechts, Inge, additional, Tjønneland, Anne, additional, Halkjær, Jytte, additional, Katzke, Verena, additional, Bajracharya, Rashmita, additional, Schulze, Matthias B., additional, Masala, Giovanna, additional, Pala, Valeria, additional, Pasanisi, Fabrizio, additional, Macciotta, Alessandra, additional, Petrova, Dafina, additional, Castañeda, Jazmin, additional, Santiuste, Carmen, additional, Amiano, Pilar, additional, Moreno-Iribas, Conchi, additional, Borné, Yan, additional, Sonestedt, Emily, additional, Johansson, Ingegerd, additional, Esberg, Anders, additional, Aglago, Elom Kouassivi, additional, Jenab, Mazda, additional, and Freisling, Heinz, additional

Published
2024
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29. Correction: Methylglyoxal, a glycolysis side-product, induces Hsp90 glycation and YAP-mediated tumor growth and metastasis

Author

Nokin, Marie-Julie, primary, Durieux, Florence, additional, Peixoto, Paul, additional, Chiavarina, Barbara, additional, Peulen, Olivier, additional, Blomme, Arnaud, additional, Turtoi, Andrei, additional, Costanza, Brunella, additional, Smargiasso, Nicolas, additional, Baiwir, Dominique, additional, Scheijen, Jean L, additional, Schalkwijk, Casper G, additional, Leenders, Justine, additional, De Tullio, Pascal, additional, Bianchi, Elettra, additional, Thiry, Marc, additional, Uchida, Koji, additional, Spiegel, David A, additional, Cochrane, James R, additional, Hutton, Craig A, additional, De Pauw, Edwin, additional, Delvenne, Philippe, additional, Belpomme, Dominique, additional, Castronovo, Vincent, additional, and Bellahcène, Akeila, additional

Published
2024
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30. Comprehensive evaluation of smoking exposures and their interactions on DNA methylation

Author

Hoang, Thanh T., primary, Lee, Yunsung, additional, McCartney, Daniel L., additional, Kersten, Elin T.G., additional, Page, Christian M., additional, Hulls, Paige M., additional, Lee, Mikyeong, additional, Walker, Rosie M., additional, Breeze, Charles E., additional, Bennett, Brian D., additional, Burkholder, Adam B., additional, Ward, James, additional, Brantsæter, Anne Lise, additional, Caspersen, Ida H., additional, Motsinger-Reif, Alison A., additional, Richards, Marie, additional, White, Julie D., additional, Zhao, Shanshan, additional, Richmond, Rebecca C., additional, Magnus, Maria C., additional, Koppelman, Gerard H., additional, Evans, Kathryn L., additional, Marioni, Riccardo E., additional, Håberg, Siri E., additional, London, Stephanie J., additional, Heijmans, Bastiaan, additional, ’t Hoen, Peter, additional, van Meurs, Joyce, additional, Jansen, Rick, additional, Franke, Lude, additional, Boomsma, Dorret, additional, Pool, René, additional, van Dongen, Jenny, additional, Hottenga, Jouke, additional, van Greevenbroek, Marleen, additional, Stehouwer, Coen, additional, van der Kallen, Carla, additional, Schalkwijk, Casper, additional, Wijmenga, Cisca, additional, Zhernakova, Sasha, additional, Tigchelaar, Ettje, additional, Slagboom, P. Eline, additional, Beekman, Marian, additional, Deelen, Joris, additional, Van Heemst, Diana, additional, Veldink, Jan, additional, van den Berg, Leonard, additional, van Duijn, Cornelia, additional, Hofman, Bert, additional, Isaacs, Aaron, additional, Uitterlinden, André, additional, Jhamai, P. Mila, additional, Verbiest, Michael, additional, Suchiman, H. Eka, additional, Verkerk, Marijn, additional, van der Breggen, Ruud, additional, van Rooij, Jeroen, additional, Lakenberg, Nico, additional, Mei, Hailiang, additional, van Iterson, Maarten, additional, van Galen, Michiel, additional, Bot, Jan, additional, Zhernakova, Dasha, additional, van ‘t Hof, Peter, additional, Deelen, Patrick, additional, Nooren, Irene, additional, Moed, Matthijs, additional, Vermaat, Martijn, additional, Luijk, René, additional, Bonder, Marc, additional, van Dijk, Freerk, additional, Arindrarto, Wibowo, additional, Kielbasa, Szymon, additional, Swertz, Morris, additional, and van Zwet, Erik, additional

Published
2024
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35. Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults

Author

Debras, Charlotte, Cordova, Reynalda, Mayén, Ana-Lucia, Maasen, Kim, Knaze, Viktoria, Eussen, Simone Jpm, Schalkwijk, Casper G., Huybrechts, Inge, Tjønneland, Anne, Halkjær, Jytte, Katzke, Verena, Bajracharya, Rashmita, Schulze, Matthias B., Masala, Giovanna, Pala, Valeria, Pasanisi, Fabrizio, Macciotta, Alessandra, Petrova, Dafina, Castañeda, Jazmin, Santiuste, Carmen, Amiano, Pilar, Moreno-Iribas, Conchi, Borné, Yan, Sonestedt, Emily, Johansson, Ingegerd, Esberg, Anders, Aglago, Elom Kouassivi, Jenab, Mazda, Freisling, Heinz, Debras, Charlotte, Cordova, Reynalda, Mayén, Ana-Lucia, Maasen, Kim, Knaze, Viktoria, Eussen, Simone Jpm, Schalkwijk, Casper G., Huybrechts, Inge, Tjønneland, Anne, Halkjær, Jytte, Katzke, Verena, Bajracharya, Rashmita, Schulze, Matthias B., Masala, Giovanna, Pala, Valeria, Pasanisi, Fabrizio, Macciotta, Alessandra, Petrova, Dafina, Castañeda, Jazmin, Santiuste, Carmen, Amiano, Pilar, Moreno-Iribas, Conchi, Borné, Yan, Sonestedt, Emily, Johansson, Ingegerd, Esberg, Anders, Aglago, Elom Kouassivi, Jenab, Mazda, and Freisling, Heinz

Abstract

Dicarbonyl compounds are highly reactive precursors of Advanced Glycation End-products (AGEs), produced endogenously, present in certain foods, and formed during food processing. AGEs contribute to development of adverse metabolic outcomes but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), and body-weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263,095 EPIC-PANACEA participants with two body-weight assessments (median follow-up time=5.4y). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age, and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0.089kg (per 1-SD increase, 95%CI=0.072, 0.107). 3-DG was inversely associated with body-weight change (-0.076kg, -0.094, -0.058). No significant association was observed for GO (0.018kg, -0.002, 0.037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52.4y). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body-weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms, and potential public-health implications.

Published
2024
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36. Microvascular Dysfunction and Whole-Brain White Matter Connectivity: The Maastricht Study

Author

Cardiovasculaire Epi Team 7a, Circulatory Health, Cardiovasculaire Epi Team 5, Brain, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, MS Interne Geneeskunde, Beran, Magdalena, van Gennip, April C E, Stehouwer, Coen D A, Jansen, Jacobus F A, Gupta, Monideepa D, Houben, Alfons J H M, Berendschot, Tos T J M, Webers, Carroll A B, Wesselius, Anke, Schalkwijk, Casper G, Backes, Walter H, de Jong, Joost J A, van der Kallen, Carla J H, van Greevenbroek, Marleen M J, Köhler, Sebastian, Vonk, Jet M J, Geerlings, Mirjam I, Schram, Miranda T, van Sloten, Thomas T, Cardiovasculaire Epi Team 7a, Circulatory Health, Cardiovasculaire Epi Team 5, Brain, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, MS Interne Geneeskunde, Beran, Magdalena, van Gennip, April C E, Stehouwer, Coen D A, Jansen, Jacobus F A, Gupta, Monideepa D, Houben, Alfons J H M, Berendschot, Tos T J M, Webers, Carroll A B, Wesselius, Anke, Schalkwijk, Casper G, Backes, Walter H, de Jong, Joost J A, van der Kallen, Carla J H, van Greevenbroek, Marleen M J, Köhler, Sebastian, Vonk, Jet M J, Geerlings, Mirjam I, Schram, Miranda T, and van Sloten, Thomas T

Published
2024

37. Disease severity-based subgrouping of type 2 diabetes does not parallel differences in quality of life: the Maastricht Study

Author

Afd Pharmacoepi & Clinical Pharmacology, PECP - Centre for Pharmaceutical Policy and Regulation, Sub Gen. Pharmacoepi and Clinical Pharm, Pharmacoepidemiology and Clinical Pharmacology, Werkman, Nikki C C, García-Sáez, Gema, Nielen, Johannes T H, Tapia-Galisteo, Jose, Somolinos-Simón, Francisco J, Hernando, Maria E, Wang, Junfeng, Jiu, Li, Goettsch, Wim G, van der Kallen, Carla J H, Koster, Annemarie, Schalkwijk, Casper G, de Vries, Hein, de Vries, Nanne K, Eussen, Simone J P M, Driessen, Johanna H M, Stehouwer, Coen D A, Afd Pharmacoepi & Clinical Pharmacology, PECP - Centre for Pharmaceutical Policy and Regulation, Sub Gen. Pharmacoepi and Clinical Pharm, Pharmacoepidemiology and Clinical Pharmacology, Werkman, Nikki C C, García-Sáez, Gema, Nielen, Johannes T H, Tapia-Galisteo, Jose, Somolinos-Simón, Francisco J, Hernando, Maria E, Wang, Junfeng, Jiu, Li, Goettsch, Wim G, van der Kallen, Carla J H, Koster, Annemarie, Schalkwijk, Casper G, de Vries, Hein, de Vries, Nanne K, Eussen, Simone J P M, Driessen, Johanna H M, and Stehouwer, Coen D A

Published
2024

39. Placental Methylglyoxal in Preeclampsia: Vascular and Biomarker Implications.

Author

Vangrieken, Philippe, Al-Nasiry, Salwan, Remels, Alex H. V., Schiffers, Paul M. H., Janssen, Emma, Nass, Stefanie, Scheijen, Jean L. J. M., Spaanderman, Marc E. A., and Schalkwijk, Casper G.

Abstract

BACKGROUND: Preeclampsia is a multifaceted syndrome that includes maternal vascular dysfunction. We hypothesize that increased placental glycolysis and hypoxia in preeclampsia lead to increased levels of methylglyoxal (MGO), consequently causing vascular dysfunction. METHODS: Plasma samples and placentas were collected from uncomplicated and preeclampsia pregnancies. Uncomplicated placentas and trophoblast cells (BeWo) were exposed to hypoxia. The reactive dicarbonyl MGO and advanced glycation end products (Nε-(carboxymethyl)lysine [CML], Nε-(carboxyethyl)lysine [CEL], and MGO-derived hydroimidazolone [MG-H]) were quantified using liquid chromatography-tandem mass spectrometry. The activity of GLO1 (glyoxalase-1), that is, the enzyme detoxifying MGO, was measured. The impact of MGO on vascular function was evaluated using wire/pressure myography. The therapeutic potential of the MGO-quencher quercetin and mitochondrial-specific antioxidant mitoquinone mesylate (MitoQ) was explored. RESULTS: MGO, CML, CEL, and MG-H2 levels were elevated in preeclampsia-placentas (+36%, +36%, +25%, and +22%, respectively). Reduced GLO1 activity was observed in preeclampsia-placentas (−12%) and hypoxia-exposed placentas (−16%). Hypoxia-induced MGO accumulation in placentas was mitigated by the MGO-quencher quercetin. Trophoblast cells were identified as the primary source of MGO. Reduced GLO1 activity was also observed in hypoxia-exposed BeWo cells (−26%). Maternal plasma concentrations of CML and the MGO-derived MG-H1 increased as early as 12 weeks of gestation (+16% and +17%, respectively). MGO impaired endothelial barrier function, an effect mitigated by MitoQ, and heightened vascular responsiveness to thromboxane A2. CONCLUSIONS: This study reveals the accumulation of placental MGO in preeclampsia and upon exposure to hypoxia, demonstrates how MGO can contribute to vascular impairment, and highlights plasma CML and MG-H1 levels as promising early biomarkers for preeclampsia. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Moderate-Intensity and High-Intensity Interval Exercise Training Offer Equal Cardioprotection, with Different Mechanisms, during the Development of Type 2 Diabetes in Rats

Author

D’Haese, Sarah, primary, Claes, Lisa, additional, de Laat, Iris, additional, Van Campenhout, Sven, additional, Deluyker, Dorien, additional, Heeren, Ellen, additional, Haesen, Sibren, additional, Lambrichts, Ivo, additional, Wouters, Kristiaan, additional, Schalkwijk, Casper G., additional, Hansen, Dominique, additional, Eijnde, BO, additional, and Bito, Virginie, additional

Published
2024
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43. Lower thickness of inner retinal layers is associated with an increased risk of incident dementia and Alzheimer’s disease – an individual participant data analysis of four prospective cohort studies (69,955 participants)

Author

van der Heide, Frank, primary, Khawaja, Anthony, additional, Berendschot, Tos T.J.M., additional, Littlejohns, Thomas J, additional, Kuzma, Elzbieta, additional, Foster, Paul J, additional, Patel, Praveen, additional, Bertelsen, Geir, additional, von Hanno, Therese, additional, Johnsen, Bente, additional, Schirmer, Henrik, additional, Rebouças, Sara Cristina Lima, additional, Grasset, Leslie, additional, Delcourt, Cécile, additional, Helmer, Catherine, additional, Webers, Carroll, additional, Kroon, Abraham A, additional, van der Kallen, Carla J.H., additional, Eussen, Simone J.P.M., additional, van Dongen, Martien, additional, Schalkwijk, Casper, additional, Bosma, Hans, additional, Köhler, Sebastian, additional, Schram, Miranda T., additional, Blokland, Gabriella, additional, Linden, David, additional, Wesselius, Anke, additional, and Stehouwer, Coen D.A., additional

Published
2023
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44. Biomarkers of microvascular dysfunction and cerebral white matter connectivity: The Maastricht Study

Author

Beran, Magdalena, primary, van Gennip, April C.E., additional, Stehouwer, Coen D.A., additional, Jansen, Jacobus F.A., additional, Gupta, Monideepa D., additional, Houben, Alfons J.H.M., additional, Berendschot, Tos T.J.M., additional, Webers, Carroll A.B., additional, Wesselius, Anke, additional, Schalkwijk, Casper, additional, Backes, Walter H., additional, de Jong, Joost J., additional, van der Kallen, Carla J.H., additional, van Greevenbroek, Marleen M.J., additional, Köhler, Sebastian, additional, Vonk, Jet M.J., additional, Geerlings, Mirjam I., additional, Schram, Miranda T., additional, and van Sloten, Thomas T., additional

Published
2023
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45. The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study

Author

Geraets, Anouk F. J., Köhler, Sebastian, Muzambi, Rutendo, Schalkwijk, Casper G., Oenema, Anke, Eussen, Simone J. P. M., Dagnelie, Pieter C., Stehouwer, Coen D. A., Schaper, Nicolaas C., Henry, Ronald M. A., van der Kallen, Carla J. H., Wesselius, Anke, Koster, Annemarie, Verhey, Frans R. J., and Schram, Miranda T.

Published
2020
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