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1. 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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3. (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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4. Brain function in classic galactosemia, a galactosemia network (GalNet) members review

Author

Panis, Bianca, primary, Vos, E. Naomi, additional, Barić, Ivo, additional, Bosch, Annet M., additional, Brouwers, Martijn C. G. J., additional, Burlina, Alberto, additional, Cassiman, David, additional, Coman, David J., additional, Couce, María L., additional, Das, Anibh M., additional, Demirbas, Didem, additional, Empain, Aurélie, additional, Gautschi, Matthias, additional, Grafakou, Olga, additional, Grunewald, Stephanie, additional, Kingma, Sandra D. K., additional, Knerr, Ina, additional, Leão-Teles, Elisa, additional, Möslinger, Dorothea, additional, Murphy, Elaine, additional, Õunap, Katrin, additional, Pané, Adriana, additional, Paci, Sabrina, additional, Parini, Rossella, additional, Rivera, Isabel A., additional, Scholl-Bürgi, Sabine, additional, Schwartz, Ida V. D., additional, Sdogou, Triantafyllia, additional, Shakerdi, Loai A., additional, Skouma, Anastasia, additional, Stepien, Karolina M., additional, Treacy, Eileen P., additional, Waisbren, Susan, additional, Berry, Gerard T., additional, and Rubio-Gozalbo, M. Estela, additional

Published
2024
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6. Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness: The Maastricht Study

Author

Foreman, Yuri D., van Doorn, William P. T. M., Schaper, Nicolaas C., van Greevenbroek, Marleen M. J., van der Kallen, Carla J. H., Henry, Ronald M. A., Koster, Annemarie, Eussen, Simone J. P. M., Wesselius, Anke, Reesink, Koen D., Schram, Miranda T., Dagnelie, Pieter C., Kroon, Abraham A., Brouwers, Martijn C. G. J., and Stehouwer, Coen D. A.

Published
2021
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9. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial

Author

Nickerson, H, Lou, O, Dutta, S, Haw, J, Anderson, C, Kean, S, Thomson, E, Gillespie, L, Gibb, J, Greenlaw, N, Keech, A, Jenkins, A, March, K, Williams, S, Coady, E, Bots, M, Dreyer, J, Jan, T, Sheffy, K, Lusky, R, Peleg, S, Shore, A, Carty, D, Donnan, P, Witham, M, Adler, A, Lonn, E, Rauchhaus, P, Lindsay, R, Brouwers, M, Van-Melckebeke, J, Hamill, T, Cuthbertson, L, Murray, A, Jolly, L, Miller, E, Hair, J, Bell, A, Carmichael, S, Douglas, E, Surtees, P, Dinnett, E, Allan, J, Watson, C, McLaughlin, M, Brindley, G, Smillie, E, Motherwell, D, MacDonald, S, Ellis, P, Stuart, D, Travers, M, Brearley, S, Greig, L, Colman, P, Nankervis, A, Forulanos, S, West, D, Vaughan, S, Bjorasen, M, Donlan, J, Vrazas, J, O'Neal, D, Horsburgh, J, Pater, H, Kent, S, Twigg, S, Fulcher, G, Denner, R, Piotrowicz, A, Januszewski, A, Coy, A, Paul, T, McDonald, C, Tereschyn, S, Schmidt, N, Weingert, M, Heard, H, Burke, S, Ooi, TC, Lochnan, H, Sorisky, A, Keely, E, Malcolm, J, Maranger, J, Favreau, C, Petherick, S, Boles, K, Rossing, P, Hansen, TW, Lund, S, Hemmingsen, B, Thorogood, N, Green, K, Robinson, T, Abouglilia, K, Nayman, D, Miller, C, Warren, R, Aizawa, K, Balasubramani, M, Toth, S, Harvey, K, Birch, G, Atkin, S, Sathyapalan, T, James, A, Javed, Z, Wilding, J, Martin, B, Birch, S, Wilcox, A, Watson, N, Oliver, N, Jugnee, N, Rutter, M, Turgut, T, Shaju, A, Yau, S, Subin, S, Walker, M, Wake, D, Millward, A, Chong, P, Hibbert, M, George, J, Schaper, N, Pinxt, J, op het Roodt, J, Phillips, Sam, Murray, L, Sleigh, L, Collier, A, Sit, LE, Allan, K, Cook, J, Campbell, K, Hodge, L, Leese, G, Reekie, G, Jaap, A, Sudworth, A, White, A, McKnight, J, Steven, L, McKay, G, Llano, A, Currie, G, Lennon, E, Johnstone, J, Shields, K, Petrie, John R, Chaturvedi, Nishi, Ford, Ian, Brouwers, Martijn C G J, Greenlaw, Nicola, Tillin, Therese, Hramiak, Irene, Hughes, Alun D, Jenkins, Alicia J, Klein, Barbara E K, Klein, Ronald, Ooi, Teik C, Rossing, Peter, Stehouwer, Coen D A, Sattar, Naveed, and Colhoun, Helen M

Published
2017
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10. Hepatic saturated fatty acid fraction is associated with de novo lipogenesis and hepatic insulin resistance

Author

Roumans, Kay H. M., Lindeboom, Lucas, Veeraiah, Pandichelvam, Remie, Carlijn M. E., Phielix, Esther, Havekes, Bas, Bruls, Yvonne M. H., Brouwers, Martijn C. G. J., Ståhlman, Marcus, Alssema, Marjan, Peters, Harry P. F., de Mutsert, Renée, Staels, Bart, Taskinen, Marja-Riitta, Borén, Jan, Schrauwen, Patrick, and Schrauwen-Hinderling, Vera B.

Published
2020
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11. The oral glucose tolerance test-derived incremental glucose peak is associated with greater arterial stiffness and maladaptive arterial remodeling: The Maastricht Study

Author

Foreman, Yuri D., Brouwers, Martijn C. G. J., Berendschot, Tos T. J. M., van Dongen, Martien C. J. M., Eussen, Simone J. P. M., van Greevenbroek, Marleen M. J., Henry, Ronald M. A., Houben, Alfons J. H. M., van der Kallen, Carla J. H., Kroon, Abraham A., Reesink, Koen D., Schram, Miranda T., Schaper, Nicolaas C., and Stehouwer, Coen D. A.

Published
2019
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13. Genetic Susceptibility to Nonalcoholic Fatty Liver Disease and Risk for Pancreatic Cancer: Mendelian Randomization.

Author

King, Sontoria D., Veliginti, Swathi, Brouwers, Martijn C. G. J., Zhewen Ren, Wei Zheng, Setiawan, Veronica W., Wilkens, Lynne R., Xiao-Ou Shu, Arslan, Alan A., Freeman, Laura E. Beane, Bracci, Paige M., Canzian, Federico, Mengmeng Du, Gallinger, Steven J., Giles, Graham G., Goodman, Phyllis J., Haiman, Christopher A., Kogevinas, Manolis, Kooperberg, Charles, and LeMarchand, Loic

Abstract

Background: There are conflicting data on whether nonalcoholic fatty liver disease (NAFLD) is associated with susceptibility to pancreatic cancer. Using Mendelian randomization (MR), we investigated the relationship between genetic predisposition to NAFLD and risk for pancreatic cancer. Methods: Data from genome-wide association studies (GWAS) within the Pancreatic Cancer Cohort Consortium (PanScan; cases n = 5,090, controls n = 8,733) and the Pancreatic Cancer Case Control Consortium (PanC4; cases n = 4,163, controls n = 3,792) were analyzed. We used data on 68 genetic variants with four different MR methods [inverse variance weighting (IVW), MR-Egger, simple median, and penalized weighted median] separately to predict genetic heritability of NAFLD. We then assessed the relationship between each of the four MR methods and pancreatic cancer risk, using logistic regression to calculate ORs and 95% confidence intervals (CI), adjusting for PC risk factors, including obesity and diabetes. Results: No association was found between genetically predicted NAFLD and pancreatic cancer risk in the PanScan or PanC4 samples [e.g., PanScan, IVW OR, 1.04; 95% confidence interval (CI), 0.88-1.22; MR-Egger OR, 0.89; 95% CI, 0.65-1.21; PanC4, IVW OR, 1.07; 95% CI, 0.90-1.27; MR-Egger OR, 0.93; 95% CI, 0.67-1.28]. None of the four MR methods indicated an association between genetically predicted NAFLD and pancreatic cancer risk in either sample. Conclusions: Genetic predisposition to NAFLD is not associated with pancreatic cancer risk. Impact: Given the close relationship between NAFLD and metabolic conditions, it is plausible that any association between NAFLD and pancreatic cancer might reflect host metabolic perturbations (e.g., obesity, diabetes, or metabolic syndrome) and does not necessarily reflect a causal relationship between NAFLD and pancreatic cancer. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study

Author

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

Published
2022
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18. Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study

Author

Simons, Pomme I. H. G., primary, Valkenburg, Olivier, additional, van de Waarenburg, Marjo P. H., additional, van Greevenbroek, Marleen M. J., additional, Kooi, M. Eline, additional, Jansen, Jacobus F. A., additional, Schalkwijk, Casper G., additional, Stehouwer, Coen D. A., additional, and Brouwers, Martijn C. G. J., additional

Published
2022
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20. Relationship between NAFLD and coronary artery disease: A Mendelian randomization study

Author

Ren, Zhewen, Simons, Pomme I H G, Wesselius, Anke, Stehouwer, Coen D A, Brouwers, Martijn C G J, Interne Geneeskunde, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Epidemiologie, RS: NUTRIM - R3 - Respiratory & Age-related Health, MUMC+: HVC Pieken Maastricht Studie (9), MUMC+: MA Interne Geneeskunde (3), MUMC+: Centrum voor Chronische Zieken (3), MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), MUMC+: MA Endocrinologie (9), MUMC+: MA Maag Darm Lever (9), MUMC+: MA Hematologie (9), MUMC+: MA Medische Oncologie (9), MUMC+: MA Nefrologie (9), and MUMC+: MA Reumatologie (9)

Subjects
RISK, Hepatology, CARDIOVASCULAR-DISEASE, EXOME-WIDE ASSOCIATION, MORTALITY, INHIBITION, EPIDEMIOLOGY, ISCHEMIC-HEART-DISEASE, CONFERS SUSCEPTIBILITY, METAANALYSIS, FATTY LIVER-DISEASE
Abstract

BACKGROUND & AIMS: There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of coronary artery disease (CAD). The aim of the present study was to assess the causal relationship between NAFLD and CAD.APPROACH & RESULTS: We performed two-sample Mendelian randomization (MR) analyses using summary-level data to assess the association between genetically predicted NAFLD (i.e. chronically-elevated serum alanine aminotransferase levels [cALT], imaging-based and biopsy-confirmed NAFLD) and risk of CAD. Analyses were repeated after exclusion of NAFLD susceptibility genes that are associated with impaired VLDL secretion. Inverse-variance weighted (IVW) MR analyses showed a statistically significant association between genetically predicted cALT and risk of CAD (odds ratio [OR]:1.116, 95% confidence interval [CI]:1.039,1.199), but not for the other NAFLD-related traits (OR:1.046, 95%CI:0.764,1.433 and OR:1.014, 95%CI:0.968,1.062 for imaging-based and biopsy-confirmed NAFLD, respectively). MR Egger regression revealed a statistically significant intercept, indicative of directional pleiotropy, for all traits. Repeat analyses after exclusion of genes associated with impaired VLDL secretion, showed consistent associations between genetically predicted NAFLD and CAD for all traits, i.e. cALT (OR:1.203, 95%CI:1.113,1.300), imaging-based (OR:2.149, 95%CI:1.276,3.620) and biopsy-confirmed NAFLD (OR:1.113, 95%CI:1.041,1.189), which persisted when more stringent biopsy-confirmed NAFLD criteria were used (OR:1.154, 95%CI:1.043,1.278) or when more stringent MR methods were applied. MR Egger regression did not show a statistically significant intercept.CONCLUSION: The two-sample MR analyses showed a robust association between genetically predicted NAFLD and CAD after exclusion of genetic variants that are implicated in impaired VLDL secretion.

Published
2022

22. Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway

Author

van Vliet, Kimber, primary, van Ginkel, Willem G., additional, Jahja, Rianne, additional, Daly, Anne, additional, MacDonald, Anita, additional, Santra, Saikat, additional, De Laet, Corinne, additional, Goyens, Philippe J., additional, Vara, Roshni, additional, Rahman, Yusof, additional, Cassiman, David, additional, Eyskens, Francois, additional, Timmer, Corrie, additional, Mumford, Nicky, additional, Gissen, Paul, additional, Bierau, Jörgen, additional, van Hasselt, Peter M., additional, Wilcox, Gisela, additional, Morris, Andrew A. M., additional, Jameson, Elisabeth A., additional, de la Parra, Alicia, additional, Arias, Carolina, additional, Garcia, Maria I., additional, Cornejo, Veronica, additional, Bosch, Annet M., additional, Hollak, Carla E. M., additional, Rubio‐Gozalbo, M. Estela, additional, Brouwers, Martijn C. G. J., additional, Hofstede, Floris C., additional, de Vries, Maaike C., additional, Janssen, Mirian C. H., additional, van der Ploeg, Ans T., additional, Langendonk, Janneke G., additional, Huijbregts, Stephan C. J., additional, and van Spronsen, Francjan J., additional

Published
2022
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23. Reply

Author

Ren, Zhewen, primary, Simons, Pomme I. H. G., additional, Wesselius, Anke, additional, Stehouwer, Coen D. A., additional, and Brouwers, Martijn C. G. J., additional

Published
2022
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28. Machine learning-based glucose prediction with use of continuous glucose and physical activity monitoring data: The Maastricht Study

Author

van Doorn, William P. T. M., primary, Foreman, Yuri D., additional, Schaper, Nicolaas C., additional, Savelberg, Hans H. C. M., additional, Koster, Annemarie, additional, van der Kallen, Carla J. H., additional, Wesselius, Anke, additional, Schram, Miranda T., additional, Henry, Ronald M. A., additional, Dagnelie, Pieter C., additional, de Galan, Bastiaan E., additional, Bekers, Otto, additional, Stehouwer, Coen D. A., additional, Meex, Steven J. R., additional, and Brouwers, Martijn C. G. J., additional

Published
2021
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31. Causal relationship between polycystic ovary syndrome and coronary artery disease: A Mendelian randomisation study.

Author

Simons, Pomme I. H. G., Cornelissen, Merel E. B., Valkenburg, Olivier, Onland‐Moret, N. Charlotte, van der Schouw, Yvonne T., Stehouwer, Coen D.A., Burgess, Stephen, and Brouwers, Martijn C. G. J.

Subjects
POLYCYSTIC ovary syndrome, CORONARY artery disease, HYPERTRICHOSIS, BODY mass index
Abstract

Objective: Polycystic ovary syndrome (PCOS) has been associated with an increased risk of coronary artery disease (CAD). However, it remains uncertain whether this increased risk is the result of PCOS per se or, alternatively, is explained by obesity, a common feature of PCOS. The aim of this study was to assess the causal association between PCOS and CAD and the role of obesity herein. Design and Methods: We conducted two‐sample Mendelian randomisation analyses in large‐scale, female‐specific datasets to study the association between genetically predicted (1) risk of PCOS and risk of CAD, (2) body mass index (BMI) and risk of PCOS and (3) BMI and risk of CAD. Primary analyses were conducted with the inverse‐variance weighted (IVW) method. Simple median, penalized weighted median and contamination mixture analyses were performed to assess the robustness of the outcomes. Results: IVW analyses did not show a statistically significant association between PCOS and CAD (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.89, 1.11). In contrast, genetically predicted BMI was statistically significantly associated with an increased odds of PCOS (OR: 3.21, 95% CI: 2.26, 4.56) and CAD (OR: 1.38, 95% CI: 1.14, 1.67). Similar results were obtained when secondary analyses were performed. Conclusion: These sex‐specific analyses show that the genetically predicted risk of PCOS is not associated with the risk of CAD. Instead, the genetically predicted risk of obesity (and its downstream metabolic effects) is the common denominator of both PCOS and CAD risk. [ABSTRACT FROM AUTHOR]

Published
2022
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32. Relationship between de novo lipogenesis and serum sex hormone binding globulin in humans

Author

Simons, Pomme I. H. G., primary, Valkenburg, Olivier, additional, Telgenkamp, Ine, additional, van der Waaij, Koen M., additional, de Groot, David M., additional, Veeraiah, Pandichelvam, additional, Bons, Judith A. P., additional, Taskinen, Marja‐Riitta, additional, Borén, Jan, additional, Schrauwen, Patrick, additional, Rutten, Joost H. W., additional, Cassiman, David, additional, Schalkwijk, Casper G., additional, Stehouwer, Coen D. A., additional, Schrauwen‐Hinderling, Vera B., additional, Hodson, Leanne, additional, and Brouwers, Martijn C. G. J., additional

Published
2021
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33. Towards precision medicine in diabetes? A critical review of glucotypes

Author

Hulman, Adam, primary, Foreman, Yuri D., additional, Brouwers, Martijn C. G. J., additional, Kroon, Abraham A., additional, Reesink, Koen D., additional, Dagnelie, Pieter C., additional, van der Kallen, Carla J. H., additional, Greevenbroek, Marleen M. J. van, additional, Færch, Kristine, additional, Vistisen, Dorte, additional, Jørgensen, Marit E., additional, Stehouwer, Coen D. A., additional, and Witte, Daniel R., additional

Published
2021
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35. Genetically proxied ketohexokinase function and risk of colorectal cancer: a Mendelian randomisation study.

Author

Buziau, Amée M., Law, Philip J., Blokland, Gabriella, Schalkwijk, Casper, Scheijen, Jean, Simons, Pomme, van der Kallen, Carla, Eussen, Simone, Dagnelie, Pieter C., van Greevenbroek, Marleen, Houlston, Richard S., Wesselius, Anke, Went, Molly, Stehouwer, Coen, and Brouwers, Martijn C. G. J.

Subjects
GASTROINTESTINAL hemorrhage, COLORECTAL cancer, DISEASE risk factors, FATTY liver
Published
2023
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37. Incidence of type 2 diabetes in familial combined hyperlipidemia

Author

Brouwers, Martijn C G J, primary, de Graaf, Jacqueline, additional, Simons, Nynke, additional, Meex, Steven, additional, ten Doeschate, Sophie, additional, van Heertum, Shadana, additional, Heidemann, Britt, additional, Luijten, Jim, additional, de Boer, Douwe, additional, Schaper, Nicolaas, additional, Stehouwer, Coen D A, additional, and van Greevenbroek, Marleen M J, additional

Published
2020
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38. The endothelial function biomarker soluble E‐selectin is associated with nonalcoholic fatty liver disease

Author

Simons, Nynke, primary, Bijnen, Mitchell, additional, Wouters, Kristiaan A. M., additional, Rensen, Sander S., additional, Beulens, Joline W. J., additional, Greevenbroek, Marleen M. J., additional, ’t Hart, Leen M., additional, Greve, Jan Willem M., additional, Kallen, Carla J. H., additional, Schaper, Nicolaas C., additional, Schalkwijk, Casper G., additional, Stehouwer, Coen D. A., additional, and Brouwers, Martijn C. G. J., additional

Published
2020
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39. Retrospective evaluation of the Dutch pre‐newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening?

Author

Haijes, Hanneke A., primary, Molema, Femke, additional, Langeveld, Mirjam, additional, Janssen, Mirian C., additional, Bosch, Annet M., additional, Spronsen, Francjan, additional, Mulder, Margot F., additional, Verhoeven‐Duif, Nanda M., additional, Jans, Judith J.M., additional, Ploeg, Ans T., additional, Wagenmakers, Margreet A., additional, Rubio‐Gozalbo, M. Estela, additional, Brouwers, Martijn C. G. J., additional, Vries, Maaike C., additional, Langendonk, Janneke G., additional, Williams, Monique, additional, and Hasselt, Peter M., additional

Published
2019
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41. Metformin and carotid intima‐media thickness in never‐smokers with type 1 diabetes: The REMOVAL trial.

Author

Timmons, Joseph G., Greenlaw, Nicola, Boyle, James G., Chaturvedi, Nish, Ford, Ian, Brouwers, Martijn C. G. J., Tillin, Therese, Hramiak, Irene, Hughes, Alun D., Jenkins, Alicia J., Klein, Barbara E. K., Klein, Ron, Ooi, Teik C., Rossing, Peter, Stehouwer, Coen D. A., Sattar, Naveed, Colhoun, Helen M., and Petrie, John R.

Subjects
CAROTID intima-media thickness, TYPE 1 diabetes, METFORMIN, DAPAGLIFLOZIN, CIGARETTE smoke
Abstract

Aim: To determine whether metformin's effects on carotid artery intima‐media thickness (cIMT) in type 1 diabetes differ according to smoking status. Methods: Regression model effect estimates for the effect of metformin versus placebo (double‐blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. Results: In 428 randomized participants (227 never‐smokers, 201 ever‐smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.012 mm, 95% CI −0.021 to −0.002; p =.0137) but not in ever‐smokers (0.003 mm, 95% CI −0.008 to 0.014; p =.5767); and similarly in non‐current smokers (−0.008 mm, 95% CI −0.015 to −0.00001; p =.0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032; p =.1887). Three‐way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking (p =.0373, prespecified) and non‐current versus current smoking (p =.0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.020 mm, 95% CI −0.034 to −0.006; p =.0067) but not in ever‐smokers (−0.006 mm, 95% CI −0.020 to 0.008; p =.4067), although this analysis was not supported by a significant three‐way interaction term. Conclusions: This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for individuals who have never smoked cigarettes. [ABSTRACT FROM AUTHOR]

Published
2021
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42. Patients With Aldolase B Deficiency Are Characterized by Increased Intrahepatic Triglyceride Content

Author

Simons, Nynke, primary, Debray, François-Guillaume, additional, Schaper, Nicolaas C, additional, Kooi, M Eline, additional, Feskens, Edith J M, additional, Hollak, Carla E M, additional, Lindeboom, Lucas, additional, Koek, Ger H, additional, Bons, Judith A P, additional, Lefeber, Dirk J, additional, Hodson, Leanne, additional, Schalkwijk, Casper G, additional, Stehouwer, Coen D A, additional, Cassiman, David, additional, and Brouwers, Martijn C G J, additional

Published
2019
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43. Movement disorders and nonmotor neuropsychological symptoms in children and adults with classical galactosemia

Author

Kuiper, Anouk, primary, Grünewald, Stephanie, additional, Murphy, Elaine, additional, Coenen, Maraike A., additional, Eggink, Hendriekje, additional, Zutt, Rodi, additional, Rubio-Gozalbo, Maria E., additional, Bosch, Annet M., additional, Williams, Monique, additional, Derks, Terry G. J., additional, Lachmann, Robin H. L., additional, Brouwers, Martijn C. G. J., additional, Janssen, Mirian C. H., additional, Tijssen, Marina A., additional, and de Koning, Tom J., additional

Published
2019
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44. Contribution of Liver Fat to Weight Loss–Induced Changes in Serum Hepatokines: A Randomized Controlled Trial

Author

Telgenkamp, Ine, primary, Kusters, Yvo H A M, additional, Schalkwijk, Casper G, additional, Houben, Alfons J H M, additional, Kooi, M Eline, additional, Lindeboom, Lucas, additional, Bons, Judith A P, additional, Schaper, Nicolaas C, additional, Joris, Peter J, additional, Plat, Jogchum, additional, Mensink, Ronald P, additional, Stehouwer, Coen D A, additional, and Brouwers, Martijn C G J, additional

Published
2019
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46. Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial.

Author

Simons, Nynke, Veeraiah, Pandichelvam, Simons, Pomme I H G, Schaper, Nicolaas C, Kooi, M Eline, Schrauwen-Hinderling, Vera B, Feskens, Edith J M, van der Ploeg, E M C (Liesbeth), Van den Eynde, Mathias D G, Schalkwijk, Casper G, Stehouwer, Coen D A, and Brouwers, Martijn C G J

Subjects
REDUCING diets, FATTY liver prevention, ACADEMIC medical centers, CONFIDENCE intervals, DIET in disease, DIET therapy, DIETARY supplements, FRUCTOSE, GLUCOSE, GLUCOSE tolerance tests, LIPIDS, LIVER, PROTON magnetic resonance spectroscopy, STATISTICAL sampling, SERUM, RANDOMIZED controlled trials, TREATMENT effectiveness, BLIND experiment, ADULTS
Abstract

Background There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. Objectives The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. Methods Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index ≥ 60 consumed a 6-wk fructose-restricted diet (<7.5 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHL content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. Results Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: −57.0 g/d; 95% CI: −77.9, −39.5 g/d; and −38.8 μmol/d; 95% CI: −91.2, −10.7 μmol/d, respectively). Although IHL content decreased in both the intervention and control groups (P  < 0.001 and P  = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: −0.7% point, 95% CI: −2.0, −0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. Conclusions Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group. This trial was registered at clinicaltrials.gov as NCT03067428. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL) : a double-blind, randomised, placebo-controlled trial

Author

Petrie, John R., Chaturvedi, Nishi, Ford, Ian, Brouwers, Martijn C. G. J., Greenlaw, Nicola, Tillin, Therese, Hramiak, Irene, Hughes, Alun D., Jenkins, Alicia J., Klein, Barbara E K, Klein, Ronald, Ooi, Teik C., Rossing, Peter, Stehouwer, Coen D. A., Sattar, Naveed, Colhoun, Helen M., Nickerson, H., Lou, O., Dutta, S., Haw, J., Anderson, C., Kean, S., Thomson, E., Gillespie, L., Gibb, J., Greenlaw, N., Keech, Anthony C., Jenkins, Mark A., March, K., Williams, S., Coady, E., Bots, M., Dreyer, J., Jan, T., Sheffy, K., Lusky, R., Peleg, S., Shore, A., Carty, D., Donnan, P., Witham, M., Adler, A.., Lonn, E, Rauchhaus, P., Lindsay, R.W., Brouwers, M., Van-Melckebeke, J., Hamill, T., Cuthbertson, L., and REMOVAL Study Group

Subjects
Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Background Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease. Methods REMOVAL was a double-blind, placebo-controlled trial undertaken at 23 hospital diabetes clinics in five countries (Australia, Canada, Denmark, the Netherlands, and the UK). Adults aged 40 years and older with type 1 diabetes of at least 5 years' duration and at least three of ten specific cardiovascular risk factors were randomly assigned (via an interactive voice response system) to oral metformin 1000 mg twice daily or placebo. Participants and site staff were masked to treatment allocation. The primary outcome was averaged mean far-wall cIMT, quantified annually for 3 years, analysed in a modified intention-to-treat population (all randomly assigned participants with post-randomisation data available for the outcome of interest at any given timepoint, irrespective of subsequent adherence or study participation), using repeated measures regression. Secondary outcomes were HbA1c, LDL cholesterol, estimated glomerular filtration rate (eGFR), incident microalbuminuria (not reported), incident retinopathy, bodyweight, insulin dose, and endothelial function, also analysed in all participants with post-randomisation data available for the outcome of interest at any given timepoint. This trial is registered with ClinicalTrials.gov, number NCT01483560. Findings Between Dec 14, 2011, and June 24, 2014, 493 participants entered a 3 month run-in to optimise risk factor and glycaemic control (single-blind placebo in the final month). Of 428 randomly assigned patients, 219 were allocated to metformin and 209 to placebo. Progression of mean cIMT was not significantly reduced with metformin (−0·005 mm per year, 95% CI −0·012 to 0·002; p=0·1664), although maximal cIMT (a prespecified tertiary outcome) was significantly reduced (−0·013 mm per year, −0·024 to −0·003; p=0·0093). HbA1c (mean 8·1% [SD 0·9] for metformin and 8·0% [0·8] for placebo at baseline) was reduced on average over 3 years by metformin (−0·13%, 95% CI −0·22 to −0·037; p=0·0060), but this was accounted for by a reduction at the 3-month timepoint (−0·24%, −0·34 to −0·13; p

Published
2017

48. Retrospective evaluation of the Dutch pre‐newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening?

Author

Haijes, Hanneke A., Molema, Femke, Langeveld, Mirjam, Janssen, Mirian C., Bosch, Annet M., Spronsen, Francjan, Mulder, Margot F., Verhoeven‐Duif, Nanda M., Jans, Judith J.M., Ploeg, Ans T., Wagenmakers, Margreet A., Rubio‐Gozalbo, M. Estela, Brouwers, Martijn C. G. J., Vries, Maaike C., Langendonk, Janneke G., Williams, Monique, and Hasselt, Peter M.

Abstract

Evidence for effectiveness of newborn screening (NBS) for propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is scarce. Prior to implementation in the Netherlands, we aim to estimate the expected health gain of NBS for PA and MMA. In this national retrospective cohort study, the clinical course of 76/83 Dutch PA and MMA patients, diagnosed between January 1979 and July 2019, was evaluated. Five clinical outcome parameters were defined: adverse outcome of the first symptomatic phase, frequency of acute metabolic decompensations (AMD), cognitive function, mitochondrial complications, and treatment‐related complications. Outcomes of patients identified by family testing were compared with the outcomes of their index siblings. An adverse outcome due to the first symptomatic phase was recorded in 46% of the clinically diagnosed patients. Outcome of the first symptomatic phase was similar in 5/9 sibling pairs and better in 4/9 pairs. Based on the day of diagnosis of the clinically diagnosed patients and sibling pair analysis, a preliminary estimated reduction of adverse outcome due to the first symptomatic phase from 46% to 36%‐38% was calculated. Among the sibling pairs, AMD frequency, cognitive function, mitochondrial, and treatment‐related complications were comparable. These results suggest that the health gain of NBS for PA and MMA in overall outcome may be limited, as only a modest decrease of adverse outcomes due to the first symptomatic phase is expected. With current clinical practice, no reduced AMD frequency, improved cognitive function, or reduced frequency of mitochondrial or treatment‐related complications can be expected. [ABSTRACT FROM AUTHOR]

Published
2020
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