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6. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author

Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Snieder, Harold, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Abecasis, Goncalo, Baras, Aris, Cantor, Michael, Coppola, Giovanni, Economides, Aris, Lotta, Luca A., Overton, John D., Reid, Jeffrey G., Shuldiner, Alan, Beechert, Christina, Forsythe, Caitlin, Fuller, Erin D., Gu, Zhenhua, Lattari, Michael, Lopez, Alexander, Schleicher, Thomas D., Padilla, Maria Sotiropoulos, Toledo, Karina, Widom, Louis, Wolf, Sarah E., Pradhan, Manasi, Manoochehri, Kia, Ulloa, Ricardo H., Bai, Xiaodong, Balasubramanian, Suganthi, Barnard, Leland, Blumenfeld, Andrew, Eom, Gisu, Habegger, Lukas, Hawes, Alicia, Khalid, Shareef, Maxwell, Evan K., Salerno, William, Staples, Jeffrey C., Jones, Marcus B., Mitnaul, Lyndon J., Gorski, Mathias, Jung, Bettina, Li, Yong, Matias-Garcia, Pamela R., Wuttke, Matthias, Coassin, Stefan, Thio, Chris H.L., Kleber, Marcus E., Winkler, Thomas W., Wanner, Veronika, Chai, Jin-Fang, Chu, Audrey Y., Cocca, Massimiliano, Feitosa, Mary F., Ghasemi, Sahar, Hoppmann, Anselm, Horn, Katrin, Li, Man, Nutile, Teresa, Scholz, Markus, Sieber, Karsten B., Teumer, Alexander, Tin, Adrienne, Wang, Judy, Tayo, Bamidele O., Ahluwalia, Tarunveer S., Almgren, Peter, Bakker, Stephan J.L., Banas, Bernhard, Bansal, Nisha, Biggs, Mary L., Boerwinkle, Eric, Bottinger, Erwin P., Brenner, Hermann, Carroll, Robert J., Chalmers, John, Chee, Miao-Li, Chee, Miao-Ling, Cheng, Ching-Yu, Coresh, Josef, de Borst, Martin H., Degenhardt, Frauke, Eckardt, Kai-Uwe, Endlich, Karlhans, Franke, Andre, Freitag-Wolf, Sandra, Gampawar, Piyush, Gansevoort, Ron T., Ghanbari, Mohsen, Gieger, Christian, Hamet, Pavel, Ho, Kevin, Hofer, Edith, Holleczek, Bernd, Xian Foo, Valencia Hui, Hutri-Kähönen, Nina, Hwang, Shih-Jen, Ikram, M. Arfan, Josyula, Navya Shilpa, Kähönen, Mika, Khor, Chiea-Chuen, Koenig, Wolfgang, Kramer, Holly, Krämer, Bernhard K., Kühnel, Brigitte, Lange, Leslie A., Lehtimäki, Terho, Lieb, Wolfgang, Loos, Ruth J.F., Lukas, Mary Ann, Lyytikäinen, Leo-Pekka, Meisinger, Christa, Meitinger, Thomas, Melander, Olle, Milaneschi, Yuri, Mishra, Pashupati P., Mononen, Nina, Mychaleckyj, Josyf C., Nadkarni, Girish N., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, Ilja M., O’Donoghue, Michelle L., Orho-Melander, Marju, Pendergrass, Sarah A., Penninx, Brenda W.J.H., Preuss, Michael H., Psaty, Bruce M., Raffield, Laura M., Raitakari, Olli T., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Rosenkranz, Alexander R., Rossing, Peter, Rotter, Jerome I., Sabanayagam, Charumathi, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Sedaghat, Sanaz, Shaffer, Christian M., Strauch, Konstantin, Szymczak, Silke, Taylor, Kent D., Tremblay, Johanne, Chaker, Layal, van der Most, Peter J., Verweij, Niek, Völker, Uwe, Waldenberger, Melanie, Wallentin, Lars, Waterworth, Dawn M., White, Harvey D., Wilson, James G., Wong, Tien-Yin, Woodward, Mark, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Yan, Wanner, Christoph, Böger, Carsten A., Köttgen, Anna, Kronenberg, Florian, Pattaro, Cristian, and Heid, Iris M.

Published
2021
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7. Cohort profile:the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands

Author

Aanstoot, Henk Jan, Varkevisser, Rita D.M., Mul, Dick, Dekker, Pim, Birnie, Erwin, Boesten, Lianne S.M., Brugts, Michael P., van Dijk, Peter R., Duijvestijn, Petronella H.L.M., Dutta, Sanjoy, Fransman, Christine, Gonera, Rob K., Hoogenberg, Klaas, Kooy, Adriaan, Latres, Esther, Loves, Sandra, Nefs, Giesje, Sas, Theo, Vollenbrock, Charlotte E., Vosjan-Noeverman, Marleen J., de Vries-Velraeds, Martine M.C., Veeze, Henk J., Wolffenbuttel, Bruce H.R., van der Klauw, Melanie M., Aanstoot, Henk Jan, Varkevisser, Rita D.M., Mul, Dick, Dekker, Pim, Birnie, Erwin, Boesten, Lianne S.M., Brugts, Michael P., van Dijk, Peter R., Duijvestijn, Petronella H.L.M., Dutta, Sanjoy, Fransman, Christine, Gonera, Rob K., Hoogenberg, Klaas, Kooy, Adriaan, Latres, Esther, Loves, Sandra, Nefs, Giesje, Sas, Theo, Vollenbrock, Charlotte E., Vosjan-Noeverman, Marleen J., de Vries-Velraeds, Martine M.C., Veeze, Henk J., Wolffenbuttel, Bruce H.R., and van der Klauw, Melanie M.

Abstract

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS:Research groups are invited to consider the use of these data and the sample collection. Future work will include additi

Published
2024

8. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, Medici, Marco, Sterenborg, Rosalie B.T.M., Steinbrenner, Inga, Li, Yong, Bujnis, Melissa N., Naito, Tatsuhiko, Marouli, Eirini, Galesloot, Tessel E., Babajide, Oladapo, Andreasen, Laura, Astrup, Arne, Åsvold, Bjørn Olav, Bandinelli, Stefania, Beekman, Marian, Beilby, John P., Bork-Jensen, Jette, Boutin, Thibaud, Brody, Jennifer A., Brown, Suzanne J., Brumpton, Ben, Campbell, Purdey J., Cappola, Anne R., Ceresini, Graziano, Chaker, Layal, Chasman, Daniel I., Concas, Maria Pina, Coutinho de Almeida, Rodrigo, Cross, Simone M., Cucca, Francesco, Deary, Ian J., Kjaergaard, Alisa Devedzic, Echouffo Tcheugui, Justin B., Ellervik, Christina, Eriksson, Johan G., Ferrucci, Luigi, Freudenberg, Jan, Fuchsberger, Christian, Gieger, Christian, Giulianini, Franco, Gögele, Martin, Graham, Sarah E., Grarup, Niels, Gunjača, Ivana, Hansen, Torben, Harding, Barbara N., Harris, Sarah E., Haunsø, Stig, Hayward, Caroline, Hui, Jennie, Ittermann, Till, Jukema, J. Wouter, Kajantie, Eero, Kanters, Jørgen K., Kårhus, Line L., Kiemeney, Lambertus A.L.M., Kloppenburg, Margreet, Kühnel, Brigitte, Lahti, Jari, Langenberg, Claudia, Lapauw, Bruno, Leese, Graham, Li, Shuo, Liewald, David C.M., Linneberg, Allan, Lominchar, Jesus V.T., Luan, Jian’an, Martin, Nicholas G., Matana, Antonela, Meima, Marcel E., Meitinger, Thomas, Meulenbelt, Ingrid, Mitchell, Braxton D., Møllehave, Line T., Mora, Samia, Naitza, Silvia, Nauck, Matthias, Netea-Maier, Romana T., Noordam, Raymond, Nursyifa, Casia, Okada, Yukinori, Onano, Stefano, Papadopoulou, Areti, Palmer, Colin N.A., Pattaro, Cristian, Pedersen, Oluf, Peters, Annette, Pietzner, Maik, Polašek, Ozren, Pramstaller, Peter P., Psaty, Bruce M., Punda, Ante, Ray, Debashree, Redmond, Paul, Richards, J. Brent, Ridker, Paul M., Russ, Tom C., Ryan, Kathleen A., Olesen, Morten Salling, Schultheiss, Ulla T., Selvin, Elizabeth, Siddiqui, Moneeza K., Sidore, Carlo, Slagboom, P. Eline, Sørensen, Thorkild I.A., Soto-Pedre, Enrique, Spector, Tim D., Spedicati, Beatrice, Srinivasan, Sundararajan, Starr, John M., Stott, David J., Tanaka, Toshiko, Torlak, Vesela, Trompet, Stella, Tuhkanen, Johanna, Uitterlinden, André G., van den Akker, Erik B., van den Eynde, Tibbert, van der Klauw, Melanie M., van Heemst, Diana, Verroken, Charlotte, Visser, W. Edward, Vojinovic, Dina, Völzke, Henry, Waldenberger, Melanie, Walsh, John P., Wareham, Nicholas J., Weiss, Stefan, Willer, Cristen J., Wilson, Scott G., Wolffenbuttel, Bruce H.R., Wouters, Hanneke J.C.M., Wright, Margaret J., Yang, Qiong, Zemunik, Tatijana, Zhou, Wei, Zhu, Gu, Zöllner, Sebastian, Smit, Johannes W.A., Peeters, Robin P., Köttgen, Anna, Teumer, Alexander, and Medici, Marco

Abstract

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024

14. Corrigendum to “A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals” [Environ. Int., A Genome-Wide Association Study of 24-Hour Urinary Excretion of Endocrine Disrupting Chemicals 183 (2024) 108396]

Author

Lu, Xueling, van der Meer, Thomas P., Kamali, Zoha, van Faassen, Martijn, Kema, Ido P., van Beek, André P., Xu, Xijin, Huo, Xia, Ani, Alireza, Nolte, Ilja M., Wolffenbuttel, Bruce H.R., van Vliet-Ostaptchouk, Jana V., and Snieder, Harold

Published
2024
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15. Cohort profile: the "Biomarkers of heterogeneity in type 1 diabetes" study - a prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes

Author

Mul, Dick, primary, Varkevisser, Rita D.M., additional, Aanstoot, Henk-Jan, additional, Dekker, Pim, additional, Birnie, Erwin, additional, Boersma, Erik, additional, Boesten, Lianne S.M., additional, Brugts, Michael P., additional, van Dijk, Peter R., additional, Duijvestijn, Petronella H.L.M., additional, Dutta, Sanjoy, additional, Fransman, Christine, additional, Gonera, Rob, additional, Hoogenberg, Klaas, additional, Kooy, Adriaan, additional, Latres, Esther, additional, Loves, Sandra, additional, Nefs, Giesje, additional, Sas, Theo, additional, Verburg, Frederik A.J., additional, Vollenbrock, Charlotte E., additional, Vosjan-Noeverman, Marleen J., additional, de Vries-Velraeds, Martine M.C., additional, Veeze, Henk J., additional, Wolffenbuttel, Bruce H.R., additional, and van der Klauw, Melanie M., additional

Published
2023
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17. Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure

Author

Huang, Yisong, Ollikainen, Miina, Muniandy, Maheswary, Zhang, Tao, van Dongen, Jenny, Hao, Guang, van der Most, Peter J., Pan, Yue, Pervjakova, Natalia, Sun, Yan V., Hui, Qin, Lahti, Jari, Fraszczyk, Eliza, Lu, Xueling, Sun, Dianjianyi, Richard, Melissa A., Willemsen, Gonneke, Heikkila, Kauko, Mateo Leach, Irene, Mononen, Nina, Kähönen, Mika, Hurme, Mikko A., Raitakari, Olli T., Drake, Amanda J., Perola, Markus, Nuotio, Marja-Liisa, Huang, Yunfeng, Khulan, Batbayar, Räikkönen, Katri, Wolffenbuttel, Bruce H.R., Zhernakova, Alexandra, Fu, Jingyuan, Zhu, Haidong, Dong, Yanbin, van Vliet-Ostaptchouk, Jana V., Franke, Lude, Eriksson, Johan G., Fornage, Myriam, Milani, Lili, Lehtimäki, Terho, Vaccarino, Viola, Boomsma, Dorret I., van der Harst, Pim, de Geus, Eco J.C., Salomaa, Veikko, Li, Shengxu, Chen, Wei, Su, Shaoyong, Wilson, James, Snieder, Harold, Kaprio, Jaakko, and Wang, Xiaoling

Published
2020
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18. 1型糖尿病管理的改进空间

Author

Varkevisser, Rita D.M., Birnie, Erwin, Mul, Dick, van Dijk, Peter R., Aanstoot, Henk Jan, Wolffenbuttel, Bruce H.R., van der Klauw, Melanie M., Health Psychology Research, Center for Liver, Digestive and Metabolic Diseases, and Life Course Epidemiology

Subjects
diabetes mellitus type 1, lipid metabolism, blood glucose, blood pressure, cholesterol, cardiovascular diseases, LDL
Abstract

Aims/Hypothesis: Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. Methods: Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c)

Published
2023

19. Serum Bicarbonate and Kidney Disease Progression and Cardiovascular Outcome in Patients With Diabetic Nephropathy: A Post Hoc Analysis of the RENAAL (Reduction of End Points in Non–Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study and IDNT (Irbesartan Diabetic Nephropathy Trial)

Author

Schutte, Elise, Lambers Heerspink, Hiddo J., Lutgers, Helen L., Bakker, Stephan J.L., Vart, Priya, Wolffenbuttel, Bruce H.R., Umanath, Kausik, Lewis, Julia B., de Zeeuw, Dick, and Gansevoort, Ron T.

Published
2015
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21. Cognition and brain abnormalities on MRI in pituitary patients

Author

Brummelman, Pauline, Sattler, Margriet G.A., Meiners, Linda C., van den Berg, Gerrit, van der Klauw, Melanie M., Elderson, Martin F., Dullaart, Robin P.F., Koerts, Janneke, Werumeus Buning, Jorien, Tucha, Oliver, Wolffenbuttel, Bruce H.R., van den Bergh, Alfons C.M., and van Beek, André P.

Published
2015
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22. The importance of vitamin B12 for individuals choosing plant-based diets

Author

Niklewicz, Ali, Smith, A. David, Smith, Alison, Holzer, Andre, Klein, Andrew, McCaddon, Andrew, Molloy, Anne M., Wolffenbuttel, Bruce H.R., Nexo, Ebba, McNulty, Helene, Refsum, Helga, Gueant, Jean Louis, Dib, Marie Joe, Ward, Mary, Murphy, Michelle, Green, Ralph, Ahmadi, Kourosh R., Hannibal, Luciana, Warren, Martin J., Owen, P. Julian, and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Diet, Vegan, Public health, Nutrition and Dietetics, Vitamin B12, Medicine (miscellaneous), Vitamins, Diet, Plant-based diets, Diet, Vegetarian/adverse effects, Vitamin B 12, Women of child-bearing age, Vegetarian and vegan populations, Planetary health, Pregnancy, Humans, Female, Dietary recommendations
Abstract

Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000 days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.

Published
2023

23. Once-Weekly Semaglutide Use in Type 2 Diabetes: Real-World Data from the SURE Netherlands Observational Study

Author

Wolffenbuttel, Bruce H.R., Brugts, Michel P., Catarig, Andrei Mircea, Clark, Alice, Kok, Maarten, Lieverse, Aloysius G., van Soest, Jaap, and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Real-world evidence, Health-related quality of life, Observational study, Glucagon-like peptide 1 receptor agonist, Glycated haemoglobin, SURE, Semaglutide, Pharmacology (medical), General Medicine, Body weight, Type 2 diabetes
Abstract

Introduction: SURE Netherlands (NCT03929679) evaluated the use of once-weekly (OW) semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), in routine clinical care for individuals with type 2 diabetes (T2D). Methods: Adults (age ≥ 18 years) with T2D were enrolled into the single-arm study. The primary endpoint was change from baseline to end of study (EOS; approx. 30 weeks) in glycated haemoglobin (HbA1c). Secondary endpoints were change from baseline to EOS in body weight (BW) and waist circumference (WC). Proportions of participants achieving predefined HbA1c targets and weight-loss responses at EOS, safety, health-related quality of life (HRQoL) and treatment satisfaction were assessed. Results: In total, 211 participants (mean age 60.5 years; diabetes duration 13.3 years) initiated semaglutide; most were receiving metformin (82.9%) and/or basal insulin (59.2%) at baseline, and 6.2% switched from another GLP-1RA. Mean baseline HbA1c, BW and WC were 8.6%, 105.2 kg and 118.8 cm. In the 186 (88.2%) participants receiving semaglutide at EOS, mean reduction in HbA1c with semaglutide was − 1.2%-points (95% [confidence interval] CI − 1.3; − 1.0; p < 0.0001), with 124 (70.5%), 95 (54.0%) and 65 (36.9%) participants achieving HbA1c targets of < 8.0%, < 7.5% and < 7.0%, respectively. Mean reduction in BW was − 7.8 kg [95% CI − 8.7; − 6.8; p < 0.0001], corresponding to relative reduction of − 7.5% [95% CI − 8.4; − 6.6; p < 0.0001]. Improvements in WC (− 8.8 cm [95% CI − 10.4; − 7.2; p < 0.0001]), HRQoL and treatment satisfaction were observed, including across most Short-Form 36 Health Survey domains. One serious adverse drug reaction (cholecystitis) was reported. Eight participants (all receiving concomitant insulin) experienced severe or documented hypoglycaemia. Conclusion: Individuals with T2D treated with OW semaglutide experienced significant and clinically relevant improvements in glycaemic control and BW from baseline. These results from a diverse real-world population in the Netherlands support the use of OW semaglutide in treating adults with T2D in routine clinical practice.

Published
2022

29. Diagnosis of Gestational Diabetes Mellitus

Author

Wolffenbuttel, Bruce H.R. and Wolffenbuttel, Bruce H.R.

Abstract

Gestational diabetes mellitus (GDM) is associated with a high risk of obstetric and neonatal complications. Adequate diagnosis and appropriate treatment are key to prevention of these complications. Most international guidelines have adopted the IADPSG 2010/WHO 2013 diagnostic criteria, for the diagnosis of GDM by recommending the following glycemic thresholds for a 75 g OGTT: fasting plasma glucose value =5.1 mmol/l (92 mg/dl); 1-h value =10.0 mmol/l (180 mg/dl); and 2-h value =8.5 mmol/l (153 mg/dl). These specific cut-off values were chosen because they predict a 75% higher chance of adverse pregnancy outcomes compared to normal glucose values. Some countries have adopted either higher levels for fasting glucose (5.6 or 7.0 mmol/l) or lower levels for 2-h post-OGTT glucose (7.8 mmol/l). There still is some debate whether it is desirable to lower the diagnostic 2-h glucose thresholds to =7.5 mmol/l for Caucasian women and =7.2 mmol/l for women from South Asian background. Several studies have shown that about 20-30% (depending on the applied diagnostic criteria) of the women screened for GDM had/have abnormal OGTT results, necessitating referral, active counseling, and treatment. By adopting the new IADPSG/WHO diagnostic criteria, the prevalence of GDM has increased, which has a major impact on the costs and the capacity of healthcare systems. Screening for GDM may follow either a one-step or a two-step approach. In the one-step approach, GDM is diagnosed based on the results of a single 75 g OGTT. The two-step screening strategy makes use of a non-fasting 50 g glucose challenge test (GCT), whereby an abnormal test result (i.e., a 1-h plasma glucose value =7.8 mmol/l) is followed by a 100 g OGTT. There also is no international consensus on whether universal or risk factor-based screening is preferred. Universal screening implies that all pregnant women will undergo screening between 24 and 28 weeks of pregnancy, while in selective screening, only women who have

Published
2022

30. NFAT5 and SLC4A10 Loci Associate with Plasma Osmolality

Author

Böger, Carsten A., Gorski, Mathias, McMahon, Gearoid M., Xu, Huichun, Chang, Yen-Pei C., van der Most, Peter J., Navis, Gerjan, Nolte, Ilja M., de Borst, Martin H., Zhang, Weihua, Lehne, Benjamin, Loh, Marie, Tan, Sian-Tsung, Boerwinkle, Eric, Grams, Morgan E., Sekula, Peggy, Li, Man, Wilmot, Beth, Moon, James G., Scheet, Paul, Cucca, Francesco, Xiao, Xiangjun, Lyytikäinen, Leo-Pekka, Delgado, Graciela, Grammer, Tanja B., Kleber, Marcus E., Sedaghat, Sanaz, Rivadeneira, Fernando, Corre, Tanguy, Kutalik, Zoltan, Bergmann, Sven, Nielson, Carrie M., Srikanth, Priya, Teumer, Alexander, Müller-Nurasyid, Martina, Brockhaus, Anne Catharina, Pfeufer, Arne, Rathmann, Wolfgang, Peters, Annette, Matsumoto, Martha, de Andrade, Mariza, Atkinson, Elizabeth J., Robinson-Cohen, Cassianne, de Boer, Ian H., Hwang, Shih-Jen, Heid, Iris M., Gögele, Martin, Concas, Maria Pina, Tanaka, Toshiko, Bandinelli, Stefania, Nalls, Mike A., Singleton, Andrew, Tajuddin, Salman M., Adeyemo, Adebowale, Zhou, Jie, Doumatey, Ayo, McWeeney, Shannon, Murabito, Joanne, Franceschini, Nora, Flessner, Michael, Shlipak, Michael, Wilson, James G., Chen, Guanjie, Rotimi, Charles N., Zonderman, Alan B., Evans, Michele K., Ferrucci, Luigi, Devuyst, Olivier, Pirastu, Mario, Shuldiner, Alan, Hicks, Andrew A., Pramstaller, Peter Paul, Kestenbaum, Bryan, Kardia, Sharon L.R., Turner, Stephen T., Study, LifeLines Cohort, Briske, Tamara Ellefson, Gieger, Christian, Strauch, Konstantin, Meisinger, Christa, Meitinger, Thomas, Völker, Uwe, Nauck, Matthias, Völzke, Henry, Vollenweider, Peter, Bochud, Murielle, Waeber, Gerard, Kähönen, Mika, Lehtimäki, Terho, März, Winfried, Dehghan, Abbas, Franco, Oscar H., Uitterlinden, Andre G., Hofman, Albert, Taylor, Herman A., Chambers, John C., Kooner, Jaspal S., Fox, Caroline S., Hitzemann, Robert, Orwoll, Eric S., Pattaro, Cristian, Schlessinger, David, Köttgen, Anna, Snieder, Harold, Parsa, Afshin, Cohen, David M., Alizadeh, Behrooz Z., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, N., G., Rots, Marianne G., S., H., Swertz, Morris, Wolffenbuttel, Bruce H.R., and Wijmenga, Cisca

Published
2017
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35. A non-invasive risk score including skin autofluorescence predicts diabetes risk in the general population

Author

Boersma, Henderikus E., van der Klauw, Melanie M., Smit, Andries J., Wolffenbuttel, Bruce H.R., Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), and Center for Liver, Digestive and Metabolic Diseases (CLDM)

Subjects
Cohort Studies, Multidisciplinary, Diabetes Mellitus, Type 2, Risk Factors, Cardiovascular Diseases, Humans, Skin
Abstract

Increased skin autofluorescence (SAF) predicts the development of diabetes-related complications and cardiovascular disease. We assessed the performance of a simple model which includes SAF to identify individuals at high risk for undiagnosed and incident type 2 diabetes, in 58,377 participants in the Lifelines Cohort Study without known diabetes. Newly-diagnosed diabetes was defined as fasting blood glucose ≥7.0 mmol/l and/or HbA1c ≥6.5% (≥48 mmol/mol) or self-reported diabetes at follow-up. We constructed predictive models based on age, body mass index (BMI), SAF, and parental history of diabetes, and compared to results with the concise FINDRISC model.At 2nd visit to Lifelines, 1113 (1.9%) participants were identified with undiagnosed diabetes and 1033 (1.8%) participants developed diabetes during follow-up. A model comprising age, BMI and SAF yielded an AUC of 0.783 and was non-inferior to the concise FINDRISC model, which had an AUC of 0.797 to predict new diabetes. At a score of 5.8, sensitivity was 78% and specificity of 66%. Model 2 which also incorporated parental diabetes history, had an AUC of 0.792, and a sensitivity of 74% and specificity of 70% at a score of 6.5. Net reclassification index (NRI) did not improve significantly (NRI 1.43% (-0.50-3.37 p=0.15). The combination of an easy to perform SAF measurement with age and BMI is a good alternative screening tool suitable for medical and non-medical settings. Parental history of diabetes did not significantly improve model performance in this homogeneous cohort.

Published
2022

40. Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes

Author

Pazoki, Raha, Vujkovic, Marijana, Elliott, Joshua, Evangelou, Evangelos, Gill, Dipender, Ghanbari, Mohsen, van der Most, Peter J., Pinto, Rui Climaco, Wielscher, Matthias, Farlik, Matthias, Zuber, Verena, de Knegt, Robert J., Snieder, Harold, Uitterlinden, André G., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Lynch, Julie A., Jiang, Xiyun, Said, Saredo, Kaplan, David E., Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Tsao, Philip S., Atkinson, Stephen R., Dehghan, Abbas, Tzoulaki, Ioanna, Ikram, M. Arfan, Herzig, Karl Heinz, Järvelin, Marjo Riitta, Alizadeh, Behrooz Z., O’Donnell, Christopher J., Saleheen, Danish, Voight, Benjamin F., Chang, Kyong Mi, Thursz, Mark R., Elliott, Paul, Pazoki, Raha, Vujkovic, Marijana, Elliott, Joshua, Evangelou, Evangelos, Gill, Dipender, Ghanbari, Mohsen, van der Most, Peter J., Pinto, Rui Climaco, Wielscher, Matthias, Farlik, Matthias, Zuber, Verena, de Knegt, Robert J., Snieder, Harold, Uitterlinden, André G., Boezen, H. Marike, Franke, Lude, van der Harst, Pim, Navis, Gerjan, Rots, Marianne, Swertz, Morris, Wolffenbuttel, Bruce H.R., Wijmenga, Cisca, Lynch, Julie A., Jiang, Xiyun, Said, Saredo, Kaplan, David E., Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Tsao, Philip S., Atkinson, Stephen R., Dehghan, Abbas, Tzoulaki, Ioanna, Ikram, M. Arfan, Herzig, Karl Heinz, Järvelin, Marjo Riitta, Alizadeh, Behrooz Z., O’Donnell, Christopher J., Saleheen, Danish, Voight, Benjamin F., Chang, Kyong Mi, Thursz, Mark R., and Elliott, Paul

Abstract

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

Published
2021

44. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author

Gorski, Mathias, primary, Jung, Bettina, additional, Li, Yong, additional, Matias-Garcia, Pamela R., additional, Wuttke, Matthias, additional, Coassin, Stefan, additional, Thio, Chris H.L., additional, Kleber, Marcus E., additional, Winkler, Thomas W., additional, Wanner, Veronika, additional, Chai, Jin-Fang, additional, Chu, Audrey Y., additional, Cocca, Massimiliano, additional, Feitosa, Mary F., additional, Ghasemi, Sahar, additional, Hoppmann, Anselm, additional, Horn, Katrin, additional, Li, Man, additional, Nutile, Teresa, additional, Scholz, Markus, additional, Sieber, Karsten B., additional, Teumer, Alexander, additional, Tin, Adrienne, additional, Wang, Judy, additional, Tayo, Bamidele O., additional, Ahluwalia, Tarunveer S., additional, Almgren, Peter, additional, Bakker, Stephan J.L., additional, Banas, Bernhard, additional, Bansal, Nisha, additional, Biggs, Mary L., additional, Boerwinkle, Eric, additional, Bottinger, Erwin P., additional, Brenner, Hermann, additional, Carroll, Robert J., additional, Chalmers, John, additional, Chee, Miao-Li, additional, Chee, Miao-Ling, additional, Cheng, Ching-Yu, additional, Coresh, Josef, additional, de Borst, Martin H., additional, Degenhardt, Frauke, additional, Eckardt, Kai-Uwe, additional, Endlich, Karlhans, additional, Franke, Andre, additional, Freitag-Wolf, Sandra, additional, Gampawar, Piyush, additional, Gansevoort, Ron T., additional, Ghanbari, Mohsen, additional, Gieger, Christian, additional, Hamet, Pavel, additional, Ho, Kevin, additional, Hofer, Edith, additional, Holleczek, Bernd, additional, Xian Foo, Valencia Hui, additional, Hutri-Kähönen, Nina, additional, Hwang, Shih-Jen, additional, Ikram, M. Arfan, additional, Josyula, Navya Shilpa, additional, Kähönen, Mika, additional, Khor, Chiea-Chuen, additional, Koenig, Wolfgang, additional, Kramer, Holly, additional, Krämer, Bernhard K., additional, Kühnel, Brigitte, additional, Lange, Leslie A., additional, Lehtimäki, Terho, additional, Lieb, Wolfgang, additional, Loos, Ruth J.F., additional, Lukas, Mary Ann, additional, Lyytikäinen, Leo-Pekka, additional, Meisinger, Christa, additional, Meitinger, Thomas, additional, Melander, Olle, additional, Milaneschi, Yuri, additional, Mishra, Pashupati P., additional, Mononen, Nina, additional, Mychaleckyj, Josyf C., additional, Nadkarni, Girish N., additional, Nauck, Matthias, additional, Nikus, Kjell, additional, Ning, Boting, additional, Nolte, Ilja M., additional, O’Donoghue, Michelle L., additional, Orho-Melander, Marju, additional, Pendergrass, Sarah A., additional, Penninx, Brenda W.J.H., additional, Preuss, Michael H., additional, Psaty, Bruce M., additional, Raffield, Laura M., additional, Raitakari, Olli T., additional, Rettig, Rainer, additional, Rheinberger, Myriam, additional, Rice, Kenneth M., additional, Rosenkranz, Alexander R., additional, Rossing, Peter, additional, Rotter, Jerome I., additional, Sabanayagam, Charumathi, additional, Schmidt, Helena, additional, Schmidt, Reinhold, additional, Schöttker, Ben, additional, Schulz, Christina-Alexandra, additional, Sedaghat, Sanaz, additional, Shaffer, Christian M., additional, Strauch, Konstantin, additional, Szymczak, Silke, additional, Taylor, Kent D., additional, Tremblay, Johanne, additional, Chaker, Layal, additional, van der Harst, Pim, additional, van der Most, Peter J., additional, Verweij, Niek, additional, Völker, Uwe, additional, Waldenberger, Melanie, additional, Wallentin, Lars, additional, Waterworth, Dawn M., additional, White, Harvey D., additional, Wilson, James G., additional, Wong, Tien-Yin, additional, Woodward, Mark, additional, Yang, Qiong, additional, Yasuda, Masayuki, additional, Yerges-Armstrong, Laura M., additional, Zhang, Yan, additional, Snieder, Harold, additional, Wanner, Christoph, additional, Böger, Carsten A., additional, Köttgen, Anna, additional, Kronenberg, Florian, additional, Pattaro, Cristian, additional, Heid, Iris M., additional, Alizadeh, Behrooz Z., additional, Boezen, H. Marike, additional, Franke, Lude, additional, Navis, Gerjan, additional, Rots, Marianne, additional, Swertz, Morris, additional, Wolffenbuttel, Bruce H.R., additional, Wijmenga, Cisca, additional, Abecasis, Goncalo, additional, Baras, Aris, additional, Cantor, Michael, additional, Coppola, Giovanni, additional, Economides, Aris, additional, Lotta, Luca A., additional, Overton, John D., additional, Reid, Jeffrey G., additional, Shuldiner, Alan, additional, Beechert, Christina, additional, Forsythe, Caitlin, additional, Fuller, Erin D., additional, Gu, Zhenhua, additional, Lattari, Michael, additional, Lopez, Alexander, additional, Schleicher, Thomas D., additional, Padilla, Maria Sotiropoulos, additional, Toledo, Karina, additional, Widom, Louis, additional, Wolf, Sarah E., additional, Pradhan, Manasi, additional, Manoochehri, Kia, additional, Ulloa, Ricardo H., additional, Bai, Xiaodong, additional, Balasubramanian, Suganthi, additional, Barnard, Leland, additional, Blumenfeld, Andrew, additional, Eom, Gisu, additional, Habegger, Lukas, additional, Hawes, Alicia, additional, Khalid, Shareef, additional, Maxwell, Evan K., additional, Salerno, William, additional, Staples, Jeffrey C., additional, Jones, Marcus B., additional, and Mitnaul, Lyndon J., additional

Published
2021
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45. Sex differences in cardiometabolic risk factors, pharmacological treatment and risk factor control in type 2 diabetes: Findings from the Dutch Diabetes Pearl cohort

Author

JC onderzoeksprogramma Cardiovascular Health, Cardiovasculaire Epi Team 5, MS Interne Geneeskunde, Circulatory Health, Global Health, De Jong, Marit, Oskam, Marieke J., Sep, Simone J.S., Ozcan, Behiye, Rutters, Femke, Sijbrands, Eric J.G., Elders, Petra J.M., Siegelaar, Sarah E., Devries, J. Hans, Tack, Cees J., Schroijen, Marielle, De Valk, Harold W., Abbink, Evertine J., Stehouwer, Coen D.A., Jazet, Ingrid, Wolffenbuttel, Bruce H.R., Peters, Sanne A.E., Schram, Miranda T., JC onderzoeksprogramma Cardiovascular Health, Cardiovasculaire Epi Team 5, MS Interne Geneeskunde, Circulatory Health, Global Health, De Jong, Marit, Oskam, Marieke J., Sep, Simone J.S., Ozcan, Behiye, Rutters, Femke, Sijbrands, Eric J.G., Elders, Petra J.M., Siegelaar, Sarah E., Devries, J. Hans, Tack, Cees J., Schroijen, Marielle, De Valk, Harold W., Abbink, Evertine J., Stehouwer, Coen D.A., Jazet, Ingrid, Wolffenbuttel, Bruce H.R., Peters, Sanne A.E., and Schram, Miranda T.

Published
2020

46. High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes: The Dutch Diabetes Pearl Cohort

Author

MS Interne Geneeskunde, Circulatory Health, Van Meijel, Lian A., De Vegt, Femmie, Abbink, Evertine J., Rutters, Femke, Schram, Miranda T., Van Der Klauw, Melanie M., Wolffenbuttel, Bruce H.R., Siegelaar, Sarah, Devries, J. Hans, Sijbrands, Eric J.G., Özcan, Behiye, De Valk, Harold W., Silvius, Bianca, Schaper, Nicolaas, Stehouwer, Coen D.A., Elders, Petra J.M., Tack, Cornelis J., De Galan, Bastiaan E., MS Interne Geneeskunde, Circulatory Health, Van Meijel, Lian A., De Vegt, Femmie, Abbink, Evertine J., Rutters, Femke, Schram, Miranda T., Van Der Klauw, Melanie M., Wolffenbuttel, Bruce H.R., Siegelaar, Sarah, Devries, J. Hans, Sijbrands, Eric J.G., Özcan, Behiye, De Valk, Harold W., Silvius, Bianca, Schaper, Nicolaas, Stehouwer, Coen D.A., Elders, Petra J.M., Tack, Cornelis J., and De Galan, Bastiaan E.

Published
2020

47. Endocrine disrupting chemicals during diet-induced weight loss – A post-hoc analysis of the LOWER study

Author

van der Meer, Thomas P., primary, Thio, Chris H.L., additional, van Faassen, Martijn, additional, van Beek, André P., additional, Snieder, Harold, additional, van Berkum, Frank N.R., additional, Kema, Ido P., additional, Makris, Konstantinos C., additional, Wolffenbuttel, Bruce H.R., additional, and van Vliet-Ostaptchouk, Jana V., additional

Published
2021
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