Martijn Brouwers

Professor

Dr Martijn Brouwers obtained his MD degree (with honours) in 2002, after which he started his PhD project that focused on hepatic steatosis in familial combined hyperlipidemia. In 2006, he worked as a trainee at the Department of Internal Medicine and Endocrinology. Since 2012, he has been a staff member (internist-endocrinologist) at Maastricht UMC+ and in 2019 he was appointed as the head of the division of Endocrinology and Metabolic Disease.

His research focusses on the cardiometabolic consequences of nonalcoholic fatty liver disease (NAFLD). NAFLD consists of a histological spectrum comprising simple steatosis, steatohepatitis (NASH), fibrosis and cirrhosis. Evidence is accumulating that NAFLD is not only a liver disease per se, it is also a risk factor for type 2 diabetes, chronic kidney disease and cardiovascular disease. This research line aims to elucidate the exact mechanistic link between NAFLD and these systemic diseases. For this, a diverse set of studies is used, ranging from (genetic) epidemiology, to ‘human knockout’ models, to randomised controlled trials and experimental animal work. This research is in part funded by the Dutch Heart Foundation, the Dutch Diabetes Foundation and the European Foundation for the Study of Diabetes.

Department ofInternal Medicine
P. Debeyelaan 25, 6229 HX Maastricht 
PO Box 5800, 6202 AZ Maastricht
T: +31(0)43 388 70 19

  • 2026
    • Dimitropoulou, N. M., Beran, M., Eussen, S. J. P. M., Dingena, C. F., Dagnelie, P. C., Van Der Kallen, C. J. H., Koster, A., Van Greevenbroek, M. M. J., Brouwers, M. C. G. J., Schram, M. T., & de Galan, B. E. (2026). Liver fat content is not elevated in people with type 1 diabetes: the Maastricht Study. Diabetologia, 69(2), 364-373. https://doi.org/10.1007/s00125-025-06597-y
  • 2025
    • van Oeteren, M. A. J., De Groot, D. M., Buziau, A. M., Scheijen, J. L. J. M., van de Waarenburg, M. P. H., Kroon, A. A., Eussen, S. J. P. M., Dagnelie, P. C., Van Greevenbroek, M. M. J., Houben, A. J. H. M., Meex, S. J. R., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2025). The effects of dietary fructose on blood pressure are modified by the food matrix. Clinical Nutrition, 55, 134-140. https://doi.org/10.1016/j.clnu.2025.10.017
    • Brouwers, M. C. G. J., Klop, B., Ribalta, J., & Cabezas, M. C. (2025). Familial Combined Hyperlipidemia: Myth or Reality?Current Atherosclerosis Reports, 27(1), Article 45. https://doi.org/10.1007/s11883-025-01289-9
    • Visker, V. P., Kvist, A. V., Vestergaard, P., van den Bergh, J. P., Brouwers, M. C. J. G., Wyers, C. E., & Driessen, J. H. M. (2025). Fracture trends in Denmark from 1997 to 2021. Osteoporosis International. Advance online publication. https://doi.org/10.1007/s00198-025-07746-0
    • Chen, H., Simons, P. I. H. G., Simons, N., van de Waarenburg, M. P. H., Bons, J. A. P., van der Ploeg, E. M. C. L., Feskens, E. J. M., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2025). Effects of glucose and fructose supplementation on serum sex hormone-binding globulin and testosterone levels: post-hoc analysis of a double-blind randomized controlled trial. Clinical Nutrition ESPEN, 69, 384-388. https://doi.org/10.1016/j.clnesp.2025.07.1123
    • Ren, Z., Wesselius, A., Kooi, M. E., van Greevenbroek, M., Dagnelie, P., Berendschot, T. T. J. M., Kroon, A. A., Houben, A. J. H. M., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2025). Steatotic liver disease interacts with a polygenic risk score for triglyceride clearance to impact the risk of hypertriglyceridaemia: The Maastricht Study. Diabetologia, 68(10), 2217-2226. https://doi.org/10.1007/s00125-025-06479-3
    • Tichler, A., Hertroijs, D. F. L., van Mastrigt, G. A. P. G., Brouwers, M. C. G. J., Ruwaard, D., & Elissen, A. M. J. (2025). Evaluating the feasibility of study methods for a future trial-based economic evaluation of a multistage shared decision-making program for type 2 diabetes mellitus: Protocol for a cluster-randomized controlled pilot study. PLOS ONE, 20(8), Article e0300944. https://doi.org/10.1371/journal.pone.0300944
    • Langeveld, M., Brouwers, M. C. G. J., van Dussen, L., Koens, L. H., Langendonk, J. G. L., & Janssen, M. C. H. (2025). Erfelijke metabole ziekten bij volwassenen. Nederlands Tijdschrift voor Geneeskunde, 169, Article D8476. https://www.ntvg.nl/artikelen/erfelijke-metabole-ziekten-bij-volwassenen
    • Janssen, L. E. F., Hiligsmann, M., Timmer, C., van der Ploeg, L. M. C., Kerckhove, K. V., Cox, T., Heras, J. D. L., Cassiman, D., & Brouwers, M. C. G. J. (2025). Treatment preferences of adult patients with hereditary fructose intolerance: A discrete choice experiment. Molecular Genetics and Metabolism, 145(4), Article 109169. https://doi.org/10.1016/j.ymgme.2025.109169
    • van Bree, B. E., van der Heijden, D. M. B., van Golde, R. J. T., Brouwers, M. C. G. J., Spaanderman, M. E. A., & Valkenburg, O. (2025). Sex hormone-binding globulin as a biomarker for metabolic risk in European women with polycystic ovary syndrome. Gynecological Endocrinology, 41(1), Article 2500462. Advance online publication. https://doi.org/10.1080/09513590.2025.2500462
    • Chen, H., Simons, P. I. H. G., & Brouwers, M. C. G. J. (2025). Is cardiovascular disease in PCOS driven by MASLD?Trends in Endocrinology and Metabolism, 36(5), 389-391. https://doi.org/10.1016/j.tem.2024.10.005
    • Tichler, A., Hertroijs, D. F. L., Ruwaard, D., Brouwers, M. C. G. J., & Elissen, A. M. J. (2025). Development of a patient decision aid for type 2 diabetes mellitus: a patient-centered approach. BMC primary care, 26(1), Article 81. https://doi.org/10.1186/s12875-025-02772-7
    • Koene, E. J., Buziau, A. M., Cassiman, D., Cox, T. M., Bons, J., Scheijen, J. L. J. M., Schalkwijk, C. G., Meex, S. J., Saxena, A. R., Esler, W. P., Schrauwen-Hinderling, V. B., Schrauwen, P., & Brouwers, M. C. (2025). Safety and efficacy of pharmacological inhibition of ketohexokinase in hereditary fructose intolerance. Journal of Clinical Investigation, 135(6), Article e187376. https://doi.org/10.1172/JCI187376
    • van Oeteren, M. A. J., Simons, N., Simons, P. I. H. G., van de Waarenburg, M. P. H., Kooi, M. E., Feskens, E. J. M., van der Ploeg, E. M. C. L., Van den Eynde, M. D. G., Houben, A. J. H. M., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2025). Fructose restriction has beneficial effects on adipose tissue distribution but not on serum adipokine levels: Post-hoc analysis of a double-blind randomized controlled trial. Clinical Obesity, 15(1), Article e12714. https://doi.org/10.1111/cob.12714
    • Buziau, A. M., Lefeber, D. J., Cassiman, D., Rubio-Gozalbo, M. E., Kwast, H., Tolan, D. R., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2025). Aldolase B Deficient Mice Are Characterized by Hepatic Nucleotide Sugar Abnormalities. Journal of Inherited Metabolic Disease, 48(1), Article e12836. https://doi.org/10.1002/jimd.12836
    • Balfoort, B. M., van den Broeck, F., Boon, C. J. F., Brouwers, M. C. G. J., Diederen, R. M. H., Dhillon, P., van Hasselt, P. M., Jaeger, B., Karuntu, J. S., Rennings, A. J. M., van Spronsen, F. J., Timmer, C., Wagenmakers, M. A. E. M., De Zaeytijd, J., Leroy, B. P., Schulze, A., van Karnebeek, C. D., Brands, M. M., & GACR “Bird's Eye View” Consortium (2025). Novel Insights Into Gyrate Atrophy of the Choroid and Retina (GACR): A Cohort Study. Journal of Inherited Metabolic Disease, 48(1), Article e12842. https://doi.org/10.1002/jimd.12842
  • 2024
    • Brouwers, M. C. G. J. (2024). Reconciling the apparently contrasting observational and genetic evidence on the association between MASLD and cardiovascular disease. Journal of Hepatology, 82(5), e269-e270. https://doi.org/10.1016/j.jhep.2024.11.042
    • Stangl, T. A., Wiepjes, C. M., Smit, R. A. J., van Hylckama Vlieg, A., Lamb, H. J., van der Velde, J. H. P. M., Winters van Eekelen, E., Boone, S. C., Brouwers, M. C. G. J., Rosendaal, F. R., den Heijer, M., Heijboer, A. C., & de Mutsert, R. (2024). Association Between Low Sex Hormone-Binding Globulin and Increased Risk of Type 2 Diabetes Is Mediated by Increased Visceral and Liver Fat: results from observational and Mendelian randomization analyses. Diabetes, 73(11), 1793-1804. https://doi.org/10.2337/db23-0982
    • van Hulten, V., Souverein, P. C., Starup-Linde, J., Viggers, R., Klungel, O. H., Vestergaard, P., Brouwers, M. C. J. G., van den Bergh, J. P., & Driessen, J. H. M. (2024). The association of type 2 diabetes-related characteristics with fracture risk at different sites. Diabetes Obesity & Metabolism, 26(11), 4887-4896. https://doi.org/10.1111/dom.15884
    • Van Hulten, V., Driessen, J. H. M., Andersen, S., Kvist, A., Viggers, R., Bliuc, D., Center, J. R., Brouwers, M. C. J. G., Vestergaard, P., & van den Bergh, J. P. (2024). Fracture risk revisited: Bone mineral density T-score and fracture risk in type 2 diabetes. Diabetes Obesity & Metabolism, 26(11), 5325-5335. https://doi.org/10.1111/dom.15890
    • Buziau, A. M., Oosterveer, M. H., Wouters, K., Bos, T., Tolan, D. R., Agius, L., Ford, B. E., Cassiman, D., Stehouwer, C. D. A., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2024). Hepatic glucokinase regulatory protein and carbohydrate response element binding protein attenuation reduce de novo lipogenesis but do not mitigate intrahepatic triglyceride accumulation in ALDOB deficiency. Molecular Metabolism, 87, Article 101984. https://doi.org/10.1016/j.molmet.2024.101984
    • Brouwers, M. C., & Cassiman, D. (2024). Rare monogenic causes of steatotic liver disease masquerading as MASLD. Journal of Hepatology, 80(6), e252-e253. https://doi.org/10.1016/j.jhep.2024.02.025
    • Ren, Z., Wesselius, A., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2024). Relationship between educational attainment and non-alcoholic fatty liver disease: A two-sample Mendelian randomization study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 56(4), 565-570. https://doi.org/10.1016/j.dld.2023.11.040
    • Panis, B., Vos, E. N., Baric, I., Bosch, A. M., Brouwers, M. C. G. J., Burlina, A., Cassiman, D., Coman, D. J., Couce, M. L., Das, A. M., Demirbas, D., Empain, A., Gautschi, M., Grafakou, O., Grunewald, S., Kingma, S. D. K., Knerr, I., Leão-Teles, E., Möslinger, D., ... Rubio-Gozalbo, M. E. (2024). Brain function in classic galactosemia, a galactosemia network (GalNet) members review. Frontiers in Genetics, 15, Article 1355962. https://doi.org/10.3389/fgene.2024.1355962
    • Chen, H., Buziau, A. M., Renteria, M. E., Simons, P. I. H. G., & Brouwers, M. C. G. J. (2024). Fructose intake from sugar-sweetened beverages is associated with a greater risk of hyperandrogenism in women: UK Biobank cohort study. European Journal of Endocrinology, 190(1), 104-112. https://doi.org/10.1093/ejendo/lvae006
  • 2023
    • Janssen, L. E. F., Cassiman, D., & Brouwers, M. C. G. J. (2023). Quality of life of adult patients with hereditary fructose intolerance. Molecular Genetics and Metabolism, 140(3), Article 107701. https://doi.org/10.1016/j.ymgme.2023.107701
    • Ren, Z., Bosma, H., Wesselius, A., Eussen, S. J. P. M., Kooi, M. E., van der Kallen, C. J. H., Koster, A., van Greevenbroek, M. M. J., Dagnelie, P., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2023). Traditional lifestyle factors partly mediate the association of socioeconomic position with intrahepatic lipid content: The Maastricht study. JHEP Reports, 5(11), Article 100855. https://doi.org/10.1016/j.jhepr.2023.100855
    • Ren, Z., Wesselius, A., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2023). Cardiovascular Implications of Metabolic Dysfunction-Associated Fatty Liver Disease. Endocrinology and Metabolism Clinics of North America, 52(3), 459-468. https://doi.org/10.1016/j.ecl.2023.01.002
    • King, S. D., Veliginti, S., Brouwers, M. C. G. J., Ren, Z., Zheng, W., Setiawan, V. W., Wilkens, L. R., Shu, X.-O., Arslan, A. A., Beane Freeman, L. E., Bracci, P. M., Canzian, F., Du, M., Gallinger, S. J., Giles, G. G., Goodman, P. J., Haiman, C. A., Kogevinas, M., Kooperberg, C., ... Et al. (2023). Genetic susceptibility to nonalcoholic fatty liver disease and risk for pancreatic cancer: Mendelian randomization. Cancer Epidemiology Biomarkers & Prevention, 32(9), 1265–1269. https://doi.org/10.1158/1055-9965.EPI-23-0453
    • Panis, B., Janssen, L. E. F., Lefeber, D. J., Simons, N., Rubio-Gozalbo, M. E., & Brouwers, M. C. G. J. (2023). Development of tools to facilitate the diagnosis of hereditary fructose intolerance. JIMD reports, 64(5), 353-359. https://doi.org/10.1002/jmd2.12379
    • Buziau, A. M., Scheijen, J. L. J. M., Stehouwer, C. D. A., Schalkwijk, C. G., & Brouwers, M. C. G. J. (2023). Effects of fructose added to an oral glucose tolerance test on plasma glucose excursions in healthy adults. Metabolism open, 18(1), Article 100245. https://doi.org/10.1016/j.metop.2023.100245
    • de Ritter, R., Sep, S. J. S., van Greevenbroek, M. M. J., Kusters, Y. H. A. M., Vos, R. C., Bots, M. L., Kooi, M. E., Dagnelie, P. C., Eussen, S. J. P. M., Schram, M. T., Koster, A., Brouwers, M. C. G., van der Sangen, N. M. R., Peters, S. A. E., van der Kallen, C. J. H., & Stehouwer, C. D. A. (2023). Sex differences in body composition in people with prediabetes and type 2 diabetes as compared with people with normal glucose metabolism: the Maastricht Study. Diabetologia, 66(5), 861-872. https://doi.org/10.1007/s00125-023-05880-0
    • Buziau, A. M., Blokland, G. A. M., Schalkwijk, C. G., Scheijen, J. L. J. M., Simons, P. I. H. G., Eussen, S. J. P. M., Dagnelie, P. C., van Greevenbroek, M. M. J., Wesselius, A., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2023). Comment on Lee et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care 2022;45. Diabetes Care, 46(4), E97-E98. https://doi.org/10.2337/dc22-1930
    • Tore, E. C., Elshorbagy, A. K., Bakers, F. C. H., Brouwers, M. C. G. J., Dagnelie, P. C., Eussen, S. J. P. M., Jansen, J. F. A., Kooi, M. E., Kusters, Y. H. A. M., Meex, S. J. R., Olsen, T., Refsum, H., Retterstøl, K., Schalkwijk, C. G., Stehouwer, C. D. A., Vinknes, K. J., & van Greevenbroek, M. M. J. (2023). Associations between plasma sulfur amino acids and specific fat depots in two independent cohorts: CODAM and The Maastricht Study. European Journal of Nutrition, 62(2), 891-904. https://doi.org/10.1007/s00394-022-03041-4
    • Buziau, A. M., Law, P. J., Blokland, G., Schalkwijk, C., Scheijen, J., Simons, P., van der Kallen, C., Eussen, S., Dagnelie, P. C., van Greevenbroek, M., Houlston, R. S., Wesselius, A., Went, M., Stehouwer, C., & Brouwers, M. C. (2023). Genetically proxied ketohexokinase function and risk of colorectal cancer: a Mendelian randomisation study. Gut, 72(3), 604-606. https://doi.org/10.1136/gutjnl-2021-326299
    • Ren, Z., Simons, P. I. H. G., Wesselius, A., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2023). Relationship between NAFLD and coronary artery disease: A Mendelian randomization study. Hepatology, 77(1), 230-238. https://doi.org/10.1002/hep.32534
    • Simons, P. I. H. G., Valkenburg, O., van de Waarenburg, M. P. H., van Greevenbroek, M. M. J., Kooi, M. E., Jansen, J. F. A., Schalkwijk, C. G., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2023). Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study. Diabetologia, 66(1), 213-222. https://doi.org/10.1007/s00125-022-05790-7
    • Tichler, A., Hertroijs, D. F., Ruwaard, D., Brouwers, M. C., Hiligsmann, M., de Jong, J. D., & Elissen, A. M. (2023). Preferred Conversation Topics with Respect to Treatment Decisions Among Individuals with Type 2 Diabetes. Patient Preference and Adherence, 17(1), 719-729. https://doi.org/10.2147/PPA.S397647
  • 2022
    • Simons, P. I. H. G., Valkenburg, O., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2022). Association between de novo lipogenesis susceptibility genes and coronary artery disease. Nutrition Metabolism and Cardiovascular Diseases, 32(12), 2883-2889. https://doi.org/10.1016/j.numecd.2022.09.003
    • Ren, Z. W., Simons, P. I. H. G., Wesselius, A., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2022). Reply. Hepatology, 76(6), E129-E130. https://doi.org/10.1002/hep.32611
    • van der Heide, F. C. T., Foreman, Y. D., Franken, I. W. M., Henry, R. M. A., Kroon, A. A., Dagnelie, P. C., Eussen, S. J. P. M., Berendschot, T. T. J. M., Schouten, J. S. A. G., Webers, C. A. B., Schram, M. T., van der Kallen, C. J. H., van Greevenbroek, M. M. J., Wesselius, A., Schalkwijk, C. G., Schaper, N. C., Brouwers, M. C. G. J., & Stehouwer, C. D. A. (2022). (Pre)diabetes, glycemia, and daily glucose variability are associated with retinal nerve fiber layer thickness in The Maastricht Study. Scientific Reports, 12(1), Article 17750. https://doi.org/10.1038/s41598-022-22748-2
    • Janssen, L. E. F., Simons, N., Simons, P. I. H. G., Schaper, N. C., Feskens, E. J. M., van der Ploeg, L. M. C., Van den Eynde, M. D. G., Schalkwijk, C. G., Houben, A. J. H. M., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2022). Effects of fructose restriction on blood pressure: Secondary analysis of a double-blind randomized controlled trial. Clinical Nutrition ESPEN, 51, 97-103. https://doi.org/10.1016/j.clnesp.2022.07.009
    • Brouwers, M. C. G. J. (2022). Fructose 1-phosphate, an evolutionary signaling molecule of abundancy. Trends in Endocrinology and Metabolism, 33(10), 680-689. https://doi.org/10.1016/j.tem.2022.07.007
    • van Vliet, K., van Ginkel, W. G., Jahja, R., Daly, A., MacDonald, A., Santra, S., De Laet, C., Goyens, P. J., Vara, R., Rahman, Y., Cassiman, D., Eyskens, F., Timmer, C., Mumford, N., Gissen, P., Bierau, J., van Hasselt, P. M., Wilcox, G., Morris, A. A. M., ... van Spronsen, F. J. (2022). Neurocognitive outcome and mental health in children with tyrosinemia type 1 and phenylketonuria: A comparison between two genetic disorders affecting the same metabolic pathway. Journal of Inherited Metabolic Disease, 45(5), 952-962. https://doi.org/10.1002/jimd.12528
    • Koene, E., Schrauwen-Hinderling, V. B., Schrauwen, P., & Brouwers, M. C. G. J. (2022). Novel insights in intestinal and hepatic fructose metabolism: from mice to men. Current Opinion in Clinical Nutrition and Metabolic Care, 25(5), 354-359. https://doi.org/10.1097/MCO.0000000000000853
    • Haring, M. P. D., Peeks, F., Oosterveer, M. H., Brouwers, M. C. G. J., Hollak, C. E. M., Janssen, M. C. H., Langendonk, J. G., Rennings, A. J. M., Wagenmakers, M. A. E. M., Verkade, H. J., Derks, T. G. J., & de Meijer, V. E. (2022). High childhood serum triglyceride concentrations associate with hepatocellular adenoma development in patients with glycogen storage disease type Ia. JHEP Reports, 4(8), Article 100512. https://doi.org/10.1016/j.jhepr.2022.100512
    • Brouwers, M. C. G. J., Simons, N., Kooi, M. E., de Ritter, R., van Dongen, M. C. J. M., Eussen, S. J. P. M., Bekers, O., Kooman, J., van Greevenbroek, M. M. J., van der Kallen, C. J. H., Schram, M. T., Schaper, N. C., Schalkwijk, C. G., & Stehouwer, C. D. A. (2022). Intrahepatic lipid content is independently associated with soluble E-selectin levels: The Maastricht study. Digestive and Liver Disease, 54(8), 1038-1043. https://doi.org/10.1016/j.dld.2022.01.130
    • van Dalem, J., Werkman, N. C. C., van den Bergh, J. P., Rossi, B., Viggers, R., Eastell, R., Burden, A. M., Stehouwer, C. D. A., Klungel, O. H., Brouwers, M. C. G. J., & Driessen, J. H. M. (2022). Use of sodium-glucose co-transporter 2 inhibitors, changes in body mass index and risk of fracture: a population-based cohort study. Diabetes Research and Clinical Practice, 190, Article 109993. https://doi.org/10.1016/j.diabres.2022.109993
    • Simons, P. I. H. G., Valkenburg, O., Telgenkamp, I., van der Waaij, K. M., de Groot, D. M., Veeraiah, P., Bons, J. A. P., Derks, T. G. J., Schalkwijk, C. G., Schrauwen-Hinderling, V. B., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2022). Serum sex hormone-binding globulin levels are reduced and inversely associated with intrahepatic lipid content and saturated fatty acid fraction in adult patients with glycogen storage disease type 1a. Journal of Endocrinological Investigation, 45(6), 1227-1234. https://doi.org/10.1007/s40618-022-01753-2
    • Buziau, A. M., Eussen, S. J. P. M., Kooi, M. E., van der Kallen, C. J. H., van Dongen, M. C. J. M., Schaper, N. C., Henry, R. M. A., Schram, M. T., Dagnelie, P. C., van Greevenbroek, M. M. J., Wesselius, A., Bekers, O., Meex, S. J. R., Schalkwijk, C. G., Stehouwer, C. D. A., & Brouwers, M. C. G. J. (2022). Fructose Intake From Fruit Juice and Sugar-Sweetened Beverages Is Associated With Higher Intrahepatic Lipid Content: The Maastricht Study. Diabetes Care, 45(5), 1116-1123. https://doi.org/10.2337/dc21-2123