title: Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk.
abstract: We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak times varied greatly between groups, ranging from 7-12 mmol/L, and 35-70 min. The group with the lowest and earliest plasma glucose peak had the lowest estimated cardiovascular risk, while the group with the most delayed plasma glucose peak and the highest 2-h value had the highest estimated risk. One group, with normal fasting and 2-h values, exhibited an unusual profile, with the highest glucose peak and the highest proportion of smokers and men. The heterogeneity in glucose response curves and the distinct cardiometabolic risk profiles may reflect different underlying physiologies. Our results warrant more detailed studies to identify the source of the heterogeneity across the different phenotypes and whether these differences play a role in the development of type 2 diabetes and cardiovascular disease.
authors.affiliation: Department of Public Health, Section of Epidemiology, Aarhus University, Aarhus, Denmark. adam.hulman@ph.au.dk.|Danish Diabetes Academy, Odense, Denmark. adam.hulman@ph.au.dk.|Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary. adam.hulman@ph.au.dk.
authors.forename: Adam
authors.initials: A
authors.lastname: Hulman
authors.affiliation: Danish Diabetes Academy, Odense, Denmark.|Department of Public Health, Section of General Practice, Aarhus University, Aarhus, Denmark.|MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, UK.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Simmons
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Vistisen
authors.affiliation: 1st Department of Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary.|Department of Epidemiology and Public Health, University College London, London, UK.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Tabák
authors.affiliation: Department of Biostatistics and Epidemiology, VU Medical Center, Amsterdam, Netherlands.|EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Dekker
authors.affiliation: Department of Biostatistics and Epidemiology, VU Medical Center, Amsterdam, Netherlands.|Unilever Research and Development, Vlaardingen, Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Alssema
authors.affiliation: Department of Biostatistics and Epidemiology, VU Medical Center, Amsterdam, Netherlands.|EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Rutters
authors.affiliation: Department of Biostatistics and Epidemiology, VU Medical Center, Amsterdam, Netherlands.|EMGO+ Institute for Health and Care Research, VU Medical Center, Amsterdam, Netherlands.
authors.forename: Anitra D M
authors.initials: AD
authors.lastname: Koopman
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Edgbaston, UK.|Institute for Metabolism and Systems Research, University of Birmingham, Edgbaston, UK.
authors.forename: Thomas P J
authors.initials: TP
authors.lastname: Solomon
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Kirwan
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Jonsson
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anette Prior
authors.initials: AP
authors.lastname: Gjesing
authors.affiliation: Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Eiberg
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Institute of Preventive Medicine, Frederiksberg and Bispebjerg University Hospital, The Capital Region, Copenhagen, Denmark.
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.affiliation: Department of Public Health, Section of Epidemiology, Aarhus University, Aarhus, Denmark.|Danish Diabetes Academy, Odense, Denmark.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Witte
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Kristine
authors.initials: K
authors.lastname: Færch
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis*; D005215:Fasting / Q000097:blood; D005260:Female; D018149:Glucose Intolerance / Q000097:blood / Q000175:diagnosis*; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012737:Sex Factors; D014481:United States
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin
keywords: Cardiometabolic risk; Glucose response curve; Latent class trajectory analysis; Oral glucose tolerance test