Akintunde O Akinkuolie1, Aruna D Pradhan1, Julie E Buring1, Paul M Ridker1, Samia Mora2. 1. Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. 2. Divisions of Preventive Medicine (A.O.A., A.D.P., J.E.B., P.MR., S.M.) and Cardiovascular Medicine (P.MR., S.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA. smora@partners.org.
Abstract
OBJECTIVES: Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N-acetyl methyl groups originating mainly from N-acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with high-sensitivity C-reactive protein. APPROACH AND RESULTS: In 26,508 initially healthy women free of diabetes mellitus, baseline GlycA and high-sensitivity C-reactive protein were quantified by nuclear magnetic resonance spectroscopy and immunoturbidimetry, respectively. During median follow-up of 17.2 years, 2087 type 2 diabetes mellitus cases occurred. In Cox models with adjustment for age, race, smoking, alcohol, activity, menopausal status, hormone use, family history, and body mass index, quartile 4 versus 1 hazard ratios and 95% confidence intervals were 2.67 (2.26-3.14) for GlycA and 3.93 (3.24-4.77) for high-sensitivity C-reactive protein; both P trend <0.0001. Associations for GlycA and high-sensitivity C-reactive protein were attenuated after additionally adjusting for lipids: 1.65 (1.39-1.95) and 2.83 (2.32-3.44), respectively, both P trend <0.0001, and after mutual adjustment: 1.11 (0.93-1.33; P trend=0.10) and 2.57 (2.09-3.16; P trend<0.0001), respectively. CONCLUSIONS: Our finding of an association between a consensus glycan sequence common to a host of acute-phase reactants and incident type 2 diabetes mellitus provides further support for inflammation in the development of type 2 diabetes mellitus. Additional studies exploring the role of enzymatic glycosylation in the prevention of type 2 diabetes mellitus are warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
OBJECTIVES: Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N-acetyl methyl groups originating mainly from N-acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with high-sensitivity C-reactive protein. APPROACH AND RESULTS: In 26,508 initially healthy women free of diabetes mellitus, baseline GlycA and high-sensitivity C-reactive protein were quantified by nuclear magnetic resonance spectroscopy and immunoturbidimetry, respectively. During median follow-up of 17.2 years, 2087 type 2 diabetes mellitus cases occurred. In Cox models with adjustment for age, race, smoking, alcohol, activity, menopausal status, hormone use, family history, and body mass index, quartile 4 versus 1 hazard ratios and 95% confidence intervals were 2.67 (2.26-3.14) for GlycA and 3.93 (3.24-4.77) for high-sensitivity C-reactive protein; both P trend <0.0001. Associations for GlycA and high-sensitivity C-reactive protein were attenuated after additionally adjusting for lipids: 1.65 (1.39-1.95) and 2.83 (2.32-3.44), respectively, both P trend <0.0001, and after mutual adjustment: 1.11 (0.93-1.33; P trend=0.10) and 2.57 (2.09-3.16; P trend<0.0001), respectively. CONCLUSIONS: Our finding of an association between a consensus glycan sequence common to a host of acute-phase reactants and incident type 2 diabetes mellitus provides further support for inflammation in the development of type 2 diabetes mellitus. Additional studies exploring the role of enzymatic glycosylation in the prevention of type 2 diabetes mellitus are warranted. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000479.
Authors: Ana Knezevic; Olga Gornik; Ozren Polasek; Maja Pucic; Irma Redzic; Mislav Novokmet; Pauline M Rudd; Alan F Wright; Harry Campbell; Igor Rudan; Gordan Lauc Journal: Glycobiology Date: 2010-03-30 Impact factor: 4.313
Authors: M I Schmidt; B B Duncan; A R Sharrett; G Lindberg; P J Savage; S Offenbacher; M I Azambuja; R P Tracy; G Heiss Journal: Lancet Date: 1999-05-15 Impact factor: 79.321
Authors: James D Otvos; Irina Shalaurova; Justyna Wolak-Dinsmore; Margery A Connelly; Rachel H Mackey; James H Stein; Russell P Tracy Journal: Clin Chem Date: 2015-03-16 Impact factor: 8.327
Authors: Paulette D Chandler; Raji Balasubramanian; Nina Paynter; Franco Giulianini; Teresa Fung; Lesley F Tinker; Linda Snetselaar; Simin Liu; Charles Eaton; Deirdre K Tobias; Fred K Tabung; JoAnn E Manson; Edward L Giovannucci; Clary Clish; Kathryn M Rexrode Journal: Am J Clin Nutr Date: 2020-08-01 Impact factor: 7.045
Authors: Andrew P Demidowich; Anna Wolska; Sierra R Wilson; Jordan A Levine; Alexander V Sorokin; Sheila M Brady; Alan T Remaley; Jack A Yanovski Journal: J Clin Lipidol Date: 2019-10-22 Impact factor: 4.766
Authors: Robert W McGarrah; Jacob P Kelly; Damian M Craig; Carol Haynes; Ryan C Jessee; Kim M Huffman; William E Kraus; Svati H Shah Journal: Clin Chem Date: 2016-11-03 Impact factor: 8.327
Authors: Jacob L Barber; William E Kraus; Timothy S Church; James M Hagberg; Paul D Thompson; David B Bartlett; Michael W Beets; Conrad P Earnest; Kim M Huffman; Rian Q Landers-Ramos; Arthur S Leon; D C Rao; Richard L Seip; James S Skinner; Cris A Slentz; Kenneth R Wilund; Claude Bouchard; Mark A Sarzynski Journal: Atherosclerosis Date: 2018-07-26 Impact factor: 5.162
Authors: Jordan A Levine; Jung Min Han; Anna Wolska; Sierra R Wilson; Tushar P Patel; Alan T Remaley; Vipul Periwal; Jack A Yanovski; Andrew P Demidowich Journal: J Clin Lipidol Date: 2020-08-04 Impact factor: 4.766
Authors: Patrick R Lawler; Akintunde O Akinkuolie; Paulette D Chandler; M Vinayaga Moorthy; Martin J Vandenburgh; Debra A Schaumberg; I-Min Lee; Robert J Glynn; Paul M Ridker; Julie E Buring; Samia Mora Journal: Circ Res Date: 2016-03-07 Impact factor: 17.367
Authors: Toma Keser; Ivan Gornik; Frano Vučković; Najda Selak; Tamara Pavić; Edita Lukić; Ivan Gudelj; Hrvoje Gašparović; Bojan Biočina; Therese Tilin; Annika Wennerström; Satu Männistö; Veikko Salomaa; Aki Havulinna; Wei Wang; James F Wilson; Nish Chaturvedi; Markus Perola; Harry Campbell; Gordan Lauc; Olga Gornik Journal: Diabetologia Date: 2017-09-13 Impact factor: 10.122
Authors: Aditya A Joshi; Joseph B Lerman; Tsion M Aberra; Mehdi Afshar; Heather L Teague; Justin A Rodante; Parasuram Krishnamoorthy; Qimin Ng; Tarek Z Aridi; Taufiq Salahuddin; Balaji Natarajan; Benjamin N Lockshin; Mark A Ahlman; Marcus Y Chen; Daniel J Rader; Muredach P Reilly; Alan T Remaley; David A Bluemke; Martin P Playford; Joel M Gelfand; Nehal N Mehta Journal: Circ Res Date: 2016-09-21 Impact factor: 17.367