Abstract

In type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced “any CVD”, and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07–2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01–2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.

Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

Details

Title
Serum urate and cardiovascular events in the DCCT/EDIC study
Author
Jenkins, Alicia J 1 ; Braffett, Barbara H 2 ; Basu Arpita 3 ; Bebu Ionut 2 ; Dagogo-Jack Samuel 4 ; Orchard, Trevor J 5 ; Wallia Amisha 6 ; Lopes-Virella, Maria F 7 ; Timothy, Garvey W 8 ; Lachin, John M 2 ; Lyons, Timothy J 9 ; Nathan, D M 10 ; Zinman, B 11 ; Crofford, O 12 ; Genuth, S 13 ; Gubitosi-Klug, R 13 ; Mayer, L 13 ; Wood, J 13 ; Miller, D 13 ; Nayate, A 13 ; Novak, M 13 ; Pendegast, S 13 ; Singerman, L 13 ; Weiss, D 13 ; Zegarra, H 13 ; Gregory, N S 14 ; Hanna, R 14 ; Chan, R 14 ; Kiss, S 14 ; Orlin, A 14 ; Rubin, M 14 ; Bhan, A 15 ; Jones, J K 15 ; Kruger, D 15 ; Edwards, P A 15 ; Remtema, H 15 ; Bergenstal, R 16 ; Dunnigan, S 16 ; Johnson, M 16 ; Carlson, A 16 ; Aiello, L P 17 ; Golden, E 17 ; Arrigg, P 17 ; Beaser, R 17 ; Bestourous, L 17 ; Cavallerano, J 17 ; Cavicchi, R 17 ; Ganda, O 17 ; Hamdy, O 17 ; Murtha, T 17 ; Schlossman, D 17 ; Shah, S 17 ; Sharuk, G 17 ; Silva, P 17 ; Silver, P 17 ; Stockman, M 17 ; Sun, J 17 ; Weimann, E 17 ; Larkin, M E 10 ; Cayford, M 10 ; de, Manbey A 10 ; 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1  Medical University of South Carolina, Division of Endocrinology, Clinical Sciences Building, Suite 822, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475); University of Sydney, National Health and Medical Research Council Clinical Trials Centre, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X) 
2  George Washington University Biostatistics Center, Rockville, USA (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
3  University of Nevada, Las Vegas, USA (GRID:grid.272362.0) (ISNI:0000 0001 0806 6926) 
4  University of Tennessee Health Science Center, Memphis, USA (GRID:grid.267301.1) (ISNI:0000 0004 0386 9246) 
5  University of Pittsburgh, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
6  Northwestern University, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
7  Medical University of South Carolina, Division of Endocrinology, Clinical Sciences Building, Suite 822, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475); Ralph H. Johnson Veterans Affairs Medical Center, Charleston, USA (GRID:grid.280644.c) (ISNI:0000 0000 8950 3536) 
8  University of Alabama at Birmingham, Birmingham VA Medical Center, Birmingham, USA (GRID:grid.265892.2) (ISNI:0000000106344187) 
9  Medical University of South Carolina, Division of Endocrinology, Clinical Sciences Building, Suite 822, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475); Diabetes Free SC, BlueCross BlueShield of South Carolina, Columbia, USA (GRID:grid.259828.c) 
10  Massachusetts General Hospital, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924) 
11  University of Toronto, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938) 
12  Vanderbilt University, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
13  Case Western Reserve University, Cleveland, USA (GRID:grid.67105.35) (ISNI:0000 0001 2164 3847) 
14  Weill Cornell Medical College, New York, USA (GRID:grid.5386.8) (ISNI:000000041936877X) 
15  Henry Ford Health System, Detroit, USA (GRID:grid.239864.2) (ISNI:0000 0000 8523 7701) 
16  International Diabetes Center, Minneapolis, USA (GRID:grid.417226.4) (ISNI:0000 0004 0434 2710) 
17  Joslin Diabetes Center, Boston, USA (GRID:grid.16694.3c) (ISNI:0000 0001 2183 9479) 
18  Mayo Clinic, Rochester, USA (GRID:grid.66875.3a) (ISNI:0000 0004 0459 167X) 
19  Medical University of South Carolina, Charleston, USA (GRID:grid.259828.c) (ISNI:0000 0001 2189 3475) 
20  Northwestern University, Evanston, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507) 
21  Diabetes Free SC, BlueCross BlueShield of South Carolina, Columbia, USA (GRID:grid.16753.36) 
22  University of California, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
23  University of Iowa, Iowa, USA (GRID:grid.214572.7) (ISNI:0000 0004 1936 8294) 
24  University of Maryland, Baltimore, USA (GRID:grid.411024.2) (ISNI:0000 0001 2175 4264) 
25  University of Michigan, Ann Arbor, USA (GRID:grid.214458.e) (ISNI:0000000086837370) 
26  University of Minnesota, Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
27  University of Missouri, Columbia, USA (GRID:grid.134936.a) (ISNI:0000 0001 2162 3504) 
28  University of New Mexico, Albuquerque, USA (GRID:grid.266832.b) (ISNI:0000 0001 2188 8502) 
29  University of Pennsylvania, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972) 
30  University of South Florida, Tampa, USA (GRID:grid.170693.a) (ISNI:0000 0001 2353 285X) 
31  University of Tennessee, Memphis, USA (GRID:grid.267301.1) (ISNI:0000 0004 0386 9246) 
32  University of Texas, Austin, USA (GRID:grid.55460.32) (ISNI:0000000121548364) 
33  University of Washington, Seattle, USA (GRID:grid.34477.33) (ISNI:0000000122986657) 
34  University of Western Ontario, London, Canada (GRID:grid.39381.30) (ISNI:0000 0004 1936 8884) 
35  Washington University, St. Louis, USA (GRID:grid.4367.6) (ISNI:0000 0001 2355 7002) 
36  Yale University, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
37  Albert Einstein College of Medicine, Bronx, USA (GRID:grid.251993.5) (ISNI:0000000121791997) 
38  George Washington University, The Biostatistics Center, Bethesda, USA (GRID:grid.253615.6) (ISNI:0000 0004 1936 9510) 
39  National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, USA (GRID:grid.94365.3d) (ISNI:0000 0001 2297 5165) 
40  Central Biochemistry Laboratory (University of Minnesota), Minneapolis, USA (GRID:grid.17635.36) (ISNI:0000000419368657) 
41  Central ECG Reading Unit (Wake Forest School of Medicine), Winston-Salem, USA (GRID:grid.241167.7) (ISNI:0000 0001 2185 3318) 
42  Central Ophthalmologic Reading Unit (University of Wisconsin), Madison, USA (GRID:grid.28803.31) (ISNI:0000 0001 0701 8607) 
43  Central Neuropsychological Reading Unit (NYU Winthrop Hospital, University of Pittsburgh), Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-021-90785-4
ProQuest document ID
2549835048
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.