Serum urate and cardiovascular events in the DCCT/EDIC study

The DCCT/EDIC research group; Study Chairpersons; Editor, EDIC Publications; Clinical Centers; Clinical Coordinating Center; Data Coordinating Center; National Institute of Diabetes and Digestive and Kidney Disease Program Office; EDIC Core Central Units

doi:10.1038/s41598-021-90785-4

Serum urate and cardiovascular events in the DCCT/EDIC study

The DCCT/EDIC research group, Study Chairpersons, Editor, EDIC Publications, Clinical Centers, Clinical Coordinating Center, Data Coordinating Center, National Institute of Diabetes and Digestive and Kidney Disease Program Office, EDIC Core Central Units

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

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.

Original language	English (US)
Article number	14182
Journal	Scientific reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-90785-4
State	Published - Dec 2021

Funding

The DCCT/EDIC has been supported by cooperative agreement Grants (1982–1993, 2012–2017, 2017–2022), and contracts (1982–2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current Grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993–2007), and Clinical Translational Science Center Program (2006–present), Bethesda, Maryland, USA. Industry Contributions: Industry contributors have had no role in the DCCT/EDIC study but have provided free or discounted supplies or equipment to support participants’ adherence to the study: Abbott Diabetes Care (Alameda, CA), Animas (Westchester, PA), Bayer Diabetes Care (North America Headquarters, Tarrytown, NY), Becton, Dickinson and Company (Franklin Lakes, NJ), Eli Lilly (Indianapolis, IN), Extend Nutrition (St. Louis, MO), Insulet Corporation (Bedford, MA), Lifescan (Milpitas, CA), Medtronic Diabetes (Minneapolis, MN), Nipro Home Diagnostics (Ft. Lauderdale, FL), Nova Diabetes Care (Billerica, MA), Omron (Shelton, CT), Perrigo Diabetes Care (Allegan, MI), Roche Diabetes Care (Indianapolis, IN), and Sanofi-Aventis (Bridgewater, NJ). Additional Statement for Collaborators: Additional support for this DCCT/EDIC collaborative study was provided by the Medical University of South Carolina Program Project supported by the National Institute of Health Grant number R01DK080043, JDRF International and the American Diabetes Association 7-12-CT-46.

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10.1038/s41598-021-90785-4

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The DCCT/EDIC research group, Study Chairpersons, Editor, EDIC Publications, Clinical Centers, Clinical Coordinating Center, Data Coordinating Center, National Institute of Diabetes and Digestive and Kidney Disease Program Office, & EDIC Core Central Units (2021). Serum urate and cardiovascular events in the DCCT/EDIC study. Scientific reports, 11(1), Article 14182. https://doi.org/10.1038/s41598-021-90785-4

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title = "Serum urate and cardiovascular events in the DCCT/EDIC study",

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 {\textquoteleft}any CVD{\textquoteright} 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.",

author = "{The DCCT/EDIC research group} and {Study Chairpersons} and {Editor, EDIC Publications} and {Clinical Centers} and {Clinical Coordinating Center} and {Data Coordinating Center} and {National Institute of Diabetes and Digestive and Kidney Disease Program Office} and {EDIC Core Central Units} and Jenkins, {Alicia J.} and Braffett, {Barbara H.} and Arpita Basu and Ionut Bebu and Samuel Dagogo-Jack and Orchard, {Trevor J.} and Amisha Wallia and Lopes-Virella, {Maria F.} and Garvey, {W. Timothy} and Lachin, {John M.} and Lyons, {Timothy J.} and Nathan, {D. M.} and B. Zinman and O. Crofford and S. Genuth and Nathan, {D. M.} and R. Gubitosi-Klug and L. Mayer and J. Wood and D. Miller and A. Nayate and M. Novak and S. Pendegast and L. Singerman and D. Weiss and H. Zegarra and Gregory, {N. S.} and R. Hanna and R. Chan and S. Kiss and A. Orlin and M. Rubin and A. Bhan and Jones, {J. K.} and D. Kruger and Edwards, {P. A.} and H. Remtema and R. Bergenstal and S. Dunnigan and M. Johnson and A. Carlson and Aiello, {L. P.} and E. Golden and P. Arrigg and R. Beaser and S. Ajroud-Driss and L. Jampol and A. Lyon and R. Mirza and M. Molitch",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41598-021-90785-4",

language = "English (US)",

volume = "11",

journal = "Scientific reports",

issn = "2045-2322",

publisher = "Nature Research",

number = "1",

}

The DCCT/EDIC research group, Study Chairpersons, Editor, EDIC Publications, Clinical Centers, Clinical Coordinating Center, Data Coordinating Center, National Institute of Diabetes and Digestive and Kidney Disease Program Office & EDIC Core Central Units 2021, 'Serum urate and cardiovascular events in the DCCT/EDIC study', Scientific reports, vol. 11, no. 1, 14182. https://doi.org/10.1038/s41598-021-90785-4

TY - JOUR

T1 - Serum urate and cardiovascular events in the DCCT/EDIC study

AU - The DCCT/EDIC research group

AU - Study Chairpersons

AU - Editor, EDIC Publications

AU - Clinical Centers

AU - Clinical Coordinating Center

AU - Data Coordinating Center

AU - National Institute of Diabetes and Digestive and Kidney Disease Program Office

AU - EDIC Core Central Units

AU - Jenkins, Alicia J.

AU - Braffett, Barbara H.

AU - Basu, Arpita

AU - Bebu, Ionut

AU - Dagogo-Jack, Samuel

AU - Orchard, Trevor J.

AU - Wallia, Amisha

AU - Lopes-Virella, Maria F.

AU - Garvey, W. Timothy

AU - Lachin, John M.

AU - Lyons, Timothy J.

AU - Nathan, D. M.

AU - Zinman, B.

AU - Crofford, O.

AU - Genuth, S.

AU - Nathan, D. M.

AU - Gubitosi-Klug, R.

AU - Mayer, L.

AU - Wood, J.

AU - Miller, D.

AU - Nayate, A.

AU - Novak, M.

AU - Pendegast, S.

AU - Singerman, L.

AU - Weiss, D.

AU - Zegarra, H.

AU - Gregory, N. S.

AU - Hanna, R.

AU - Chan, R.

AU - Kiss, S.

AU - Orlin, A.

AU - Rubin, M.

AU - Bhan, A.

AU - Jones, J. K.

AU - Kruger, D.

AU - Edwards, P. A.

AU - Remtema, H.

AU - Bergenstal, R.

AU - Dunnigan, S.

AU - Johnson, M.

AU - Carlson, A.

AU - Aiello, L. P.

AU - Golden, E.

AU - Arrigg, P.

AU - Beaser, R.

AU - Ajroud-Driss, S.

AU - Jampol, L.

AU - Lyon, A.

AU - Mirza, R.

AU - Molitch, M.

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

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Serum urate and cardiovascular events in the DCCT/EDIC study

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