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Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study

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Abstract

Epidemiologic evidence supports a link between serum uric acid (SUA) and vascular complications in diabetes, but it remains unclear whether SUA improves the ability of conventional risk factor to predict complications. We hypothesized that SUA at baseline would independently predict the development of vascular complications over 6 years and that the addition of SUA to American Diabetes Association’s ABC risk factors (HbA1c, BP, LDL-C) would improve vascular complication prediction over 6 years in adults with type 1 diabetes. Study participants (N = 652) were 19–56 year old at baseline and re-examined 6 years later. Diabetic nephropathy was defined as incident albuminuria or rapid GFR decline (>3.3 %/year) estimated by the CKD-EPI cystatin C. Diabetic retinopathy (DR) was based on self-reported history, and proliferative diabetic retinopathy (PDR) was defined as laser eye therapy; coronary artery calcium (CAC) was measured using electron-beam computed tomography. Progression of CAC (CACp) was defined as a change in the square-root-transformed CAC volume ≥2.5. Predictors of each complication were examined in stepwise logistic regression with subjects with complications at baseline excluded from analyses. C-statistics, integrated discrimination indices and net-reclassification improvement were utilized for prediction performance analyses. SUA independently predicted development of incident albuminuria (OR 1.8, 95 % CI 1.2–2.7), rapid GFR decline (1.9, 1.1–3.3), DR (1.4, 1.1–1.9), PDR (2.1, 1.4–3.0) and CACp (1.5, 1.1–1.9). SUA improved the discrimination and net-classification risk of vascular complications over 6 years. SUA independently predicted the development of vascular complications in type 1 diabetes and also improved the reclassification of vascular complications.

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Acknowledgments

Support for this study was provided by NHLBI Grant R01 HL61753, HL79611, and HL113029, JDRF Grant 17-2013-313, and DERC Clinical Investigation Core P30 DK57516. The study was performed at the Adult CTRC at UCD support by NIH-M01-RR00051, at the Barbara Davis Center for Childhood Diabetes and at Colorado Heart Imaging Center in Denver, CO. Dr. Maahs was supported by a Grant from NIDDK (DK075360), Dr. Snell-Bergeon by an American Diabetes Association Junior Faculty Award (1-10-JF-50) and an American Diabetes Association Career Development Award (7-13-CD-10). Drs. Petter Bjornstad and Janet K. Snell-Bergeon are guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Conflict of interest

RJJ has patent applications related to the lowering of uric acid and or blocking fructose metabolism as a means for slowing diabetic nephropathy or improving insulin resistance, and has shares with XORT Therapeutics related to these patents. Drs. Bjornstad, Snell-Bergeon and Maahs have no conflict of interest to disclose.

Human and animal rights disclosure

The study was approved by the Colorado Multiple Institutional Review Board and therefore performed in accordance with the ethical standards laid down in appropriate versions of the 1964 Declaration of Helsinki.

Informed consent disclosure

All participants provided informed consent.

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Authors and Affiliations

  1. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA

    Petter Bjornstad, David M. Maahs, Laura Pyle, Marian Rewers & Janet K. Snell-Bergeon

  2. Barbara Davis Center for Diabetes, University of Colorado Denver, 1775 Aurora Court, Aurora, CO, 80045, USA

    Petter Bjornstad, David M. Maahs, Marian Rewers & Janet K. Snell-Bergeon

  3. Department of Nephrology, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs, Christopher J. Rivard & Richard J. Johnson

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  1. Petter Bjornstad
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  2. David M. Maahs
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  4. Laura Pyle
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  5. Marian Rewers
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  7. Janet K. Snell-Bergeon
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Correspondence to Petter Bjornstad.

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Bjornstad, P., Maahs, D.M., Rivard, C.J. et al. Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study. Acta Diabetol 51, 783–791 (2014). https://doi.org/10.1007/s00592-014-0611-1

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