Publication Description
Inflammation and Progressive Nephropathy in Type 1 Diabetes in the Diabetes Control and Complications Trial Julie Lin , MD, MPH 1 , Robert J. Glynn , PHD 2 3 , Nader Rifai , PHD 4 , JoAnn E. Manson , MD, DRPH 2 5 , Paul M. Ridker , MD, MPH 2 6 , David M. Nathan , MD 7 and Debra A. Schaumberg , SCD, OD, MPH 2 5 8 1 Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 2 Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 3 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 4 Department of Laboratory Medicine, Children's Hospital, Harvard Medical School, Boston, Massachusetts 5 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 6 Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 7 Diabetes Center, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 8 Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, Massachusetts Corresponding author: Debra A. Schaumberg, dschaumberg{at}rics.bwh.harvard.edu Abstract OBJECTIVE —Progressive nephropathy represents a substantial source of morbidity and mortality in type 1 diabetes. Increasing albuminuria is a strong predictor of progressive renal dysfunction and heightened cardiovascular risk. Early albuminuria probably reflects vascular endothelial dysfunction, which may be mediated in part by chronic inflammation. RESEARCH DESIGN AND METHODS —We measured baseline levels of four inflammatory biomarkers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 sICAM-1], soluble vascular cell adhesion molecule-1, and soluble tumor necrosis factor-α receptor-1) in stored blood samples from the 1,441 participants of the Diabetes Control and Complication Trial (DCCT). We used mixed-effects regression models to determine the average annual change in urinary albumin excretion rate (AER) by tertiles of each biomarker. We also used Cox proportional hazards models to estimate the relative risk of incident sustained microalbuminuria according to levels of each biomarker. RESULTS —After adjustment for baseline age, sex, duration of diabetes, A1C, and randomized treatment assignment, we observed a significantly higher 5.9 μg · min −1 · year −1 increase in AER among those in the highest compared with the lowest tertile of baseline sICAM-1 ( P = 0.04). Those in the highest tertile of sICAM-1 had an adjusted relative risk of 1.67 (95% CI 0.96–2.92) of developing incident sustained microalbuminuria ( P trend = 0.03). CONCLUSIONS —Higher baseline sICAM-1 levels predicted an increased risk of progressive nephropathy in type 1 diabetes and may represent an early risk marker that reflects the important role of vascular endothelial dysfunction in this long-term complication. Footnotes Published ahead of print at http://care.diabetesjournals.org on 16 September 2008. P.M.R. is listed as an inventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in vascular disease. P.M.R. and J.E.M. are listed as coinventors on a pending patent held by Brigham and Women's Hospital that relates to inflammatory biomarkers in diabetes prediction. This article was not prepared under the auspices of the Diabetes Control and Complication Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study and does not represent analyses or conclusions of the DCCT/EDIC study group or the National Institutes of Health. J.L. and D.A.S. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted August 30, 2008. Received February 6, 2008. DIABETES CARE