Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial.
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.


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-alpha 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 microg x min(-1) x 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.
Lin
Julie
J
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Glynn
Robert J
RJ
Rifai
Nader
N
Manson
JoAnn E
JE
Ridker
Paul M
PM
Nathan
David M
DM
Schaumberg
Debra A
DA
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D000068800:Etanercept
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