title: Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial.
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.
  
  
  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.
authors.affiliation: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Lin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Glynn
authors.forename: Nader
authors.initials: N
authors.lastname: Rifai
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: David M
authors.initials: DM
authors.lastname: Nathan
authors.forename: Debra A
authors.initials: DA
authors.lastname: Schaumberg
mesh_terms: 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
chemical_list: 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
references.citation: Metabolism. 2006 Sep;55(9):1177-85
references.pmid: 16919536
references.citation: J Clin Endocrinol Metab. 2000 Aug;85(8):2970-3
references.pmid: 10946914
references.citation: Am J Kidney Dis. 1993 May;21(5):480-5
references.pmid: 8488815
references.citation: Circ Res. 1999 Jul 23;85(2):199-207
references.pmid: 10417402
references.citation: Vascul Pharmacol. 2007 Apr;46(4):229-37
references.pmid: 17218160
references.citation: Curr Vasc Pharmacol. 2005 Jan;3(1):63-8
references.pmid: 15638783
references.citation: Curr Diab Rep. 2007 Jun;7(3):242-8
references.pmid: 17547842
references.citation: Diabet Med. 2000 Sep;17(9):644-9
references.pmid: 11051283
references.citation: J Clin Endocrinol Metab. 2001 Aug;86(8):3805-8
references.pmid: 11502815
references.citation: J Vasc Res. 2005 Sep-Oct;42(5):399-407
references.pmid: 16088213
references.citation: Diabetes. 2003 Oct;52(10):2586-93
references.pmid: 14514644
references.citation: Am J Cardiol. 2007 May 1;99(9):1246-51
references.pmid: 17478152
references.citation: Diabetologia. 2003 Oct;46(10):1402-7
references.pmid: 12928771
references.citation: J Clin Endocrinol Metab. 2001 Jul;86(7):3257-65
references.pmid: 11443198
references.citation: Circulation. 2002 Oct 1;106(14):1777-82
references.pmid: 12356629
references.citation: Clin J Am Soc Nephrol. 2008 Mar;3(2):317-323
references.pmid: 37001131
references.citation: Biochem Biophys Res Commun. 1992 Sep 16;187(2):584-9
references.pmid: 1382417
references.citation: Diabetologia. 2007 Nov;50(11):2280-8
references.pmid: 17768606
references.citation: Am J Nephrol. 2007;27(6):554-64
references.pmid: 17823503
references.citation: J Cardiometab Syndr. 2006 Summer;1(3):190-6
references.pmid: 17679826
references.citation: Metabolism. 2000 Feb;49(2):147-50
references.pmid: 10690935
references.citation: Circulation. 2002 Aug 13;106(7):820-5
references.pmid: 12176954
references.citation: Diabetes Res Clin Pract. 2006 Aug;73(2):191-7
references.pmid: 16442660
references.citation: J Clin Invest. 2001 May;107(10):1255-62
references.pmid: 11375415
references.citation: Circulation. 2005 May 17;111(19):2446-53
references.pmid: 15867184