Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications

Maria F Lopes-Virella, Rickey E Carter, Gregory E Gilbert, Richard L Klein, Miran Jaffa, Alicia J Jenkins, Timothy J Lyons, W Timothy Garvey, Gabriel Virella, Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Cohort Study Group, Maria F Lopes-Virella, Rickey E Carter, Gregory E Gilbert, Richard L Klein, Miran Jaffa, Alicia J Jenkins, Timothy J Lyons, W Timothy Garvey, Gabriel Virella, Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Cohort Study Group

Abstract

Objective: Because endothelial cell dysfunction and inflammation are key contributors to the development of complications in type 1 diabetes, we studied risk factors related to endothelial dysfunction and inflammation (C-reactive protein and fibrinogen, soluble vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin, and fibrinolytic markers) in a subgroup of patients from the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Intervention and Complications (EDIC) study cohort.

Research design and methods: We determined which of these risk factors or clusters thereof are associated with the presence of and subsequent development of nephropathy and macrovascular complications (reflected by carotid intima-media thickness [IMT]).

Results: After adjustment for conventional risk factors (age, sex, DCCT treatment group, diabetes duration, A1C, systolic blood pressure, waist-to-hip ratio, total and HDL cholesterol, and smoking status), fibrinogen remained strongly associated with progression of internal and common carotid IMT (P < 0.01) and soluble E-selectin had a strong association with nephropathy (P < 0.01).

Conclusions: The best predictor for IMT progression in the DCCT/EDIC cohort was plasma fibrinogen, and the levels of soluble E-selectin discriminate patients with albuminuria better than conventional risk factors.

References

    1. Tsimikas S, Willerson J, Ridker P: C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol 47:C19–C31, 2006
    1. Lopes-Virella MF, Virella G: Diabetes and atherosclerosis. In Contemporary Cardiology: Diabetes and Cardiovascular Disease, 2nd ed. Johnstone MT, Veves A, Eds. Totowa, NJ, Humana Press, 2006, p. 225–228
    1. Targher G, Zenari L, Bertolini L, Falezza G, Muggeo M, Zoppini G: Plasma total homocysteine levels are associated with von Willebrand factor, soluble intercellular adhesion molecule-1, and soluble tumor necrosis factor-α receptors in young type 1 diabetic patients without clinical evidence of macrovascular complications. Diabetes Care 24:1496–1497, 2001
    1. Targher G, Zenari L, Bertolini L, Muggeo M, Zoppini G: Elevated levels of interleukin-6 in young adults with type 1 diabetes without clinical evidence of microvascular and macrovascular complications. Diabetes Care 24:956–957, 2001
    1. Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, Stehouwer CD: Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care 26:2165–2173, 2003
    1. Skrivarhaug T, Bangstad HJ, Stene LC, Sandvik L, Hanssen KF, Joner G: Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway. Pediatr Diabetes 7:239–246, 2006
    1. Devaraj S, Glaser N, Griffen S, Wang-Polagruto J, Miguelino E, Jialal I: Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55:774–779, 2006
    1. Myrup B, de Maat M, Rossing P, Gram J, Kluft C, Jespersen J: Elevated fibrinogen and the relation to acute phase response in diabetic nephropathy. Thromb Res 81:485–490, 1996
    1. Hayaishi-Okano R, Yamasaki Y, Katakami N, Ohtoshi K, Gorogawa S, Kuroda A, Matsuhisa M, Kosugi K, Nishikawa N, Kajimoto Y, Hori M: Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes. Diabetes Care 25:1432–1438, 2002
    1. Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH: Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia 46:1402–1407, 2003
    1. Klein RL, Hunter SJ, Jenkins AJ, Zheng D, Semler AJ, Clore J, Garvey WT: Fibrinogen is a marker for nephropathy and peripheral vascular disease in type 1 diabetes: studies of plasma fibrinogen and fibrinogen gene polymorphism in the DCCT/EDIC cohort. Diabetes Care 26:1439–1448, 2003
    1. Targher G, Bertolini L, Zoppini G, Zenari L, Falezza G: Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in type 1 diabetic patients without clinically manifest macroangiopathy. Diabet Med 22:999–1004, 2005
    1. Chironi G, Pagnoux C, Simon A, Pasquinelli-Balice M, Del-Pino M, Gariepy J, Guillevin L: Increased prevalence of subclinical atherosclerosis in patients with small-vessel vasculitis. Heart 93:96–99, 2007
    1. Soedamah-Muthu SS, Chaturvedi N, Schalkwijk CG, Stehouwer CD, Ebeling P, Fuller JH: Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macrovascular complications in type 1 diabetic patients. J Diabet Complications 20:188–195, 2006
    1. Costacou T, Lopes-Virella MF, Zgibor JC, Virella G, Otvos J, Walsh M, Orchard TJ: Markers of endothelial dysfunction in the prediction of coronary artery disease in type 1 diabetes. J Diabet Complications 19:183–193, 2005
    1. Huvers FC, De Leeuw PW, Houben AJ, De Haan CH, Hamulyak K, Schouten H, Wolffenbuttel BH, Schaper NC: Endothelium-dependent vasodilatation, plasma markers of endothelial function, and adrenergic vasoconstrictor responses in type 1 diabetes under near-normoglycemic conditions. Diabetes 48:1300–1307, 1999
    1. Romano M, Pomilio M, Vigneri S, Falco A, Chiesa PL, Chiarelli F, Davi G: Endothelial perturbation in children and adolescents with type 1 diabetes: association with markers of the inflammatory reaction. Diabetes Care 24:1674–1678, 2001
    1. Nathan DM, Lachin J, Cleary P, Orchard T, Brillon DJ, Backlund JY, O'Leary DH, Genuth S, Diabetes Control and Complications Trial, Epidemiology of Diabetes Interventions and Complications Research Group: Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med 348:2294–2303, 2003
    1. The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977–986, 1993
    1. Jenkins AJ, Rothen M, Klein RL, Moller K, Eldridge L, Zheng D, Durazo-Arvizu R, McGee D, Lackland D, Thorpe SR, Garvey WT, Lyons TJ: Cross-sectional associations of C-reactive protein with vascular risk factors and vascular complications in the DCCT/EDIC cohort. J Diabet Complications 22:153–163, 2008
    1. Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology 98:786–806, 1991
    1. Lopes-Virella MF, McHenry MB, Lipsitz S, Yim E, Wilson PF, Lackland DT, Lyons T, Jenkins AJ, Virella G: Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes. Atherosclerosis 190:359–369, 2007
    1. Nagelkerke NJD: A note on general definition of the coefficient of determination. Biometrika 78:691–692, 1991
    1. Harrell FEJ: Regression Modeling Strategies with Applications to Linear Models, Logistic Regression, and Survival Analysis. New York, Springer-Verlag, 2001
    1. Leinonen ES, Hiukka A, Hurt-Camejo E, Wiklund O, Sarna SS, Mattson Hulten L, Westerbacka J, Salonen RM, Salonen JT, Taskinen MR: Low-grade inflammation, endothelial activation and carotid intima-media thickness in type 2 diabetes. J Intern Med 256:119–127, 2004

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