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Clinical and nutritional correlates of C-reactive protein in type 2 diabetic nephropathy

      Abstract

      Background: Patients with diabetic nephropathy are at elevated cardiovascular risk. C-reactive protein (CRP) has been used to successfully predict cardiovascular events. Objective: We identified clinical and biochemical characteristics that correlate with CRP levels in diabetic nephropathy patients. Design: Baseline data obtained from 722 patients in the Irbesartan Diabetic Nephropathy Trial included age, sex, body mass index (BMI), systolic blood pressure (BP), serum creatinine, plasma low- and high-density cholesterol, triacylglycerol, serum albumin, hemoglobin A1C, 24 h urinary protein excretion, plasma total homocysteine (tHcy), folate, B12, pyridoxal 5′-phosphate (PLP, active form of Vitamin B6), and plasma CRP levels. Results: In univariate analyses CRP was positively associated with female sex (r=0.08; P=0.04), BMI (r=0.34; P<0.01), serum creatinine (r=0.21; P<0.01), hemoglobin A1C (r=0.08; 0.04), and inversely associated with PLP (r=−0.17; P<0.01) and folate (r=−0.09; P=0.02). A stepwise multiple regression model found CRP directly correlated with BMI (P<0.01) and serum creatinine (P<0.01), and inversely correlated with PLP (P<0.01). The final model explained 16% of the total variance of CRP. Conclusions: These results extend previous findings of an inverse relationship between Vitamin B6 and CRP. The lack of association between CRP and certain established or emerging cardiovascular risk factors offers novel information regarding cardiovascular risk in this population.

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      References

        • Grundy S.M.
        • Benjamin I.J.
        • Burke G.L.
        • Chait A.
        • Eckel R.H.
        • Howard B.V.
        • et al.
        Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association.
        Circulation. 1999; 100: 1134-1146
        • Dinneen S.F.
        • Gerstein H.C.
        The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature.
        Arch. Int. Med. 1997; 157: 1413-1418
        • Wollesen F.
        • Brattstrom L.
        • Refsum H.
        • Ueland P.M.
        • Berglund L.
        • Berne C.
        • et al.
        Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus.
        Kidney Int. 1999; 55: 1028-1035
        • Ross R.
        Atherosclerosis—an inflammatory disease.
        N. Engl. J. Med. 1999; 340: 115-126
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • Tracy R.P.
        • Hennekens C.H.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        N. Engl. J. Med. 1997; 336: 973-979
        • Ridker P.M.
        • Rifai N.
        • Pfeffer M.A.
        • Sacks F.M.
        • Moye L.A.
        • Goldman S.
        • et al.
        Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) investigators.
        Circulation. 1998; 98: 839-844
        • Yeun V.
        • Levine R.
        • Mantadilok V.
        • Kaysen G.A.
        C-reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients.
        Am. J. Kidney Dis. 2000; 35: 469-476
        • Lewis E.J.
        • Hunsicker L.G.
        • Clarke W.R.
        • Berl T.
        • Pohl M.A.
        • Lewis J.B.
        • et al.
        Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
        N. Engl. J. Med. 2001; 345: 851-860
        • Araki A.
        • Sako Y.
        Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection.
        J. Chromatogr. 1987; 422: 43-52
        • Shin Y.S.
        • Rasshofer R.
        • Friedrich B.
        • Endres W.
        Pyridoxal-5′-phosphate determination by a sensitive micromethod in human blood, urine and tissues; its relation to cystathioninuria in neuroblastoma and biliary atresia.
        Clin. Chim. Acta. 1983; 127: 77-85
      1. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. The evidence report. Bethesda: U.S. Department of Health and Human Services, National Institutes of Health, National Heart, Lung, and Blood Institute; 1998. p. 228.

        • Jacques P.F.
        • Selhub J.
        • Bostom A.G.
        • Wilson P.W.
        • Rosenberg I.H.
        The effect of folic acid fortification on plasma folate and total homocysteine concentrations.
        N. Engl. J. Med. 1999; 340: 1449-1454
        • Friso S.
        • Jacques P.F.
        • Wilson P.W.
        • Rosenberg I.H.
        • Selhub J.
        Low circulating Vitamin B6 is associated with elevation of the inflammation marker C-reactive protein independently of plasma homocysteine levels.
        Circulation. 2001; 103: 2788-2791
        • Ridker P.M.
        • Hennekens C.H.
        • Buring J.E.
        • Rifai N.
        C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.
        N. Engl. J. Med. 2000; 342: 836-843
        • Ortega O.
        • Rodriguez I.
        • Gallar P.
        • Carreno A.
        • Ortiz M.
        • Espejo B.
        • et al.
        Significance of high C-reactive protein levels in pre-dialysis patients.
        Nephrol. Dial Transplant. 2002; 17: 1105-1109
        • Selhub J.
        Homocysteine metabolism.
        Annu. Rev. Nutr. 1999; 19: 217-246
        • Stone W.J.
        • Warnock L.G.
        • Wagner C.
        Vitamin B6 deficiency in uremia.
        Am. J. Clin. Nutr. 1975; 28: 950-957
        • Bates C.J.
        • Pentieva K.D.
        • Prentice A.
        • Mansoor M.A.
        • Funch S.
        Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over.
        Br. J. Nutr. 1999; 81: 191-201
        • Roubenoff R.
        • Dellaripa P.
        • Nadeau M.R.
        • Abad L.W.
        • Muldoon B.A.
        • Selhub J.
        • et al.
        Abnormal homocysteine metabolism in rheumatoid arthritis.
        Arthritis Rheum. 1997; 40: 718-722
        • Robinson K.
        • Arheart K.
        • Refsum H.
        • Brattstrom L.
        • Boers G.
        • Ueland P.
        • et al.
        Low circulating folate and Vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease.
        Circulation. 1998; 97: 437-443
        • Visser M.
        • Bouter L.
        • McQuillan G.
        • Wener M.H.
        • Harris T.B.
        Elevated C-reactive protein levels in overweight and obese adults.
        JAMA. 1999; 282: 2131-2135
        • Ford E.
        Body mass index, diabetes, and C-reactive protein among U.S. adults.
        Diabetes Care. 1999; 22: 1971-1977
        • Mohamed-Ali V.
        • Goodrick S.
        • Rawesh A.
        • Katz D.R.
        • Miles J.M.
        • Yudkin J.S.
        Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo.
        J. Clin. Endocrinol. Metab. 1997; 82: 4196-4200
        • Calle E.E.
        • Thun M.J.
        • Petrelli J.M.
        • Rodriguez C.
        • Heath Jr, C.W.
        Body-mass index and mortality in a prospective cohort of U.S. adults.
        N. Engl. J. Med. 1999; 341: 1097-1105
        • Kaysen G.A.
        The microinflammatory state in uremia: causes and potential consequences.
        J. Am. Soc. Nephrol. 2001; 12: 1549-1557
        • Festa A.
        • D’Agostino Jr., R.
        • Howard G.
        • Mykkanen L.
        • Tracy R.P.
        • Haffner S.M.
        Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS).
        Circulation. 2000; 102: 42-47
        • Anderson J.L.
        • Muhlestein J.B.
        • Horne B.D.
        • Carlquist J.F.
        • Bair T.L.
        • Madsen T.E.
        Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease.
        Circulation. 2000; 102: 1227-1232
        • Stehouwer C.D.
        • Gall M.A.
        • Twisk J.W.
        • Knudsen E.
        • Emeis J.J.
        • Parving H.H.
        Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death.
        Diabetes. 2002; 51: 1157-1165
        • Schalkwijk C.G.
        • Poland D.C.
        • van Dijk W.
        • Kok A.
        • Emeis J.J.
        • Draper A.M.
        Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation.
        Diabetologia. 1999; 42: 351-357
        • Festa A.
        • D’Agostino R.
        • Howard G.
        • Mykkanen L.
        • Tracy R.P.
        • Haffner S.M.
        Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study.
        Kidney Int. 2000; 58: 1703-1710