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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #165027
Title: PROTEINURIA AS A PREDICATOR OF TOTAL PLASMA HOMOCYSTEINE LEVELS IN TYPE 2 DIABETIC NEPHROPATHY

Author
item FRIEDMAN, ALLON - TUFTS-HNRC
item HUNSICKER, LAWRENCE - UNIV IOWA COLLEGE OF MED
item SELHUB, JACOB - TUFTS-HNRC
item BOSTOM, ANDREW - RHODE ISLAND HOSPITAL

Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/1/2002
Publication Date: 11/1/2002
Citation: Friedman, A.N., Hunsicker, L.G., Selhub, J., Bostom, A.G. 2002. Proteinuria as a predicator of total plasma homocysteine levels in type 2 diabetic nephropathy. Diabetes Care. 25:2037-2041.

Interpretive Summary: Many patients with diabetes develop proteinuria or increased excretion of protein in the urine, that is usually a sign of increased risk of cardiovascular disease. Previous studies also showed that proteinuria is also accompanied by increase in the level of the amino acid homocysteine in the blood. Homocysteine plays important functions in the body however it becomes harmful when present in increased concentration in the blood. High blood levels of homocysteine is related to increased risk of cardiovascular disease. Based on these facts, it was thought that the increased risk of cardiovascular disease among diabetic patients with proteinuria was due to the high homocysteine. These suggestions were based on studies with limited number of patients. In this study we analyzed over 700 diabetic patients and found that high homocysteine in plasma is not related to proteinuria.

Technical Abstract: Patients with diabetes who manifest proteinuria are at increased risk for cardiovascular events. Some studies suggest that proteinuria exerts its cardiovascular effects at least partly through a positive association with total plasma homocysteine (tHcy). Modestly sized but better designed contrary studies find no such link through a limited range of serum creatinine and proteinuria. We tested the hypothesis that proteinuria independently predicts tHcy levels in a larger cohort of type 2 diabetic patients with nephropathy throughout a much broader range of kidney disease and proteinuria. Baseline data for the cross-sectional study were obtained from 717 patients enrolled in the multicenter Irbesartan Diabetic Nephropathy Trial. All subjects had type 2 diabetes, hypertension, and proteinuria and were between 29 and 78 years of age. Data included age, sex, BMI, serum creatinine and albumin, LDL and HDL cholesterol, triglyceride, proteinuria and albuminuria, plasma folate, B12, and pyridoxal 5'-phosphate (PLP), HbA(1c), and tHcy levels. Crude analyses revealed significant associations between tHcy and age, creatinine,B12, folate, and HbA(1c), with serum albumin approaching significance. Only serum creatinine, plasma folate, B12, serum albumin, sex, HbA(1c), and age were independent predictors of tHcy after controlling for all other variables. By finding no independent correlation between proteinuria (or albuminuria) and tHcy levels, this study improves the external validity of previous negative findings. Therefore, it is unlikely that the observed positive association between proteinuria and cardiovascular disease is directly related to hyperhomocysteinemia.