Total homocysteine is associated with nephropathy in non—insulin-dependent diabetes mellitus

• Published in: Metabolism, clinical and experimental Vol. 48; no. 9; pp. 1096 - 1101
• Main Authors: Stabler, Sally P., Estacio, Raymond, Jeffers, Barrett W., Cohen, Jeffrey A., Allen, Robert H., Schrier, Robert W.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.1999; Elsevier
• Subjects: Adult; Aged; Albuminuria - metabolism; Associated diseases and complications; Biological and medical sciences; Cystathionine - blood; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - blood; Diabetic Nephropathies - complications; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Homocysteine - blood; Humans; Hyperhomocysteinemia - etiology; Hyperhomocysteinemia - metabolism; Hypertension - metabolism; Kidney Function Tests; Male; Medical sciences; Methylmalonic Acid - blood; Middle Aged; Regression Analysis; Vitamins - blood; United States; North America; America; Endocrinopathy; Human; Kidney disease; Hypertension; Urinary system disease; Cardiovascular disease; Non insulin dependent diabetes; Blood plasma; Nephropathy; Methylmalonic acid; Adult; Complication; Elderly; Comparative study
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(99)90121-X

Non—insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with premature vascular disease. We tested the hypothesis that homocysteine is associated with vascular disease and other diabetic complications in patients with NIDDM. The current investigation is a cross-sectional analysis of baseline variables for participants in the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Men and women aged 40 to 74 years with NIDDM and a mean diastolic blood pressure (BP) of 80 mm Hg or higher were eligible. We measured serum levels of total homocysteine (tHcy), cystathionine, and methylmalonic acid (MMA) and correlated these values with clinical and other laboratory measures of the complications of diabetes mellitus in 452 subjects. tHey was higher in males than in females and correlated with the duration of hypertension and systolic BP. tHcy was significantly correlated with MMA ( r = .35, P < .0001) and cystathionine ( r = .53, P < .0001) levels and inversely correlated with serum B 12 ( r = −.23, P < .0001) and folate ( r = −.18, P < .0001). It was significantly correlated with serum creatinine ( r = .28, P < .0001 for males and r = .39, P < .0001 for females) and inversely correlated with creatinine clearance ( r = −.19, P < .005 for males and r = −.30, P < .0001 for females). tHcy was not increased in subjects with cardiovascular disease or retinopathy, but it was increased in those with neuropathy (10.3 v 9.3 μmol/L, P < .05) and macroalbuminuria (11.0 v 9.2 μmol/L, P < .005). Of these subjects, 2.2% met the criteria for vitamin B 12 deficiency and 1% met the criteria for folate deficiency. We conclude that elevations of tHcy in this population appear to be the result of a combination of vitamin deficiency and decreased renal function and do not appear to be a predictor of cardiovascular disease.