Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes

BACKGROUND: Diabetic nephropathy is a common complication in patients with type 2 diabetes that may increase atherothrombotic risk. Hyperhomocysteinemia (HHcy) further increases the risk in those patients. We studied concentrations of total homocysteine (tHcy) and its related metabolites S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) in relation to B-vitamin status and renal function in patients with type 2 diabetes who developed diabetic nephropathy. METHODS: The study included 93 patients with renal failure and type 2 diabetes. Chronic kidney disease was classified into four subgroups according to the National Kidney Foundation based on glomerular filtration rate plus pathologic abnormalities or markers of kidney damage. RESULTS: Serum or plasma concentrations of the metabolites increased significantly with worsening of renal function, whereas serum concentrations of the B vitamins (folate, vitamins B12 and B6) did not differ appreciably between the groups. Moreover, plasma concentrations of AdoHcy and AdoMet were markedly increased in patients with kidney failure compared with those in stage 2 (median AdoHcy, 112.7 vs 10.5 nmol/L; median AdoMet, 162.0 vs 80.0 nmol/L). The AdoMet/AdoHcy ratio was more than 80% lower in patients with renal failure compared with stage 2. Vitamin B12 was a significant determinant of concentrations of AdoMet, tHcy, methylmalonic acid (MMA), and cystathionine. CONCLUSIONS: Increased plasma concentrations of tHcy and methionine cycle intermediates (AdoMet, AdoHcy) are related to disturbed renal function in patients with type 2 diabetes. Vitamin B12 and/or folate are significant predictors of tHcy, cystathionine, MMA, and AdoMet. The effect of therapeutic doses of the B vitamins on AdoMet, AdoHcy, and their ratio should be tested in renal patients.