Blood S-adenosylmethionine concentrations and lymphocyte methylenetetrahydrofolate reductase activity in diabetes mellitus and diabetic nephropathy

The erythrocyte concentrations of the body's chief physiologic methyl donor S-adenosylmethionine (SAM) and of its metabolite and inhibitor S-adenosylh omocysteine (SAH), the plasma concentrations of total homocysteine (tHcy), and the activity of N-5,N-10 methylenetetrahydrofolate reductase (MTHFR) in lymphocytes were determined in healthy subjects and patients with diabetes mellitus without complications and at various stages of diabetic nephropat hy, categorized according to the degree of progression of the disease. Thes e groups were as follows: 1, control; 2, diabetics with no complications; 3 , patients with albuminuria; 4, patients with an elevated plasma creatinine ; and 5, patients on dialysis. No parameter studied exhibited significant d ifferences between the type 1 and the type 2 diabetics. In control subjects , the blood concentrations of SAM were proportional to the activity of MTHF R; in diabetics, it was not. Consistent with previous observations, progres sion of nephropathy was accompanied by increased concentrations of tHcy. In creased erythrocyte concentrations of SAH, decreased erythrocyte concentrat ions of SAM, SAM/SAH ratios, and lymphocyte MTHFR activity also accompanied disease progression. The blood concentrations of SAH paralleled those of t Hcy, while the concentrations of SAM showed a bimodal relationship with tho se of tHcy. These results provide further evidence that alterations in the blood concentrations of SAM and related compounds are abnormal in patients with diabetes, particularly in those with nephropathy. The deficiency of SA M may lead to methyl deficiencies, which may contribute to the high morbidi ty and mortality in patients with diabetic nephropathy. We have also demons trated a decrease in lymphocyte MTHFR activity in patients with advanced ne phropathy, suggesting that hyperhomocysteinemia in these patients may be du e to a generalized metabolic abnormality. Further studies are needed to det ermine the pathogenesis of these abnormalities and whether they are present in renal failure due to causes other than diabetes or whether they are spe cific to diabetic nephropathy. Copyright (C) 2001 by W.B. Saunders Company.