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Metformin therapy lowers plasma levels of asymmetric dimethylarginine (ADMA) in hyperglycemic patients with type 2 diabetes. Previous studies observed a significant relationship between insulin resistance and plasma concentrations of ADMA and that elevated plasma ADMA levels may contribute to endothelial dysfunction observed in insulin-resistant patients.
Researchers, at Stanford University School of Medicine in Stanford, California in the United States, found that patients treated with metformin, either as monotherapy or with sulfonylurea, had a favourable increase in their ratio of plasma L-arginine-to-ADMA ratio.
The Stanford University study included 31 patients with type 2 diabetes and poor glycemic control (fasting plasma concentrations greater than 9.7 mmol/L). Sixteen of the patients had been using diet to manage their hyperglycemia and 15 were taking a maximal dose of sulfonylurea. The researchers measured the patients’ fasting plasma glucose, dimethylarginine, and L-arginine concentrations before, and three months after, they began metformin therapy at a maximally effective dose.
Fasting plasma glucose concentrations decreased a similar degree in patients treated with either metformin alone or with metformin added to a sulfonylurea compound, the investigators reported.
The improvement in glycaemic control was associated with similar decreases in plasma ADMA concentrations in patients receiving only metformin. Plasma ADMA concentrations in patients receiving metformin plus sulfonylurea similarly declined. Plasma L-arginine concentrations were comparable in both groups at baseline and did not change in response to metformin. "Thus, metformin treatment was associated with a favourable increase in the plasma L-arginine/ADMA ratio," T. Asagami and his coauthors wrote.
"These results provide the first evidence that plasma ADMA concentrations decrease in association with improved glycemic control in patients with type 2 diabetes and demonstrate that the magnitude of the change in metformin-treated patients was similar, irrespective of whether it was used as monotherapy or in combination with sulfonylurea treatment," the investigators concluded.
Metabolism 2002; 51: 843-846