Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss

Context: Plasma asymmetric dimethylarginine ( ADMA) concentrations are higher in apparently healthy, insulin-resistant (IR) individuals and decrease in response to thiazolidenedione treatment. Objective: The objective of the study was to determine whether ADMA concentrations would also fall when insulin sensitivity is enhanced with weight loss in obese individuals. Design/Setting/Patients/Intervention: Twenty obese women classified as IR or insulin sensitive ( IS) on the basis of their steady-state plasma glucose (SSPG) concentration during the insulin suppression test underwent 12 wk of dietary weight loss. Outcome Measures: Plasma glucose, insulin, and ADMA were measured at baseline and after weight loss; change in insulin resistance was quantified by repeating the SSPG after the dietary intervention. Results: Although weight loss was similar in the two groups, significant improvements in SSPG, glucose, and insulin concentrations were confined to the IR group. Baseline plasma ADMA concentrations (mean +/- SD) were higher in IR subjects (1.69 +/- 0.44 vs. 1.18 +/- 0.45 mu mol/liter, P = 0.02) and decreased to 1.20 +/- 0.22 mu mol/liter (P < 0.001) with weight loss. In contrast, ADMA levels did not change with a similar extent of weight loss in the IS group. Conclusion: Plasma ADMA levels are higher in obese, IR women than in equally obese, IS women and decrease in response to weight loss when associated with enhancement of insulin sensitivity.