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Plasma Asymmetric Dimethylarginine Concentrations Are Elevated in Obese Insulin-Resistant Women and Fall with Weight Loss

Divisions of Endocrinology (T.M.) and Cardiovascular Medicine (F.A., G.M.R., P.S.T., J.B., C.L.), Stanford University School of Medicine, Stanford, California 94305-5103; and Universitaetsklinik fuer Innere Medizin (M.S.), 6020 Innsbruck, Austria

Address correspondence and requests for reprints to: Dr. Philip S. Tsao, Ph.D., Stanford University, Falk Building, 300 Pasteur Drive, Stanford, California 94305-5103. E-mail: ptsao{at}cvmed.stanford.edu.

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 µmol/liter, P = 0.02) and decreased to 1.20 ± 0.22 µmol/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.

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