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Submitted on June 29, 2005
Accepted on February 16, 2006
Dr. McLaughlin: Stanford University School of Medicine, Division of Endocrinology; Drs. Abbasi, Reaven, Tsao, and Ms. Lamendola: Stanford University School of Medicine, Division of Cardiovascular Medicine; Dr. Stuhlinger: Universitaetsklinik fuer Innere Medizin, Anichstrasse 35, 6020 Innsbruck, Austria, 43-512 - 5040 (phone), 43-512-504-2767 (fax)
* To whom correspondence should be addressed. 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 thiazolidinedione treatment. Objective: To determine if 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 weeks of dietary weight loss (Stanford Hospital). 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/L, P = 0.02), and decreased to 1.20 ± 0.22 µmol/L (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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