Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes

Abstract

Aims/hypothesis. The concentration of asymmetrical dimethyl-L-arginine (ADMA), an endogenous inhibitor of the nitric oxide synthase, is increased in patients at risk or with cardiovascular disease. We have investigated ADMA concentrations in women with a history of gestational diabetes (GDM), who could develop endothelial dysfunction and Type II (non-insulin-dependent) diabetes mellitus after delivery, and in healthy control subjects. Methods. Previous GDM patients were grouped according to their BMI as obese (≥25 kg/m2, n=46) or non-adipose (<25 kg/m2, n=31). Serum samples were taken 14 to 16 weeks after delivery and after 1 year. The control group comprised 17 healthy women (BMI<25 kg/m2). ADMA concentrations were analysed by high performance liquid chromatography. Results. ADMA concentrations were comparable between obese and non-adipose GDM patients (0.58±0.02 and 0.57±0.02 μmol/l, respectively), and higher than in the control group (0.47±0.03 μmol/l; p<0.006). Insulin resistance as estimated by the insulin sensitivity index was more frequent among the obese than the non-adipose GDM women (p<0.05) and control subjects (p<0.05, both). No change in ADMA concentrations was found after 1 year in women with GDM. There was only a slight correlation between ADMA and BMI (r=0.26, p<0.02), triglycerides (r=0.29, p<0.004), or fasting plasma glucose (r=0.21, p<0.05), and not with the insulin sensitivity index or other parameters. In a multiple regression analysis ADMA serum concentrations were only associated with triglycerides. Conclusion/interpretation. Circulating ADMA concentrations are increased in normoglycaemic women with previous GDM. This increase is independent from other risk factors or surrogate markers for diabetes or cardiovascular events.