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/m 2 , n=46) or non-adipose (<25 kg/m 2 , 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/m 2 ). 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. [Diabetologia (2002[Diabetologia ( ) 45:1372[Diabetologia ( -1378 Keywords Gestational diabetes, asymmetrical dimetylarginine, nitric oxide, insulin resistance, cholesterol. . L-arginine can also be methylated by intracellular methyltransferases [3], but the exact regulation of this pathway is not known. The methylated L-arginine metabolite, asymmetrical dimethyl-L-arginine (ADMA), inhibits the cellular L-arginine uptake and nitric oxide synthase activity in endothelial cells competitively [4]. The allosteric symmetrical dimethyl-L-arginine (SDMA) is produced in equivalent amounts, but is not a structural antagonist in nitric oxide synthesis [5].It has been speculated that accumulation of endogenous L-arginine metabolites and low availability of LNitric oxide is synthesized from the amino acid L-arginine by constitutive and inducible nitric oxide synthases [1] and plays an important role in the regulation

Early Exercise Training After Renal Transplantation and Asymmetric Dimethylarginine: The Effect of Obesity

“…The absence of improved glycemic control is consistent with previous results showing that physical activity does not automatically improve glycemic control in patients after renal transplantation not receiving a controlled diet [29]. Blood lipids slightly improve after six months of training and no significant association with ADMA could be found implying that changes in ADMA are independent of these parameters, and this finding is consistent with data reported from several other studies [30].…”

“…This effect likely results from DDAH up-regulation [29,30,31]. The study design did not allow to compare the effects of cyclosporine A- and tacrolimus-based regimes.…”

A systematic review of metabolite profiling in gestational diabetes mellitus

“…It is considered a potential mediator of endothelial dysfunction [42], and clinical studies have observed increased levels of ADMA in individuals with several cardiometabolic diseases, including insulin resistance [43], hypercholesterolaemia [44], atherosclerosis [45], hypertension [46], chronic heart failure [47], type 2 diabetes mellitus [48], chronic renal failure [49] and histories of GDM [50-52]. Several clinical studies and reviews have also highlighted the potential role of ADMA as an independent predictor of the progression of atherosclerosis, cardiovascular death and all-cause mortality [42, 53-56].…”

Asymmetric Dimethylarginine Is Associated with Developmental Programming of Adult Kidney Disease and Hypertension in Offspring of Streptozotocin-Treated Mothers

“…We found that 50% maternal caloric restriction causes low nephron numbers and renal dysfunction, which are associated with increased plasma ADMA level in the adult offspring [8]. In addition, elevated concentrations of ADMA have been reported in patients with different types of diabetes [10]–[13] and their related complications [14], [15]. However, little attention has been given on whether maternal diabetes impairs the ADMA-NO pathway, resulting in developmental programming in the kidneys of the offspring.…”