ADMA in diabetic patients

ADMA may play an important role as a risk marker in the pathogenesis of diabetes mellitus and its cardiovascular complications. In a series of studies from different investigators it was repeatedly reported that patients with type II diabetes have significantly elevated ADMA levels [54-56]. Interestingly, even a single high-fat meal can acutely increase ADMA levels in type II diabetic patients [55]. Molecular mechanisms underlying the elevation of ADMA plasma levels in diabetes mellitus may be oxidative stress-induced dysregulation of the enzyme that inactivates ADMA, dimethylarginine dimethylaminohydrolase (DDAH) [57] or angiotensin II-dependent mechanisms that are also being discussed [58].

Experimental models of diabetes mellitus in animals have confirmed the relationship between ADMA and this metabolic disease: Rats that have been made diabetic by the injection of streptozotocin have significantly elevated ADMA levels as compared to control rats [57, 59].
Yet another, clinically relevant observation stems from therapeutic intervention studies. Patients with impaired glucose tolerance show significantly higher ADMA levels even before the onset of clinically overt diabetes [56]. Pharmacological restoration of insulin sensitivity with rosiglitazone leads to a reduction of ADMA levels [56], and metformin treatment has been shown to exert a similar effect [60].