Arginase Inhibition in Type 1 and Type 2 Diabetes Mellitus

The Effect of Arginase Inhibition on Vascular Endothelial Function in Patients With Type 1 and Type 2 Diabetes

To evaluate the efficacy of arginase inhibition on endothelial function in patients with type 1 diabetes and type 2 diabetes.

Detailed Description: The study is performed on one group of patients with type 1 diabetes and one group of patients with type 2 diabetes. Forearm blood flow is determined by venous occlusion plethysmography. Endothelium-dependent vasodilatation is determined during intra-brachial artery infusion of serotonin (21, 70 and 210 ng/min). Endothelium-independent vasodilatation is determined by infusion of sodium nitroprusside (SNP; 1, 3 and 10 µg/min). Each dose is given for 2 min at a rate of 2.5 ml/min. Data are expressed as percentage change in forearm blood from baseline flow. Twelve subjects are included in each group. On the day of the study the subject arrives to the laboratory after having a light breakfast. Forearm vessels of the non-dominant arm are cannulated and forearm blood flow is determined as described above. Baseline endothelium-dependent and endothelium-independent vasodilatation is determined by intra-arterial infusions of serotonin and SNP, respectively. Thereafter an intra-arterial infusion of the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) is administered as an intra-arterial infusion at a rate of 0.1 mg/min and is maintained for 120 min. The dose is based on a previous study by our group demonstrating improved endothelial function. Endothelium-dependent and -independent vasodilatation is reassessed at 120 min of infusion.

Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).

Endothelium-dependent and -independent vasodilatation before and after 120 min intra-arterial administration of arginase the inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA).

Inclusion Criteria: Type 1 diabetes Type 2 diabetes Exclusion Criteria: Age >80 years Acute coronary or ischemic event during the last three months Vascular surgery of the arm Peripheral vascular disease affecting the arm Ongoing anticoagulant medication Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.