Arginase Inhibition in Type 1 and Type 2 Diabetes Mellitus

Karolinska Institute

Status: Completed

Conditions: Type 1 Diabetes; Type 2 Diabetes

Treatments: Diagnostic Test: Nω-hydroxy-nor-arginine

Study type: Interventional

Funder types: Other

Identifiers

NCT05806502

T1DM study

Details and patient eligibility

About

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

Full description

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.

Enrollment: 12 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Type 1 diabetes

Experimental group

Description:

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).

Treatment:

Diagnostic Test: Nω-hydroxy-nor-arginine

Type 2 diabetes

Experimental group

Description:

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).

Treatment:

Diagnostic Test: Nω-hydroxy-nor-arginine