Glycemic Control and Endothelial Function in Patients With Type 2 Diabetes

The study is performed on one group of patients with type 2 diabetes and one group of age-matched healthy controls

Inclusion criteria

• Type 2 diabetes
• Poor glycaemic control defined as a mean day blood glucose >12 mmol/L.

Exclusion criteria

• Age >80 years.
• HbA1c <70 mmol/mol
• Myocardial infarction/unstable angina within 6 weeks prior to the study.
• Treatment with oral anticoagulants (Warfarin or New oral anticoagulants)
• Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.
• Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.
• Participant in an ongoing study.
• Unwillingness to participate following oral and written information.

Healthy controls Inclusion criteria

• No medical history of cardiovascular disease 2. Fasting blood glucose <6.0 mmol/l or plasma glucose <7.0 mmol/l Exclusion criteria

• Age >80 years.
• Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.
• Participant in an ongoing study.
• Unwillingness to participate following oral and written information.

Endothelium-dependent vasodilatation is determined by venous occlusion plethysmography during intra-arterial 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.

Sixteen patients and age-matched healthy controls are included. 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, during an intra-arterial infusion of saline. Thereafter an intra-arterial infusion of the arginase inhibitor N-omega-hydroxy-nor-l-arginine (nor-NOHA) is started and is maintained for 120 min at a rate of 0.1 mg/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.

Following determination of baseline endothelial function (poor glycemic control), the patients are put on optimized glucose lowering therapy with insulin and/or oral glucose lowering medication according to clinical routine at the day-care center of the department of Endocrinology, Karolinska University Hospital for at least 8 weeks. Treatment target is mean day blood glucose <9 mmol/L and fasting blood glucose 4-6 mmol/L. After this, endothelium-dependent and -independent vasodilatation before and following arginase inhibition is re-assessed as described above.The healthy control group is only investigated on one occasion.

Inclusion criteria

• Type 2 diabetes
• Poor glycaemic control defined as a mean day blood glucose >12 mmol/L.

Exclusion criteria

• Age >80 years.
• HbA1c <70 mmol/mol
• Myocardial infarction/unstable angina within 6 weeks prior to the study.
• Treatment with oral anticoagulants (Warfarin or New oral anticoagulants)
• Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.
• Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.
• Participant in an ongoing study.
• Unwillingness to participate following oral and written information.