Glycemic Control and Endothelial Function in Patients With Type 2 Diabetes

NCT ID: NCT03480945

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 16 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-01-01
• Study Completion Date: 2019-07-31

Brief Summary

Study objective To evaluate the mechanism behind endothelial dysfunction in patients with type 2 diabetes in relation to the level of glycaemic control.

Primary endpoint: Change in endothelium dependent vasodilatation (EDV).

Detailed Description

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

Inclusion criteria:

1. Type 2 diabetes

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

Exclusion criteria:

1. Age >80 years.

2. HbA1c <70 mmol/mol

3. Myocardial infarction/unstable angina within 6 weeks prior to the study.

4. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants)

5. Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.

6. Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

7. Participant in an ongoing study.

8. Unwillingness to participate following oral and written information.

Healthy controls Inclusion criteria

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

1. Age >80 years.

2. Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

3. Participant in an ongoing study.

4. 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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

serotonin

Endothelium-dependent dilatation

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

nitroprusside

Eligibility Criteria

Inclusion Criteria

1. Type 2 diabetes

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

Exclusion Criteria

1. Age >80 years.

2. HbA1c <70 mmol/mol

3. Myocardial infarction/unstable angina within 6 weeks prior to the study.

4. Treatment with oral anticoagulants (Warfarin or New oral anticoagulants)

5. Raynaud's phenomenon, peripheral vasculopathies, arterial shunting or other vascular surgery of the study arm.

6. Any concomitant disease or condition that may interfere with the possibility for the patient to comply with or complete the study protocol.

7. Participant in an ongoing study.

8. Unwillingness to participate following oral and written information.

• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Karolinska Institutet

OTHER

Sponsor Role: lead

Responsible Party

John Pernow

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Karolinska Institutet, Karolinska University Hospital

Stockholm, , Sweden

Countries

Sweden

Other Identifiers

AIDdiabetes

Identifier Type: -

Identifier Source: org_study_id