Glycemic Control and Endothelial Function in Patients With Type 2 Diabetes

Type 2 Diabetes Mellitus Clinical Trial

— AIDdiabetes  

Official title:

Evaluation of the Mechanism Underlying Endothelial Dysfunction in Patients With Type 2 Diabetes With Poor and Optimized Glycaemic Control

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03480945
• Other study ID #: AIDdiabetes
• Status: Completed
• Start date: January 1, 2016
• Est. completion date: July 31, 2019

Study information

• Verified date: February 2020
• Source: Karolinska Institutet
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 31, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Diagnostic Test:
• serotonin
Endothelium-dependent dilatation

Locations

Country	Name	City	State
Sweden	Karolinska Institutet, Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endothelial function	Change in endothelium-dependent dilatation	8 weeks