Glycemic Control and Endothelial Function in Patients With Type 2 Diabetes (AIDdiabetes)

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

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).

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Diagnostic test: serotonin

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.

• Study Type: Observational
• Enrollment (Actual): 16

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 17176
    • Karolinska Institutet, Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Study Population

Type 2 diabetes Healthy controls

Description

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.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endothelial function	Change in endothelium-dependent dilatation	8 weeks

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: March 20, 2018
• First Submitted That Met QC Criteria: March 26, 2018
• First Posted (Actual): March 29, 2018

Study Record Updates

• Last Update Posted (Actual): February 21, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Serotonin Agents; Serotonin Receptor Agonists; Nitric Oxide Donors; Serotonin; Nitroprusside
• Other Study ID Numbers: AIDdiabetes

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No