Neurovascular Coupling and Autonomic Neuropathy in Type 2 Diabetes

Unravelling the Association Between Neurovascular Uncoupling and Autonomic Neuropathy in Patients With Type 2 Diabetes

Diabetes is a growing global health care challenge. Diabetes patients may also suffer from cardiovascular autonomic neuropathy (CAN) which may affect cerebral perfusion. The main purpose of this project is to investigate the association between CAN and disturbances in the neurovascular coupling in type 2 diabetes patients. Moreover, the purpose is also to investigate coherence between CAN and the enteric nervous system. Finally, this project aims at delineating microstructural changes in the brain tissues as a consequence of CAN.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 2 Diabetes; Cardiovascular Autonomic Neuropathy
• Intervention / Treatment: Other: CO2-enriched air; Other: Meal response test

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

Study Locations

• Denmark
  • Gentofte, Denmark, 2820
    • Steno Diabetes Center Copenhagen
  • Hvidovre, Denmark, 2650
    • Danish Research Centre for Magnetic Resonance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with type 2 diabetes and cardiovascular autonomic neuropathy. Patients with type 2 diabetes but no cardiovascular autonomic neuropathy Healthy controls.

Description

Inclusion Criteria:

• A diagnosis of type 2 diabetes (Patients)
• Age between 50-70 years (All)
• Presence of CAN as diagnosed by cardiovascular reflex tests with two or three pathological results (Patients with CAN only)
• Exclusion of CAN as diagnosed by cardiovascular reflex tests with no pathological results (Patients without CAN and HC only)

Exclusion Criteria:

• Participants receiving treatment with direct effects on noradrenergic or cholinergic signaling (for example beta-blockers, tricyclic antidepressants, SSRI's) (All)
• Acute infections (All)
• Thyroid disease (All)
• Substance or alcohol abuse (All)
• Atrial fibrillation or flutter (All)
• Respiratory failure (All)
• Participants in active laser treatment for retinopathy, will be excluded from the Valsalva test (Patients)
• Non-diabetic causes of neuropathy including a medical history of vitamin B12 deficiency, folic acid deficiency, rheumatoid arthritics, amyloidosis, HIV, syphilis, Borreliosis, drug induced neuropathy and neuropathy caused by toxins (All)
• Claustrophobia (All)
• Implanted pacemakers or remaining pacemaker electrodes (All)
• Previous heart or brain surgery with use of metal clips (All)
• Any form of non-MR-compatible implants
• Non-compliance with the study protocol as judged by the investigators (All)
• Concurrent participation in an intervention study (Patients)
• Participants who by judgments of the investigator, is incapable of participating (All)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy control	Other: CO2-enriched air; To assess cardiovascular reactivity; Other: Meal response test; Meal response test to assess changes in splanchnic blood flow.
T2DM +CAN	Other: CO2-enriched air; To assess cardiovascular reactivity; Other: Meal response test; Meal response test to assess changes in splanchnic blood flow.
T2DM -CAN	Other: CO2-enriched air; To assess cardiovascular reactivity; Other: Meal response test; Meal response test to assess changes in splanchnic blood flow.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurovascular coupling	Ratio between oxygen delivery/oxygen consumption by MRI during visual and hypercapnic stimulation	1 hour
Cerebrovascular reactivity	Change in CBF between normocapnia and hypercapnia	1 hour
Structural differences in brain tissue		1 hour
Regional splanchnic blood (superior mesenteric artery) flow increase in response to meal test		3 hours
Change in blood levels of gastrointestinal hormones and markers of metabolism following meal test		3 hours

Collaborators and Investigators

• Sponsor: Hartwig R. Siebner
• Collaborators: Steno Diabetes Center Copenhagen
• Investigators: Principal Investigator: Hartwig R. Siebner, MD, Prof, Danish Research Centre for Magnetic Resonance

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): July 31, 2025

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

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; Nervous System Diseases
• Other Study ID Numbers: H-20031245

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