Neurovascular Coupling and Autonomic Neuropathy in Type 2 Diabetes

Study Overview
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Brief Summary
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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.

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

Conditions
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Type 2 Diabetes, Cardiovascular Autonomic Neuropathy

Intervention / Treatment
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* Other: CO2-enriched air
* Other: Meal response test


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| T2DM +CAN<br> | Other: CO2-enriched air<br>* To assess cardiovascular reactivity<br>Other: Meal response test<br>* Meal response test to assess changes in splanchnic blood flow.<br>|
| T2DM -CAN<br> | Other: CO2-enriched air<br>* To assess cardiovascular reactivity<br>Other: Meal response test<br>* Meal response test to assess changes in splanchnic blood flow.<br>|
| Healthy control<br> | Other: CO2-enriched air<br>* To assess cardiovascular reactivity<br>Other: Meal response test<br>* Meal response test to assess changes in splanchnic blood flow.<br>|

What is the study measuring?
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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 |