Disentangling the effect of Brain Insulin Resistance on brain health (BIR-BrainHealth)
Diabetes type 1 and diabetes type 2
All participants will undergo a comprehensive clinical evaluation to characterize diabetes duration, severity, and systemic comorbidities. The cognitive performance of the participants will be assessed using a neuropsychological test battery of standardized tests. Tests will be grouped by cognitive domains, and each domain score is calculated as the mean of the individual component z-scores. A cognitive composite (global score) will be derived from the mean of the domains: learning and memory, executive function and working memory, processing speed, and attention. Blood, urine and stool will be collected for biomarker development and characterization of patients with BIR. A multi-omics approach will be applied to identify reliable biomarkers of BIR, incorporating lipidomics, metabolomics, proteomics, and transcriptomics. Magnetic resonance imaging (MRI) will be performed to assess BIR and structural brain changes, including atrophy. All MRS-scans will be performed on a research-optimized 3 Tesla MRI scanner. BIR will be evaluated by measuring changes in cerebral perfusion from administration of intranasal insulin delivered via nasal spray. A subset of participants will undergo additional advanced MRI-scanning for assessments of cerebrovascular function. Brain perfusion, blood–brain barrier integrity, and capillary perfusion distribution will be measured using dynamic contrast-enhanced MRI. Cerebrovascular reactivity will be measured by perfusion-weighted MRI during inhalation of air enriched with 5% CO2, a potent cerebral vasodilator. Cerebral blood flow responses to neuronal activation induced by visual stimulation will be assessed using perfusion-weighted MRI. Lastly, in a subset of participants the brain glucose sensing will be assessed using functional MRI (fMRI). fMRI will be measured prior to, during and following oral ingestion of water containing 75 grams of glucose. The glucose drink is given through a long straw while the participants are lying in the scan
1. Type 1 diabetes with a duration of ≥10 years 2. Type 2 diabetes with a duration of ≥5 years 3. Healthy controls
1. HbA1c >100 mmol/mol 2. Other type of diabetes 3. Weight >140 Kg 4. Treatment with drugs that cannot be paused for 12 hours 5. Diagnosis of dementia 6. Active and recent (1year) malignant disease 7. History of major stroke 8. Major depression and/or treatment with antipsychotics 9. History of traumatic brain injury 10. Other medical condition or disorder (e.g., epilepsy, recent concussion) that in the opinion of the investigator precludes compliance with the protocol, evaluation of the results or represent an unacceptable risk for the participant’s safety. 11. Inability to perform neuropsychological tests (e.g., severe vision and hearing impairment that cannot be improved with aids such as glasses and hearing aids, or language barrier.) 12. Severe claustrophobia 13. Foreign bodies of metal in the body which prohibits brain MRI scans (e.g. pacemaker or screws/plates from surgery in the head or neck region) 14. Participants who do not wish to be informed about accidental findings by MRI 15. eGFR measurement <45 within 3 months of study visit