Disentangling the Effect of Brain Insulin Resistance on Brain Health

ConditionsDiabetes Type 2 Diabetes Type 1

Trial statusRecruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age50-80

SponsorHenrik Bo Wiberg Larsson

About this trial

People with diabetes are at increased risk of developing dementia, including Alzheimer's disease and vascular dementia. In addition, persons with diabetes have more pronounced age-related brain atrophy and cognitive difficulties compared to people without diabetes. The mechanisms behind the effects on the brain of diabetes are still unclear. New research suggests that the brains of some people with diabetes do not respond normally to insulin signals, a condition known as brain insulin resistance (BIR). To date, there have been no large clinical studies investigating BIR and its impact on brain health, but several smaller studies suggest that BIR may be a cause of cognitive decline and impaired brain health in people with diabetes. Another mechanism that may contribute to impaired brain health in people with diabetes is damage to the blood vessels in the brain. Damage to blood vessels is a well-known complication of diabetes, but how it affects the brain is not fully described. In this project, we will investigate the relationship between BIR and brain blood vessel dysfunction and its relationship to cognition and brain function. This is done by examining patients with type 1 diabetes (T1D), type 2 diabetes (T2D) and healthy controls. The participants will undergo MRI brain scans to assess the impact of BIR on the brain physiology and to evaluate brain blood vessel health. Participants will undergo comprehensive assessments of their cognitive abilities and thorough health examination.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

age 50-80 years

Diagnosis of either type 1 diabetes or type 2 diabetes

Diabetes duration of ≥10 years for individuals with type 1 diabetes and ≥5 years for individuals with type 2 diabetes

Disqualifiers

HbA1c >100 mmol/mol

Other type of diabetes

Weight >140 Kg

Treatment with drugs that cannot be paused for 12 hours

Trial population

It is planned to recruit participants in the Greater Copenhagen area in Denmark and the Ulm area in Germany. The participants will be recruited from the outpatient clinic at Steno Diabetes Center Copenhagen and Ulm University Hospital and primary care settings in Denmark and Germany. In addition to this, participants will be sought by physical advertisements in the local area, through recruitment platforms (join.trialtree.com) and social media.

Trial design

Design model

Case-control

Time perspective

Cross-sectional

Treatments tested in this trial

Not listed

Trial groups

150 Participants

are grouped into 3 trial groups

Group A: Type 1 Diabetes

Group B: Type 2 Diabetes

Group C: Controls

Trial outcomes

Primary outcomes

Correlation between brain insulin response and cognitive measures

Brain insulin response is assessed by measuring changes in cerebral blood flow following intranasal insulin administration, using arterial spin labelling (ASL) MRI. The neuropsychological test battery includes the following: * Rey Auditory Verbal Learning Test (RAVLT) * Trail Making Test (TMT) part A and B * Symbol Digit Modalities Test (SDMT) * RBANS Digit Span forward (Version A) * Wechsler Adult Intelligence Scale III Letter-Number Sequencing test (WAIS-LNS) * Verbal Fluency test (phonetic and semantic) * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses Motor function (Grooved Pegboard) Montreal Cognitive Assessment (MoCA)

Time frame

Baseline (only measured once)

Correlation between cerebrovascular reactivity and cognitive measures

Cerebrovascular reactivity is assessed by measuring changes in cerebral blood flow responses to inhalation of hypercapnic air (air enriched with 5% CO2). Cerebral blood flow is measured using combined blood-oxygen-level-dependent (BOLD) MRI, ASL MRI, and phase contrast mapping (PCM) MRI. The neuropsychological test battery includes the following: * Rey Auditory Verbal Learning Test (RAVLT) * Trail Making Test (TMT) part A and B * Symbol Digit Modalities Test (SDMT) * RBANS Digit Span forward (Version A) * Wechsler Adult Intelligence Scale III Letter-Number Sequencing test (WAIS-LNS) * Verbal Fluency test (phonetic and semantic) * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses Motor function (Grooved Pegboard) Montreal Cognitive Assessment (MoCA)

Time frame

Baseline (only measured once)

Secondary outcomes

Blood-brain-barrier permability

Differences in blood-brain-barrier permeability between groups, measured by dynamic contrast enhanced MRI.

Time frame

Baseline (only measured once)

Neurovascular coupling

Differences in cerebral blood flow responses to visual stimulation between groups, assessed with ASL MRI.

Time frame

Baseline (only measured once)

Hypothalamic glucose sensing

Differences in cerebral blood flow response in the hypothalamus to glucose ingestion between groups, assessed by combined BOLD and ASL MRI.

Time frame

Baseline (only measured once)

Other outcomes

Brain insulin response

Differences in brain insulin response between groups, assessed by measuring changes in cerebral blood flow following intranasal insulin administration using ASL MRI.

Time frame

Baseline (only measured once)

Cerebrovascular reactivity

Differences in cerebrovascular reactivity between groups, assessed by measuring changes in cerebral blood flow in response to inhalation of hypercapnic air (air enriched with 5% CO2). Cerebral blood flow is measured using combined blood-oxygen-level-dependent (BOLD) MRI, ASL MRI, and phase contrast mapping (PCM) MRI.

Time frame

Baseline (only measured once)

Brain atrophy and white matter lesion

Differences in brain atrophy and white matter lesion load between groups, assessed by T1- weighted structural MRI and Fluid-Attenuated Inversion Recovery (FLAIR) MRI.

Time frame

Baseline (only measured once)

Correlation between brain atrophy and white matter lesions load and cognitive measures

Brain atrophy and white matter lesion load is assessed by T1- weighted structural MRI and FLAIR MRI. The neuropsychological test battery includes the following: * Rey Auditory Verbal Learning Test (RAVLT) * Trail Making Test (TMT) part A and B * Symbol Digit Modalities Test (SDMT) * RBANS Digit Span forward (Version A) * Wechsler Adult Intelligence Scale III Letter-Number Sequencing test (WAIS-LNS) * Verbal Fluency test (phonetic and semantic) * Rapid Visual Processing (RVP) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) using A' (RVP-A) and mean latency for correct responses Motor function (Grooved Pegboard) Montreal Cognitive Assessment (MoCA)

Time frame

Baseline (only measured once)