Disentangling the Effect of Brain Insulin Resistance on Brain Health

NCT07374705 | Recruiting

• 2 other identifiers: NNF24OC0087481H-25045491
• Study Type: observational
• Target: 150
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Diabetes Type 2; Diabetes Type 1

Keywords

Diabetes; Brain Insulin Resistance; cognitive performance; cognitive dysfunction; structural changes in the brain; cerebrovascular function; brain health; blood-brain-barrier; diabetes type 1; diabetes type 2; biomarkers

Outcome Measures

Primary Outcomes (2)

• 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)

  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)

  Baseline (only measured once)

Secondary Outcomes (3)

• Blood-brain-barrier permability

  Baseline (only measured once)

• Neurovascular coupling

  Baseline (only measured once)

• Hypothalamic glucose sensing

  Baseline (only measured once)

Other Outcomes (20)

• Brain insulin response

  Baseline (only measured once)

• Cerebrovascular reactivity

  Baseline (only measured once)

• Brain atrophy and white matter lesion

  Baseline (only measured once)

Study Arms (3)

Type 1 Diabetes

Individuals who have a type 1 diabetes diagnose and meet the inclusion and exclusion criteria.

Type 2 Diabetes

Individuals who have a type 2 diabetes diagnose and meet the inclusion and exclusion criteria.

Controls

Individuals who do not have a diabetes diagnose and meet the inclusion and exclusion criteria.

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study 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.

You may qualify if:

• 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

You may not qualify if:

• HbA1c \>100 mmol/mol
• Other type of diabetes
• Weight \>140 Kg
• Treatment with drugs that cannot be paused for 12 hours
• Diagnosis of dementia
• Active and recent (1year) malignant disease
• History of major stroke
• Major depression and/or treatment with antipsychotics
• History of traumatic brain injury
• 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.
• 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.)
• Severe claustrophobia
• 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)
• Participants who do not wish to be informed about accidental findings by MRI
• eGFR measurement \<45 within 3 months of study visit

Sponsors & Collaborators

• Henrik Bo Wiberg Larsson: lead
• Steno Diabetes Center Copenhagen: collaborator
• University of Ulm: collaborator

Study Sites (3)

Rigshospitalet

Glostrup Municipality, 2600, Denmark

RECRUITING

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

RECRUITING

University of Ulm

Ulm, 89081, Germany

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (serum, plasma, buffy coat), urine, and faecal samples are collected and processed by trained personnel and stored at the research biobank at Steno Diabetes Center Copenhagen and at University of Ulm.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Diabetes Mellitus; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Henrik BW Larsson, Professor

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

• Jørgen Rungby, Professor

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

• Flemming Pociot, Professor

  Steno Diabetes Center Copenhagen

  PRINCIPAL INVESTIGATOR

• Martin Heni, Professor

  University of Ulm

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Henrik BW Larsson, Professor

CONTACT

+45 24824294; henrik.bo.wiberg.larsson@regionh.dk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: January 29, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: February 25, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

DK (2); DE (1)