Comparison of Differencens in VO2-max, Perfusion of the Heart and Brain and Cognitive Performance Between Patients with Type 2 Diabetes and Healthy Age Matched Controls.

The goal of this clinical trial is to compare baseline measurements relevant to microvascular disease between patients with diabetes and increased risk of microvascular disease with healthy age-matched control.

The researchers wish to examine if small vessel disease is a disease that affects several organs at once in the same individuals by examining it in the brain and heart in the same participants. The researchers will also test if cardiorespiratory conditioning (VO2-max), blood perfusion to the heart and brain and cognitive performance are correlated in patients with microvascular disease.

To adress these aims the researchers have defined the following assumptions that they will refute or confirm through this study:

• Patients with type 2 diabetes and increased risk of small vessel disease have significantly reduced perfusion capacity of the brain and heart compared to healthy controls as part of a multisystem disease
• Perfusion capacity of the brain and heart, the cardiorespiratory fitness level of the subjects and cognitive performance are directly linked.

48 patients with diabetes and 24 healthy age-matched controls will undergo baseline testing that include:

• Cardiopulmonal Exercise Test (CPET) to determine cardiopulmonal conditioning (VO2-max)
• Isometric knee strength (if logistically possible)
• Echocardiography
• Blood perfusion capacity of the heart and brain via [15O]H2O-PET scans
• Brain MRI to determine structural damages
• Blood samples for basic health check (relevant to inclusion, exclusion and safety) and blood samples looking at endothelial and neurological damage for a biobank
• Cognitive testing (SCIP-D and CANTAB)

Afterwards the researchers will compare the results between the two groups and see if there is a correlation between VO2-max, blood perfusion to the heart and brain and cognitive performance.

Inclusion criteria

for the patients with type 2 diabetes:

Diabetes type II diagnose with one of the following:

• Duration over 5 years
• Moderate microalbuminuria
• Non-proliferative diabetic retinopathy

• Speaks and understands Danish (required for reliable cognitive testing)
• Able to provide informed and written consent

Exclusion criteria

or the patients with type 2 diabetes:

Moderate to high intensity training >1 times/week.

• Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF <45%), asthma.
• Previous stroke or significant neurological disease including cognitive dysfunction.
• Ongoing depression.
• Hypothyroidism
• Unable or unwilling to participate in training, e.g., due to injury, arthrosis or lung disease.

Inclusion criteria

for the healthy age-matched controls:

• Age > 60 years
• No diagnosis of T2D according to WHO's criteria.
• Speaks and understands Danish (required for reliable cognitive testing)
• Able to provide informed and written consent

Exclusion criteria

for the healthy age-matched controls:

• Moderate to high intensity training >2 times/week.
• Previous AMI, atrial fibrillation, significant cardiac valve disease, HFrEF (LVEF <45%), asthma.
• Previous stroke or significant neurological disease including cognitive dysfunction.
• Ongoing depression.
• Hypothyroidism
• Unable or unwilling to participate in training, e.g., due to injury, arthrosis or lung disease.