Assessing Heart and Brain Metabolism in Type II Diabetes Mellitus Patients Using Carbon-13 MRI

This study aims to see how well hyperpolarized 13C-pyruvate works to image the brain and heart of T2DM patients taking semaglutide, compared to those not taking it.

Group 1: You will undergo two heart MRI scans. The first scan will take place before you begin taking semaglutide (referred to as Day 1). The second scan will occur at least 4 months after starting semaglutide. Both scans will use a special 13C pyruvate injection as a contrast agent. These MRI scans should take about 60 to 75 minutes each.

Group 2: You will undergo two brain MRI scans. The first scan will take place before you begin taking semaglutide (referred to as Day 1). The second scan will occur at least 4 months after starting semaglutide. Both scans will use a special 13C pyruvate injection as a contrast agent. These MRI scans should take about 60 to 75 minutes each.

Group 3: You will undergo two heart MRI scans. The first scan will be scheduled for a specific date, agreed upon by you and the research team (referred to as Day 1). The second scan will take place at least four months after the initial scan. Both scans will use a special 13C pyruvate injection. These MRI scans should take about 60 to 75 minutes each.

Group 4: You will undergo two brain MRI scans. The first scan will be scheduled for a specific date, agreed upon by you and the research team (referred to as Day 1). The second scan will take place at least four months after the initial scan. Both scans will use a special 13C pyruvate injection. Each MRI scan should take about 60 to 75 minutes.

All participants will complete standard cognitive tests within five days prior to each scan, (two assessments in total) to evaluate brain function. Alternatively, these tests may be performed on the day of the scan, prior to the procedure.

Blood samples will be collected before each scan for a total of two samples. Blood samples will be stored in a secure, access-controlled laboratory freezer at Sunnybrook Research Institute. Each sample will be labeled with a unique study code and will not contain any directly identifying information. A master code list linking study codes to participant identifiers will be stored separately in a password-protected file on a secure server, accessible only to the principal investigator and authorized study staff. Upon completion of the study and after the retention period of 15 years, all remaining blood samples will be destroyed in accordance with Sunnybrook Research Institute biosafety procedures to ensure that samples cannot be reused or linked back to participants.

All clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC).

Inclusion criteria

• Adult participants of all ethnic groups/race categories (≥ 18 years of age)
• Blood lactate ≥ 2 mmol/L ≤ 5 mmol/L
• Blood pressure target < 130/80
• No history of macrovascular or microvascular disease
• For participants in Groups 1 and 2: Prescribed a semaglutide dose of 0.5 mg S/C weekly
• For participants in Groups 3 and 4: HbA1c between 7-9% on evidence-based medications as per the Diabetes Canada guidelines, but not GLP-1RA semaglutide
• Written informed consent

Exclusion criteria

• History of macrovascular or microvascular disease
• Automatic implantable cardiac-defibrillators (AICD) or pacemaker, either at time of study or required within 3 months of the study
• Participants on anticonvulsants, benzodiazepines, immunosuppressants and/or antiarrhythmics
• Any clinically significant or unstable medical condition that might limit their ability to complete the study
• Any malignancy not considered cured, except basal cell carcinoma of the skin
• Body mass index greater than 40.0
• Claustrophobia and/or inability to undergo MRI without sedation
• Contraindications to MRI as indicated on the standard MRI safety screening questionnaire
• Participant declines or is unable to