Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Complications in Diabetic Patients

Study Overview
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Brief Summary
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A recent pilot study, GLIMPSE (NCT02690168), was recently completed which demonstrated that the rate of glial acetate metabolism (GAM) is closely associated with susceptibility to fasting-induced hypoglycemia in healthy adults. Insulin-induced hypoglycemia is a common complication of diabetes treatment and is a major barrier to the maintenance of healthy glucose levels in individuals with diabetes. The primary purpose of the study is to test the proof-of-concept that there is an association between the rate of GAM and susceptibility to insulin-induced hypoglycemia. In order to observe such a relationship the rate of GAM will be measured in a patient population known to frequently experience hypoglycemia, i.e., individuals with type 1 diabetes mellitus (T1DM).

Official Title
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Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Complications in Diabetic Patients: A Proof of Concept Study.

Conditions
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Diabetes, Hypoglycemia

Intervention / Treatment
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* Other: 13C-MRS procedure/Acetate infusion
* Device: Continuous glucose monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female Ages 18-40 years Diagnosed with type 1 diabetes with positive antibodies or dependent on insulin therapy HbA1c of ≤8.5% Modified Clarke's Hypoglycemia Questionnaire score of 12-24 Willing to participate in continuous glucose monitoring (CGM) Exclusion Criteria: Contraindication to MRI Consume >10 alcoholic drinks/week Current use of CGM Current use of insulin pump Current use of any diabetes medication other than insulin, e.g. SGLT1/2 inhibitors. Current use of steroids, e.g. cortisone, and prednisone. History of chronic smoking or have quit less than 10 years ago History of cancer in the past 5 years (individuals with basal cell or squamous cell skin cancer would be allowed) History of seizures Significant, cardiac, vascular, pulmonary, gastrointestinal, neurologic, hematologic, rheumatologic, or psychiatric disease Significant liver disease as defined as more than twice the upper limit of normal for liver enzymes Significant renal disease as defined as a estimated glomerular filtration rate less than 30 Pregnant, planning to become pregnant, or breastfeeding Have been hospitalized or treated in the past 3 months for severe hypoglycemia Based on the investigative team's clinical judgement, a subject may not be appropriate for participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm 1<br>Participants will have there glial acetate metabolism assessed via 13C MRS at baseline and then again 14 days later. Participants will wear blinded continuous glucose monitoring devices for  4 weeks. | Other: 13C-MRS procedure/Acetate infusion<br>* Glial metabolism will be measured via MRS utilizing a simultaneous intravenous infusion of 13C labeled acetate. An intravenous catheter will be placed in a vein of each arm, one to infuse 13C-acetate and the other to draw blood samples.<br>Device: Continuous glucose monitoring<br>* Participants will wear blinded continuous glucose monitoring devices (dexcom, G6) for approximately 4 weeks. Sensors will be replaced every 7-10 days.<br>* Other names: CGM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent 13C enrichment of bicarbonate measured via carbon-13 magnetic resonance spectroscopy (13C-MRS) |  | Once at Study Visit 1 day and 1 day at Study Visit 3, 14 days apart |