Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Counterregulation
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-40
SponsorPennington Biomedical Research Center
About this trial
Hypoglycemic complications are a major impediment to the maintenance of healthy glucose levels in persons with diabetes. The investigators recently completed a clinical pilot and feasibility study (GLIMPSE, NCT02690168), which identified a novel biomarker, glial acetate metabolism, that appears to predict the susceptibility to hypoglycemia. By providing an assay to predict hypoglycemic events and therefore diabetic complications, the development of this biomarker could significantly improve the treatment of persons with diabetes.
The goal of this study is to determine the efficacy of our biomarker for predicting susceptibility to insulin-induced hypoglycemia. In order to accomplish this goal the investigatiors will pair our 13C magnetic resonance spectroscopy procedure to assess glial acetate metabolism, developed in the GLIMPSE study, with a hyperinsulinemic-hypoglycemic clamp procedure, developed in the HYPOCLAMP study (NCT03839511). The two procedures will be separated by a three day interval. The investigators will then correlate the participants' rates of glial acetate metabolism with their neuroendocrine responses to the hypoglycemic clamp. This proof of concept study will test the hypothesis that glial acetate metabolism is inversely proportional to the neuroendocrine response to hypoglycemia, that is, as glial acetate metabolism increases the neuroendocrine response will decrease.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Healthy male or female
Ages 18-40 years
BMI between 20 kg/m2 and 30 kg/m2 (±0.5 kg/m2 will be accepted)
Medically cleared for participation in the study
Disqualifiers
Contraindication to MRI
Consume >10 alcoholic drinks/week
History of chronic smoking or have quit less than 10 years ago
History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
Trial design
Design model
Single group
Treatments tested in this trial
hyperinsulinemic-hypoglycemic clamp
Other interventionAn intravenous catheter will be placed in an antecubital vein for infusion of insulin and glucose. A second catheter will be placed retrograde in a dorsal vein of the contra-lateral hand for blood withdrawal. The hand will be placed in a heating box or pad at 70°C for arterialization of venous blood. A primed infusion of regular insulin (120 mU/min/m2) will be initiated and continued for approximately 2 hours. Beginning 20 minutes prior to the start of the insulin infusion, arterialized venous blood glucose will be measured at 5 minute intervals via a Hemocue or YSI analyzer. Following initiation of insulin infusion, blood glucose will be allowed to fall to 50 mg/dL and then maintained at this level using a variable infusion of exogenous dextrose (20% solution). Our goal is to achieve steady-state (blood glucose stabilized at 50 +/- 5 mg/dL) within the first 45 minutes following the start of insulin infusion.
13C-MRS procedure/Acetate infusion
Other interventionGlial 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
Treatment groups
10 Participants
are divided into 1 treatment groupGroup A: Arm 1Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Percent 13C enrichment of bicarbonate measured via carbon-13 magnetic resonance spectroscopy (13C-MRS)
Glial acetate metabolism
Time frame
Every ten minutes for 120 minutes following administration of 1-13C acetateSecondary outcomes
1
Change in serum epinephrine levels
The change is serum epinephrine during the hypoglycemic clamp will be determined relative to baseline levels
Time frame
epinephrine will be measured every 15 minutes for 135 minutes.Sponsors and contacts
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Source ClinicalTrials.gov