Evaluating Glial Acetate Metabolism as a Biomarker of Hypoglycemic Counterregulation

NCT ID: NCT04207619

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-19
• Study Completion Date: 2026-09-30

Brief Summary

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.

Conditions

Diabetes; Hypoglycemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Arm 1

Participants will have their glial acetate metabolism measured by carbon-13 magnetic resonance spectroscopy as well as their neuroendocrine response to hypoglycemia 3 days later.

Group Type: EXPERIMENTAL

hyperinsulinemic-hypoglycemic clamp

Intervention Type: OTHER

An 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

Intervention Type: OTHER

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

Interventions

hyperinsulinemic-hypoglycemic clamp

An 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.

Intervention Type: OTHER

13C-MRS procedure/Acetate infusion

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Average screening blood pressure >140/90 mmHg
• History of cardiovascular disease
• Pregnant, planning to become pregnant, or breastfeeding
• Use of medications affecting glucose metabolism, e.g., benzodiazepines, thiazide diuretics, cortisone, and prednisone.
• Use of beta-adrenergic antagonists.
• Based on the investigative team's clinical judgement, a subject may not be appropriate for participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pennington Biomedical Research Center

OTHER

Sponsor Role: lead

Responsible Party

David McDougal

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David McDougal, PhD

Role: PRINCIPAL_INVESTIGATOR

PBRC

Locations

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Amber Dragg

Role: CONTACT

amber.dragg@pbrc.edu

225-763-3050

Bethany Gildersleeve

Role: CONTACT

Bethany.Gildersleeve@pbrc.edu

225-763-2709

Facility Contacts

Department of Recruiting

Role: primary

recruiters@pbrc.edu

225-763-3000

Other Identifiers

PBRC 2019-047

Identifier Type: -

Identifier Source: org_study_id