Hypoglycemia, Type 1 Diabetes
Conditions
Keywords
brain metabolism, cognitive function
Brief summary
This study is designed to examine the value of infusing BHB in type 1 diabetic subjects during experimentally induced hypoglycemic episode in conjunction with testing of cognitive function. This will lay the basis for subsequent trials exploring the novel use of therapeutic doses of oral ketone formulations that are currently under commercial development, which could serve as adjunct therapies to protect the brain from hypoglycemia in type 1 diabetic subjects experiencing recurrent hypoglycemia.
Detailed description
Healthy controls as well as type 1 diabetic subjects will undergo a hyperinsulinemic-hypoglycemic clamp with concomitant BHB or saline (control) infusion in random order. During each experimental condition the participants will complete a battery of validated cognitive tests that are sensitive to the cognitive impairment typically caused by hypoglycemia. An additional healthy control arm was added to the study design after the initial registration as a 2 arm study, to provide imaging results of normal healthy responses to hypoglycemia.
Interventions
Both healthy subjects and type 1 diabetic subjects will receive a bolus-continuous infusion of 40umol/min/kg of BHB for 5 min, followed by a 12µmol/min/kg of BHB or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study.
OTHERNormal Saline
Both healthy subjects and type 1 diabetic subjects will receive a bolus-continuous infusion of 40umol/min/kg of BHB for 5 min, followed by a 12µmol/min/kg of BHB or infusion of a comparable volume of normal saline (placebo) to control for possible volume effects for the remainder of the study.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Intervention model description
The added 3rd arm does not apply to the crossover design.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Type 1 diabetes mellitus of \> 5 years (C-peptide negative, age 18-60 years, on intensive insulin therapy (HbA1c \<7.5%) 2. Non-diabetic volunteers, age 18-65 years that do not meet any of the
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive Function | Under clamped hypoglycemia (50 min from start) | Subjects from all groups will be studied using the NIH Toolbox Cognition Battery, which includes measurements of Executive Function, Attention, Episodic Memory, Language, Processing Speed and Working Memory. |
Countries
United States
Outcome results
None listed