Hypoglycemia
Conditions
Keywords
Hypoglycemia, Autonomic Nervous System, baroreflex sensitivity, muscle sympathetic nerve activity, lower body negative pressure
Brief summary
The goals of this proposal are to determine the effects of hypoglycemia on the autonomic nervous system.
Interventions
Sponsors
Beth Israel Deaconess Medical Center
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers * Males and females age 18 to 50 years
Exclusion criteria
* Pregnancy * Lactation * Subjects who smoke or are on other forms of nicotine will be excluded * Clinically evident coronary artery, cerebrovascular, or peripheral vascular disease, or presence of systemic illness that might affect autonomic function. Such illnesses include diabetes mellitus, congestive heart failure, hypertension, renal, pulmonary, hepatic disease, anemia, malignancies, untreated thyroid disease, and alcoholism. * Current major depressive illness * Any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded. * Use of medications other than thyroxine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Baroreflex Sensitivity | 16 hours after euglycemic and hypoglycemic clamps as compared to baseline | The change in baroreflex sensitivity (milliseconds/mm Hg) is calculated as baroreflex sensitivity (milliseconds/mm Hg) on day 3 \[assessed 16 hours after the clamp\] minus baroreflex sensitivity (milliseconds/mm Hg) on day 1 \[baseline assessment on the day prior to the clamp\]). Change in baroreflex sensitivity in euglycemic clamp arm is compared to change in baroreflex sensitivity in hypoglycemic arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Sympathetic Nerve Activity | 16 hours after euglycemic and hypoglycemic clamps | Muscle sympathetic nerve activity (MSNA), at rest and immediately after nitroprusside, was measured on Day 3 about 16 hours after the euglycemic and hypoglycemic clamps. |
| Catecholamine Response to Lower-body Negative Pressure | 16 hours after euglycemic and hypoglycemic clamps | Plasma norepinephrine response to lower body negative pressure (at the minus 40 mm Hg data point) on Day 3 about 16 to 20 hours after completion of the euglycemic or hypoglycemic clamp. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Euglycemic Clamp/ Washout Period/ Hypoglycemic Clamp 1. Participant undergoes a euglycemic hyperinsulinemic clamp
2. Participant undergoes a 1-3 month washout period
3. Participant undergoes a hypoglycemic hyperinsulinemic clamp | 11 |
| Hypoglycemic Clamp/ Washout Period/ Euglycemic Clamp 1. Participant undergoes a hypoglycemic hyperinsulinemic clamp
2. Participant undergoes a 1-3 month washout period
3. Participant undergoes a euglycemic hyperinsulinemic clamp | 11 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Euglycemic Clamp/ Washout Period/ Hypoglycemic Clamp | Hypoglycemic Clamp/ Washout Period/ Euglycemic Clamp | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 11 Participants | 22 Participants |
| Age, Continuous | 28 years STANDARD_DEVIATION 6 | 29 years STANDARD_DEVIATION 8 | 28 years STANDARD_DEVIATION 7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 6 Participants | 9 Participants | 15 Participants |
| Region of Enrollment United States | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 10 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 0 / 22 | 0 / 20 |
| serious Total, serious adverse events | 0 / 22 | 0 / 20 |
Outcome results
Primary
Change in Baroreflex Sensitivity
The change in baroreflex sensitivity (milliseconds/mm Hg) is calculated as baroreflex sensitivity (milliseconds/mm Hg) on day 3 \[assessed 16 hours after the clamp\] minus baroreflex sensitivity (milliseconds/mm Hg) on day 1 \[baseline assessment on the day prior to the clamp\]). Change in baroreflex sensitivity in euglycemic clamp arm is compared to change in baroreflex sensitivity in hypoglycemic arm.
Time frame: 16 hours after euglycemic and hypoglycemic clamps as compared to baseline
Population: 20 subjects completed both arms, but only 18 had the change in BRS outcome for both arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Euglycemic Clamp | Change in Baroreflex Sensitivity | 2.3 ms/mmHg | Standard Deviation 6.3 |
| Hypoglycemic Clamp | Change in Baroreflex Sensitivity | -1.6 ms/mmHg | Standard Deviation 4.3 |
Secondary
Catecholamine Response to Lower-body Negative Pressure
Plasma norepinephrine response to lower body negative pressure (at the minus 40 mm Hg data point) on Day 3 about 16 to 20 hours after completion of the euglycemic or hypoglycemic clamp.
Time frame: 16 hours after euglycemic and hypoglycemic clamps
Population: Of the 22 subjects who started the protocol, 20 completed both arms.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Euglycemic Clamp | Catecholamine Response to Lower-body Negative Pressure | 3.0 nmol/L | Standard Deviation 0.3 |
| Hypoglycemic Clamp | Catecholamine Response to Lower-body Negative Pressure | 2.0 nmol/L | Standard Deviation 0.2 |
Secondary
Muscle Sympathetic Nerve Activity
Muscle sympathetic nerve activity (MSNA), at rest and immediately after nitroprusside, was measured on Day 3 about 16 hours after the euglycemic and hypoglycemic clamps.
Time frame: 16 hours after euglycemic and hypoglycemic clamps
Population: 20 subjects completed both arms, but only 5 had the muscle sympathetic nerve activity outcome for both arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Euglycemic Clamp | Muscle Sympathetic Nerve Activity | With Nitroprusside | 53.4 bursts/ minute | Standard Deviation 3.7 |
| Euglycemic Clamp | Muscle Sympathetic Nerve Activity | At rest | 33.64 bursts/ minute | Standard Deviation 3.3 |
| Hypoglycemic Clamp | Muscle Sympathetic Nerve Activity | At rest | 26.4 bursts/ minute | Standard Deviation 4.8 |
| Hypoglycemic Clamp | Muscle Sympathetic Nerve Activity | With Nitroprusside | 40.1 bursts/ minute | Standard Deviation 2.7 |