Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy
| Status: | Recruiting |
|---|---|
| Conditions: | Endocrine |
| Therapuetic Areas: | Endocrinology |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 4/21/2016 |
| Start Date: | February 2016 |
| End Date: | July 2017 |
| Contact: | Recruiting |
| Email: | clinicaltrials@pbrc.edu |
| Phone: | 225-763-3000 |
Hypoglycemia-associated autonomic failure (HAAF), a condition commonly developed in diabetic
patients, which causes them to have severely low blood sugar levels. This condition makes
clinical management of blood sugar in diabetic patients very challenging. This research
seeks to better understand how diabetic patients develop HAAF, and what can be done to
prevent it.
patients, which causes them to have severely low blood sugar levels. This condition makes
clinical management of blood sugar in diabetic patients very challenging. This research
seeks to better understand how diabetic patients develop HAAF, and what can be done to
prevent it.
Following the detection of severe hypoglycemia by the central nervous system (CNS), a series
of physiological countermeasures are triggered which return serum glucose to euglycemic
levels. This vital homeostatic response frequently becomes dysfunctional in both type 1 and
type 2 diabetics, leaving them particularly vulnerable to life threatening bouts of
hypoglycemia. This dysfunction, often termed hypoglycemia-associated autonomic failure
(HAAF), is thought to be caused by maladaptive changes in the CNS. Currently, progress
towards rectifying this HAAF is severely hindered by a lack of knowledge regarding the exact
nature of these maladaptive changes and the antecedent events which cause them. Previous
work by the PI, as well as others, has identified altered glial metabolism as a potential
biological substrate driving HAAF. The alterations in glial metabolism associated with HAAF
are strikingly similar to those induced by prolonged dietary restriction in rodents. This
raises the intriguing possibility that HAAF may be driven by glial adaptations, normally
induced only by prolonged starvation, which are triggered in diabetic individuals by
treatment-induced exposure to severe hypoglycemia. The primary goal of our pilot project is
to conduct a prospective observational study in humans to test the hypothesis that prolonged
fasting will induce changes in glial metabolism similar to those previously measured in
individuals with HAAF. The investigators will accomplish this goal via the following
specific aims: Aim 1: Using a prospective observational study design in humans, test whether
a 72 hour fast will induce acute alterations in glial metabolism, Aim 2: Determine if
changes in plasma glucose and leptin levels following prolonged fasting are correlated with
changes in glial adaptation. The investigators will utilize innovative 13C magnetic
resonance spectroscopy to measure alterations in glial metabolism and substrate preference
following acute dietary restriction in healthy young individuals. By demonstrating that
metabolic adaptations of glial cells induced by prolonged fasting are similar to those
previously associated with HAAF, the investigators can provide key insights into the
precursors that may lead to the development of HAAF in diabetic individuals.
of physiological countermeasures are triggered which return serum glucose to euglycemic
levels. This vital homeostatic response frequently becomes dysfunctional in both type 1 and
type 2 diabetics, leaving them particularly vulnerable to life threatening bouts of
hypoglycemia. This dysfunction, often termed hypoglycemia-associated autonomic failure
(HAAF), is thought to be caused by maladaptive changes in the CNS. Currently, progress
towards rectifying this HAAF is severely hindered by a lack of knowledge regarding the exact
nature of these maladaptive changes and the antecedent events which cause them. Previous
work by the PI, as well as others, has identified altered glial metabolism as a potential
biological substrate driving HAAF. The alterations in glial metabolism associated with HAAF
are strikingly similar to those induced by prolonged dietary restriction in rodents. This
raises the intriguing possibility that HAAF may be driven by glial adaptations, normally
induced only by prolonged starvation, which are triggered in diabetic individuals by
treatment-induced exposure to severe hypoglycemia. The primary goal of our pilot project is
to conduct a prospective observational study in humans to test the hypothesis that prolonged
fasting will induce changes in glial metabolism similar to those previously measured in
individuals with HAAF. The investigators will accomplish this goal via the following
specific aims: Aim 1: Using a prospective observational study design in humans, test whether
a 72 hour fast will induce acute alterations in glial metabolism, Aim 2: Determine if
changes in plasma glucose and leptin levels following prolonged fasting are correlated with
changes in glial adaptation. The investigators will utilize innovative 13C magnetic
resonance spectroscopy to measure alterations in glial metabolism and substrate preference
following acute dietary restriction in healthy young individuals. By demonstrating that
metabolic adaptations of glial cells induced by prolonged fasting are similar to those
previously associated with HAAF, the investigators can provide key insights into the
precursors that may lead to the development of HAAF in diabetic individuals.
Inclusion Criteria:
- Male
- BMI 20.0-24.9 kg/m2
- 18-40 years old
- Willing to reside at Pennington Biomedical for 4 days
Exclusion Criteria:
- Type 1 diabetes mellitus
- Type 2 diabetes mellitus
- Fasting glucose ≥ 110 mg/dL (determined at screening visit)
- Hyperketonuria >15 mg/dL, (determined at screening visit)
- Contraindication to MRI
- History of or current eating disorder
- History of obsessive compulsive disorder
- Current use of any medication (excluding over-the-counter pain medication)
- Contraindication to prolonged fasting
- Consume >10 alcoholic drinks/week
We found this trial at
1
site
6400 Perkins Rd
Baton Rouge, Louisiana 70808
Baton Rouge, Louisiana 70808
(225) 763-2500
Phone: 225-763-3000
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