Testing Glial Pathways to HAAF in Human Subjects Using Carbon 13 Magnetic Resonance Spectroscopy
Condition: Diabetes Complications; Hypoglycemia
MeSH terms: Hypoglycemia; Diabetes Complications
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Fasting
Intervention type(s): Behavioral
Intervention description(s): 72 hour fasting
Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Healthy Men
      
Biospecimen description: 
      Blood banking
    
Keywords: Fasting; Carbon-13 Magnetic Resonance Spectroscopy; Neuroimaging