The Effect of Acute Lysine Administration on α-aminoadipic Acid (Sub-study)
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      This sub-study aims to assess the effect and breakdown of lysine administration, specifically
      examining whether it leads to increased plasma 2-AAA in healthy humans.
    

Detailed description: 
      The significance of diabetes and related co-morbidities as considerable health concerns in
      the US and worldwide is clearly supported by the high incidence (estimated 9.3% of the US
      population), mortality burden (7th leading cause of death in the US), and rising costs ($245
      billion/year). Strategies to identify individuals at high diabetic risk, and to modulate
      disease processes in these individuals before the onset of overt disease, would have a
      significant impact in reducing mortality, morbidity and healthcare costs. For this approach
      to be successful, early markers of disease that predict at-risk individuals before onset of
      dysregulated glycemic control are required, as well as discovering novel pathways for
      therapeutic targeting.

      The purpose of the study is to investigate a novel biomarker, α-aminoadipic acid (2-AAA),
      which may influence the risk of diabetes. 2-AAA has been identified as a novel predictor of
      diabetes development in humans, identifying at-risk individuals before any detectable glucose
      abnormalities. 2-AAA is a naturally occurring metabolite in the body, and it has no known
      adverse effects at normal physiological levels. 2-AAA is generated in the body from the
      breakdown of lysine. Lysine is one of the twenty essential amino acids, meaning that it is
      essential for human function, but that our body cannot manufacture it. Thus, it is acquired
      from dietary sources (such as meat, eggs, soybeans and legumes), with a recommended daily
      intake of 30 mg/kg/day. Amino acids are the building blocks of proteins, which are what allow
      our cells, organs and body to maintain structure and function. The investigators are
      interested in whether 2-AAA is increased in the body after consumption of lysine.

      The investigators' specific aim is to determine whether acute lysine administration leads to
      increased plasma 2-AAA in humans. Catabolism of lysine leads to generation of 2-AAA. In this
      study, the investigators will determine whether a single dose of 13C isotope labeled lysine
      leads to increased plasma 2-AAA present in the blood and urine of humans. In this sub-study,
      the investigators will ask 2 lean, healthy subjects (preferably individuals who participated
      in a previous study visit) to drink a beverage containing C-13 labeled lysine and the
      investigators will measure the level of 2-AAA in their blood plasma and urine at baseline
      (before ingestion) and serially post-ingestion. The amount of lysine subjects will be given
      is equivalent to that which is found in a 5 oz. serving of beef. This sub-study will allow us
      to further establish and understand the relationship between lysine and 2-AAA in healthy
      subjects, and inform future studies on how to study the effects of 2-AAA on diabetes risk.
    

Intervention name(s): C-13 labeled Lysine; Normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Carbon-13 is a stable naturally occurring heavy isotope of carbon. Inclusion of a 13C label on lysine allows for subsequent differentiation between endogenous and exogenous lysine and 2-AAA for calculation of clearance and excretion of the lysine bolus.; Because patients will have multiple blood draws during the course of the study, subjects will have an IV placed to reduce the number of needle sticks. To keep the vein open for blood collections, we will infuse Normal (0.9%) Saline (NS) at a rate of approximately 10ml/hr in order to keep the line open.
Other intervention name(s): Normal (0.9%) Saline (NS)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science