Modulating Glucose Tolerance With Dietary Tyrosine

Several biochemical mechanisms explaining how Roux-en-Y Gastric Bypass (RYGB) provides an effective treatment for obesity associated type 2 diabetes mellitus (T2DM) and improves hyperglycemia independently of weight loss have been proposed. Two are of particular interest; a) the hindgut hypothesis suggesting that nutrient delivery to the distal intestine drives the production of "incretins" which enhance insulin secretion (e.g. glucagon-like peptide-1 (GLP-1)), and b) the foregut hypothesis, positing that foregut bypass reduces the secretion of factors (i.e. anti-incretins) that normally defend against hypoglycemia. The investigators have been actively investigating this topic and have developed a hypothesis based on past studies that they wish to test in a limited human clinical study. In addition, preclinical data suggest that there exists a gut-to-beta cell pathway, responsive to nutritional tyrosine, regulating insulin secretion, and this pathway provides a mechanism for the early postoperative improvements in hyperglycemia observed in RYGB.

i. Inclusion Criteria

• Capable of giving written as well as oral informed consent.
• A fasting plasma glucose level (FPG) < 126 mg/dL (< 7.0 mmol/L) and an Hb1ac in the 5.7-6.4 % range.
• BMI in the range of 18-45 kg/m2.
• Normal Complete blood count (CBC), renal and liver function tests.

ii. Exclusion Criteria:

• Any diabetes medication within previous three (3) months.
• Fasting plasma Glucose (FPG) >126 mg/dl or HbA1c > 6.4%
• Current use (or within 6 months) of antipsychotic, anti-anxiety, or antidepressant medications (e.g. monoamine oxidase (MAO) inhibitors, 5-Hydroxytryptophan (5HT) inhibitors, tricyclic antidepressants, L-DOPA), reserpine, β-2-receptor agonists (e.g., terbutaline), steroids, weight loss medication, anticoagulant medication, over-the-counter nutritional supplements other than standard vitamin and mineral supplements
• History of Phenylketonuria or other inherited disorders of amino acid metabolism.
• History of movement disorder such as Parkinson's disease or Huntington's disease
• Cardiovascular, renal, pulmonary, gastrointestinal, migraines or other medical conditions deemed significant by investigators
• History of/ or psychiatric illness such as major depression, bipolar disease, anxiety or schizophrenia.
• History of bariatric surgery with the exception of gastric band if the band has been removed
• Female of child-bearing age, currently pregnant, breastfeeding or not using a form of birth control.
• Previous or current use of cocaine, methamphetamine, ecstasy (3-4 methylenedioxymethamphetamine (MDMA))
• Current daily intake of caffeine >500 mg/day (>4-5 cups of coffee; >10 12-oz cans of soda)
• Consumption of more than 1 alcoholic drink per day or smoking more than 5 cigarettes/day.
• Systolic Blood Pressure (SBP) > 150 mmHg; Diastolic Blood Pressure (DBP) > 100 mmHg.
• Recent history (in the past three months) of more than a 3% gain or loss in body wt.
• Difficulty in swallowing capsules.
• Concurrent use of antacids or proton pump inhibitors (e.g.,Prilosec Prevacid, dexilant, Aciphex, Protonix, Nexium, Vimovo, Zegerid)