Study of Arginine and Nitric Oxide in Patients With Diabetes

Both arginine and its derivative nitric oxide (NO) have been implicated in the regulation of glucose homeostasis. Arginine is a β cell secretagogue, potentiating glucose stimulated insulin secretion. Further, it has been shown that glucose can stimulate NO production in primary β cells, and NO then enhances insulin secretion.

On the other hand, because the only known fate of citrulline is its conversion to arginine, citrulline supplementation could be a more efficient and safe way to increase intracellular arginine. Compared to enteral arginine, citrulline administration to healthy humans elicited a greater increase in plasma arginine and NO products, suggesting a greater increase in cellular arginine availability for NO synthesis. Therefore dietary citrulline supplementation will result in greater arginine availability and NO synthesis than arginine supplementation per se in KPD patients. In addition, because the consequences of diminished NO production in usual type 2 diabetes includes vascular dysfunction, an overall increase in NO production in response to citrulline supplementation will result in an improvement in vascular function assessed by arterial flow-mediated dilation

Inclusion criteria

• New onset (defined as receiving a diagnosis within the past 1 year) diagnosis of unprovoked" A-β+ ketosis-prone diabetes
• Aged 20-65 years
• In good health except for diabetes without clinical evidence of micro- or macrovascular complications by history, physical exam and blood chemistries

Exclusion criteria

• Chronic or acute illness
• History of myocardial infarction or coronary artery disease or stroke,
• Renal insufficiency (eGFR <90mL/min/1.73m2; <30 mg albumin / g creatinine in urine)
• Abnormal liver, thyroid, gonadal or adrenal functions
• On medications other than metformin,
• On any hormonal replacement therapy
• Pregnancy