Study of Arginine and Nitric Oxide in Patients With Diabetes



Status:Recruiting
Conditions:Diabetes
Therapuetic Areas:Endocrinology
Healthy:No
Age Range:20 - 65
Updated:1/18/2019
Start Date:July 1, 2018
End Date:June 2020
Contact:FAROOK JAHOOR, PhD
Email:fjahoor@bcm.edu
Phone:7137987084

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Arginine and Nitric Oxide Synthesis in the Pathogenesis of Ketosis-prone Diabetes

This study will test the effect of arginine versus citrulline versus placebo supplementation
In three groups of ketosis-prone diabetes (KPD) patients on arginine and nitric oxide
production and on glucose- and arginine-stimulated insulin secretion and arterial
flow-mediated dilation.

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
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