Study of Arginine and Nitric Oxide in Patients With Diabetes

Ketosis Prone Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03566524
• Other study ID #: DK101411
• Status: Completed
• Phase: N/A
• Start date: July 1, 2018
• Est. completion date: June 30, 2022

Study information

• Verified date: July 2022
• Source: Baylor College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 65 Years

Eligibility

Inclusion Criteria:

• New onset (defined as receiving a diagnosis within the past 1 year) diagnosis of unprovoked" A-ß+ 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Ketosis
• Ketosis Prone Diabetes

Intervention

Dietary Supplement:
• Citrulline
Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.
• Alanine
Ketosis prone diabetes patients (n=10) will be randomly assigned to receive either dietary supplement of citrulline or alanine as placebo. They will then cross over to the other supplement.

Locations

Country	Name	City	State
United States	Baylor St Lukes Medical Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Baylor College of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Arginine production	The change in the amount of arginine produced from baseline in response to supplements of citrulline versus alanine (placebo) will be assessed by stable isotope tracers after 3 weeks of supplementation.	Three weeks
Secondary	Change in Nitric Oxide Synthesis	The change in the amount of nitric oxide produced produced from baseline in response to supplements of citrulline versus alanine (placebo) will be assessed by stable isotope tracers after 3 weeks of supplementation.	Three weeks
Secondary	Change in Arterial function	The change in in arterial function (assessed by endopat) from baseline in response to supplements of citrulline versus alanine placebo will be assessed after 3 weeks of supplementation.	Three weeks
Secondary	Change in Insulin secretion	The change in glucose stimulated insulin secretion from baseline in response to supplements of citrulline versus alanine placebo will be assessed after 3 weeks of supplementation.	Three weeks