Ketosis Prone Diabetes
Conditions
Brief 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.
Detailed 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
Interventions
DIETARY_SUPPLEMENTCitrulline
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.
DIETARY_SUPPLEMENTAlanine
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.
Sponsors
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Arginine production | Three weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Nitric Oxide Synthesis | Three weeks | 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. |
| Change in Arterial function | Three weeks | 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. |
| Change in Insulin secretion | Three weeks | 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. |
Countries
United States
Outcome results
None listed