Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT05477134 |
Other study ID # |
H-51936 |
Secondary ID |
|
Status |
Recruiting |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
February 6, 2023 |
Est. completion date |
August 2027 |
Study information
Verified date |
October 2023 |
Source |
Baylor College of Medicine |
Contact |
Mustafa Tosur, MD |
Phone |
832-822-3780 |
Email |
mustafa.tosur[@]bcm.edu |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Type 2 diabetes (T2D), once considered only "a disease of older ages," is now a significant
public health concern in youth. Although it is characterized by insulin resistance and
impaired insulin secretion, its precise etiology and pathogenesis are not yet fully
understood. This study aims to (1) explore arginine metabolism in youth with T2D via safe,
minimally invasive kinetic experiments using stable isotope tracers and targeted
metabolomics, and (2) determine the effect of exogenous arginine administration on β-cell
function in youth with T2D, potentially supporting the use of this safe, low-cost, and
readily available nutrient to improve pediatric diabetes outcomes.
Description:
In parallel with the youth obesity epidemic, type 2 diabetes (T2D) in youth is becoming a
significant public health concern. The incidence of pediatric T2D increased by 50% during the
past decade, and recent data show that T2D accounts for one in four newly-diagnosed diabetes
cases in children. Youth with T2D have an aggressive disease course and a rapid decline in
β-cell function, and many also have multiple cardiovascular disease risk factors at an early
age. The disease is characterized by insulin resistance and impaired insulin secretion, but
the molecular underpinnings of T2D are not yet fully elucidated. This study aims to uncover
the role of arginine metabolism in the pathogenesis of youth with T2D and the effect of
exogenous arginine administration on β-cell function in them.
Arginine is a known stimulant of insulin secretion in pancreatic β-cells. Nitric oxide (NO)
is synthesized from arginine by NO synthase, and arginine stimulates insulin secretion in
both NO-mediated and NO-independent mechanisms by stimulating guanylate cyclase, membrane
depolarization, and metabolic by-products. The effects of arginine in pancreatic β-cells are
dependent on the cells' available arginine concentration. Kinetic techniques using isotope
tracer infusions and targeted metabolomics provide a unique opportunity to determine
"intracellular" arginine availability and its relative contribution of various pathways to
this pool. Such studies in adults with T2D have shown that arginine and NO play roles in the
pathogenesis of T2D by affecting insulin secretion and insulin sensitivity. In the
preliminary data on children with T2D, the investigators found that children with T2D had
lower fasting arginine, citrulline (arginine precursor), and glutamine (citrulline precursor)
levels. In this proposal, the investigators will seek kinetic validation of these
hypothesis-generating observations to investigate the role of arginine metabolism in youth
with T2D. Our central hypothesis is that youth with T2D have inadequate arginine availability
(Aim 1), leading to suboptimal β-cell function, which can be restored by exogenous arginine
administration (Aim 2). If our hypotheses are proven, arginine supplementation will play a
clinically vital role in improving diabetes outcomes in this population as a safe, low-cost,
and readily available nutrient.