Clinical trial NCT01467063: Glutamine and Insulin Sensitivity in Type I Diabetes
Official title: Dietary Amino Acids and Insulin Sensitivity in Children With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type I Diabetes Mellitus
Keywords: Type I Diabetes
Insulin Resistance
Glutamine
Amino Acids
Glucagon like peptide 1
Glutathione
Citrulline
Arginine
Nitric Oxide
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: Thrasher Research Fund
First posted: 2011-11-08
Enrollment: 13
Sex: ALL
Minimum age (years): 13
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Insulin is crucial to help the body metabolize ('burn') sugar (glucose). Even though juvenile (type 1) diabetes (T1D) is primarily due to the lack of insulin, patients with T1D tend to become less sensitive to insulin, particularly during adolescence.

The overall objective of this project is to gain further insight into the possible benefits of supplementation with glutamine (GLN), a natural dietary amino acid, enhancing insulin sensitivity in adolescents with T1D. To elucidate the impact of glutamine, the investigators will use a method called the 'euglycemic, hyperinsulinemic clamp': it consists of giving an IV drip of insulin, while the drop in blood sugar is prevented by giving variable, precisely measured amounts of glucose by vein: the amount of glucose required to prevent a drop in blood sugar reflects the body's sensitivity to insulin. The investigators will also give an IV drip of glucose and arginine (a building block of protein) 'tagged' with non-radioactive isotopes to better understand how glutamine may work. This procedure will be performed in 2 groups of 10 adolescents in the morning either after a strenuous exercise performed the previous afternoon (group 1; n=10), or after a sedentary day (group 2; n=10). Each subject will be studied twice, once after taking oral GLN, once after placebo, in separate clinical research center (CRC) admissions a few weeks apart, in random order.

Should the investigators hypothesis prove to be true, it would warrant long term studies to determine whether sustained dietary GLN supplementation can decrease insulin requirements and ultimately improve diabetes control in teenagers with T1DM, If successful, this approach could potentially have a significant positive impact in terms of adolescent health.


Eligibility criteria: Inclusion Criteria:

* Type I diabetes diagnosed for \> 12 months.
* Minimal weight of 40 kg
* Tanner stage IV or beyond
* All insulin programs, including intermediate/short acting insulins, Lantus/Detemir and short acting insulin or insulin pump therapy.
* HbA1C between 7.5 and 10%
* BMI between 10th to 85th percentile
* Patients on stable thyroid replacement therapy will be allowed to participate.

Exclusion Criteria:

* Celiac disease (any patient with history of positive serology or consuming a gluten-free diet)
* Cystic Fibrosis
* Chronic steroid therapy
* Chronic medications that may interfere with glucose metabolism or liver function
* History of mental retardation
* Presence of diabetic complications
* Positive pregnancy test
* Presence of significant anemia (Hb\<11 g/dL)
* Presence of intercurrent infection

Primary outcomes:
measure: Insulin Sensitivity
timeFrame: During the Hyperinsulinemic-Euglycemic Clamp, an average of 3 hours
Secondary outcomes:
measure: Glucagon-like Peptide 1 (GLP-1)
timeFrame: Post-Infusion
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
Study officials:
affiliation: Nemours Children's Clinic
name: Dominique Darmaun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mauras N, Xing D, Fox LA, Englert K, Darmaun D. Effects of glutamine on glycemic control during and after exercise in adolescents with type 1 diabetes: a pilot study. Diabetes Care. 2010 Sep;33(9):1951-3. doi: 10.2337/dc10-0275. Epub 2010 Jun 28.
citation: Torres-Santiago L, Mauras N, Hossain J, Weltman AL, Darmaun D. Does oral glutamine improve insulin sensitivity in adolescents with type 1 diabetes? Nutrition. 2017 Feb;34:1-6. doi: 10.1016/j.nut.2016.09.003. Epub 2016 Sep 20.