Glutamine and Insulin Sensitivity in Type I Diabetes

NCT01467063 | Completed Results

• 1 other identifier: IRC# 11-29
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Type I Diabetes Mellitus

Keywords

Type I Diabetes; Insulin Resistance; Glutamine; Amino Acids; Glucagon like peptide 1; Glutathione; Citrulline; Arginine; Nitric Oxide

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  Insulin sensitivity as measured by hyperinsulinemic-euglycemic clamp. Insulin sensitivity was calculated by dividing the average glucose infusion rate (mL glucose infusion/kg body weight/min) by the average insulin concentration (uU/mL).

  During the Hyperinsulinemic-Euglycemic Clamp, an average of 3 hours

Secondary Outcomes (1)

• Glucagon-like Peptide 1 (GLP-1)

  Post-Infusion

Study Arms (2)

Glutamine

ACTIVE COMPARATOR

Dietary Supplement: Glutamine

Placebo

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Interventions

Glutamine DIETARY_SUPPLEMENT

Participants will keep a diary of food intake and activity as well as wear an accelerometer (to measure overall movement) for 2-3 days prior to the admission. Subject will come to the Clinical Research Center for approximately 24 hours. They will receive a drink containing Glutamine (0.25 g/kg/dose). Afterwards they will have an afternoon exercise session consisting of 15-min bouts of exercise, interspersed with 5-min rest periods in between for a total of 75min. Blood glucose will be checked during rest intervals. They will be served a controlled dinner. Before bedtime another dose of the same drink will be given. Overnight blood glucose will be monitored closely. In the morning, another dose of the same drink will be given. Subjects will have two isotope infusions (non-radioactive) running concomitantly and a hyperinsulinemic-euglycemic clamp will be performed. Afterwards lunch will be served and subject discharged home.

Glutamine

Placebo DIETARY_SUPPLEMENT

Participants will keep a diary of food intake and activity as well as wear an accelerometer (to measure overall movement) for 2-3 days prior to the admission. Subject will come to the Clinical Research Center for approximately 24 hours. They will receive a PLACEBO drink. Afterwards they will have an afternoon exercise session consisting of 15-min bouts of exercise, interspersed with 5-min rest periods in between for a total of 75min. Blood glucose will be checked during rest intervals. They will be served a controlled dinner. Before bedtime another dose of the same drink will be given. Overnight blood glucose will be monitored closely. In the morning, another dose of the same drink will be given. Subjects will have two isotope infusions (non-radioactive) running concomitantly and a hyperinsulinemic-euglycemic clamp will be performed. Afterwards lunch will be served and subject discharged home.

Placebo

Eligibility Criteria

• Age: 13 Years - 19 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Nemours Children's Clinic: lead
• Thrasher Research Fund: collaborator

Study Sites (1)

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

Related Publications (2)

• 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.

  PMID: 20585005 BACKGROUND

• 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.

  PMID: 28063503 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Glutamine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Neutral

Results Point of Contact

• Title: Dominique Darmaun
• Organization: Nemours Children's Health System

Ddarmaun@nemours.org

904-697-3674

Study Officials

• Dominique Darmaun, MD, PhD

  Nemours Children's Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prinicipal Investigator

Study Record Dates

• First Submitted: November 2, 2011
• First Posted: November 8, 2011
• Study Start: October 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 14, 2021
• Results First Posted: January 29, 2021

Record last verified: 2021-07

Locations

US (1)