Insulin Deprivation Effects on Protein Synthesis in Type 1 Diabetes

Overseen By Rose Decker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must be taking: Insulin

Must not be taking: Degludec

Disqualifiers: Celiac, Pregnancy, Smoking, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

70 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants with Type 1 Diabetes should be treated with certain types of insulin delivery methods, like continuous subcutaneous insulin infusion or multiple daily injections, but not with Degludec.

What data supports the effectiveness of the treatment Dextrose, Glucose, and related compounds on protein synthesis in Type 1 Diabetes?

The research indicates that insulin does not significantly stimulate muscle protein synthesis in Type 1 Diabetes, but it reduces protein breakdown. While the treatment involves glucose and related compounds, the studies do not directly support their effectiveness in enhancing protein synthesis in this context. ^{1 2 3 4 5}

Is insulin deprivation safe for humans with type 1 diabetes?

The research indicates that acute insulin deprivation in type 1 diabetic patients does not affect muscle protein synthesis, suggesting it may be safe in the short term. However, this does not provide comprehensive safety data, and further studies would be needed to confirm long-term safety. ^{1 5 6 7 8}

How does the muscle biopsy treatment differ from other treatments for type 1 diabetes?

Muscle biopsy is a diagnostic procedure used to study muscle protein synthesis in type 1 diabetes, rather than a treatment to manage the condition. Unlike insulin therapy, which aims to regulate blood sugar levels, muscle biopsy helps researchers understand how insulin affects muscle protein synthesis, providing insights into the disease's impact on muscle health. ^{1 3 5 9 10}

What is the purpose of this trial?

This research is being done to better understand how insulin effects muscle, blood, and the body in people with Type 1 Diabetes.

Research Team

K. Sreekumaran Nair, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for individuals who can legally consent and have Type 1 Diabetes. It aims to explore how insulin affects various body functions in these patients.

Inclusion Criteria

- Able to provide written consent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo insulin deprivation or treatment, with blood draws and muscle biopsies following consumption of Jell-O with amino acids

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

Treatment Details

Interventions

• Dextrose
• Jell-O with Amino acids
• Muscle Biopsy

Trial Overview The study investigates the impact of insulin deprivation and high blood sugar on protein synthesis in muscles. Participants will undergo a muscle biopsy, consume Jell-O with amino acids, and receive dextrose.

Participant Groups

Group I: Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia Experimental Treatment 3 Interventions

Subjects will be continue their baseline insulin infusion for 2 hours and then receive an intravenous dextrose infusion to maintain elevated blood sugar levels. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Group II: Type 1 Diabetes Mellitus (T1DM) Insulin Treated Experimental Treatment 2 Interventions

Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Group III: Type 1 Diabetes Mellitus (T1DM) Insulin Deprived Experimental Treatment 2 Interventions

Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Group IV: Non-Diabetic Controls Experimental Treatment 2 Interventions

Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Group V: Diabetes after Total Pancreatectomized (DATP) Insulin Treated Experimental Treatment 2 Interventions

Subjects will continue their baseline insulin infusion while maintaining a target blood glucose range. Blood draws will be obtained to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Group VI: Diabetes after Total Pancreatectomized (DATP) Insulin Deprived Experimental Treatment 2 Interventions

Subjects will have their insulin infusions replaced with saline and have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

References

1. United States pubmed.ncbi.nlm.nih.gov

Skeletal muscle myosin heavy chain synthesis in type 1 diabetes. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Insulin selectively attenuates breakdown of nonmyofibrillar proteins in peripheral tissues of normal men. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Voluntary physical activity and leucine correct impairments in muscle protein synthesis in partially pancreatectomised rats. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Protein metabolism in skeletal muscle, diaphragm, and heart of diabetic rats. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Failure of insulin infusion to stimulate fractional muscle protein synthesis in type I diabetic patients. Anabolic effect of insulin and decreased proteolysis. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Attenuated responses of muscle protein synthesis to fasting and insulin in adult female rats. [2017]

8. United States pubmed.ncbi.nlm.nih.gov

Short-term insulin and nutritional energy provision do not stimulate muscle protein synthesis if blood amino acid availability decreases. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Effects of insulin and amino acids on leg protein turnover in IDDM patients. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Inability to stimulate skeletal muscle or whole body protein synthesis in type 1 (insulin-dependent) diabetic patients by insulin-plus-glucose during amino acid infusion: studies of incorporation and turnover of tracer L-[1-13C]leucine. [2019]