Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People with Type 1 Diabetes Mellitus

Not Applicable

Not yet recruiting

• Conditions: Type 1 Diabetes
• Interventions: Procedure: Muscle Biopsy; Other: Jell-O with Amino acids; Dietary Supplement: Dextrose

• Registration Number: NCT05985135
• Lead Sponsor: Mayo Clinic

Brief Summary

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

Detailed Description

Insulin's contribution in controlling glucose homeostasis has been well appreciated but, its role in maintaining proteome homeostasis is less understood. Some animal and human studies have demonstrated that insulin signaling regulates protein synthesis and degradation as well as posttranslational modifications at the tissue level. Insulin's effect on the muscle's mitochondrial proteo-stasis has also been elucidated. Insulin deprivation increases global synthesis of splanchnic proteins based on isotope dilution studies across splanchnic bed. Most plasma proteins are derived from liver and preliminary studies suggest that synthesis rates of some plasma proteins increase while others decrease. Fractional rates of synthesis of various plasma proteins from the liver have been demonstrated in insulin deprivation state. These proteins might be implicated in the development of some of the complications from diabetes mellitus type 1. (T1DM) especially of macrovascular. Researchers have recently developed an isotope-based methodology to simultaneously measure in vivo synthesis rates of multiple plasma proteins in human.

In order to further investigate the effects of insulin deprivation researchers will apply the novel non-radioactive stable isotope-based approach on the rate of different plasma protein synthesis in T1DM and Diabetes after total pancreatectomy (DATP) in comparison with non-diabetic controls. Researchers will study pancreatectomized people because like T1DM they also are insulin deficient but unlike pancreatectomized people also are deficient in glucagon. Some tantalizing data from many studies indicate that glucagon also have catabolic effect not only on liver derived proteins but also on skeletal muscle-based proteins. Since skeletal muscle has no glucagon receptors, researchers hypothesize that unknown factors are released to the circulation that act on skeletal muscle to release amino acids for consumption in liver. Researchers will measure amino metabolites, acyl carnitines, organic acids, and ceramides in plasma and determine the blood exosome cargo by mass spectrometry-proteins and lipids and miRNA by PCR.

Researchers have previously shown reduced muscle mitochondrial ATP production during insulin deprivation in both T1D humans and diabetic mice and here researchers will measure mitochondrial energy dynamics in all study participants by the established techniques available in our lab.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2023-08-02
• Study First Submitted QC: 2023-08-02
• Study First Posted: 2023-08-14
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-07
• Last Update Posted: 2024-10-09
• Study Start: 2024-12-01
• Primary Completion: 2028-08
• Study Completion: 2028-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Type 1 Diabetes Mellitus (T1DM) Insulin Deprived	Muscle Biopsy	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.
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia	Dextrose	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.
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia	Jell-O with Amino acids	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.
Diabetes after Total Pancreatectomized (DATP) Insulin Deprived	Muscle Biopsy	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.
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia	Muscle Biopsy	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.
Non-Diabetic Controls	Jell-O with Amino acids	Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
Diabetes after Total Pancreatectomized (DATP) Insulin Deprived	Jell-O with Amino acids	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.
Type 1 Diabetes Mellitus (T1DM) Insulin Deprived	Jell-O with Amino acids	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.
Type 1 Diabetes Mellitus (T1DM) Insulin Treated	Muscle Biopsy	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.
Type 1 Diabetes Mellitus (T1DM) Insulin Treated	Jell-O with Amino acids	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.
Diabetes after Total Pancreatectomized (DATP) Insulin Treated	Muscle Biopsy	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.
Non-Diabetic Controls	Muscle Biopsy	Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
Diabetes after Total Pancreatectomized (DATP) Insulin Treated	Jell-O with Amino acids	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.

Primary Outcome Measures

Name	Time	Method
Protein synthesis	Approximately 7 hours	Measurement of isotope abundance in peptides derived from the digested proteins

Trial Locations

Locations (1)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States