Impact of Insulin Deprivation and Hyperglycemia on Plasma Protein Synthesis in People With Type 1 Diabetes Mellitus and Diabetes After Total Pancreatectomy
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- Mayo Clinic
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Protein synthesis
研究概览
简要总结
This research is being done to better understand how insulin effects muscle, blood, and the body in people with Type 1 Diabetes.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Type 1 Diabetes Group:
- •- Able to provide written consent.
排除标准
- •Type 1 Diabetes Group::
- •BMI < 20 or > 32 kg/m^
- •Celiac disease.
- •Pregnancy.
- •Reported history of illicit substance use.
- •History of active cardiovascular, cerebrovascular, or peripheral vascular disease.
- •Active renal disease evidenced by estimated glomerular filtration rate (GFR) < 50 mL/min/1.73 m^
- •Severe peripheral or autonomic neuropathy.
- •Dementia or any other neurologic disease.
- •Uncontrolled psychiatric disease.
- •Any learning disability.
- •Thyroid-stimulating hormone (TSH) ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.
- •Hemoglobin A1c > 9.0%.
- •Type 2 Diabetes Mellitus (T2DM), or impaired fasting glucose.
- •Detectable C peptide.
- •Inclusion Criteria - Control Group:
- •Able to provide written consent.
- •T1DM treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) (not Degludec).
- •Exclusion Criteria - Control Group:
- •BMI < 20 or > 32 kg/m^
- •Celiac disease.
- •Pregnancy.
- •Reported history of illicit substance use.
- •History of active cardiovascular, cerebrovascular, or peripheral vascular disease.
- •Active renal disease evidenced by estimated GFR < 50 mL/min/1.73 m^
- •Severe peripheral or autonomic neuropathy.
- •Dementia or any other neurologic disease.
- •Uncontrolled psychiatric disease.
- •Any learning disability.
- •TSH ≥ 7 or TSH ≤ 7 and free T4 ≤ 0.
- •T2DM, or impaired fasting glucose.
研究组 & 干预措施
Type 1 Diabetes Mellitus (T1DM) Insulin Deprived
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.
干预措施: Jell-O with Amino acids (Other)
Type 1 Diabetes Mellitus (T1DM) Insulin Treated
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.
干预措施: Muscle Biopsy (Procedure)
Type 1 Diabetes Mellitus (T1DM) Insulin Treated
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.
干预措施: Jell-O with Amino acids (Other)
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
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.
干预措施: Muscle Biopsy (Procedure)
Diabetes after Total Pancreatectomized (DATP) Insulin Deprived
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.
干预措施: Jell-O with Amino acids (Other)
Type 1 Diabetes Mellitus (T1DM) Insulin Deprived
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.
干预措施: Muscle Biopsy (Procedure)
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
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.
干预措施: Jell-O with Amino acids (Other)
Non-Diabetic Controls
Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
干预措施: Muscle Biopsy (Procedure)
Non-Diabetic Controls
Subjects will have blood draws to monitor glucose levels along with a muscle biopsy following consumption of a Jell-O with Amino acids.
干预措施: Jell-O with Amino acids (Other)
Diabetes after Total Pancreatectomized (DATP) Insulin Treated
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.
干预措施: Muscle Biopsy (Procedure)
Diabetes after Total Pancreatectomized (DATP) Insulin Treated
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.
干预措施: Jell-O with Amino acids (Other)
Diabetes after Total Pancreatectomized (DATP) Insulin Deprived
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.
干预措施: Muscle Biopsy (Procedure)
Type 1 Diabetes Mellitus (T1DM) Insulin-Treated with Hyperglycemia
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.
干预措施: Dextrose (Dietary Supplement)
结局指标
主要结局
Protein synthesis
时间窗: Approximately 7 hours
Measurement of isotope abundance in peptides derived from the digested proteins
次要结局
未报告次要终点
研究者
K. Sreekumaran Nair
Principal Investigator
Mayo Clinic