Tissue-Specific Metabolic Reprogramming in Diabetic Complications. Glycemic Clamp Studies to Determine the Real Time Synthesis Rates of Glucose Derived Metabolites in Individuals With Type 1 Diabetes and Healthy Controls.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia
研究概览
简要总结
We will perform blood sugar studies to assess changes in metabolic (biochemical processes that occur within us) profiles associated with high blood sugar and diabetes.
详细描述
Objective
To assess steady state and dynamic metabolite changes in subjects with type 1 diabetes with and without microvascular complications and to understand intrinsic differences from non-diabetics in metabolite levels and flux.
The hypothesis is that diabetic complications arise from tissue-specific metabolic reprogramming resulting in alterations in fuel utilization which lead to dysfunction of the tissue. To test this hypothesis, we will use sensitive and specific mass spectrometer based metabolomic analysis to measure steady state metabolite levels in plasma and urine from controls subjects and subjects with T1DM, without and with diabetic complications during euglycemic and hyperglycemic clamp studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General entry criteria:
- •Must have type 1 diabetes > 5 years duration. 18 years of age or older
- •Subjects in the microalbuminuria group will have a history of urinary microalbumin to creatinine ration between 30-300 m/g confirmed on repeat testing while the non-albuminuric group will have a value of less than 30 mg/g.
- •Subjects in advanced complications group will have confirmed Retinopathy, Peripheral and/or Autonomic Neuropathy and nephropathy.
- •Non diabetic individuals will be matched for age and gender and will have normal glucose tolerance, normal lipid metabolism, and normal blood pressure.
排除标准
- •Age less than 18 . Women of child-bearing potential who may be pregnant or lactating History of pancreas, kidney or liver transplant History of drug or alcohol use. History of cancer other than basal cell carcinoma or squamous cell skin cancer. Presence of a condition that in the opinion of the investigator would make it unlikely for the subject to complete the study.
研究组 & 干预措施
Type 1 Diabetes no complications.
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: Euglycemic clamp (normal blood sugar clamp) for 4 hours (Procedure)
Type 1 Diabetes no complications.
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours (Procedure)
Type 1 Diabetes with microalbuminuria
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours (Procedure)
Type 1 Diabetes with microalbuminuria
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: Euglycemic clamp (normal blood sugar clamp) for 4 hours (Procedure)
Type 1 Diabetes with advanced complications.
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: Euglycemic clamp (normal blood sugar clamp) for 4 hours (Procedure)
Type 1 Diabetes with advanced complications.
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours (Procedure)
Aged and sex matched healthy control volunteers
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: Euglycemic clamp (normal blood sugar clamp) for 4 hours (Procedure)
Aged and sex matched healthy control volunteers
Each cohort group will be admitted to the Michigan Clinical Research Unit for Blood glucose Clamp studies. Each subject will have a Euglycemic clamp (normal blood sugar clamp) for 4 hours and a hyperglycemic clamp (elevated blood sugar to 300) for 4 hours. Once the subject is clamped, bloods and urine will be collected to assay for specific metabolomics and proteomic biomarkers. We will perform the same clamps for each cohort.
干预措施: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours (Procedure)
结局指标
主要结局
Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia
时间窗: One time study visit /subject for an average of up to 24 h.
Investigators will perform 4 hour Euglycemic and 4 hr hyperglycemic glucose clamps on each subject once. The Investigators will have 4 different groups of subjects. At specific time points during the clamps, the investigators will draw blood samples for measurement of metabolic assays and flux . The investigators will also collect spot urine samples for metabolic assay and flux.
次要结局
未报告次要终点
研究者
Rodica Pop-Busui
Associate Professor Internal Medicine, MEND Division
University of Michigan