Tissue-Specific Metabolic Reprogramming in Diabetic Complications (DP3)

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.

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours; Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Group 1: T1DM subjects without complications:

Group 2: T1DM subjects with microalbuminuria . Group 3: T1DM subjects with advanced diabetes complications Group 4: Age-and-sex-matched healthy control subjects .

Inclusion Criteria:

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.

Exclusion Criteria:

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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours; Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: 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.	Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours; Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: 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.	Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours; Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Experimental: 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.	Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours; Procedure: hyperglycemic clamp (elevated blood sugar to 300) for 4 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia	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.	One time study visit /subject for an average of up to 24 h.

Collaborators and Investigators

• Sponsor: University of Michigan
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Rodica Pop-Busui, MD,PhD., University of Michigan

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 29, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): June 28, 2018
• Last Update Submitted That Met QC Criteria: June 26, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Complications
• Other Study ID Numbers: HUM00060967; 1DP3DK094292-01 (U.S. NIH Grant/Contract)