Tissue-Specific Metabolic Reprogramming in Diabetic Complications

NCT01823406 | Completed

• 2 other identifiers: HUM000609671DP3DK094292-01
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (4)

Type 1 Diabetes no complications.

EXPERIMENTAL

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

Type 1 Diabetes with microalbuminuria

EXPERIMENTAL

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

Type 1 Diabetes with advanced complications.

EXPERIMENTAL

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

Aged and sex matched healthy control volunteers

EXPERIMENTAL

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

Interventions

Euglycemic clamp (normal blood sugar clamp) for 4 hours PROCEDURE

Aged and sex matched healthy control volunteers; Type 1 Diabetes no complications.; Type 1 Diabetes with advanced complications.; Type 1 Diabetes with microalbuminuria

hyperglycemic clamp (elevated blood sugar to 300) for 4 hours PROCEDURE

Aged and sex matched healthy control volunteers; Type 1 Diabetes no complications.; Type 1 Diabetes with advanced complications.; Type 1 Diabetes with microalbuminuria

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Glucose Clamp Technique; WW Domain-Containing Oxidoreductase

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Chemistry Techniques, Analytical; Investigative Techniques; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Rodica Pop-Busui, MD,PhD.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Internal Medicine, MEND Division

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: April 4, 2013
• Study Start: May 1, 2012
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: June 28, 2018

Record last verified: 2018-06

Locations

US (1)