Tissue-Specific Metabolic Reprogramming in Diabetic Complications (DP3)

University of Michigan

Status

Completed

Conditions

Type 1 Diabetes Mellitus

Treatments

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

Procedure: Euglycemic clamp (normal blood sugar clamp) for 4 hours

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT01823406

HUM00060967

1DP3DK094292-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

35 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose

Diagnostic

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

35 participants in 4 patient groups

Type 1 Diabetes no complications.

Experimental group

Description:

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.

Treatment:

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 group

Description:

Treatment:

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 group

Description: