Type 1 Diabetes Mellitus
Conditions
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.
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.
Interventions
PROCEDUREEuglycemic clamp (normal blood sugar clamp) for 4 hours
PROCEDUREhyperglycemic clamp (elevated blood sugar to 300) for 4 hours
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Michigan
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion 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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in the levels of TCA cycle metabolites between groups during euglycemia and hyperglycemia | 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. |
Countries
United States
Outcome results
None listed