Tissue-Specific Metabolic Reprogramming in Diabetic Complications

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.

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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