Regulation of Brain Glucose Metabolism in Type 1 Diabetes

This study is a prospective randomized placebo-controlled double-blind crossover study designed to address the hypothesis that dichloroacetate has the ability to re-activate brain glucose metabolism under clamped hypoglycemia. The study population is comprised of intensively treated persons with T1D with frequent exposure to hypoglycemia, who have cognitive deficits under hypoglycemia that could be attributed to changes in brain glucose oxidation. The investigators will test the experimental compound DCA in a study that determines whether restoring brain glucose metabolism under hypoglycemia helps maintain cognitive function.

Inclusion criteria

T1DM subjects with:

• a history of severe hypoglycemia and/or hypoglycemia unawareness or
• a history of severe hypoglycemia with a blood glucose <54 mg/dL, requiring the assistance of another person (with recovery after the administration of oral carbohydrate, intravenous glucose, or glucagon) or
• at least 2 values <54mg/dl during 2 weeks of CGMS testing during the week prior to study.

Exclusion criteria

• Age < 18 years or >55 years.
• Body weight >85 kg at screening visit
• BMI > 30 (female) and >30 (male) kg/m2.
• Untreated proliferative retinopathy
• carriers of glutathione transferase Z1 (GSTZ-1) gene polymorphisms that predispose to DCA accumulation and toxicity