Type 1 Diabetes and Depression: Role of Brain Glutamate
Condition: Type1diabetes; Depressive Symptoms; Major Depressive Disorder
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Depression; Depressive Disorder; Depressive Disorder, Major
Study type: Interventional

Summary: 
      The goal of this study is to examine the effect of chronic and acute hyperglycemia in type 1
      diabetes mellitus (T1DM) on brain glutamate levels using magnetic resonance spectroscopy
      (MRS), and associations of brain glutamate with symptoms of depression.
    

Detailed description: 
      The research of this study is focused on elucidating the relationship between the
      perturbations in glucose metabolism associated with T1DM and the higher prevalence of major
      depressive episodes in this patient population. Converging evidence associating high brain
      levels of glutamate with T1DM and depression leads to the hypothesis that the link between
      diabetes-related glucose metabolic disorders and depression is excessive brain glutamate. The
      overarching aim of the study is to examine the effect of chronic and acute hyperglycemia in
      T1DM on brain glutamate levels. Four subject groups were studied and characterized: T1DM
      patients with and without concurrent depressive symptoms, and non-diabetic subjects with and
      without concurrent depressive symptoms. Two brain regions were examined : the anterior
      cingulate cortex (ACC), known to play an essential role in the regulation of emotions, and a
      control occipital cortex region. Regional brain glutamate concentrations were measured using
      high-field (3 Tesla) localized multidimensional magnetic resonance spectroscopy (MRS),
      regional indices of brain function were assessed using functional magnetic resonance imaging
      (fMRI), concurrent depression symptom severity and depression history were evaluated using
      psychiatric assessment, extensive medical evaluation of patients was performed including
      evaluation of glycemic control (HbA1c), evaluation of behavioral performance on emotional and
      cognitive tasks and evaluation of regional brain cortical thickness using high-resolution
      structural MRI. For all subjects, MRS brain glutamate was assessed during basal euglycemia
      and, for a subset of subjects per group, during an acute hyperglycemic clamp. To control for
      potential confounding effects of hyperinsulinemia, brain glutamate was also assessed during a
      euglycemic hyperinsulinemic clamp in a subset of healthy controls without diabetes or
      depressive symptoms.
    

Intervention name(s): Glucose Clamp
Intervention type(s): Procedure
Intervention description(s): Subjects receive variable rates of glucose or insulin infusions to adjust and maintain desired plasma glucose or insulin levels.
Other intervention name(s): Hyperglycemic, Euglycemic, or Hyperinsulinemic Euglycemic Clamp
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: There are 4 subject groups for this study: 1) T1DM without current depressive symptoms with no history of major depressive disorder; 2) T1DM with current depressive symptoms and with a history of major depressive disorder; 3) Non-diabetic controls without current depressive symptoms and with no history of major depression; 4) Non-diabetic controls with current depressive symptoms and with major depression history. For all subjects, MRS brain glutamate is assessed during basal euglycemia, and for a subset of subjects per group, during an acute hyperglycemic clamp. To control for potential confounding effects of hyperinsulinemia, brain glutamate is also assessed during a euglycemic hyperinsulinemic clamp in a subset of controls (group 3).
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Hyperglycemia; Euglycemic hyperinsulinemic clamp; Euglycemia; Magnetic Resonance Spectroscopy; Magnetic Resonance Imaging; Glutamate