Relation of White Blood Cell Function to Diabetes
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Study type: Observational

Summary: 
      Background:

      Patients who are pre-diabetic or have adult onset (type 2) diabetes have a significantly
      greater risk of developing heart, blood vessel, or kidney diseases.

      Recent studies have shown that abnormalities in white blood cell function may increase the
      chances of developing insulin resistance, the underlying problem in diabetic or pre-diabetic
      patients.

      Objectives:

      To determine levels of insulin sensitivity in selected volunteers.

      To compare the white blood cells of non-diabetic, pre-diabetic, and type 2 (adult onset)
      diabetic volunteers to evaluate possible differences in white blood cell function.

      Eligibility:

      Individuals between 21 and 60 years of age who (1) are non-diabetic, (2) are pre-diabetic
      (glucose intolerant or insulin resistant), or (3) have type 2 diabetes that is controlled by
      diet and/or medications other than insulin.

      Design:

      Evaluations before treatment:

        -  Blood tests, including screening procedures for blood-transmitted diseases such as
           hepatitis B and C, insulin sensitivity and glucose tolerance tests, and liver and kidney
           function tests.

        -  Pregnancy tests for women of childbearing age.

      Two tests will be performed during the study period:

        -  Glucose tolerance test to determine how well the body uses glucose.

        -  Blood drawn to study white blood cells.

      Participants will be financially compensated for the time spent during the study.
    

Detailed description: 
      Type II diabetes mellitus is rapidly becoming a global pandemic with a deleterious impact on
      cardiovascular morbidity and mortality. Understanding its pathophysiology is important for
      the development of future therapeutic interventions. Interestingly, mitochondrial dysfunction
      in skeletal muscle and adipose tissue are early events in the development of type II diabetes
      mellitus and are proposed to play a role in exacerbating insulin resistance. The genetic
      disruption of macrophage mitochondrial biology in preclinical studies results in the
      development of insulin resistance and concurrent mitochondrial dysfunction in peripheral
      tissue including skeletal muscle and the liver. Whether this disruption of mitochondrial
      function is evident in human mononuclear cells is unknown. We propose that the disruption of
      mitochondrial function in circulating cells may contribute to not only peripheral insulin
      resistance but may also evoke the myriad of vascular complications associated with diabetes.

      To test these assumptions, we propose an initial proof of concept study to evaluate
      mitochondrial biology in circulating monocytes in normal volunteers, pre-diabetic and
      diabetic subjects to assess whether mitochondrial disruption/dysfunction evolves with the
      progression to type II diabetes. In parallel, gene expression and proteomic analysis will be
      performed to evaluate whether the development of insulin resistance and diabetes confers a
      specific modulation in the biological signature of monocytes with disease progression. To
      delineate these concepts we will evaluate study subjects' glucose tolerance and insulin
      sensitivity and draw blood to examine peripheral monocytes. Biological readouts will include:
      1) the quantification of the mitochondrial genomic and electron transfer chain content; 2)
      the determination of mitochondrial reactive oxygen species capacity and defenses; 3) the
      pattern of monocyte differentiation and 4) the unbiased assessment of monocyte gene
      expression and proteome.

      If the mitochondrial hypothesis is operational, this study will show that the mitochondrial
      disruption/dysfunction is a more generalized finding in type II diabetes. This would
      establish targeting the modification of mitochondrial function in various tissue/cell types
      as a novel strategy in the prevention and/or reversal of insulin resistance and diabetes.
    

Time perspective: Prospective
Keywords: Mitochondrial Function in Monocytes; Macrophages and Diabetes or Insulin Resistance; Peripheral Blood Mononuclear Cells; Diabetes; Monocyte; Macrophages; Proteome; Type 2 Diabetes; Insulin Resistance; Insulin Sensitivity; Pre-Diabetes; Healthy Volunteer; HV