Effect of Iron Reduction by Phlebotomy for Type 2 Diabetes
Condition: Type 2 Diabetes Mellitus; Prediabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional

Summary: 
      High tissue iron is a risk factor for diabetes even within the broad normal range of normal
      human values. In order to demonstrate the benefits of reducing iron on glucose homeostasis
      and to better define the parameters for larger clinical trials, the investigators will
      subject individuals with prediabetes (impaired glucose tolerance, IGT) or early type 2
      diabetes to phlebotomy in order to reduce serum ferritin concentrations and determine the
      effect on glucose homeostasis as revealed by oral and frequently sampled intravenous glucose
      tolerance testing.
    

Detailed description: 
      Male and female subjects aged 35-65 will be recruited from the clinic populations at the
      Medical Centers of the Universities of Colorado, New Mexico, or Utah who have prediabetes, or
      diabetes relatively well-controlled (Hemoglobin A1c [HbA1c] ≤ 8.0%) with a single oral agent.
      Diabetes/prediabetes status is verified by oral glucose tolerance testing (OGTT) using
      criteria of the American Diabetes Association. Serum ferritin will be determined, and
      subjects chosen with values in the upper 50% of the normal range, 110-400 ng/mL for males, or
      80-240 for females. Exclusion criteria include: hereditary hemochromatosis; cancer (except
      cases currently with no evidence of disease); serum creatinine >1.5; anemia (Hgb < lower
      limit of normal); chronic inflammatory conditions (rheumatologic conditions such as
      rheumatoid arthritis or giant cell arteritis, or chronic infections such as hepatitis B or C)
      that could affect ferritin; erythrocyte sedimentation rate or C-reactive protein>1.5 times
      the upper limit of normal (UNL); serum transaminases 2 x UNL; hemophilia, warfarin therapy,
      or history of GI bleeding; and current glucocorticoid therapy.

      After determination of eligibility, subjects are randomized in a 2:1 ratio for treatment and
      controls arms. In the fasted state, blood is drawn for determination of adiponectin and
      lipids (HDL, direct LDL, triglycerides). Subjects have the option of participating in a
      frequently sampled intravenous glucose tolerance test (FSIVGTT). All subjects receive
      counseling to follow a healthy diet and regular exercise. Phlebotomy occurs at the rate of
      500 ml (one Unit) of blood per month over the period of 3-6 months. At two-month intervals,
      serum ferritin and complete blood counts are determined. When serum ferritin reaches the
      lowest quartile of normal (<50 ng/mL for females and <70 ng/mL for males, but no sooner than
      3 months or later than 6 months after beginning phlebotomy, metabolic status will be
      reassessed by fasting lipids, adiponectin, OGTT, and optionally, FSIVGTT. Controls are
      recalled for repeat testing 6-8 months after enrollment.

      120 min OGTT and FSIVGTT are performed on separate days after an overnight fast. FSIVGTT data
      are analyzed using MINMOD Millennium software. Areas under the glucose curve (AUCglucose) are
      calculated using the trapezoidal method.
    

Intervention name(s): Phlebotomy
Intervention type(s): Procedure
Intervention description(s): Patients donate blood until tissue iron levels are in the lowest quartile of normal.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: iron; diabetes; phlebotomy