Iron Reduction by Phlebotomy to Improve Diabetes Control

Investigators propose that high iron triggers a number of events in different tissues, some
of which will predispose to diabetes. Investigators will therefore study normal individuals
who have higher than average iron levels in tissues, test your glucose control through
standard blood tests like the hemoglobin A1c and by placing a continuous glucose monitor
before and after participants have donated blood to determine if decreasing iron levels had
any effect.

In addition, iron may also play a role in the progression of fatty liver to scarring and
cirrhosis. Since 75% of people with diabetes have some degree of fatty liver, investigators
would also like to study how the liver reacts to the lowering of iron.

There will be two optional sub studies conducted only at Wake Forest University Health
Sciences they are: 1) Liver substudy that will look at liver complication of diabetes and the
role it plays in the progression of fatty liver to scarring and cirrhosis. Investigators will
look at how liver reacts to the lowering of iron. 2)Glucose Tolerance Mechanism substudy that
will look at the mechanism the body uses to regulate blood sugar levels by insulin, this will
require the frequently sample intravenous glucose tolerance test (FSIVGTT).

Inclusion Criteria:

- Ages 40-75

- At least 3 months since diagnosis of prediabetes or diabetes

- HgbA1C value within three months or at screening of 5.7 -6.4% for those with
prediabetes and 7-8.5% for those with diabetes (the upper limit of the latter to
reduce the likelihood of major changes in glycemic intervention during the trial
period, and the lower limit to allow some room improvement)

- Serum ferritin levels within 1 year or at the time of screening in the upper half of
the normal range (>85 ng/mL for women >110ng/mL for men)

Exclusion Criteria:

- Documented anemia

- Hemoglobin levels with 0.5 g/dL of the lower limit of normal (<12.52 g/dL for women
13.5 g/dL for men)

- Recent blood loss

- Bleeding diatheses (coagulation abnormalities or treatment with anticoagulants)

- Serious chronic infections or chronic inflammatory conditions that could elevate
ferritin as an "acute phase reactant

- C-reactive protein greater than the upper limit of normal to further validate the lack
of significant chronic inflammation

- Active cancer diagnosis (excluding skin cell cancers other than melanoma)

- Renal insufficiency (eGFR<60 ml/min)

- History of orthostatic hypotension

- Heavy alcohol use (NIH criteria, for me greater than 4 drinks on any day or 14/week)

- Pregnancy or premenopausal women of childbearing age, unless unable to become pregnant
because of oral contraceptive use or surgical loss of ovaries or uterus.