Iron Reduction for the Treatment of Diabetes and Nonalcoholic Fatty Liver Disease

This is a treatment study to determine if reducing the body's iron stores by blood donation will improve diabetes control and other problems associated with diabetes such as fatty liver disease.

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).

Eligibility Criteria:
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 for improvement)
* Undiagnosed on no medication HgA1C 6.5-6.9
* C-reactive protein levels up to 11.0
* Aim 2-serum ALT\> 1.5 times the upper limit of normal, or; liver stiffness of \> 12.5 kPa by Fibroscan transient elastography
* Serum ferritin levels within 1 year or at the time of screening in the upper half of the normal range (\>50 ng/mL for women; \>100ng/mL for men)

Exclusion Criteria:

* Documented anemia
* Hemoglobin levels within 0.5 g/dL of the lower limit of normal (\<12.5 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 men, 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
* Aim 2 - individuals meeting the additional inclusion criteria for aim 2 will be tested for anti-HAV IgM, HBs Ag, anti-HBc. IgM, anti HCV IgM and IgG. Subjects who prove positive for any of these viral serologies, except for HCV IgG will be excluded. The latter will be tested for HCV RNA by PRC, and if negative they will be eligible for enrollment