Reducing Risk of Type 2 Diabetes: Hydroxychloroquine Use in Pre-Diabetes

The purpose of this study is to determine the short-term effects of the antimalarial medication, hydroxychloroquine (HCQ), compared with placebo using frequently sampled intravenous glucose tolerance testing (FSIGTT) methodology to study changes in insulin secretion and glucose tolerance in subjects at risk for developing Type 2 diabetes.

Diabetes is approaching epidemic proportions in the United States. Efforts to implement effective strategies for diabetes prevention have been limited by poor long term adherence to lifestyle modifications and potential side effects and costs of pharmacologic interventions. This study evaluates the mechanisms of action of a generic drug that may be a useful alternative to existing interventions to prevent the development of Type 2 diabetes mellitus.

• Drug: hydroxychloroquine
  Thirteen weeks 400 mg oral hydroxychloroquine capsule taken after frequently sampled intravenous glucose tolerance testing (FSIGTT)
  Other Name: Plaquenil
• Other: Sugar pill
  Thirteen weeks oral inert substance taken in capsule daily
  Other Name: microcellulose

• Experimental: hydroxychloroquine
  Thirteen weeks of daily hydroxychloroquine therapy following FSIGTT testing
  Intervention: Drug: hydroxychloroquine
• Placebo Comparator: Sugar pill
  Thirteen weeks of daily sugar pill following FSIGTT testing
  Intervention: Other: Sugar pill

Inclusion Criteria:

1. Age > or = 18, able to provide informed consent
2. Body-mass index greater than or equal to 25

3. Presence of at least one indicator of insulin resistance from the following list:

   • Family history of Type 2 diabetes (parent, sibling)
   • Fasting glucose 100 - 125 mg/dl
   • Fasting serum insulin greater than or equal to 7uU/ml
   • Personal history of gestational diabetes
4. Negative pregnancy test for women with childbearing potential

Exclusion Criteria:

1. Diagnosis of diabetes mellitus Type 1 or Type 2
2. Active autoimmune disease, chronic infection, current malignancy (excluding basal cell carcinoma), or other active inflammatory state that, in the opinion of the investigators, would affect insulin sensitivity
3. Oral corticosteroid use in prior six months, or expectation of needing corticosteroid therapy in upcoming six months
4. Known allergy or intolerance to HCQ
5. Known glucose-6 phosphate dehydrogenase deficiency
6. Known eye disease associated with retinal pigmentation abnormalities
7. Known diabetic retinopathy requiring past or planned laser therapy
8. Inability to comply with visit schedule and protocol requirements
9. Inability to manage and take medication as instructed
10. Current or planned pregnancy in upcoming 12 months
11. Inability or unwillingness to use reliable method of contraception (for women of childbearing years, men, or men's partners with childbearing potential), such as oral contraceptive pills, barrier method (diaphragm and condom with spermicide), intrauterine device, or depo-provera injections for 3 months prior to enrollment
12. Anemia (HGB < 9)
13. Any history of bariatric (weight loss) surgery
14. Current use of the medication Glucophage (metformin)
15. Weight changes of 6 pounds or more in the past 4 weeks
16. Any other underlying or concomitant condition, which in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk