Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations

Exclusion Criteria

• •1. Changes in doses of diabetes medications (including metformin, insulin, sulfonylureas, thiazolidinediones, leptin, GLP-1 agonists, DPP4 inhibitors, etc.) in the preceding 10 weeks.
• •2. Any medical condition or medication that will increase risk to the subject (e.g. ischemic or structural heart disease, congestive heart failure, uncontrolled hypertension, or arrhythmia) or that will interfere with interpretation of study data.
• •3. Disorders that would lead to erratic gastrointestinal absorption or loss of thyroid hormone from the gut (severe diarrhea, celiac disease, use of bile acid sequestrants, excessive consumption of soybean products).
• •4. Any form of endogenous hyperthyroidism or hypothyroidism at baseline.
• •5. Current or recent (past 8 weeks) use of thyroid hormone or anti-thyroid drugs.
• •6. Extreme disorders of thyroid hormone binding to thyroid binding globulin (excess or deficiency) or protein loss (nephrotic range proteinuria) that would lead to difficulties achieving a consistent thyroid hormone level for study.
• •7. Known presence of a rare clinical disorder that leads to thyroid hormone insensitivity (known T3 receptor mutations, selenocysteine insertion sequence-binding protein 2 (SBP2) abnormalities, monocarboxylate transporter defects).
• •8. Current use of beta blockers
• •9. Pregnancy or breast feeding
• •10. Any EKG abnormality that could increase risk of T3 treatment (resting sinus tachycardia (age adjusted norms), atrial fibrillation, myocardial ischemia, left or right ventricular excitation block, left ventricular hypertrophy or extrasystoles)
• •11. Known allergy or hypersensitivity to any form of thyroid hormone
• •12. Known adrenal insufficiency
• •13. Dependence on oral anticoagulant medications (adults only)
• •14. Use of tricyclic anti-depressants, as transient cardiac arrhythmias have been observed with the concomitant use of thyroid hormone.
• •15. Use of cholestyramine.
• •16. History of clinically significant osteoporosis per investigator judgment (e.g. previous fragility fracture)
• •6 MONTHS STUDY: