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

Summary

Background: \- Insulin receptor mutation causes high blood sugars and sometimes diabetes complications. Researchers want to see if thyroid hormone helps. Objectives: \- To see if thyroid hormone treatment changes how the body handles sugar in people with insulin receptor mutation and improves blood sugar in people with diabetes. Eligibility: \- People ages 12 65 with an insulin receptor mutation. Design: * Study part 1:19-day clinic stay. Participants will be monitored for 4 days. Then for 15 days they will take a thyroid hormone pill 3 times a day. Participants will have: * Blood tests. * Heart rate and skin temperature monitored. * All their food provided. * Two 5-hour sessions in a special room. They will wear special clothes and sometimes sit still. * Two small tubes inserted in veins. One will deliver tiny amounts of sugar and fat with a non-radioactive tracer. Participants will also drink water with a tracer. The other tube will collect blood. * A sweet drink. Participants may have finger stick blood sugar tests. * Glucose-monitoring device inserted into body fat for two 24-hour periods. * Adults may have samples of fat and muscle taken. * Heart ultrasound. * PET-CT scan in a machine. An intravenous catheter will be placed in an arm vein. A small amount of radioactive substance will be injected. * DEXA scan of body fat and bone density. * Participants with poorly controlled diabetes will then take thyroid hormone at home for 6 months. They will have blood drawn and sent to the study team monthly. * After about 3 months, they will have an overnight visit. After 6 months, they will have a 4-day visit.

Timeline

Start

2015-04-17

Primary completion

2018-09-18

Completion

2018-09-18

Publications

• Background Kahn CR, Flier JS, Bar RS, Archer JA, Gorden P, Martin MM, Roth J. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med. 1976 Apr 1;294(14):739-45. doi: 10.1056/NEJM197604012941401.
• Background Skarulis MC, Celi FS, Mueller E, Zemskova M, Malek R, Hugendubler L, Cochran C, Solomon J, Chen C, Gorden P. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab. 2010 Jan;95(1):256-62. doi: 10.1210/jc.2009-0543. Epub 2009 Nov 6.
• Background Musso C, Cochran E, Moran SA, Skarulis MC, Oral EA, Taylor S, Gorden P. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore). 2004 Jul;83(4):209-222. doi: 10.1097/01.md.0000133625.73570.54.
• Sekizkardes H, Chung ST, Chacko S, Haymond MW, Startzell M, Walter M, Walter PJ, Lightbourne M, Brown RJ. Free fatty acid processing diverges in human pathologic insulin resistance conditions. J Clin Invest. 2020 Jul 1;130(7):3592-3602. doi: 10.1172/JCI135431.
• Kushchayeva YS, Startzell M, Cochran E, Auh S, Sekizkardes H, Soldin SJ, Kushchayev SV, Dieckmann W, Skarulis M, Abdul Sater Z, Brychta RJ, Cypess AM, Lin TC, Lightbourne M, Millo C, Brown RJ. Thyroid Hormone Effects on Glucose Disposal in Patients With Insulin Receptor Mutations. J Clin Endocrinol Metab. 2020 Mar 1;105(3):e158-71. doi: 10.1210/clinem/dgz079.

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