Combined Immunosuppressive Therapy Induces Remission in Patients With Severe Type B Insulin Resistance: A Prospective Cohort Study.

Abstract

OBJECTIVE:

Type B insulin resistance due to autoantibodies against the insulin receptor is characterized by diabetes refractory to massive doses of insulin, severe hypercatabolism, hyperandrogenism, and a high mortality rate. We analyzed the efficacy of combined immunosuppressive therapy in the management of this extreme form of diabetes.

RESEARCH DESIGN AND METHODS:

We performed a prospective cohort study including patients with confirmed insulin receptor autoantibodies, monitored for median 72 months (25th, 75th interquartile range 25, 88), and treated with rituximab, high-dose pulsed steroids, and cyclophosphamide until remission, followed by maintenance therapy with azathioprine. Remission was defined as the amelioration of the hyperglycemia and discontinuation of insulin and/or normalization of hyperandrogenemia.

RESULTS:

All data are given as median (25th, 75th interquartile range). Twenty-two patients aged 42 (25, 57) years, 86.4% women, fulfilled inclusion criteria. At baseline, fasting glucose was 307 (203, 398) mg/dL, HbA1c was 11.8% (9.7, 13.6), total testosterone (women) was 126 (57, 571) ng/dL (normal 8-60), and daily insulin requirement was 1,775 (863, 2,700) units. After 5 (4, 6.3) months, 86.4% (19 of 22) of patients achieved remission, documented by discontinuation of insulin in all patients, normal fasting glucose of 80 (76, 92) mg/dL, HbA1c of 5.5% (5.2, 6), and testosterone (women) of 28 (20, 47) ng/dL. During follow-up of 72 (25, 88) months, 13.6% (3 of 22) of patients developed disease recurrence, occurring 24 (22, 36) months after initial remission, which responded to repeated therapy. None of the patients died.

CONCLUSIONS:

Combined immunosuppressive therapy has changed the natural history of this disease, from 54% mortality to a curable form of diabetes and, as such, should be recommended in patients with type B insulin resistance.

• Authors: Joanna Klubo-Gwiezdzinska, Maria Lange, Elaine Cochran, Robert K Semple, Cornelia Gewert, Rebecca J Brown, Phillip Gorden
• Journal: Diabetes care (Diabetes Care) Vol. 41 Issue 11 Pg. 2353-2360 (11 2018) ISSN: 1935-5548 [Electronic] United States
• PMID: 30201849 (Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Antigens, CD
• Autoantibodies
• Immunosuppressive Agents
• Insulin
• Rituximab
• Dexamethasone
• Cyclophosphamide
• INSR protein, human
• Receptor, Insulin
• Azathioprine
• Methylprednisolone

Topics

• Adult
• Antigens, CD (immunology)
• Autoantibodies (blood)
• Azathioprine (therapeutic use)
• Cohort Studies
• Cyclophosphamide (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Diabetes Mellitus, Type 1 (drug therapy, immunology, metabolism)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Humans
• Hyperglycemia (blood, drug therapy, immunology)
• Immunosuppressive Agents (administration & dosage, adverse effects)
• Insulin (administration & dosage, adverse effects)
• Insulin Resistance (immunology)
• Maintenance Chemotherapy
• Male
• Methylprednisolone (administration & dosage, adverse effects)
• Middle Aged
• Receptor, Insulin (immunology)
• Remission Induction (methods)
• Rituximab (administration & dosage, adverse effects)
• Severity of Illness Index
• Syndrome