Imuunosuppressive Therapy in Treatment of Refractory Hypoglycemia in Type B Insulin Resistance - Case Report with a Diagnostic Dilemma
Presentation Number: SAT 613
Date of Presentation: April 1st, 2017
Lavanya Viswanathan*1 and Imali Sirisena2
1Temple University, Philadelphia, PA, 2Temple University Hospital, Philadelphia, PA
Type B insulin resistance is a rare syndrome caused by autoantibodies to the insulin receptor It causes a spectrum of symptoms ranging from severe hyperglycemia with extreme insulin resistance to intractable hypoglycemia. Here we present a patient with a presentation and phenotype consistent with Type B insulin resistance also demonstrating the diagnostic dilemma in this condition.
A 60 year old African American female with past history of SLE and Hashimoto’s hypothyroidism presented with significant weight loss, nausea and vomiting. She reported frequent episodes of hypoglycemia.
She had been hospitalized hypoglycemia one year prior. Labs were - Insulin 661 uIU/ml; Range 2-19, Proinsulin 58.4 pmol/L;< 18.8, C-Peptide 9.1 ng/ml; Range 0.8-3, HbA1C 7.3% with glucose 49 mg/dl. A cosyntropin stimulation test yielded appropriate cortisol She responded to Intravenous Immunoglobulin (IVIg) therapy x 3 cycles with prednisone 60 mg daily. She was diagnosed with type 2 diabetes and discharged on insulin.
One year later she again had refractory hypoglycemia. She again had hyperinsulinemia with hypoglycemia. A trial of IV Ig, Azathioprine and prednisone was given. Insulin receptor antibody levels were weakly positive when she was euglycemic.
Insulin receptor autoantibodies inhibit insulin action at the insulin receptors. These antibodies have both an insulin mimetic effect and cause insulin resistance giving a biphasic response of hypo- and hyperglycemia in the same patient. Antibody testing is by immunoprecipitation preferably in the hyperglycemic phase. The hypoglycemic phase can have low antibody titers as it has partial agonist activity. Insulin receptor antibodies were detected in our patient albeit at a low level. However given her clinical presentation, treatment response and the absence of these antibodies in the general population, we feel that this is consistent with Type B insulin resistance. On literature review, there have been three other case reports with spontaneous hypoglycemia and elevated antibody levels but no clear identifiable pathogenesis. Though previous studies have associated hypoglycemia with a negative clinical prognosis our patient has done better than most.
Spontaneous remission occurs in 1/3 rd of patients but treatment has been unsatisfactory in those who do not. Treatment in the hyperglycemic phase is usually with large insulin doses. High dose steroids, immunosuppressants and plasmapheresis, but data is limited.
Treatment was delayed by variation in antibody titers which precluded testing during hypoglycemia. This condition requires a high index of suspicion and low threshold for empiric treatment as it can be fatal. Future research is needed to improve diagnosis and treatment of this disease.
Nothing to Disclose: LV, IS