Successful remission of type B insulin resistance syndrome without rituximab in an elderly male

Abstract

Summary Type B insulin resistance syndrome (TBIR) is a rare autoimmune disease caused by antibodies against the insulin receptor. It should be considered in patients with dysglycaemia and severe insulin resistance when other more common causes have been ruled out. We report a case of a 72-year-old male with a 4-year history of type 2 diabetes who presented with hypercatabolism, vitiligo, acanthosis nigricans, and hyperglycaemia resistant to massive doses of insulin (up to 1000 U/day). Detection of anti-insulin receptor antibodies confirmed TBIR. The patient received six pulses of methylprednisolone and daily treatment with cyclophosphamide for 6 months. Response to treatment was evident after the fourth pulse of methylprednisolone, as indicated by weight gain, decreased glycosylated haemoglobin and decreased requirement of exogenous insulin that was later discontinued due to episodes of hypoglycaemia. Remission was eventually achieved and the patient is currently asymptomatic, does not require insulin therapy, has normal glycaemia and is awaiting initiation of maintenance therapy with azathioprine. Thus, TBIR remitted without the use of rituximab. This case highlights the importance of diagnosis and treatment in a timely fashion, as well as the significance of clinical features, available laboratory findings and medication. Large controlled studies are required to standardise a therapeutic protocol, particularly in resource-constrained settings where access to rituximab is limited. Learning points: Type B insulin resistance syndrome is a rare autoimmune disorder that should be considered in patients with dysglycaemia, severe insulin resistance and a concomitant autoimmune disease. Serological confirmation of antibodies against the insulin receptor is not necessary in all cases due to the high associated mortality without timely treatment. Although there is no standardised immunosuppressive treatment, a protocol containing rituximab, cyclophosphamide and steroids has shown a significant reduction in previously reported mortality rates. The present case, reports successful remission in an atypical patient using cyclophosphamide and methylprednisolone, which is an effective therapy in countries in which rituximab is not covered by health insurance. When there is improvement in the hypercatabolic phase, the insulin dose should be reduced and/or discontinued to prevent hypoglycaemia; a mild postprandial hyperglycaemic state should be acceptable.

Coexistence of Type B Insulin Resistance and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in Type 2 Diabetes Mellitus: Various Manifestations With the Same Pathophysiologic Base?

“…It should be noted that most patients do not meet all the criteria for a specific autoimmune disease. 6 Occasionally, patients develop initial or secondary hypoglycemia, in some cases with unsuppressed insulin, which could be due to defective degradation of insulin–insulin receptor complexes. 9 Although the treatment is mainly done empirically, several case reports suggested therapeutic benefits of different agents, including cyclophosphamide, corticosteroids, azathioprine, rituximab, and plasmapheresis.…”

“…9 Although the treatment is mainly done empirically, several case reports suggested therapeutic benefits of different agents, including cyclophosphamide, corticosteroids, azathioprine, rituximab, and plasmapheresis. [3][4][5][6][7] However, combination immunosuppressive therapy is also reported in this regard. In a prospective cohort study, 22 patients with confirmed TBIRS were administered combination of rituximab, cyclophosphamide and high-dose pulsed steroids until remission (defined as hyperglycemia amelioration and insulin discontinuation and/or hyperandrogenemia normalization) followed by maintenance therapy with azathioprine.…”

“…As TBIRS is a rarely reported disease, the treatment has traditionally been empirical, and several case reports of therapeutic efforts with cyclophosphamide, glucocorticoids, azathioprine, rituximab, and plasmapheresis have been published. 3 - 7 …”

“…As TBIRS is a rarely reported disease, the treatment has traditionally been empirical, and several case reports of therapeutic efforts with cyclophosphamide, glucocorticoids, azathioprine, rituximab, and plasmapheresis have been published. [3][4][5][6][7] This report presents a 59-year old patient who suffered from uncontrolled type 2 DM who presented with simultaneous TBIRS and CIDP ultimately responded well to corticosteroid therapy, resulting in markedly improved blood glucose levels and neurological manifestations.…”