Endocrine Abstracts (2019) 65 P236 | DOI: 10.1530/endoabs.65.P236

Case reports of immunosuppression therapy for anti-insulin receptor and anti-insulin antibodies in patients attending the national severe insulin resistance service

Charlotte Jenkins Liu1, Claire Adams1, David Church1, Catherine Flanagan1, Lisa Gaff1, David Jayne1, Audrey Melvin1, Stephen O’Rahilly1, Eirini Pizirtzidou1, David Savage1, Robert Semple1,2, Elaine Withers1 & Anna Stears1

1Addenbrookes Hospital, Cambridge, UK; 2University of Edinburgh, Edinburgh, UK

Introduction: Immune mediated cases of severe insulin resistant diabetes are very rare. We report responses to immunosuppression with rituximab in two patients.

Case 1: A 31 year old black African female, BMI 22.84 kg/m², was referred with new onset diabetes, diagnosed shortly following a miscarriage. She had weight loss, acanthosis nigricans, nocturnal hypoglycaemia and severe hyperandrogenism . She was on an insulin pump and required >1000 units insulin per 24 h. Fasting insulin 4749 pmol/l, leptin 1.2 ug/l, normal lipids, HbA1c 83 mmol/mol (9.7%). Immunoprecipitation studies confirmed the presence of anti-insulin receptor antibodies. Rituximab infusions were given 6 monthly for two years. After two doses of rituximab, she had gained 13 kg, required no diabetes medication, her HbA1c was 33 mmol/mol and insulin 59 pmol/l. She reported no further hypoglycaemia and was back at work.

Case 2: A 64 yr old Asian male, BMI 24.91 kg/m², with sub-optimally controlled type 2 diabetes treated with porcine insulin. Reported multiple insulin intolerances. Frequent episodes of hyper/hypoglycaemia. No response to previous steroid or mycophenolate. No acanthosis nigricans or features of lipodystrophy. Fasting insulin >100 000 pmol/l, triglycerides 2.4 mmol/l, HbA1c 102 mmol/mol (11.5%). Anti-insulin antibodies were detected at a high titre and further analysis confirmed these were functional antibodies. Rituximab therapy was commenced. One month post first dose rituximab insulin doses were reduced, HbA1c 93 mmol/mol (10.7%), fasting insulin 79 920 pmol/l. This initial improvement is encouraging and further improvement is expected.

Conclusion: In patients with insulin resistant diabetes, especially those with intermittent hypoglycaemia, consider immune mediated causes of resistant diabetes as this is potentially reversible with immunosuppressive therapy.