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.