Type B Severe Insulin Resistance Syndrome presenting to the Young Adult Diabetes Clinic and Rheumatology Team

S Jones1, M Hogarth2, K Baynes1

1Department of Diabetes & Endocrinology

2Department of Rheumatology, Ealing Hospital, London North West University Healthcare NHS Trust


Clinical Presentation: A 22 year old patient was diagnosed with diabetes mellitus after urinalysis detected glycosuria when attending a rheumatology clinic for possible SLE. Blood glucose 25 mmol/l, HbA1c 101 mmol/mol, blood ketones 2.5 mmol/l with no acidosis. She was started on subcutaneous insulin after education from diabetes nurse team and reviewed in diabetes clinic. Despite escalating insulin doses her ketosis settled only slowly over a number of weeks. Her blood glucose levels also remained high (range 8 mmol/l – ‘Hi’) and even worsened despite no apparent intercurrent infection nor use of corticosteroids. When she was using 160 units of insulin daily with ongoing poor diabetes control she was admitted for inpatient assessment.

Clinical Investigations: Clinical examination showed mild synovitis of small joints. BMI 24 kg/m2. There was acanthosis nigricans of neck and axillae. There was no evidence for lipodystrophy nor hirsutism. There were no clinical features of Cushing’s syndrome nor acromegaly.

Diabetes auto-antibodies were negative (anti-GAD, islet cell antibodies, anti-Zinc finger domain antibodies). Fasting insulin c-peptide was raised at 12.2 mcg/l (Ref 1.1-4.4). Anti-nuclear and Ro antibodies were positive. Complement C3 was low 0.6 (Ref 0.9-1.8) and C4 borderline low 0.11 (Ref 0.1-0.4).

During an intravenous insulin infusion 8-10 units insulin per hour were required to lower blood glucose to less than 15 mmol/l. The patient was started on high strength subcutaneous insulins with Toujeo (U300 insulin glargine) and Humalog 200 (U200 insulin lispro) (and metformin) with a total daily insulin dose of 220 units.

A blood sample was sent to the UK National Severe Insulin Resistance service at Cambridge which returned positive for anti-insulin receptor antibodies.

Clinical Progress: The patient was seen at the National Severe Insulin Resistance service and treated with immunosuppression therapy including prednisolone and rituximab. One year after starting this therapy she has stopped all treatment for diabetes and her HbA1c 45 mmol/mol.

Conclusions: Type B severe insulin resistance is a rare autoimmune disorder most frequently associated with SLE. Poor diabetes control is common in the young adult clinic, but clinicians should remain vigilant to physiological rather than behavioural causes for this.