A 38 year-old female presents with resistance to subcutaneous insulin, however good response to intravenously administered insulin. Her background history is of chronic hereditary pancreatitis diagnosed at the age of 17. She underwent total pancreatectomy with autologous pancreatic islet cell transplantation in 2010. Oral glucose tolerance test was normal prior to surgery. Insulin was required post-operatively, and by one year post-islet cell transplant she required a total daily dose (TDD) of 180 units (3.4units/kg/day) of subcutaneous insulin with serum insulin level of <2mIU/L (reference range: 0-16mIU/L) despite a detectable C-peptide level of 0.21nmol/l (reference range: 0.30-0.60).
Poor control of diabetes was complicated by recurrent hospital admissions for recurrent hyperglycemia and ketosis, diabetic amyotrophy, mononeuritis, peripheral neuropathy and gastroparesis. In November 2012 the patient presented with persistent hyperglycemia. The TDD of insulin reached 250 units per day (4.0units/kg/day) with blood glucose levels reaching a minimum of 26 mmol/l and HbA1c 130mmol/mol (14.1%). Anti-insulin antibodies were negative, no antibody binding of insulin was found post-IgG precipitation, adiponectin was elevated at 43.2ug/mL (reference range: 3.0-30.0ug/mL), and in vitro a decline in insulin level was seen following subcutaneous insulin administration in a sample of the patient’s subcutaneous fat.
Subcutaneous insulin was changed to intravenous insulin infusion with requirements decreasing to 43 units per day (0.78units/kg/day) and blood glucose levels reached as low as 4.1mmol/l. The patient was planned for placement of an intraperitoneal port for long term insulin administration. However, in January 2013 she developed an acute upper gastrointestinal bleed from an enterovenous fistula which was complicated by peritonitis, precluding her from intraperitoneal delivery of insulin. She continues on intravenous insulin with requirements that have remained stable at 40 units per day (0.63units/kg/day) over five months and HbA1c is 39 mmol/mol (5.7%).
Subcutaneous insulin resistance is a rare syndrome characterised by severe resistance to subcutaneous insulin with normal intravenous insulin sensitivity. Long term insulin delivery solutions are being explored.