NIV Congres

Case: A 45-year old woman, known with uncomplicated diabetes mellitus type 1 since the age of 20, complained about ‘attacks’ of hypoglycemia, once a month, in 2007. Insulin glargine and insulin aspart were adapted. Nonetheless, in the following years these hypoglycemic periods became more frequent. Additional diagnostics excluded MODY, celiac disease and adrenal insufficiency. In 2011, our patient used only 1 unit of glargine and no aspart at all. The symptoms persisted. Biochemical analyses during hypoglycemia showed low serum glucose, insulin, pro-insulin and C-peptide concentrations. Therefore, we excluded factitia or an insulinoma as possible causes. We also excluded an insufficient counter regulation, insulin and insulin receptor antigens and IGF or BIG-IGFII overproduction. Without an appropriate explanation for these hypoglycemia’s, glargine was discontinued. Unfortunately, a diabetic keto-acidosis arose. In a tertiary referral hospital glargine was changed for insulin isofaan (NPH). The patient was referred back without new insights. A few weeks later, she was presented again with hypoglycemia. This time, we found low levels of glucose and C-peptide, but high levels of insulin. This suggests factitia. We presumed incorrect measurement in former insulin samples with our commercial assay. These previous samples were tested by different assays, and now showed high insulin levels. The diagnosis factitia was confirmed.

Discussion: Insulin is measured with immunochemical methods using polyclonal or monoclonal antibodies to bind insulin. Monoclonal antibodies are specific in the detection of pure human insulin, but can show little to no cross reactivity with pro-insulin or recombinant insulin. Polyclonal antibodies however, do show such cross reactivity. Most medical laboratories use commercial (monoclonal) methodsto measure insulin of which 75% is not capable of detecting pro-insulin or exogen insulin. Insulin glargine and insulin aspart are insulin analogs that are not detected in our monoclonal assay. Because our patient switched to insulin NPH, pure human insulin, we could detect exogen insulin as the cause of hypoglycemia.

Conclusion: This case illustrates the importance of knowledge about pitfalls in the diagnostic approach in hypoglycemia. Be aware of the specifications of your insulin assay to prevent false negative results in insulin measurements.