ESPE2023 Free Communications Diabetes and insulin 2 (6 abstracts)
1Leeds Children's Hospital, Leeds, United Kingdom. 2UK NEQAS Guildford Peptide Hormones and Trace Elements Berkshire and Surrey Pathology Services Peptide Hormones Section Clinical Laboratory, Guildford, United Kingdom. 3Department of Clinical Biochemistry Cambridge University Hospitals Trust, Cambridge, United Kingdom. 4Cambridge NIHR Biomedical research Centre, Cambridge, United Kingdom. 5Scarborough Hospital, Scarborough, United Kingdom. 6Wellcome MRC Institute of Metabolic Science, Cambridge, United Kingdom. 7Department of Clinical Biochemistry, Cambridge, United Kingdom
Background: Hypoglycaemia in patients with a high concentration of insulin and low concentration of C-peptide can be secondary to administration of exogenous insulin. This often results in safeguarding measures, with significant consequences for the patient and family. We report a novel case of a patient with symptomatic hypoglycaemia. Initial results suggested high insulin and low C-peptide levels, but subsequent testing revealed a pro-insulin processing disorder.
Case report: This female patient was born at term in good condition. At 12 hours of age she had postnatal collapse with hypothermia, seizures and apnoeas. MRI showed subdural haemorrhages and brain and spinal infarcts. She developed severe cerebral palsy, cortical blindness and had global developmental delay. She had severe early onset obesity and multi-drug resistant epilepsy. At 3 years of age she was started on a ketogenic diet, and was found to have episodes of hypoglycaemia. Results from a hypoglycaemia screen demonstrated hyperinsulinaemia (128 pmol/L), with C-peptide below reportable range (<94 pmol/L). This led to concerns about exogenous insulin administration and she was admitted into hospital. While in a hospital setting she was found to have high insulin immunoreactivity using the Iso-Insulin ELISA, in contrast to a lower insulin result generated using an alternative immunoassay (DiaSorin LIAISON XL), with samples taken when her blood glucose was 3 mmol/l. The C-peptide levels using the Mercodia ELISA was below reportable range as before, however C-peptide measured using an alternative immunoassay (DiaSorin LIAISON XL) was higher. In-house measurement of proinsulin and split 32,33 proinsulin were markedly above their respective upper reference limits, with a high proinsulin/insulin molar ratio, suggesting a proinsulin processing disorder. Information provided by the assay manufacturers reported substantial cross-reactivity of proinsulin in the Iso-Insulin ELISA and the LIAISON XL C-peptide immunoassay but not in the Mercodia C-peptide ELISA or the LIAISON XL insulin immunoassay
Conclusion: The laboratory investigation of this patient was complicated by the high proinsulin (and 31,32 proinsulin), causing a positive bias in insulin immunoassay but not C-peptide immunoassay (Mercodia), artefactually skewing the insulin/C-peptide molar ratio upwards. This case highlights a novel condition that generated initial high insulin and low C-peptide results that was not due to exogenous insulin administration. In complex cases, repeating testing whilst the patient is in a place of safety may help to elucidate if there is a possibility of an alternative mechanism of action, and use of different immunoassays may be required.