Fatal Insulin Overdoses: Case Report and Update on Testing Methodology

Abstract

Suicidal insulin overdoses are an under-recognized and uncommon cause of death, often relying on scene and nonspecific autopsy findings. Here, we present a case report of a fatal exogenous insulin overdose in a patient with type 1 diabetes. In our case, there were no contributory autopsy findings; however, serum analog aspart insulin levels were c. 10× the predicted therapeutic upper limit (4000, reference 6.6-55 uU/mL), which correlated with scene findings. This was specifically determined by a newly developed immunocapture liquid chromatography-tandem mass spectrometry assay, able to discriminate between various synthetic insulin analogs. Total insulin levels by immunoassay were highly elevated on the Siemens Advia Centaur, but not the Roche platforms (4741 vs. 5.2 uU/mL, respectively), showing variable sensitivity of detection within the same analog depending on assay. We discuss the prevalence and features to look for at autopsy in these types of cases. Additionally, analytical options for testing insulin levels, including new methodologies, guidance on collection of samples, as well as an outline of available historical reference range data are discussed.

Detection of intact insulin analogues in post‐mortem vitreous humour—Application to forensic toxicology casework

“…Despite some insulin‐related deaths being captured in the literature, insulin ODs are somewhat rare, misinterpreted and/or underreported 2,6–9,19–22 . In the 2 years prior to this method being developed an estimated 10 suspected intentional ODs were received by the Toxicology Section of ChemCentre's Forensic Science Laboratory.…”

“…Despite some insulin-related deaths being captured in the literature, insulin ODs are somewhat rare, misinterpreted and/or underreported. 2,[6][7][8][9][19][20][21][22] In the 2 years prior to this method being developed an estimated 10 suspected intentional ODs were received by the Toxicology Section of ChemCentre's Forensic Science Laboratory. These cases were 'identified' as suspected ODs by supporting documents, crime scene findings, suicide notes detailing insulin administration or requests from the consulting forensic pathologist.…”

“…As required for the analysis of insulin in blood/plasma, 20 3.6 ng/ml. 2,[7][8][9] With some instances, detection has been achieved up to 8 days PM, indicating some window of opportunity for detection and stability in the VH.…”

“…As required for the analysis of insulin in blood/plasma, 20 proper collection of VH samples, with immediate freezing and storage between −20°C and −80°C until analysis is imperative for subsequent detection. With appropriate collection of the VH at autopsy, transportation and sample storage for Case 1, the stability of M1 in VH was demonstrated by the successful detection 3 months after the initial receival and identification (Figure.…”

Analysis of insulin and insulin analogs from dried blood spots by means of liquid chromatography–high resolution mass spectrometry

“…On the other hand, the glucose‐lowering effects after administration to healthy humans can result in uncontrolled and life‐threatening hypoglycemia. Several case reports where insulin was purportedly and/or evidently used as toxin were published accordingly …”