Insulin Overdose Research Articles

Insulin-Related Suicides-3 Cases.

Insulin is a pancreas-produced hormone, which is essential for normal life. In persons with diabetes, who lack sufficient production of endogenous insulin, the availability of exogenously-produced and administered insulin represents an extremely valuable, life-preserving medical advancement. Unfortunately, as with many other medications, overdosage with insulin can and does occur, sometimes in an intentional suicidal manner. Another possible insulin-related suicidal action involves the intentional cessation of insulin therapy by someone who relies on insulin for survival. In this case series, we present 3 cases of insulin-related suicides, including two related to intentional insulin overdose and one where a known diabetic purposefully stopped taking insulin in order to commit suicide.

The Application of Online and Offline Hybrid Mode in Pharmacology Laboratory Teaching: A Case Study of the "Insulin Overdose Response and Rescue Experiment"

Pharmacology, as a core course for Pharmaceutical Engineering students, is a basic medical course, which is usually composed of "theoretical courses" and "experimental courses". Pharmacology experiments are a visual validation of the theoretical knowledge learned in the classroom. Through practical operation and observation of experimental results, we can have a deeper understanding of the concepts of drug mechanism of action, pharmacodynamics and pharmacokinetics. In order to meet diversified learning needs, optimize the utilization of teaching resources, and promote independent learning and collaboration ability, online and offline blended teaching is the mainstream teaching mode in the "Internet+" era, which provides a suitable environment and starting point for the ideological and political construction of the curriculum and the practice of the goal of cultivating people with virtue. It is especially necessary to conduct online and offline teaching methods for pharmacology experiments. This article uses the example of "insulin overdose reaction and rescue experiment" to demonstrate the blended teaching mode of online and offline teaching. It attempts to start with the necessity of strengthening students' innovative practical ability cultivation in pharmacology experiment teaching, analyze the problems exposed in current pharmacology experiment teaching in detail, and propose optimization measures such as effectively integrating teaching resources, designing different experimental projects, innovating experiment teaching mode, and emphasizing students' innovative practice based on the mastered situation, in order to provide reference for the blended teaching mode of pharmacology experiment online and offline.

Intentional Insulin Overdose and Depression in Subjects with and Without Diabetes Mellitus: A Commentary.

Insulin is an essential medication for people with type 1 diabetes mellitus and for some people with type 2 diabetes. Interestingly, insulin abuse has been reported as a mode of suicide, not only among people with diabetes, but also among their relatives, and among medical and paramedical personnel who have access to insulin. The aim of the present commentary was to raise awareness of potential depression-related intentional insulin overdose and its complications, as well as of the diagnosis and treatment of this entity. Insulin overdose may lead to severe and prolonged hypoglycemia, hypoglycemic coma, and death. Moreover, hypokalemia, hypomagnesemia, hypophosphatemia, and elevated liver enzymes are common. Insulin overdose should be suspected among people with diabetes in case of unexplained prolonged hypoglycemia and among people without diabetes who exhibit hypoglycemia and may have access to diabetic medications. The ratio of insulin to C-peptide helps distinguish exogenous insulin administration from endogenous secretion. The cornerstone of therapy is prompt administration of concentrated glucose infusions for days with simultaneous oral intake, when possible, and intense glucose monitoring to prevent hypoglycemia. Moreover, monitoring of serum electrolyte levels is recommended. Finally, psychiatric evaluation aiming at early identification of depression and suicidality is of paramount importance.

A retrospective study of 29 fatal cases of insulin overdose

PurposeTo summarize recent cases of fatal insulin poisoning both domestically and internationally, thereby offering valuable insights for the forensic identification of insulin overdose cases. MethodsLiterature published since 2000 on fatal insulin overdose were systematically searched and screened. Data encompassing variables such as year, age, sex, cause of death, scene conditions, occupations, medical histories of victims and perpetrators, autopsy timing, dosage and administration methods, forensic pathology, and toxicological analysis, were compiled for rigorous statistical analysis. ResultsAmong the 29 fatal cases of insulin poisoning, suicides and homicides accounted for 55.2 % and 41.4 %, respectively. Precisely 34.5 % of victims or perpetrators were associated with the medical industry, 27.6 % had diabetes, and 24.1 % had mental illnesses such as depression. Intravenous injection resulted in quicker death than did subcutaneous injection. In some cases, immunohistochemical staining of insulin and protamine at injection sites yielded positive results. The average molar ratio of insulin to C-peptide in post-mortem blood was 13.76 ± 5.167, indicating a significant diagnostic value for insulin poisoning. ConclusionAssessment of cases of fatal insulin overdose should be thorough, incorporating case investigation, scene examination, medical records review, autopsy findings, pathological examinations, and laboratory tests, alongside considering the condition of the body and timing of death autopsy. Using mass spectrometry to detect insulin proves valuable, particularly in cases of poor body preservation.

Intentional insulin overdose in a type 2 diabetic patient and depressive disorder

Intentional insulin overdose in a type 2 diabetic patient and depressive disorder

Glucose-Driven Droplet Formation in Complexes of a Supramolecular Peptide and Therapeutic Protein.

Biology achieves remarkable function through processes arising from spontaneous or transient liquid-liquid phase separation (LLPS) of proteins and other biomolecules. While polymeric systems can achieve similar phenomena through simple or complex coacervation, LLPS with supramolecular materials has been less commonly shown. Functional applications for synthetic LLPS systems are an expanding area of emphasis, with particular focus on capturing the transient and dynamic state of these structures for use in biomedicine. Here, a net-cationic supramolecular peptide amphiphile building block with a glucose-binding motif is shown that forms LLPS structures when combined with a net-negatively charged therapeutic protein, dasiglucagon, in the presence of glucose. The droplets that arise are dynamic and coalesce quickly. However, the interface can be stabilized by addition of a 4-arm star PEG. When the stabilized droplets formed in glucose are transferred to a bulk phase containing different glucose concentrations, their stability and lifetime decrease according to bulk glucose concentration. This glucose-dependent formation translates into an accelerated release of dasiglucagon in the absence of glucose; this hormone analogue itself functions therapeutically to correct low blood glucose (hypoglycemia). These droplets also offer function in mitigating the most severe effects of hypoglycemia arising from an insulin overdose through delivery of dasiglucagon in a mouse model of hypoglycemic rescue. Accordingly, this approach to use complexation between a supramolecular peptide amphiphile and a therapeutic protein in the presence of glucose leads to droplets with functional potential to dissipate for the release of the therapeutic material in low blood glucose environments.

Forensic Hypoglycaemia & Neuroglycopenia — A Clinical Legal Social Endocrinology Challenge for 2024, Forensic Law in Hypoglycaemia 4

Forensic Hypoglycaemia & Neuroglycopenia — A Clinical Legal Social Endocrinology Challenge for 2024, Forensic Law in Hypoglycaemia 4

Biochemical Toxicological Study of Insulin Overdose in Rats: A Forensic Perspective.

Due to nonspecific pathological changes and the rapid degradation of insulin in postmortem blood samples, the identification of the cause of death during insulin overdose has always been a difficulty in forensic medicine. At present, there is a lack of studies on the toxicological changes and related mechanisms of an insulin overdose, and the specific molecular markers of insulin overdose are still unclear. In this study, an animal model of insulin overdose was established, and 24 SD rats were randomly divided into a control group, insulin overdose group, and a recovery group (n = 8). We detected the biochemical changes and analyzed the toxicological mechanism of an insulin overdose. The results showed that after insulin overdose, the rats developed irregular convulsions, Eclampsia, Opisthotonos, and other symptoms. The levels of glucose, glycogen, and C-peptide in the body decreased significantly, while the levels of lactate, insulin, and glucagon increased significantly. The decrease in plasma K+ was accompanied by the increase in skeletal muscle K+. The PI3K-AKT signaling pathway was significantly activated in skeletal muscle, and the translocation of GLUT4/Na+-K+-ATPase to sarcolemma was significantly increased. Rare glycogenic hepatopathy occurred in the recovery group after insulin overdose. Our study showed that insulin overdose also plays a role in skeletal muscle cells, mainly through the PI3K-Akt signaling pathway. Therefore, the detection of signaling pathway proteins of the skeletal muscle cell membrane GLUT4 and Na+-K+-ATPase has a certain auxiliary diagnostic value for forensic insulin overdose identification. Glycogen detection in the liver and skeletal muscle is important for the diagnosis of insulin overdose, but it still needs to be differentiated from other causes of death. Skeletal muscle has great potential for insulin detection, and the ratio of insulin to the C-peptide (I:C) can determine whether an exogenous insulin overdose is present.

Undetected Exogenous Insulin Administration in a Child: Assessment of Assay Limitations and Impact on the Practice of Laboratory Medicine

Abstract Introduction/Objective The development of new synthetic insulin analogues over the past few decades has significantly impacted the management of hypoglycemia. However, accurately measuring these analogues presents challenges due to variable cross-reactivity with many insulin assays. Failure to consider cross-reactivity may lead to the misdiagnosis of exogenous insulin administration. Methods/Case Report A 13-year-old female with a history of type 1 DM was presented to an outside hospital emergency department with symptoms indicative of hypoglycemia. Multiple child protective services (CPS) referrals are noted. The patient had experienced several episodes of hypoglycemia over the prior week with blood glucose in the 30-40 mg/dL range. There were no associated symptoms of diarrhea, emesis, or fatigue. The patient was transferred to a pediatric hospital were preliminary investigations indicated abnormally low blood glucose levels with low insulin and C-peptide levels. Further evaluation was initiated to determine the underlying cause of these episodes and to ensure appropriate adjustments in insulin dosing and regimen. Initially, the Elecsys insulin assay (Roche Diagnostics) was utilized to quantify insulin levels which shows a low cross-reactivity for insulin lispro and glargine. To validate the hypothesis of an undetected exogenous insulin overdose, blood samples were sent to another laboratory employing The Advia Centaur insulin assay (Siemens) which exhibits a higher cross-reactivity for insulin lispro and glargine (89%-143%, respectively), indicating a higher recognition and measurement sensitivity for these insulin analogues. The analysis using this assay revealed significantly elevated insulin levels, corroborating the presence of an insulin overdose. The sample at the time of presentation at the outside hospital was confirmed to be 434.1 mU/L. A sample collected 17 hours later had an insulin level of 23.5 mU/L. Results (if a Case Study enter NA) NA Conclusion This case study highlights the critical issue of undetected insulin overdose in a child and emphasizes the limitations of the initial insulin assay employed. Improving assay sensitivity and reliability will enhance patient care and safety. This case study reminds clinicians and laboratory professionals of the need for ongoing quality assurance and vigilance in their practices.

Potential biomarkers in hypoglycemic brain injury.

Oxidative stress is a major underlying mechanism in hypoglycemic brain injury. Several oxidative stress-related proteins were identified through previous proteomics and literature review. The aim of the present study was to evaluate the potential of these proteins as biomarkers in hypoglycemic brain injury. Forty male Sprague Dawley rats were randomly and equally divided into four groups: control, acute hypoglycemia, hypoglycemia resuscitation 24h, and hypoglycemia resuscitation 7days. The hypoglycemic brain injury rat model was successfully constructed according to the Auer model. Real-time fluorescent quantitative polymerase chain reaction, western blot analysis, and immunohistochemical staining were used to quantify the expression of oxidative stress-related proteins. We also verified the expression level of selected protein in the brain samples of fatal insulin overdose cases. The expression of oxidative stress-related proteins PEX1/5/12 was down-regulated in hypoglycemic brain injury (P < 0.05), while the expressions of DJ-1 and NDRG1 were up-regulated (P < 0.05). Compared with the control group, the serum oxidative stress indexes SOD and MDA in the acute hypoglycemia group were significantly different (P < 0.01). The expressions of DJ-1 and NDRG1 in the hippocampus, cortex, and hypothalamus of rats were increased (P < 0.05). The expressions of DJ-1 and NDRG1 proteins in the cortex of the autopsy samples of insulin overdose were increased (P < 0.05). Oxidative stress-related proteins showed potential value as specific molecular markers in hypoglycemic brain injury, but further confirmatory studies are needed.

Intentional overdose of glargine insulin: Determination of the parent compound in postmortem blood by LC‐HRMS

Insulin glargine is a long-acting insulin analog that is converted after enzymatic cleavage of the arginine pair of the β-chain into its main metabolite M1 (21A -Gly-insulin), which is responsible for the hypoglycemic activity. In all the overdose cases described in the literature, only M1 concentrations have been reported, whereas insulin glargine was always absent or below the limit of quantitation. In this study, we present a case of suicide of a young nurse by injection of insulin glargine in which the parent molecule was found at a toxic concentration in blood. The determination and the discrimination of insulin glargine from human insulin and other synthetic analogs in the blood specimen were performed by liquid chromatography coupled to high-resolution mass spectrometry (Waters XEVO G2-XS QToF) and extraction after precipitation in the presence of bovine insulin (internal standard), with a mixture of acetonitrile/methanol +1% formic acid followed by purification on solid phase extraction cartridges C18. Glargine insulin tested highly positive in the blood with a concentration of 1.06 mg/L. Due to the difficulty in obtaining a M1 pure standard, the metabolite could not be dosed. This unique presence of the parent molecule, reported for the first time, can be explained by inter-individual variability in the rate of conversion to metabolite. Intravenous injection versus subcutaneous injection can also explain the presence of insulin glargine. Finally, the dose injected may have been so high that saturation of the proteolytic enzymes responsible for conversion to M1 should have occurred.

Effects of somatostatin receptor type 2 antagonism during insulin-induced hypoglycaemia in male rats with prediabetes.

To examine if glucagon counterregulatory defects exist in a rat model of prediabetes (pre-T2D) and toassess if a selective somatostatin receptor 2 antagonist (SSTR2a), ZT-01, enhances the glucagon response to insulin-induced hypoglycaemia. Hyperglycaemia was induced in 8- to 9-week-old male, Sprague-Dawley rats via 7 weeks of high-fat diet followed by a single, low-dose intraperitoneal injection of streptozotocin (30 mg/kg). After 2 weeks of basal insulin therapy (0-4U/d insulin glargine, administered subcutaneously [SC]) to facilitate partial glycaemic recovery and a pre-T2D phenotype, n=17 pre-T2D and n=10 normal chow-fed control rats underwent the first of two hypoglycaemic treatment-crossover experiments, separated by a 1-week washout period. On each experimental day, SSTR2a (3mg/kg ZT-01, SC) or vehicle was administered 1hour prior to insulin-induced hypoglycaemia (insulin aspart, 6U/kg, SC). Glucagon counterregulation was marginally reduced with the induction of pre-T2D. Treatment with SSTR2a raised peak plasma glucagon levels and glucagon area under the curve before and after insulin overdose in both and pre-T2D rats. Blood glucose concentration was elevated by 30 minutes after SSTR2a treatment in pre-T2D rats, and hypoglycaemia onset (≤3.9 mmol/L) was delayed by 15 ± 12 minutes compared with vehicle (P < 0.001), despite similar glucose nadirs in the two treatment groups (1.4 ± 0.3 mmol/L). SSTR2a treatment had no effect on blood glucose levels in the control group or on the hypoglycaemia-induced decline in plasma C-peptide levels in either group. Treatment with an SSTR2a increases glucagon responsiveness and delays the onset of insulin-induced hypoglycaemia in this rat model of pre-T2D where only a modest deficiency in glucagon counterregulation exists.

Identification, measurement, and evaluation of blood concentrations of insulin glargine and insulin lispro by UPLC–MS–MS in a dead body suspected of insulin overdose

Insulin preparations, which are drug treatments for diabetes, cause fatal hypoglycemia when an overdose is administered. Cases of homicide and suicide using these preparations have been reported and are of great forensic interest. However, there are few reports assessing the postmortem concentration of insulin preparations, and it is often difficult to determine the cause of death. In the present study, we report a case of a suspected insulin glargine and insulin lispro overdose for suicide. A woman in her 30s had a history of mental illness and diabetes. The day before her death, she reported to her boyfriend that she had taken large doses of insulin preparations and prescription drugs. An autopsy revealed no fatal injuries or lesions. Drug screening tests revealed several prescription drugs, none of which showed toxic concentrations. Analysis using LC-MS/MS detected insulin glargine in the peripheral and cardiac blood at 429 μU/mL and 1362 μU/mL, respectively, whereas insulin lispro was detected in both the peripheral and cardiac blood at levels below the lower limit of quantification (LLOQ; <50 μU/mL). The cause of death was considered likely to be hypoglycemia caused by an overdose of insulin glargine. Insulin glargine is rapidly metabolized after subcutaneous administration and is rarely detected in the blood when used at therapeutic doses. There are no other reports on the quantification of insulin glargine parent compounds in postmortem samples, and this case provides important data on postmortem blood concentrations of insulin glargine intoxication.

Neuropathology of hypoglycaemic brain injury

It has long been recognised that the neurobiochemistry of hypoglycaemic brain injury differs markedly from that of hypoxic-ischaemic brain injury. The neuropathology of hypoglycaemic brain injury may also be distinctive. Such distinctive changes, aiding discrimination from hypoxic-ischaemic brain injury, are though commonly absent even in cases of biochemically proved profound hypoglycaemia. Neuronal depletion or necrosis may only be observed in 29% of cases. Autopsy findings in cases of suspected insulin overdose or overdose from oral hypoglycaemic agents may not uncommonly be non-specific. It should be appreciated that neuronal death due to hypoglycaemic brain injury may only intervene after a sustained period of blood glucose levels below 1 mmol/l and after EEG tracing has become silent. The neuropathology of hypoglycaemic brain injury may also be modified by concurrent hypoxia resulting from concomitant cardiorespiratory depression and by seizures. Atypical presentations also include strikingly asymmetric involvement of the cerebral hemispheres. It should further be appreciated that the postmortem findings in cases of hypoglycaemic brain injury may include neurogenic pulmonary oedema (seen in over half of cases). The majority of cases of suspected hypoglycaemic drug overdose represent suicides (66%) with the remainder representing accidental poisoning and homicide, with insulin the most commonly drug implicated (around 95%). In paediatric practice, hypoglycaemia frequently occurs in newborn infants who previously suffered asphyxia, offspring of diabetic mothers and with a low birth weight for gestational age. The immature brain is relatively resistant to the damaging effects of hypoglycaemia. Hypoglycaemia in this age group combined with hypoxic-ischaemic injury, in particular asphyxia, may though be more deleterious to the immature brain than either condition alone.

Suicide and attempted suicide by insulin: A systematic review

Background: Intentional insulin overdose either in people with diabetes or without can be used to attempt suicide. Massive insulin administration may result in coma and unexplained hypoglycemia. In this study, we aim at reviewing the demographic data of suicidal cases, the relation of psychiatric illness to dying by suicide and attempting suicide using insulin, route of insulin administration and outcome, post-mortem findings in suicide by insulin and collaborative evidence, initial presentation, blood glucose level and complications in attempting suicide cases. Methods: PubMed, Web of Science, and Scopus databases were searched on October 4, 2021, using a comprehensive strategy review. The following search terms were applied: (Insulin) AND (toxicity OR overdose OR toxicology OR poisoning OR intoxication) AND (Suicide OR attempted suicide OR Self-harm OR Self harm). The search strategy was set based on PRISMA guideline; 11 papers were eligible for inclusion and additional 23 studies were added from the citation search. All English articles related to suicide and attempted suicide using insulin were included and no specific timeline or filter was used. Any non-English article and accidental or homicidal cases were excluded from the review. Results: The analysis included 179 victims, aged between 13 to 76 years with male predominance and people with diabetes, especially T1DM, having higher prevalence, with subcutaneous injection being the most common route of administration. In addition, psychiatric illnesses and multiple suicide attempts were identified in many cases besides the use of insulin in a combination with other medications. Conclusions: Dying by suicide using insulin is uncommon, however, as diabetes mellitus prevalence increases worldwide, it is expected that intentional insulin overdose will also increase. Furthermore, psychiatric illnesses and easy access to insulin are important factors that should be put into consideration.

Evaluation of a Digital Health Tool for Titration of Basal Insulin in People With Type 2 Diabetes: Rationale and Design of a Randomized Controlled Trial.

Optimal insulin titration is essential in helping people with type 2 diabetes mellitus (T2DM) to achieve adequate glycemic control. Barriers of people with diabetes to implementation of titration include lack of self-efficiency and self-management skills, increased diabetes-related distress, low treatment satisfaction, poor well-being, as well as concerns about hypoglycemia and insulin overdose. My Dose Coach is a digital health tool for optimizing titration of basal insulin that combines a smartphone app for patients with T2DM and a Web portal for healthcare professionals. This is a prospective, open-label, multicenter, randomized controlled parallel study conducted in approximately 50 centers in Germany that are specialized in the treatment of diabetes. Patients in the intervention group will use the titration app and will be registered on the Web portal by their treating physician. Control group patients will continue their current basal insulin titration without using the app. The primary outcome is the mean change in HbA1c levels at the 12-week follow-up. The secondary outcome measures include patient-reported outcomes such as diabetes-related distress, self-management, empowerment, self-efficacy, treatment satisfaction, and psychological well-being as well as fasting blood glucose values. This digital health tool has been previously implemented in several independent pilot studies. The findings from this multicenter randomized controlled trial can provide further evidence supporting the effectiveness of this tool in patients with T2DM and serve as a basis for its clinical integration. German Register for Clinical Studies-DRKS-ID: DRKS00024861.

Massive insulin overdose in a dog requiring extended observation and management

Massive insulin overdose in a dog requiring extended observation and management

Insulin and Oral Hypoglycemic Drug Overdose in Post-Mortem Investigations: A Literature Review.

Background and Objectives: Insulin and oral hypoglycemic agents are drugs widely used in the world population due to their therapeutic effects on diabetes mellitus. Despite these benefits, they can also cause accidental or voluntary drug overdose. This review aims to evaluate post-mortem investigations in cases of suspected hypoglycemic drug overdose. Materials and Methods: We performed a comprehensive search using the Preferred Reporting Items for Systematic Review (PRISMA) standards; we systematically searched the PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EM-BASE) databases from the point of database inception until August 2022. The following inclusion criteria were used: (1) original research articles, (2) reviews and mini-reviews, (3) case reports/series, (4) and only papers written in English. Results: Thirty-three scientific papers, including original research articles, case reports, and case series, fulfilled the inclusion criteria. A total of 109 cases of insulin or hypoglycemic drug overdose were found. There were 71 cases of suicide (65%), 25 cases of accidental poisoning (23%), and 13 cases of homicide (12%). The most commonly used drug was insulin (95.4%). Autopsy and post-mortem examinations were performed in 84 cases, while toxicological investigations were performed in 79 cases. The most common gross findings in the autopsy were pulmonary edema (55.7%) and congestion (41.8%), while the most common histological finding was neuronal depletion or necrosis (29.1%). Conclusions: In the suspicion of death from insulin or overdose from oral hypoglycemic agents, autopsy findings may be nonspecific, and the search for injection marks can be positive at the external examination. Significant post-mortal alterations can interest biological samples and an early autopsy investigation is recommended.

Difficulties in interpreting a therapeutic blood concentration of insulin lispro in postmortem blood: A case report

Illustrate the complexity of interpreting a postmortem therapeutic blood concentration of insulin in a probable case of suicide using insulin lispro. The identification and quantification of insulin and its analogues continues to be a challenge in the field of forensic toxicology. Its use is not always limited to the treatment of diabetes but is often used illicitly. Numerous cases of suicides and suicide attempts have been described in the literature and nevertheless, this number still seems to be underestimated due to both the inability of laboratories to identify and discriminate between synthetic analogues of human insulin and due to the chemical instability of insulin especially in postmortem samples. Our case concerns a 63-year-old man who was found dead by his brother at home. Three empty Humalog® insulin pens and a letter mentioning his suicide intention were found next to his bed. At the request of the prosecutor, an external examination of the corpse was performed and revealed only an asphyxial syndrome not specific to a cause of death. The presence of a blood glucose monitoring device on the right arm was also observed, suggesting that the subject was diabetic. External examination was unable to determine the exact cause of death. For this reason, the pathologist was oriented on a toxic death. In order to proceed to further toxicological investigations, peripheral blood, urine and hair samples were collected. It is important to underline that, due to the long period elapsed between the external examination and the pathologist's conclusion (enabling the initiation of the toxicological analysis) and due to administrative delays, insulin testing was performed only 9 months after the samples collection. Blood and urine samples were stored at +4 °C until analysis. The identification and quantification of insulin lispro was performed in the postmortem blood after precipitation in the presence of bovine insulin (internal standard), by a mixture of acetonitrile/methanol (ratio 1:1) followed by a step of ultrafiltration using Amicon® centrifugal filters (3 kDa) and a step of immunopurification using Iso-Insulin ELISA coated wells. The analysis was performed with a UHPLC- Q-TOF (XEVO G2-XS). Detection of insulin lispro was performed using the precursor molecular ion m/z 1162.543 (charge state 5 +). Since human insulin and insulin lispro share the exact same molecular mass (5807 Da), discrimination cannot be made using the multi-charged molecular ion. The distinction is based on fragment m/z 217 which is present only in insulin lispro spectrum. Toxicological tests performed on the blood sample did not reveal any xenobiotic of toxic nature. Insulin lispro was detected in the femoral blood sample at 1,1 ng/mL, whereas human insulin was not detected. Following the administration of a therapeutic dose of 0.2 U/kg of insulin Humalog ®, a maximum concentration of 1.66 ± 0.42 ng/mL is achieved. Consequently, the concentration found in our case was therapeutic. Nevertheless, given the unstable nature of insulin, especially in postmortem blood, it is not possible to exclude that death was caused by an insulin overdose. The long period between collection and analysis (9 months), the hemolyzed state of the blood, the storage of the sample in unsuitable tubes and the fact that we were able to detect even small concentrations of insulin lispro suggest that the concentration at the time of death was much higher. The pathologist concluded that the cause of death was probably an overdose of insulin lispro. This case highlights that the interpretation of a postmortem insulin concentration requires a complex approach involving the assessment of many factors such as the subject's medical history and the time, mode and state of preservation of the sample.

Characteristics of fatal insulin overdoses

This study was undertaken to review fatal cases of insulin overdose in South Australia (SA) over a 20-year period to assess rates and characteristics of insulin-related deaths among insulin-dependent diabetics and non-diabetics for all manners of death. Records from the National Coronial Information System (NCIS) and Forensic Science SA (FSSA) were searched for all cases of fatal insulin overdose in South Australia (SA) between 2000 and 2019. Collected variables included age, sex, cause of death, scene findings, manner of death, decedent medical and personal histories, biochemistry, toxicology, histopathology, and autopsy findings. Statistical analyses were performed using R (version 4.1.2). Forty cases of insulin overdose were identified in SA between 2000 and 2019. Twenty-nine cases (72.5%) were suicides, with the remaining cases classified as accidental or undetermined intent. Thirteen of the 22 insulin-dependent diabetics (59%) had a history of depression, 10 of whom had previously demonstrated suicidal ideation. The current study has shown that suicides using insulin among insulin-dependent diabetics are equally as prevalent, if not more so than fatal accidental insulin overdoses. This can largely be attributed to insulin-dependent diabetic access to a potentially lethal substance. Suicide prevention strategies should focus on insulin-dependent diabetics with a history of depression, particularly for those with access to rapid-acting insulin.