Insulin and the law

Abstract

Hypoglycaemia, if it can be proved, may be used as a defence against almost any criminal charge provided it can be established that the perpetrator was in a state of neuroglycopenic (hypoglycaemic) automatism at the time of the offence. Hypoglycaemia produced by exogenous insulin can also be used as a suicidal or homicidal weapon. This paper discusses some of the pitfalls confronting the investigator of suspected insulin misuse including problems arising from the increasing prevalence of insulin analogues and the unreliability of immunoassays for their detection and measurement in the forensic context.

Introduction

Insulin is probably the most familiar legal drug or medicine mentioned in law courts. It is so because insulin causes hypoglycaemia and this can, provided it is proved to have been present at the time, be used as defence against almost any criminal charge ranging from shop-lifting to murder. It can also, much more rarely, be used as a weapon.

Insulin can be used to attempt suicide but is rarely successful because the perpetrator/victim is usually discovered and resuscitated before irreversible brain damage has occurred. This usually takes some 6 h or more to appear ¹ and is probably due to the release of neurotoxic amino acids in the brain rather than, as is widely believed, fuel deprivation.

When death does occur from insulin-induced hypoglycaemia, it is important to distinguish suicide from unintentional or ‘natural’ death as in the ‘dead-in-bed-syndrome’. ²

Case report

A young person with diabetes, with no history of depression, was found dead in her bed. The coroner was informed and ordered an autopsy. The pathologist found no anatomical cause for her death and requested an insulin assay on postmortem blood collected from a peripheral blood vessel. The result, circa 1000 pmol/L, was some 3–4 times the level expected with a therapeutic dose of insulin. The pathologist intended to describe the young woman’s death as due to hypoglycaemia caused by an excessive dose of insulin and the coroner, when informed, was mindful to attribute her death to suicide.

But first, he consulted the girl’s parents who sought advice from an expert. Enquiries established that their daughter was on determir (Levermir®) – an insulin analogue – rather than on (human type) insulin as had been supposed. Because determir binds reversibly to albumin making it temporarily unavailable to the tissues, its total plasma concentration, after normal therapeutic doses, is some three to –six times higher than with human type insulin given in similar doses. The concentration found in her postmortem serum was therefore what might have been expected had she taken her medication normally. The coroner recorded her death as due to natural causes, i.e. dead-in-bed-syndrome, which is normally two to four times more common in males than females, thereby reassuring her parents and removing any stigma of suicide.

This case illustrates the importance of referring to insulin analogues by their proper name rather than as insulin – especially since the majority of insulin immunoassay kits currently in use are calibrated to measure human insulin and not its analogues: some of which are underestimated – or not detected at all – while others are over-estimated. ³ Specifying what is being sought is especially important in cases of suspected illicit insulin usage such as its misuse as an anabolic agent in sports, in horse-doping and, of course, homicide. It is also the reason why, whenever the reliability of an insulin immunoassay is in contention – as is often the case in medico-legal cases involving insulin – the sample should be subjected to liquid chromatography/mass-spectrometric (LC/MS) assay before the result is considered definitive.

Factitious hypoglycaemia

Homicidal use of insulin is an example of deception-motivated insulin-induced hypoglycaemia of which classical factitious hypoglycaemia is the commonest. Features common to classical factitious and homicidal insulin misuse are: the clinical history is often unavailable, unreliable or deliberately misleading; both can be caused by insulin analogues as well as by insulin, and laboratory data in support of the diagnosis must be ‘fool-proof’ if serious errors are to be avoided.

The use of insulin as a murder weapon is rare and the number of cases reported in detail in the biomedical literature is vanishingly small, decreasing from a peak of 34 cases in the decade 1990–1999 to less than five in the period 2010–2015.

Insulin is the third most common cause of adverse drug events occurring in hospitals but accounted for only 11% of the murders resulting from deliberate injection of noxious substances by health-care workers reviewed by Yorker et al. ⁴

Insulin poisoning in a hospital or nursing home environment is extremely difficult to establish unless appropriate investigations are undertaken whenever hypoglycaemia is detected by point-of-care testing (POCT) in anyone who is not receiving insulin or sulphonylureas therapeutically.

It is recommended that a venous sample of blood is collected immediately whenever a ‘POCT diagnosis’ of hypoglycaemia is made (i.e. POCT glucose concentration less than 3 mmol/L) before treatment with glucose or glucagon is given, unless the patient is known to be on insulin or sulphonylurea therapy.

Because POCT cannot be relied upon for diagnosing hypoglycaemia, the venous sample should immediately be analysed in the laboratory for its glucose concentration and a plasma sample prepared from it for storage at −20℃. This can later be analysed for beta-hydroxybutyrate and its insulin, C-peptide, proinsulin, growth hormone and cortisol concentration by immunoassay should hypoglycaemia be confirmed in the laboratory and no satisfactory explanation for it found.

Only if immunoreactive insulin is inappropriately high need the sample be analysed for insulin analogues (and sulphonylureas) by LC/MS. ⁵ It is a wise precaution to collect venous blood for the next few days to monitor progress and for evidence of misconduct should it come to trial.

Investigation of unexplained hypoglycaemia is especially relevant in elderly sick patients, in whom it is common. They are also the commonest victims of malicious insulin administration in hospitals and nursing homes. Unexplained hypoglycaemia also occurs as a rare complication of many drugs not ordinarily associated with alterations in glucose homeostasis as well as in patients suffering from urinary tract infections and other causes of septicaemia in which hyperglycaemia is much more common.

Many hospitals have protocols describing what should be done in any case of unexpected POCT hypoglycaemia. They specify that a venous sample of blood should always be collected before treatment with glucose or glucagon is given. Such protocols are often/usually ignored leading to untold misery in some cases of suspected insulin misuse. ⁶