Intentional overdose with insulin: prognostic factors and toxicokinetic/toxicodynamic profiles

Abstract

Introduction: Prognostic factors in intentional insulin self-poisoning and the significance of plasma insulin levels are unclear. We therefore conducted this study to investigate prognostic factors in insulin poisoning, in relation to the value of plasma insulin concentration.

Methods: We conducted a prospective study, and used logistic regression to explore prognostic factors and modelling to investigate toxicokinetic/toxicodynamic relationships.

Results: Twenty-five patients (14 female and 11 male; median [25th to 75th percentiles] age 46 [36 to 58] years) were included. On presentation, the Glasgow Coma Scale score was 9 (4 to 14) and the capillary glucose concentration was 1.4 (1.1 to 2.3) mmol/l. The plasma insulin concentration was 197 (161 to 1,566) mIU/l and the cumulative amount of glucose infused was 301 (184 to 1,056) g. Four patients developed sequelae resulting in two deaths. Delay to therapy in excess of 6 hours (odds ratio 60.0, 95% confidence interval 2.9 to 1,236.7) and ventilation for longer than 48 hours (odds ratio 28.5, 95% confidence interval 1.9 to 420.6) were identified as independent prognostic factors. Toxicokinetic/toxicodynamic relationships between glucose infusion rates and insulin concentrations fit the maximum measured glucose infusion rate (Emax) model (Emax 29.5 [17.5 to 41.1] g/hour, concentration associated with the half-maximum glucose infusion rate [EC50] 46 [35 to 161] mIU/l, and R2 range 0.70 to 0.98; n = 6).

Conclusion: Intentional insulin overdose is rare. Assessment of prognosis relies on clinical findings. The observed plasma insulin EC50 is 46 mIU/l.

Figure 1

MRI findings in hypoglycemia-related encephalopathy. Cerebral fast fluid-attenuated inversion recovery magnetic resonance imaging (MRI) in a patient suffering from a severe hypoglycaemia-related encephalopathy on day 3 after deliberate insulin self-poisoning. The disseminated hypersignals of the cerebral gray matter (plain arrows) disappeared on day 30, whereas neurological impairments persisted.

Figure 2

Delay from insulin self-injection to pre-hospital management versus duration of ICU stay. Shown is the correlation between the delay from insulin self-injection to pre-hospital management and the duration of intensive care unit (ICU) stay in 22 cases of insulin self-poisoning.

Figure 3

Duration of glucose infusion versus self-injected insulin dose. Shown is the correlation between the duration of glucose infusion and the self-injected insulin dose in 25 cases of insulin self-poisoning.

Figure 4

Plasma toxicokinetics of insulin in six severely insulin-poisoned patients.

Figure 5

TK/TD relation between glucose infusion rate and plasma insulin concentrations. Shown are the toxicokinetic/toxicodynamic (TK/TD) relationships between glucose infusion rate and plasma insulin concentrations in six acutely insulin-poisoned patients.