title: Intentional overdose with insulin: prognostic factors and toxicokinetic/toxicodynamic profiles.
abstract: BACKGROUND
  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).
  
  
  CONCLUSIONS
  Intentional insulin overdose is rare. Assessment of prognosis relies on clinical findings. The observed plasma insulin EC50 is 46 mIU/l.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Réanimation Médicale et Toxicologique, INSERM U705, CNRS, UMR 7157, Université Paris 7, 2 Rue Ambroise Paré, 75010, Paris, France. bruno.megarbane@lrb.aphp.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Mégarbane
authors.forename: Nicolas
authors.initials: N
authors.lastname: Deye
authors.forename: Vanessa
authors.initials: V
authors.lastname: Bloch
authors.forename: Romain
authors.initials: R
authors.lastname: Sonneville
authors.forename: Corinne
authors.initials: C
authors.lastname: Collet
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Launay
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Baud
mesh_terms: D000328:Adult; D062787:Drug Overdose; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000493:pharmacokinetics / Q000506:poisoning*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D016728:Self-Injurious Behavior / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy
chemical_list: D007328:Insulin