insulin-glargine and Drug-Overdose

Reports of intentional massive overdoses of insulin are infrequent. A review of the literature revealed no reports of overdose attempts with either insulin glargine or insulin aspart. We report the case of a 33-year-old woman without diabetes mellitus who intentionally injected herself with an overdose of both products, which belonged to her husband. She arrived at the emergency department 15 hours after her suicide attempt, which took place the night before. Her husband had checked her blood glucose level throughout the night and had given her high-carbohydrate drinks and foods. The patient had a history of obsessive-compulsive disorder, major depression, and numerous suicide attempts. She recovered from the resulting hypoglycemia after 40 hours of dextrose infusion and was transferred to a mental health facility. The main danger associated with insulin overdose is the resultant hypoglycemia and its effects on the central nervous system; hypokalemia, hypophosphatemia, and hypomagnesemia also can develop with excess insulin administration. Dextrose infusion, with liberal oral intake when possible, and monitoring for electrolyte changes, making adjustments as needed, are recommended for the treatment of intentional insulin overdose.

Topics: Adult; Animals; Blood Glucose; Drug Overdose; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting; Suicide, Attempted; Treatment Outcome

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.

Topics: Blood Glucose; Chromatography, Liquid; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Tandem Mass Spectrometry

Topics: Animals; Cattle; Chromatography, Liquid; Drug Overdose; Humans; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Long-Acting

The application of proteomic techniques to forensic science widens the range of analytical capabilities available to forensic laboratories when answering complex toxicology problems. Currently, these techniques are underutilised in post-mortem toxicology because of the historic focus on smaller (<1,000 amu) drug molecules. Definitive confirmation of an insulin overdose by analysis of post-mortem biological matrices is rare and challenging, however can assist coronial investigations pertaining to accidental or intentional overdoses in both diabetic and nondiabetic populations. A semiautomated micro-solid phase extraction paired with mass spectrometry-based insulin methodology was developed and validated for routine use in a Forensic Coronial Toxicology Laboratory. This resulting work reports the first Australian cases where synthetic insulins were confirmed by mass spectrometry in the vitreous humour of Type 1 diabetics who intentionally or accidentally overdosed on their prescription medication glargine and aspart. The detection of glargine M1 in Case 1, aspart in Case 2 and glargine M1 was indicated in Case 3. This paper highlights advancements in forensic coronial toxicology and the promising potential of proteomic analysis in a forensic context.

Topics: Australia; Autopsy; Diabetes Mellitus, Type 1; Drug Overdose; Forensic Toxicology; Humans; Hypoglycemic Agents; Insulin; Insulin Aspart; Insulin Glargine; Male; Mass Spectrometry; Pilot Projects; Proteomics; Solid Phase Extraction; Vitreous Body

The analysis of biological specimens collected at autopsy for the presence of exogenous insulin(s) is of special interest in select death investigations as they may be suspected in the cause of a death. Technical challenges include the limited stability of insulin, and the forensic requirement of differentiating endogenous insulin from pharmaceutical analogs. A novel method was developed for the detection and quantification of human insulin, Glulisine, Lispro, Aspart, Glargine and Detemir in vitreous fluid. An immunoaffinity extraction procedure is performed followed by separation of the insulin α- and β-chains. Liquid chromatography tandem mass spectrometry analysis of the β-chain allows for the unequivocal identification of each insulin analog. The analytical measurement range for each insulin was 0.5-25 ng/mL. The method was evaluated for accuracy, precision, carryover, interferences and stability. Eight vitreous fluid samples collected from cases where untoward insulin use was suspected were subjected to analysis. Positive results were obtained from three samples, and a detailed case history is provided for one of these cases. Even though insulin instability in postmortem biological fluid remains a challenge, this method allows for a reliable forensic-level analysis in vitreous fluid.

Topics: Adult; Drug Overdose; Female; Forensic Toxicology; Humans; Insulin; Insulin Aspart; Insulin Glargine; Insulin Lispro; Suicide; Vitreous Body; Workflow

A 49-year-old man presented with recurrent altered conscious state suggestive of encephalitis. This was followed by an episode of severe hypoglycemia requiring protracted intravenous glucose administration. Comparing the pharmacokinetic time curves of serum insulin levels on two insulin immunoassays with different insulin analog cross-reactivity allowed the likely diagnosis of surreptitious glargine overdose to be made rapidly.. The differing insulin analog cross-reactivity of serum insulin immunoassays, in this case the Abbott ARCHITECT and Roche Elecsys, allows the presence of insulin analog to be detected. Through comparison of time curves the characteristic signature of the specific causative insulin analog can be identified. This information confirms surreptitious insulin overdose in a timely manner, therefore avoiding the expensive and time-consuming investigations required to exclude alternate causes of severe hypoglycemia.

Topics: Drug Overdose; Humans; Hypoglycemia; Insulin; Insulin Glargine; Pharmacokinetics

Topics: Adult; Drug Overdose; Female; Humans; Hypoglycemia; Injections, Subcutaneous; Insulin; Insulin Glargine; Suicide, Attempted; Time Factors

Intentional insulin glargine overdose is rarely reported in the literature, but usually results in prolonged hypoglycemia requiring intensive care unit admission.. We report a case of using octreotide to treat prolonged hypoglycemia after a large insulin glargine overdose.. A 56-year-old man with type 2 diabetes mellitus presented to the Emergency Department after a multidrug overdose including up to 3,300 units insulin glargine. He required admission to the intensive care unit for mechanical ventilation and blood-glucose monitoring every 30 to 60 min. He received a continuous dextrose infusion for >100 h for persistent hypoglycemia. Octreotide, a somatostatin analogue, was given on day 4 of admission in an attempt to inhibit any insulin secretion from the pancreas that might be occurring in response to the dextrose infusion and to minimize the amount of fluid being given. After three doses, improvements in the patient's blood glucoses were seen, however, this could have coincided with complete absorption of the insulin.. Prolonged hypoglycemia often occurs after large overdoses of insulin glargine due to a depot effect at the site of injection. Octreotide is a potential adjunctive treatment to dextrose in patients with a functioning pancreas.

Topics: Drug Overdose; Gastrointestinal Agents; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Male; Middle Aged; Octreotide; Treatment Outcome

Insulin overdose can cause harm due to hypoglycaemia, effects on electrolytes and acute hepatic injury. The established long-acting insulin analogue preparations (detemir and glargine) can present specific management problems because, in overdose, their effects are extremely prolonged, often lasting 48-96 hours. The primary treatment is continuous intravenous 10% or 20% glucose infusion with frequent capillary blood glucose monitoring. Surgical excision of the insulin injection site has been used successfully, even days after the overdose occurred. Once the effects of overdose have receded, diabetes treatment must be restarted with care, especially in patients with type 1 diabetes. Monitoring serum insulin concentration has been successfully used to predict when the effects of the overdose will cease.

Topics: Adult; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 1; Drug Overdose; Electrolytes; Glucose; Humans; Hypoglycemia; Infusions, Intravenous; Insulin Detemir; Insulin Glargine; Insulin, Long-Acting; Male; Sweetening Agents

A 26-year-old man with Type 1 diabetes presented with an overdose of 4800 units of the long-acting insulin analogue, glargine (Lantus). Glucose supplementation of approximately 800 g/day was associated with acute hepatic injury.. On day 4, a depot of insulin was excised from the patient's abdominal wall; this was followed by a reduction in his glucose requirements and improvement in liver function.. This report highlights the risk of acute hepatic injury during the treatment of insulin overdose and the importance of careful glucose supplementation. It also demonstrates how earlier excision of an insulin depot could potentially prevent this problem and hasten recovery.

Topics: Abdomen; Adult; Device Removal; Diabetes Mellitus, Type 1; Drug Overdose; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Glargine; Insulin, Long-Acting; Liver; Male; Treatment Outcome

Insulin glargine is a relatively new medication in the treatment of diabetes mellitus, and there have only been six case reports of overdoses in the literature with this specific insulin.. We present a unique case of insulin glargine overdose that presented with persistent hypoglycemia and required prolonged in-hospital treatment.. A 51-year-old woman with insulin-dependent diabetes and a history of suicide attempts by medication overdose presented to the Emergency Department the morning after she had self-administered 2700 units of her insulin glargine in an attempted suicide. She was treated with continuous intravenous dextrose infusion with liberal oral intake, and continued to have recurrent hypoglycemic episodes 96 h into her hospital stay. She was discharged on hospital day 5 after psychiatric clearance without any permanent complications.. A single massive overdose of insulin glargine can present with prolonged hypoglycemia. Emergency physicians should have a low threshold for initiating continuous dextrose infusions and admitting these patients for frequent blood glucose and serum electrolyte monitoring, preferably in an intensive care setting.

Topics: Diabetes Mellitus; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Suicide, Attempted

We present a case of a significant insulin overdose that was managed by monitoring daily plasma insulin levels. A 39-year-old male with poorly controlled diabetes mellitus presented to the Emergency Department via emergency medical services after an attempted suicide by insulin overdose. In the attempted suicide, he injected 800 U of insulin lispro and 3800 U of insulin glargine subcutaneously over several parts of his abdomen. The patient was conscious upon arrival to the emergency department. His vital parameters were within normal range. The abdominal examination, in particular, was nonfocal and showed no evidence of hematomas. He was awake, alert, conversant, tearful, and without any focal deficits. An infusion of 10% dextrose was begun at 100 mL/h with hourly blood glucose (BG) checks. The patient was transferred to the intensive care unit where his BG began to decrease and fluctuate between 50 and 80 mg/dL, and the rate of 10% dextrose was increased to 200 mL/h where it was maintained for the next 48 hours. The initial plasma insulin level was found to be 3712.6 uU/mL (reference range 2.6-31.1 uU/mL). At 10 hours, this had decreased to 1582.1 uU/ml. On five occasions, supplemental dextrose was needed when the BG was <70 mg/dL. Thirty-four hours after admission, the plasma insulin level was 724.8 uU/mL. Fifty-eight hours after admission, the plasma insulin level was 321.2 uU/mL, and the 10% dextrose infusion was changed to 5% dextrose solution at 200 mL/h. The plasma insulin levels continued to fall daily to 112.7 uU/mL at 80 hours and to 30.4 uU/mL at 108 hours. He was transferred to an inpatient psychiatric facility 109 hours after initial presentation. Monitoring daily plasma insulin levels and adjusting treatment on a day-to-day basis in terms of basal glucose infusions provides fewer opportunities for episodic hypoglycemia. Furthermore, it was easier to predict daily glucose requirements and eventual medical clearance based on the plasma levels.

Topics: Adult; Diabetes Mellitus, Type 2; Drug Monitoring; Drug Overdose; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin Lispro; Insulin, Long-Acting; Male; Suicide, Attempted

Topics: Adult; Drug Overdose; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Potassium; Suicide, Attempted

Insulin glargine (Lantus, Aventis Pharmaceuticals, Bridgewater, NJ) is a long-acting once-daily dosed form of insulin intended to maintain a constant baseline insulin level. As a relatively new medication, there is limited experience in overdoses of Lantus. We present a case of a 37-year-old male insulin-dependent diabetic presenting with refractory hypoglycemia secondary to an intentional overdose of Lantus insulin to illustrate the varied management concerns in overdoses of long-acting insulins. The patient was managed with oral intake, intravenous dextrose bolus, peripheral 10% dextrose solution, 25% dextrose sliding scale via central line, and psychiatry evaluation for suicide attempt. Other potential treatments discussed for possible use with long-acting insulin overdoses include incision and drainage of the injection site, glucagon, and octreotide.

Topics: Adult; Drug Overdose; Glucose; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Male; Suicide, Attempted; Sweetening Agents

Topics: Blood Glucose Self-Monitoring; Diabetes Mellitus; Drug Overdose; Female; Humans; Hypoglycemia; Insulin; Insulin Glargine; Insulin, Long-Acting; Middle Aged; Self Administration

Intentional insulin overdose in diabetic patients is a rather rare critical situation. We report the case of a patient suffering from type 1 diabetes who was found comatose with a plasma glucose close to zero after having injected herself massive doses of both aspart and glargine insulin analogues. The prevention of hypoglycaemic episodes in this patient required a long-term glucose infusion (i.e., 59 hours) which significantly exceeds the usual time-effect profile of glargine. This observation emphasizes again that clinicians should be aware of the extremely prolonged action of long acting insulin analogue glargine after intentional massive injection in order to avoid a too early interruption of glucose infusion and a subsequent risk of relapse of severe hypoglycaemic episodes.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Overdose; Female; Glucose; Humans; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Insulin Aspart; Insulin Glargine; Insulin, Long-Acting

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Drug Overdose; Emergency Medicine; Female; Glucose; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Intravenous; Insulin; Insulin Glargine; Insulin, Long-Acting; Suicide, Attempted