Intravenous Overdose of Insulin Glargine without Prolonged Hypoglycemic Effects

Thornton, Stephen L.; Gutovitz, Scott

doi:10.1016/j.jemermed.2011.06.038

Cited by 5 publications

(4 citation statements)

References 14 publications

(21 reference statements)

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“…When injected intravenously, insulin glargine accounts for 15%–37% of total circulating insulin while when injected subcutaneously, the parent molecule was almost never found. Thornton et al in 2012 [24] presented a case of a patient accidentally receiving 100 units of insulin glargine intravenously instead of subcutaneously. As the long‐lasting properties of insulin glargine are due to its absorption kinetic, intravenously it acts like regular human insulin.…”

Section: Resultsmentioning

confidence: 99%

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

Arbouche

Walch

Raul

et al. 2023

Journal of Forensic Sciences

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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.

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Section: Resultsmentioning

confidence: 99%

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

Arbouche

Walch

Raul

et al. 2023

Journal of Forensic Sciences

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“…The median total insulin dose was 900 international units (IU) (range 26–4800 IU). Insulin was administered subcutaneously, except in one case where it was administered IV . Alcohol was consumed in relation to the overdose in 13% (n = 6) of cases.…”

Section: Resultsmentioning

confidence: 99%

“…short‐acting and long‐acting insulin analogues). Ultimately, 45 case reports were included for the data extraction. Please refer to fig.…”

Section: Methodsmentioning

confidence: 99%

A Systematic Review on Insulin Overdose Cases: Clinical Course, Complications and Treatment Options

Johansen

Christensen

2018

Basic Clin Pharma Tox

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A large overdose of insulin is a serious health matter. Information concerning administration and duration of intravenous (IV) glucose, other treatment options or complications besides hypoglycaemia following large insulin overdoses is not readily apparent from the literature. A systematic search, compilation and review of case reports on insulin overdoses, published 1986-2017, was performed in PubMed, EMBASE, Cochrane and PROSPERO databases. Of 1523 published articles, 45 cases of insulin overdoses were included with a total median insulin dose of 900 international units (IU) (range 26-4800 IU). Hospitalization occurred in 44 cases with a median hospitalization duration of 94 hr (range 12-721 hr), and one-third (n = 15) admitted to the intensive care unit. First-line treatment was IV glucose treatment in 95% of cases. Treatment options besides IV glucose that were reported beneficial included glucagon IV or intramuscular (IM), octreotide IV or IM, surgical excision, hydrocortisone IV and oral intake of complex carbohydrates. Prevalent complications were intermittent cerebral impairment (73%), hypokalaemia (49%), other electrolyte disturbances (42%), and hepatic disturbances (7%) and cardiac toxicity (e.g. cardiac arrhythmia) (9%). Long-term consequences were one case of lasting hypoglycaemic encephalopathy and one death. In conclusion, following large insulin overdoses, in-hospital admission and treatment with IV glucose may be needed for up to a week. Monitoring of electrolytes and hepatic and cardiac functions seems important. Several experimental treatment options may be considered in addition to glucose administration. With appropriate pre- and in-hospital treatment, cases with severe hypoglycaemia and neurologic complications may have a favourable outcome.

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“…Moreover, only 39.7% of the patients using insulin exhibit glycemic control, while the others showed significant blood sugar fluctuations. These fluctuations were related to the insulin as prescribed for the injection dose of insulin (insufficient injection of insulin could not achieve the hypoglycemic effect, and excessive injection insulin will cause hypoglycemia, limb numbness, double vision, muscle tremor, ataxia, and shock) [5,6]. In order to resolve these problems, the development of insulin dosage forms has been investigated.…”

Section: Introductionmentioning

confidence: 99%

Galactose-based polymer-containing phenylboronic acid as carriers for insulin delivery

Zhong

Song

et al. 2020

Nanotechnology

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The galactose-based polymer is a promising drug delivery material. Herein, a new galactose-based block copolymer, termed as 6-O-vinyl sebacic acid-D-galactopyranosyl ester block 3-acrylamide phenylboric acid p(OVNG-b-AAPBA) was successfully synthesized by ‘block copolymer’ method. The structure of p(OVNG-b-AAPBA) was proved by nuclear magnetic hydrogen spectrum (1 HNMR) and infrared (IR), the thermal stability was observed by thermogravimetric analyzer, and the molecular weights (Mw and Mn) were demonstrated by Gel permeation chromatography (GPC). The above test results suggested that the polymer of p(OVNG-b-AAPBA) was successfully synthesized, and it had optimal molecular weight and thermal stability, which could be used for investigating the drug delivery system. Then, this block copolymer was prepared to the nanoparticle (NP), these NPs had a satisfactory morphology, and their safety was verified by MTT and chronic animal toxicology test. In addition, insulin was encapsulated by the p(OVNG-b-AAPBA) NPs, the drug loading rate and encapsulation efficiency increased with that of AAPBA in the polymer. Finally, this study confirmed that these NPs can effectively maintain the blood sugar of diabetic mice at 96 h. In conclusion, the current study suggested that the insulin-loaded galactose-based polymer-block-3-acrylamide phenylboric acid NPs had slow-release/glucose-responsive drug release performance, which might play an active role in the diabetes therapy.

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Intravenous Overdose of Insulin Glargine without Prolonged Hypoglycemic Effects

Cited by 5 publications

References 14 publications

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

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

A Systematic Review on Insulin Overdose Cases: Clinical Course, Complications and Treatment Options

Galactose-based polymer-containing phenylboronic acid as carriers for insulin delivery

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