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Drug-induced hyperinsulinemic hypoglycemia: An update on pathophysiology and treatment

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Abstract

The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide.

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Data availability

The data to support the findings of this study are included within the article.

Abbreviations

ADRs:

Adverse drug reactions

APDs:

Antipsychotic drugs

ASA:

Acetylsalicylic acid

CHI:

Congenital hyperinsulinism

COX:

Cycloxogenase

DA:

Dopamine

D2/D3R:

Dopamine receptor type 2/3

DHH:

Drug-induced HH

DPP-4:

Enzyme dipeptidyl peptidase-4 enzyme

DR:

Dopamine receptors

E:

Epinephrine

GABA:

Gamma-aminobutyric acid

GLP-1:

Glucagon-like peptide-1

GLUT2:

Glucose transporter type 2

GSIS:

Glucose-stimulated insulin secretion

HH:

Hyperinsulinemic hypoglycemia

IAS:

Insulin autoimmune syndrome

i.m.:

Intramuscular

i.v.:

Intravenous

KATP:

ATP-sensitive potassium channels

MFA:

Meclofenamic acid

NE:

Norepinephrine

NEFA:

Non-esterified fatty acids

NSAIDs:

Nonsteroidal anti-inflammatory drugs

OR:

Opioid receptors

PGE2:

Prostaglandin E2

S:

Serotonine

SR:

Serotonine receptors

SUR-1:

Sulfonylurea receptor

α2R:

α2-Adrenergic receptor

β2R:

β2-Adrenergic receptor

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Authors and Affiliations

  1. Department of Women’s and Children’s Health, Pediatric Unit, Azienda Provinciale per i Servizi Sanitari APSS, Largo Medaglie d’oro 9, Trento, Italy

    Evelina Maines, Letizia Leonardi, Massimo Soffiati & Roberto Franceschi

  2. Hospital Pharmacy Unit, Azienda Provinciale per i Servizi Sanitari APSS, Largo Medaglie d’oro 9, Trento, Italy

    Silvana Anna Maria Urru & Annalisa Campomori

  3. School of Hospital Pharmacy, University of Sassari, Sassari, Italy

    Elisabetta Fancellu

  4. CIBIO - Department of Cellular, Computational and Integrative Biology, Università degli Studi di Trento, Trento, Italy

    Giovanni Piccoli

  5. Division of Metabolism and Research Unit of Metabolic Biochemistry, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Arianna Maiorana

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  1. Evelina Maines
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  2. Silvana Anna Maria Urru
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  3. Letizia Leonardi
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  4. Elisabetta Fancellu
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  5. Annalisa Campomori
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  6. Giovanni Piccoli
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  7. Arianna Maiorana
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  8. Massimo Soffiati
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  9. Roberto Franceschi
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Correspondence to Evelina Maines.

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Maines, E., Urru, S.A.M., Leonardi, L. et al. Drug-induced hyperinsulinemic hypoglycemia: An update on pathophysiology and treatment. Rev Endocr Metab Disord 24, 1031–1044 (2023). https://doi.org/10.1007/s11154-023-09828-y

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