title: Octreotide reverses hyperinsulinemia and prevents hypoglycemia induced by sulfonylurea overdoses.
abstract: Emergency therapy of sulfonylurea overdoses with glucose is often unsatisfactory because glucose stimulates insulin release and initiates a need for escalating quantities of hypertonic glucose to maintain normoglycemia. We tested the hypothesis that octreotide, an analog of somatostatin, would reverse hyperinsulinemia induced by a sulfonylurea overdose. Eight normal subjects received glipizide (1.45 mg/kg) on three occasions. Within 3 h, all subjects became hypoglycemic (< 50 mg/dL) and were initially treated with 50% dextrose followed by 1) dextrose infusion, 2) octreotide (30 ng/kg.min, iv), or 3) diazoxide (300 mg, iv, every 4 h). Euglycemia (85 mg/dL) was maintained with supplementary dextrose in treatment limbs 2 and 3. Insulin concentrations were 4-5 times greater with dextrose alone or in combination with diazoxide than with octreotide (P < 0.01). Dextrose requirements during diazoxide or dextrose alone were not different, but were both greater than those during octreotide treatment (P < 0.0001). All therapies were stopped at 13 h. Glucose levels remained above 3.6 mmol/L (65 mg/dL) in six of eight subjects receiving octreotide for the remaining 4 h. Glucose fell to below 3.6 mmol/L within 1.5 h of stopping either dextrose or diazoxide in each subject. Overall, octreotide reduced and in four of eight subjects entirely eliminated the need for exogenous glucose after a large overdose of glipizide. We conclude that octreotide is safe and effective and should be strongly considered as a logical therapeutic alternative for this metabolic emergency.
authors.affiliation: Department of Medicine, University of New Mexico School of Medicine, Albuquerque 87131-5271.
authors.forename: P J
authors.initials: PJ
authors.lastname: Boyle
authors.forename: K
authors.initials: K
authors.lastname: Justice
authors.forename: A J
authors.initials: AJ
authors.lastname: Krentz
authors.forename: R J
authors.initials: RJ
authors.lastname: Nagy
authors.forename: D S
authors.initials: DS
authors.lastname: Schade
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003981:Diazoxide / Q000627:therapeutic use; D062787:Drug Overdose; D005260:Female; D005947:Glucose / Q000627:therapeutic use; D006801:Humans; D006946:Hyperinsulinism / Q000188:drug therapy*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007262:Infusions, Intravenous; D008297:Male; D015282:Octreotide / Q000627:therapeutic use*; D009994:Osmolar Concentration; D010455:Peptides / Q000037:antagonists & inhibitors; D013453:Sulfonylurea Compounds / Q000009:adverse effects*
chemical_list: D001786:Blood Glucose; D010455:Peptides; D013453:Sulfonylurea Compounds; D005947:Glucose; D003981:Diazoxide; D015282:Octreotide