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.

Summary.To determine the role of growth hormone in overnight insulin requirements and lipolysis, five patients with chronic growth hormone deficiency and Type 1 (insulindependent) diabetes mellitus and six control patients with diabetes were each studied on two separate nights. Insulin was infused at a variable rate throughout one night to maintain euglycaemia and fixed at 04.00 hours on another. During the variable infusion, euglycaemia was maintained in control patients by a 36% increase in insulin infusion rate between 03.00 and 08.00 hours while a 46% decrease in the rate was required in growth hormone deficient patients (p < 0.02). Despite this difference, mean free insulin values were equivalent. This finding is suggestive of increased insulin clearance in growth hormone sufficient patients. Glucose levels rose in control and fell in growth hormone deficient patients when insulin infusion rates were fixed at 04.00 hours. Glycerol production and non-esterified fatty acid concentrations were significantly lower in the growth hormone deficient diabetic patients, p < 0.001, and when normalized with a heparin infusion, had no effect on insulin requirements. We conclude that: (1) growth hormone contributes to the development of the "dawn phenomenon," possibly by increasing insulin clearance (2) growth hormone helps sustain nocturnal lipolysis in Type i diabetes and (3) non-esterified fatty acids are not involved in the dawn phenomenon.

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