Hypoglycemia medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2] Amandeep Singh M.D.[3]

Overview

Medical treatment of hypoglycemia depends on the severity of symptoms and the cause. If asymptomatic, repeating the measurement in short time and avoiding critical tasks. Twenty grams of glucose is usually sufficient to raise the blood glucose in a severe hypoglycemic and symptomatic patients. Glucose should be administered subcutaneously or intramuscularly or 25% of dextrose serum should be given intravenously. In case of postprandial hypoglycemia, the patient should have frequent small meals or snacks and foods should be high in fiber, avoiding foods with high sugar content. Surgery is the best treatment for insulinoma.

Medical Therapy

Asymptomatic: 

Asymptomatic patients with a blood glucose of ≤70 mg/dL do not need treatment and should be monitored. Protective measurements should be done to prevent complications. Protective measurements include:

• Measure blood glucose frequently
• Avoid critical tasks including driving
• Ingestion of carbohydrates
• Adjust the regimen to avoid further attacks

Symptomatic:

• Patients should have a source of carbohydrates available all times.
• Twenty grams is usually sufficient to raise the blood glucose.
• In patients taking alpha-glucosidase inhibitor (acarbose), dextrose should be used to treat hypoglycemia because acarbose slows the digestion of carbohydrates.

Severe: 

• A subcutaneous or intramuscular injection of 0.5 to 1.0 mg of glucagon will correct hypoglycemia within 15 minutes.
• If failed this attempt or in severe cases, 25% or 50% dextrose intravenously (IV) followed by subcutaneous glucose.
• If these measures are not available:
  • Squeezing a glucose gel in the space between the teeth and buccal mucosa with patient head tilted on the side to prevent aspiration.
  • If glucose gel is not available, putting table sugar under the tongue may save patient.

• Hypoglycemia due to hormone deficiencies such as hypopituitarism or adrenal insufficiency usually ceases when the appropriate hormone is replaced.
• Patients with diabetes history who has loss of consciousness and there is no method to determine nature of coma; hypoglycemia or hyperglycemia, then glucose should be given empirically. This will correct hypoglycemia and will not be particularly harmful if blood glucose concentration is high.
• Intranasal glucagon was effective in treating insulin-induced hypoglycemia in adults with type 1 diabetes in some studies but it is still under investigation.

Postprandial hypoglycemia

• Frequent (every three hours) small meals or snacks.
• The patient should use foods high in fiber, avoiding foods high in sugar.
• Regular exercise regimen has been recommended.

Insulinoma

Surgery is the best treatment for insulinoma and other pancreatic masses but if multiple metastases or bad general condition medical therapy is accepted:

1. Adult

• Parenteral
  • Preferred regimen (1): Octreotide 30 mg IM (depot) every 4 weeks until tumor progression or death
  • Preferred regimen (2): Octreotide 100-500 μg SQ q 8-12h（can be increased to maximum 1500 μg daily for 1 year
  • Preferred regimen (3): Lanreotide 120 mg SQ every 4 weeks until tumor progression
• Oral
  • Preferred regimen : Diazoxide 3-8 mg/kg OR 200-300 mg PO q8h for 14-21 days (1200 mg max to be divided in 3 doses and max is 400 mg/dose)^[1][2]
  • Alternative regimen (1): Phenytoin 300-600 mg PO q daily^[3]
  • Alternative regimen (2): Everolimus 10 mg PO q daily until disease progression
  • Verapamil and Propranolol to control symptoms are used either as alone or in combination
  • Glucocorticoids and Glucagon have been used in combination with diazoxide.

2. Pediatric

• Preferred regimen: Diazoxide initial dose: 10 mg/kg/day divided into 3 equal doses q 8 hours
• Maintenance dosing range: 8 to 15 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours

Malignant (metastatic) Insulinoma

Chemotherapy

It is used in the different combination of the following drugs:

• Streptozocin 500 mg/m²/day IV for 5 consecutive days every 6 weeks
• Doxorubicin 40-75 mg/m² IV every 21 to 28 days
• 5 Fluorouracil(5-FU)
• Temozolamide 200 mg/m² PO QHS days 10 to 14 of a 28-day treatment cycle (in combination with capecitabine)
• Bevacizumab
• Capecitabine

Neonatal hypoglycemia

• The goal is to prevent neurologic complications of neonatal hypoglycemia.
• The management differs between symptomatic and asymptomatic patients:

Oral feeds

The goal of management is to normalize patients blood glucose levels and prevent them from becoming symptomatic. Guidelines from the American Association of Pediatrics recommend that oral feeding should be given as quickly as possible for asymptomatic patients.

• Blood glucose concentrations should be measured frequently starting 20 to 30 minutes after the initial feeding and repeating with subsequent feedings.
• Plasma glucose levels should be greater than 50 to 60 mg/dL to prevent neurological sequales
• Infants less than 4 hours of age with plasma glucose <25 mg/dL.
• If plasma glucose concentration fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 25 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration
• Infants between 4 and 24 hours of age and with plasma glucose <35 mg/dL
• If plasma glucose level fails to increase, parenteral glucose is administered. If the plasma glucose increases to above 35 mg/dL, oral feedings should continue every two to three hours with preprandial measurements of plasma glucose concentration.
• If a patient becomes symptomatic or if plasma glucose fails to increase above 45 mg/dL after three oral feedings, then parenteral glucose should be given.

Symptomatic patients

The goal is to maintain plasma glucose concentrations >70 mg/dL.

• Guidelines developed by the American Academy of Pediatrics suggest an aggressive treatment in these patients because of the neurodevelopmental impairment associated:
  • Who are less than 48 hours of life with plasma glucose levels <50 mg/dL 
  • Who are greater than 48 hours of life with plasma glucose levels <60 mg/dL
  • Asymptomatic patients at risk for hypoglycemia or in patients in whom a low glucose concentration was identified as an incidental laboratory finding:
  • Who are less than 4 hours of life with plasma glucose levels <25 to 40 mg/dl
  • Who are between 4 and 24 hours of life with plasma glucose <35 to 45 mg/dl
  • Who are between 24 and 48 hours of life with plasma glucose levels <45 to 50 mg/dl
  • Who are greater than 48 hours of life with plasma glucose levels <60 mg/dl
  • In newborns with a suspected or confirmed genetic hypoglycemia disorder (such as a family history of a hypoglycemia disorder or physical exam features consistent with Beckwith-Wiedemann syndrome)

• An intravenous bolus of 200 mg/kg dextrose is given over 5 m followed by the continuous administration of parenteral dextrose infusion at a rate of 6 to 8 mg/kg of dextrose per minute.
• Therapy should be initiated while awaiting laboratory confirmation of low blood glucose levels.
• The maximum rate of infusion for treatment is the maximum amount of fluids that neonate can deal with.
• Dextrose at a concentration of 12.5 percent or less can be infused through an umbilical arterial catheter.
• Patient's fluid should be monitored for volume overload or hyponatremia, diuretics may be indicated if volume overload occurred
• Other interventions should be considered if the glucose infusion rate is 12 mg/kg per minute with non-responsive patients:
  • Administration of glucagon should be considered patients with persistent plasma glucose <50 mg/dl.
  • Twenty to thirty mcg/kg iv infusion, intramuscular or even subcutaneous to infants with persistent hypoglycemia despite parenteral glucose infusion.
  • A repeat dose of glucagon is given if the patient didn't respond within 20 minutes of glucagon administration. Glycogen storage disorder should be suspected in these cases.
  • Hydrocortisone 2 to 6 mg/kg per day for 2 days only to avoid side effects. It stimulates gluconeogenesis and decreases glucose uptake by cells.
  • Diazoxide and somatostatin in patients with hyperinsulinism and pancreatectomy if the patient isn't responsive.
• When the glucose concentration is stabilized, oral glucose is used by tapering for 4 days but the blood glucose level should be monitored.