Hypoglycemia

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Background

  • Brain depends on glucose as primary source of energy, but is unable to synthesize or store glucose

Common Anti-hyperglycemic Drugs and Pharmacology

Drug Pharmacology
Onset Peak Duration
Rapid-acting insulin
  • Aspart (Novolog)
  • Lispro (Humalog)
15-30min 1-2h 3-5h
Short-acting insulin
  • Regular
30-60min 2-4h 6-10h
Intermediate-acting insulin
  • NPH (Humulin, Novolin)
1-3h 4-12h 18-24h
Long-acting insulin
  • Glargine (Lantus)
2-4h None 24h
Sulfonylurea
  • Glimepiride
  • Glipizide (Glucotrol)
  • Glyburide (Glycron, Micronase)
2-6h 12-24h

Clinical Features[1]

Neuroglycopenic

Autonomic

Differential Diagnosis

Differential diagnosis of hypoglycemia

Hypoglycemia

Drugs

Systemic Illness

Malignancy

  • Insulinoma
  • Non-islet cell
  • Insulin/receptor autoantibodies
  • High tumor burden

Other

Precipitants of anti-hyperglycemic induced hypoglycemia

  • Decreased glucose
    • Missed meal
    • Consumption (exercise, illness)
  • Increased drug
    • Error (patient, provider)
    • Intentional overdose
    • Increased availability
      • Hepatic failure
      • Renal failure
      • Drug interaction

Evaluation

Workup

  • Patients with known diabetes who are not systemically ill and can identify a clear precipitant, no extensive workup is required.
  • In severely ill patients, consider:
    • BMP
    • LFT
    • EtOH
    • Infectious workup: CXR, UA, urine and blood cultures
    • ECG, troponin
    • Other studies (not normally done in ED): insulin, C-peptide, pro-insulin, glucagon, growth hormone, cortisol, B-OH, insulin antibodies
      • Exogenous insulin shows suppressed C-peptide levels (artificial insulin does not contain C-peptide)
      • MEN-1 genetic testing for insulinoma suspicion[3]
      • Elevated proinsulin and C-peptide during hypoglycemic episode in context of insulinoma

Evaluation[4]

"Whipple's Triad"

  • Symptoms suggestive of hypoglycemia
    • See Clinical Features
  • Low glucose
    • Serum glucose <60mg/dL
    • Generally symptomatic at <55mg/dL though threshold is variable depending on chronicity
  • Resolution of symptoms after administration of glucose

Management

Algorithm for the management of hypoglycemia
  • If altered mental status
    • Dextrose 50% 50mL bolus (equals "one amp")
      • Contains 25mg glucose
  • If awake
    • Oral glucose
  • Glucagon[5]
    • Efficacy dependent on hepatic glycogen stores (less effective in chronic ETOH, cirrhosis, malnourished, neonate, in-born errors, glycogen storage disease, etc.)[6]
    • Onset of action slower than IV dextrose (7-10min)
    • 1mg SC or IM

Hypoglycemia from Sulfonylureas[7][8]

Activated charcoal[9]

  • Administer activated charcoal, preferably within 1 hr of ingestion
  • Multiple doses may be beneficial, especially for glipizide

Glucose Treatment

  • Initial Therapy regardless of known cause
Adults
  • 50mL D50W bolus
  • Start a D10 1/2NS drip (100mL/hr)
Children
  • 1mL/kg of D50W OR
  • 2mL/kg D25W OR 5-10mL/kg D10W
  • Neonate: 5-10 mL/kg D10W

Octreotide[10]

  • Theoretical benefit to reduce risk of recurrent hypoglycemia
  • Hyperpolarization of the beta cell results in inhibition of Ca influx and prevents insulin release
  • 50-100 mcg subcutaneous in adults with repeat dosing Q6hrs
  • 2 mcg/kg (max 150mcg) subcutaneously Q6hrs should be used in children
  • Continuous infusion of 50-125 mcg/hr is an alternative in adults
  • Administer octreotide for 24 hours, then after discontinuing, monitor for hypoglycemia for another 24 hours

Special Considerations

  • Glucagon 5mg IM may be used as temporizing measure, e.g. while obtaining IV access
    • Dependent on glycogen stores which may be depleted in prolonged hypglycemia
    • Also short duration of action
    • Caution in using glucagon drip
      • Glucagon also has an insulin-releasing effect
      • May subsequently cause initial paradoxical hypoglycemia

Hypoglycemia from Long Acting Insulin

  • Similar treatment as for Sulfonylureas except no role for Octreotide
  • Treatment should include oral intake as well as maintenance glucose containing drip either D5 or D10

Insulinoma[11]

  • Symptomatic management as above
  • Short acting octreotide, start at 50 μg SC TID, max 1500 μg per day
    • SSTR2 and SSTR5 receptors at various levels on insulinomas, producing different response levels
    • Octreotide can inhibit growth hormone and glucagon secretion, thereby worsening hypoglycemia in some pts[12]
  • Long term medical management prior to surgery
    • Diazoxide, start at 50 mg TID, max 400 mg per day, effective in ~50% of pts
    • Long acting octreotide, 30 mg IM q28 days

Disposition

Admission or observation for oral anti-hyperglycemic agent or intermediate- to long-acting insulin. Consider discharge after 4h uneventful observation if:[13]

  • Hypoglycemia fully and rapidly reversed without continuous infusion of dextrose
  • Tolerated a full meal in ED
  • Clear and innocuous cause identified with recurrence unlikely
  • Adequate patient understanding, home support/monitoring, and ability to detect/prevent recurrence with close primary care follow-up

Insulinoma[14]

  • Admission for 48-72 hrs of monitored fasting with q4 BGLs, insulin, C-peptide, proinsulin
  • Then localization studies with US, CT, or MRI

See Also

References

  1. Jalili M. Type 2 Diabetes Mellitus In: Tintinalli's Emergency Medicine. 7th ed. McGraw Hill. 2011:1431-1432
  2. Grant CS. Insulinoma. Baillieres Clin Gastroenterol. 1996;10(4):645–671.
  3. O’Riordain DS, O’Brien T, van Heerden JA, Service FJ, Grant CS. Surgical management of insulinoma associated with multiple endocrine neoplasia type I. World J Surg. 1994;18(4):488–493; discussion 493–494.
  4. Jalili M. Type 2 Diabetes Mellitus In: Tintinalli's Emergency Medicine. 7th ed. McGraw Hill. 2011:1431-1432
  5. Carstens S, Sprehn M. Prehospital treatment of severe hypoglycaemia: a comparison of intramuscular glucagon and intravenous glucose. Prehosp Disaster Med. 1998 Apr-Dec;13(2-4):44-50
  6. Cydulka RK, Maloney GE. Diabetes Mellitus and Disorders of Glucose Homeostasis, in Marx JA, Hockberger RS, Walls RM, et al (eds): Rosen’s Emergency Medicine: Concepts and Clinical Practice, ed 8. St. Louis, Mosby, Inc., 2013, (Ch) 126: p 1652-1667.
  7. Rowden AK, Fasano CJ. Emergency management of oral hypoglycemic drug toxicity. Emerg Med Clin N Am 2007; 25:347-356
  8. Howland MA. Antidotes in Depth: Octreotide. In: Flomenbaum NE, Goldfrank LR, Hoffman RS et al, eds: Goldfrank’s Toxicologic Emergencies. New York NY, 2006;770-773
  9. Tran D et al. Oral Hypoglycemic Agent Toxicity Treatment & Management. Jul 14, 2015. http://emedicine.medscape.com/article/1010629-treatment#showall.
  10. Fasano CJ et al. Comparison of Octreotide and standard therapy versus standard therapy alone for the treatment of sulfonylurea-induced hypoglycemia. Ann Emerg Med 2008; 51:400-406
  11. Mathur A, Gorden P, Libutti SK. Insulinoma. Surg Clin North Am. 2009;89(5):1105–1121.
  12. Arnold R, Wied M, Behr TH. Somatostatin analogues in the treatment of endocrine tumors of the gastrointestinal tract. Expert Opin Pharmacother. 2002;3(6):643–656.
  13. Self, W. H., & McNaughton, C. D. (2013). Hypoglycemia. In Emergency Medicine (2nd ed., pp. 1379-1390). Elsevier.
  14. Taye A and Libutti SK. Diagnosis and management of insulinoma: current best practice and ongoing developments. Dove Press. 25 August 2015 Volume 2015:5 Pages 125—133.