Hypoglycemia is the most common and severe complication in diabetic patients:

• 30-40% of patients with T1DM each year.
• 10-30% with T2DM each year.
• without treatment can lead to cardiovascular events, seizures, brain damage and death.

Most patients can be discharged, except in cases of long-acting antidiabetic medication usage or neuroglycopenia unresponsive to carbohydrate administration.

Diagnosis of Hypoglycemia

Whipple’s triad:

1. Signs or symptoms consistent with hypoglycemia (autonomic or neuroglycopenic symptoms):

• Neurogenic (autonomic) – trembling, palpitations, sweating, anxiety, hunger, nausea, paresthesias.
• Neuroglycopenic – poor concentration, confusion, weakness, drowsiness, vision changes, headache, dizziness, speech difficulties.

2. Blood Glucose (BG) < 4 mmol/L in diabetic patients receiving insulin/insulin secretagogue therapy OR BG < 3 mmol/L in spontaneous hypoglycemia.

3. Resolution of symptoms after raising plasma glucose level.
Hypoglycemia Stratification

1. Mild: Autonomic symptoms of hypoglycemia are present; patient is able to self-treat.
2. Moderate: Both autonomic and neuroglycopenic symptoms are present; patient is able to self-treat.
3. Severe: Patient requires assistance to correct BG and may have loss of consciousness. BG typically < 2.8 mmol/L.

Treatment in Patient with Diabetes

Mild-to-moderate:

15 g carbohydrate PO, ideally as glucose or sucrose tablets/solution. In those with diabetes, BG should be measured 15 minutes after administration². Second dose if BG remains <4.0 mmol/L.

Severe:

Conscious: 20 g carbohydrate PO, ideally as glucose tablet or equivalent. In 15 minutes, additional 15 g glucose PO if BG remains <4.0 mmol/L.

Unconscious: 10-25 g glucose (20-50 mL D50W) IV over 1-3 minutes. In pediatric patients, this is lowered to 0.5 to 1 g/kg.

• If IV unavailable, 1 mg glucagon SC/IM increases BG within 60 minutes. Effectiveness reduced with alcohol consumption, fasting, or advanced hepatic disease.
• Thiamine administration should not delay glucose supplementation.

Once the hypoglycemia is reversed, if next meal is > 1 hour, 15g carbohydrate and a protein source should be consumed.

In sulfonylurea overdose and refractory hypoglycemia, octreotide has been shown to increase BG and reduce recurrent hypoglycemia. Following dosages are generally recommended:

• IV: 50 µg bolus and infusion of 25 µg/h (1 µg/kg/h in peds).
• SC: 50-100 µg in adults (1-2 µg/kg in peds) every 6-12 hours.

Treatment in Patient without Diabetes

Treatment follows the same protocol for glucose administration as in diabetic hypoglycemia.

Hypoglycemia in non-diabetic patients is a red flag.

Whenever suspected to be secondary cause, blood should be drawn prior to administration of glucose. For diagnostic purposes, this sample should include:

1. Blood glucose.
2. Insulin.
3. C-peptide.
4. Pro-insulin.
5. β-hydroxybutyrate concentration.
6. Screen for oral hypoglycemic agents and insulin antibodies.
7. Blood Alcohol Content.

Consider

Drug-related causes:

• Insulin.
• Oral hypoglemic agents:
  • Metformin when used with sulfonylureas.
  • SGLT2 inhibitors (i.e. dapagliflozin and empagliflozin).
  • Sulfonylureas (i.e. Glyburide).
  • Thiazolidinediones (i.e. Actos and Avandia).
• Beta-blockers.
• Haloperidol.
• MAO inhibitors.
• Pentamidine.
• Quinidine.
• Quinine.
• Sulfamethoxazole – trimethoprim (Septra).
• Gatifloxacin.
• Indomethacin.

2. Concurrent illnesses.

3. Exogenous hyperinsulinism – an oral hypoglycemic agent that may not be reported in history (i.e. malicious administration).

4. Endogenous hyperinsulinism is rare:

• Insulinoma.
• Noninsulinoma pancreatogenous hypoglycemia syndrome.
• Post-gastric bypass hypoglycemia.
• Insulin autoimmunity.

Disposition

Admission recommended:

• Long-acting antidiabetic agents (non-short acting insulins, sulfonylureas, meglitinides).
• Neuroglycopenia that does not rapidly resolve.
• Fever without an obvious source in poorly controlled diabetics.

Discharge likely:

• Resolution of neuroglycopenia.
• New-onset diabetics who do not meet the mentioned criteria for admission, and do not have metabolic decompensation.
• Follow-up with their primary care provider within 24-48 hours for education, dietary evaluation and discussion of treatment.

1. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. (2018). Canadian Journal of Diabetes, 42, S1–S325.

   
   

2. Umpierrez, G., & Korytkowski, M. (2016). Diabetic emergencies-ketoacidosis, hyperglycaemic hyperosmolar state and hypoglycaemia. Nature Reviews Endocrinology, 12(4), 222–232.

   
   

3. Klein-Schwartz, W., Stassinos, G. L., & Isbister, G. K. (2016). Treatment of sulfonylurea and insulin overdose. British Journal of Clinical Pharmacology, 81(3), 496–504.

   
   

4. Martens, P., & Tits, J. (2014). Approach to the patient with spontaneous hypoglycemia. In European Journal of Internal Medicine, 25(5), pp. 415–421). Elsevier.

   
   

5. Tintinalli, J. E., Ma, O. J., Yealy, D. M., Meckler, G. D., Stapczynski, J. S., Cline, D., & Thomas, S. J. (2016). Tintinallis emergency medicine: a comprehensive study guide (8th Ed). New York: McGraw Hill Education.