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    Metabolic / Endocrine

    Last Updated Feb 21, 2024
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    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.

    Diagnostic Process

    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


    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.


    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.



    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.



    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.

    Quality Of Evidence?


    Treatment of hypoglycemia – Quality of evidence is low. Based on formal consensus.

    Addition of thiamine – Quality of evidence is low. Based on a series of case reports.

    Addition of octreotide – Quality of evidence is low. Based on a series of case reports, a small RCT and a small crossover study.


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