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    Hyperglycemia – Diagnosis

    Metabolic / Endocrine

    Last Updated May 25, 2021
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    By Matthew Wahab, Ellie Bay

    Context

    Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are the main hyperglycemic emergencies that should be considered for any patient with significant hyperglycemia.

    • DKA more common than HHS with a higher incidence in type 1 diabetes.
    • HHS more common in older type 2 diabetics and has a higher mortality rate.
    • A high index of suspicion for these conditions is important as ~50% of deaths happen in the first 2-3 days.

    Precipitants:

    • Infection (e.g., UTI, pneumonia).
    • Insulin reduction or omission (e.g., noncompliance, pump malfunction).
    • New diabetes mellitus diagnosis.
    • Acute illness (e.g., MI, stroke, thyrotoxicosis, pancreatitis).
    • Trauma.

    Medications:

      • Atypical antipsychotics.
      • Diuretics.
      • Steroids.
      • Lithium.
      • Beta-blockers.
      • Some chemotherapy agents.
      • Sglt2 inhibitors.
    • Toxins (e.g., alcohol, cocaine).
    • Pregnancy.
    • May require admission to an ICU or step-down unit.

    Not all patients with hyperglycemia have a history of diabetes or are subsequently diagnosed with diabetes. Stress-induced hyperglycemia can occur in acutely ill patients (e.g., sepsis, trauma, burns) and has increased morbidity and mortality.

    Diagnostic Process

    Common clinical features:

    • Hyperglycemia – polyuria, polydipsia, weakness, fatigue, weight loss, signs of volume depletion.
    • DKA – acute onset; signs/symptoms of hyperglycemia, diffuse abdominal pain, nausea, vomiting, tachypnea (Kussmaul), acetone/fruity breath, altered LOC.
    • HHS – insidious onset; signs/symptoms of hyperglycemia, decreased LOC, signs of severe volume depletion, seizures.
    • Look for precipitating factor in both DKA and HHS.

    Initial Assessment:

    • Volume status.
    • Level of consciousness.
    • Look for precipitating factor(s).
    • Assess for potential complications.

    Investigations:

    • Serum glucose. Capillary BG is not accurate in severe acidosis and interstitial glucose levels should not be used for diagnosis.
    • Consider HbA1c (does not change acute management).
    • If DKA or HHS is suspected:
      • Electrolytes.
      • Serum glucose.
      • Anion gap +/- lactate.
      • Creatinine.
      • Serum osmolality, Serum and urine ketones, beta-hydroxybutyric acid (if possible).
      • Venous Blood gases.
      • ECG – assess for acute coronary syndrome.
      • Additional tests can be guided by suspicion of precipitating factor(s).
    • DKA:
      • Arterial pH ≤ 7.3.
      • Serum bicarbonate ≤ 15mmol/L.
      • Anion gap > 12mmol/L.
      • Positive urine/serum ketones.
      • Plasma glucose ≥ 14mmol/L.
    • It’s important not to interpret these values as hard and fast rules as there are exceptions to each:
      • Ketones may be negative if beta-OHB production is favored.
      • Bicarbonate may be normal/high if there’s a concomitant severe metabolic alkalosis.
      • Normoglycemia is possible with SGLT2 inhibitor use, in pregnancy, if insulin was just given, in T1DM with vomiting, or in cases of starvation, alcohol abuse, or liver failure.
    • HHS:
      • BG ≥ 34mmol/L.
      • Serum osmolality > 320mOsm/kg.
      • Minimal/no acidosis (ketones can be present).
    • Considerations for interpreting lab values:
      • Hyperglycemia causes osmotic shifts of water from the intra- to extra-cellular space causing relative hyponatremia. Correction factor 1.6 mEq/L for every 5.5 mmol/L BS above normal (another source uses 2.4 mEq/L).
      • Often total body K+ depleted, but serum K+ is typically normal/high initially due to the shift of K+ to extracellular space.
      • Serum PO43-, Ca2+ and Mg2+ may also be high despite total body depletion.
      • Some substances (e.g., acetaminophen, ascorbic acid, peritoneal dialysis) can lead to false increases in capillary and home blood glucose monitoring tests.
      • Nitroprusside test for ketones does not measure beta-hydroxybutyric acid.

    Diagnosis of Diabetes:

    Diabetes Canada: an adult with symptomatic hyperglycemia can be diagnosed with diabetes if they have 1 of the following:

    • Fasting BG ≥ 7.0mmol/L.
    • HgB A1C ≥ 6.5%.
    • 2h BG in a 75g OGTT ≥ 11.1mmol/L.
    • Random BG ≥ 11.1mmol/L.

    Stress-induced Hyperglycemia:

    • HbA1c can help distinguish stress-induced hyperglycemia from newly diagnosed diabetes.
    • Patients with known diabetes can experience stress-related hyperglycemia.

    Quality Of Evidence?

    Justification

    Diagnosis of diabetes – Based on consensus – Low.

    Low

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