Diabetic Emergencies

Lecturer: Bader Alyahya

1. Hypoglycemia

Definition:

• Triad: Glucose less than $2.5\text{ mmol/L}$ + Signs/symptoms + Response to Glucose.
• More common in Type 1 than Type 2 diabetes.
• It is the most common cause of coma associated with diabetes.
• Associated with significant morbidity and mortality.

Causes

1. Type 1: Taking insulin with missing meal.
2. Type 2: High dose of oral hypoglycemic.

Other potential causes:

• Overaggressive insulin therapy.
• Longer history of diabetes.
• Autonomic neuropathy.
• Decreased epinephrine secretion or sensitivity.

Clinical Picture

Signs and symptoms are caused by excessive secretion of catecholamines and CNS dysfunction:

• Adrenergic: Sweating, Tremors, Nervousness, Tachycardia, Hunger.
• Neuroglycopenic: Neurologic symptoms ranging from bizarre behavior and confusion to seizure and coma.

Hypoglycemia Unawareness:

• Hypoglycemia without warning symptoms.
• Even a single hypoglycemic episode can reduce neurohumoral counter-regulatory responses to subsequent episodes.

Management & Disposition

Treatment:

• D50% 1-2 vials (IV - IO - Central).
• If no line: Glucagon 1-2 mg IM.
• Note: If profound hypoglycemia $\to$ give octreotide (somatostatin).

Disposition:

• Insulin induced hypoglycemia: Can be discharged except for Lantus insulin (long acting).
• Oral hypoglycemic induced: Needs admission for 24h (due to half life of drug).

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2. Diabetic Ketoacidosis (DKA)

Insulin Function & Physiology

Mechanism of Insulin Action: Diagram Description:

• Basal State: Insulin and Glucose are separate; Glucose channel is closed.
• Insulin Action: Insulin inserts into the receptor $\to$ unlocks glucose channel $\to$ Glucose enters cell.
• Concept: Insulin is the key that unlocks the glucose channel.

Hormonal Balance (Whiteboard Notes):

• Anabolic hormones (Insulin):
  • Fatty acid $\to$ lipids
  • Amino acid $\to$ protein
  • Glucose $\to$ glycogenesis
• Catabolic hormones (Glucagon, Epinephrine, Norepinephrine, Cortisone):
  • Lipids $\to$ Fatty acid
  • Protein $\to$ Amino acid
  • Glucose $\to$ glycogenolysis

General Principles

• 5% of Type 2 DM has overlap or may have DKA.
• MODY Type 3 DM: DM Type 1 in old age or DM Type 2 in young age.
• Euglycemic DKA: 10% of DKA patients have normal Blood glucose (e.g., took insulin dose before ER).
• Diagnosis: Complete certainty depends on Anion Gap.
  • Normal anion gap = 100% DKA excluded.
  • Absence of Ketones in urine doesn’t exclude DKA (early presentation involves $\alpha$-hydroxybutyric acid which does not appear in standard urine ketone tests).
  • pH may be normal in mixed Metabolic acidosis and alkalosis.

Ketones:

1. $\beta$-hydroxybutyric acid (Most common, does not appear in urine tests).
2. $\alpha$-ketoacetate (Appears in urine).
3. Acetone (Fruity smell).

Pathophysiology

Complete or relative absence of Insulin and excess Counter-regulatory hormones result in:

1. Hyperglycemia (Gluconeogenesis)
2. Ketone formation (Lipolysis $\to$ FFAs $\to$ Liver)
3. Wide anion gap metabolic acidosis

Sequence of Events:

• Insulin Deficiency: Anabolic hormone lost $\to$ Catabolic hormones take over (Gluconeogenesis).
• Hyperglycemia $\to$ Glycosuria $\to$ Osmotic diuresis $\to$ Dehydration (Tachycardia, Hypotension) & Electrolyte Losses ($K^{+}$).
• Dehydration $\to$ Renal Failure / Shock / CV Collapse.
• Ketosis $\to$ Acidosis (Low pH) $\to$ Kussmaul breathing, Acetone smell, Abdominal pain (stretch of liver capsule).

Diagnostic Criteria

Suspect DKA if:

• pH $\le 7.3$
• Bicarbonate $\le 15\text{ mmol/L}$
• Anion gap $>12\text{ mmol/L}$
  • Formula: Serum Na – (chloride + bicarbonate)
• Ketones: Positive serum or urine ketones (Urine/Serum).
• Plasma glucose $\ge 14\text{ mmol/L}$ ($>250\text{ mg/dl}$) (but may be lower).
• Precipitating factor present.

Precipitating Causes & treat cause

1. Omission of insulin injection (MOST COMMON CAUSE).
2. Dislodged or obstructed insulin pump.
3. Infection / Sepsis (Primary reason for failure to respond).
4. Pregnancy.
5. Medication.
6. CVA.
7. GI Hemorrhage.
8. Pancreatitis.
9. Myocardial infarction (Small troponin rise may occur without ischemia; ECG changes may reflect hyperkalemia).
10. Thyrotoxicosis.
11. New diagnosis of diabetes.
12. Idiopathic (approx. 15%).

Investigations

• VBG, electrolytes, serum/urine ketones, Renal profile.
• Note: Urine test can only detect AcAc.
• High anion-gap can be the only clue to presence of metabolic acidosis.
• Sodium Correction: Add $1.6\text{mEq}$ to reported Na for every $100\text{mg}$ of glucose over $100\text{mg/dL}$.
• WBC: Increased due to stress & hemoconcentration (absolute bands $>10,000$ predict infection).

Management

Pillars of Treatment: Fluids, Potassium, Acidosis.

1. Fluids (Resuscitation)

• Goal: Replace Fluids with IV 0.9% NaCl until Euvolemic.
• Loss of water is typically 4-6L in DKA.
• Hypotensive: Bolus “fill the tank” $\to$ 2L.
• Normal BP: 1L bolus $\to$ 500ml/hr (4h) $\to$ 250 ml/hr (4h).
• Check Glucose hourly. When glucose reaches $250\text{ mg/dL}$ ($14\text{ mmol/L}$) $\to$ switch to D5% with Insulin.

2. Potassium ($K^{+}$)

• Hypokalemia is the most life-threatening electrolyte abnormality.
• Physiology: Acidosis shifts $K^{+}$ OUT of cells (Pseudohyperkalemia). Treating acidosis shifts $K^{+}$ back IN (risk of severe hypokalemia).
• Rule: Correct $K^{+}$ FIRST, then start insulin.
  • $K^{+}<3.3$: Give 40 mmol KCl + NO Insulin until $K^{+}\ge 3.3$.
  • $K^{+}3.3-5.5$: Give 10-40 mmol KCl (Less aggressive in renal failure).
  • $K^{+}>5.5$: No KCl, monitor.
• Other electrolytes: No IV Phosphate used in ED.

3. Acidosis (Insulin)

• Start Infusion: $0.1\text{ U/kg/h}$.
• Goal: used Treat the acidosis (normalize Anion Gap), NOT just the glucose.
• Note: ~25% of glucose decrease is driven by fluids alone.
• Maintain insulin until anion gap normalizes.
• Monitor: Glucose every 1h; VBG and Electrolytes every 2h for 6-8h.

4. Bicarbonate ($HC{O}_3$)

• Not routinely used. Only if pH $\le 6.9-7.0$.
• Give 1 ampoule/h until pH $\ge 7.0$.
• Complications of $HC{O}_3$:
  1. Hypokalemia.
  2. Paradoxical CNS acidosis.
  3. Worsening intracellular acidosis.
  4. Impaired O2 curve to left.
  5. Hypertonicity / Na overload.
  6. Delayed recovery from alkalosis.
  7. Elevation of lactate.
  8. Cerebral edema.

Mortality Factors:

• Low $HC{O}_3$ ($<10$), Infection/AMI, Old age, Severe hypotension/coma.
• Increased Osmolality, BUN, and Blood Glucose.
• Cerebral Edema: (Risk in young/new-onset). If neurologic change occurs $\to$ Mannitol before CT.
  • Note: Vascular thrombosis can occur (CNS).
• Underlying renal and CVS dis. Prolong and severe coma.

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3. Hyperosmolar Hyperglycemic State (HHS)

Also known as: Non-Ketotic Hyperosmolar Coma.

Overview & Pathogenesis

• Represents an extreme of the disease process (DKA vs HHS).
• Mechanism: Relative insulin deficiency (enough to prevent ketosis, not enough to prevent hyperglycemia).
• HHS vs DKA:
  • Severe Hyperglycemia ($>600\text{ mg/dl}$) & Hyperosmolality ($>315\text{ mOsm/kg}$).
  • Absence of ketogenesis.
  • Profound dehydration (8-12L water loss).
  • Higher Mortality (40-60%) due to older age and comorbidities. versus DKA (5-15%)
  • Hypokalemia, Sodium variable, Azotemia, Metabolic acidosis (lactic or uremic)

Biochemical Pathway differences:

• DKA: Increased Hormone Sensitive Lipase $\to$ FFA to liver $\to$ Ketogenesis $\to$ Acidosis.
• HHS: Increased Gluconeogenic enzymes $\to$ Hyperglycemia; but Hormone Sensitive Lipase activity prevents/limits ketogenesis $\to$ Hyperosmolarity.

Precipitating Causes

70-80% have an identifiable cause:

• Infections: Pneumonia, UTI, Sepsis.
• Events: Stroke, MI.
• Medications: diuresis, phenytoin, diazoxide, steroids, mannitol, cimetidine, immunosuppressive agents, etc.

Recognition

• Onset: Insidious (Days to Weeks).
• Clinical: Confusion, Seizure, Coma + Marked Shock/Dehydration.
• Labs: High Glucose, High Osmolality, No Ketones, Variable Sodium, Azotemia.

Management

Strategy similar to DKA:

1. Fluids: Initiate aggressive rehydration to treat hypovolemia, as patients typically lose 20–25% of their total body water.

   • Goal: Replace ½ of the fluid deficit within the first 12 hours and restore urine output to 50 ml/hour.
   • Fluid Selection:
     • Unstable: Normal Saline.
     • Stable: ½ NS or NS (requires close monitoring of fluid status).

2. Insulin: Note that patients are generally less resistant to insulin compared to DKA cases.

3. Dextrose: Add to regimen when blood glucose approaches 300 mg/dl.

4. Electrolytes:

   • Potassium: Replace once urine output is established.
   • Phosphate: Replace as needed.

• Treat precipitating causes
• Monitor intake and output
• Evaluate for other causes of coma

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Comparison: DKA vs HHS

Feature	Diabetic Ketoacidosis (DKA)	Hyperglycemic Hyperosmolar State (HHS)
Patient Profile	Younger, Type 1 Diabetes (mostly)	Older, Type 2 Diabetes (typically)
Onset	Acute (Hours to 1-2 days)	Insidious (Days to weeks)
Insulin Status	Absolute Deficiency	Relative Deficiency
Pathophysiology	Ketosis & Acidosis	Hyperosmolarity & Dehydration (No Ketosis)
Glucose	$>250\text{ mg/dL}$	$>600\text{ mg/dL}$ (Profound)
pH (Arterial)	$<7.3$	$>7.3$
Bicarbonate	$<15\text{ mEq/L}$	$>15\text{ mEq/L}$
Ketones	Moderate/Severe	Minimal/Absent
Osmolality	No hyperosmolality (typically)	$>320\text{ mOsm/L}$
Gap	Anion Gap $>12$	No Anion Gap
Volume Loss	4-6 Liters	8-12 Liters (Severe)
Mortality	5-15%	40-60%
Source: AACE (American Association of Clinical Endocrinologists)

Key Messages

• A normal or mildly elevated blood glucose does not rule out DKA (e.g., in pregnancy or SGLT2 inhibitor use).
• DKA Treatment: IV Insulin ($0.1\text{ units/kg/h}$) + Fluids + Potassium.
• Bicarbonate: Only for extreme acidosis ($\text{pH}\le 7.0$).