12.3 Acute Diabetic Emergencies (DKA & HHS)

Acute decompensated diabetic metabolic emergencies—diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS)—represent life-threatening medical crises with distinct pathophysiology, biochemical parameters, and resuscitation protocols. Mastery of the Joint British Diabetes Societies (JBDS) guidelines for fluid, insulin, and electrolyte titration is a cornerstone of the MRCP(UK) Part 1 examination.

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1. Diabetic Ketoacidosis (DKA): Pathophysiology & Diagnostic Criteria

Pathophysiological Cascade

DKA arises from absolute or relative insulin deficiency compounded by an exaggerated surge of counter-regulatory stress hormones (glucagon, catecholamines, cortisol, growth hormone):

1. Unchecked Lipolysis: Adipose tissue triglyceride lipolysis releases non-esterified free fatty acids (FFAs) into the portal circulation.
2. Hepatic Ketogenesis: In the liver, diminished malonyl-CoA levels relieve physiological inhibition of carnitine palmitoyltransferase-1 (CPT-1). FFAs are actively transported into hepatic mitochondria, undergoing beta-oxidation into acetyl-CoA, which condenses into acetoacetate and beta-hydroxybutyrate.
3. Acid-Base Disturbance: Accumulation of organic ketoacids generates a severe high anion gap metabolic acidosis with compensatory respiratory alkalosis (Kussmaul breathing: rapid, deep respirations to blow off carbon dioxide).
4. Osmotic Diuresis & Dehydration: Hyperglycaemia exceeds the renal absorptive threshold, triggering osmotic diuresis with marked loss of water, sodium, potassium, phosphate, and magnesium (average adult water deficit: $5\text{–}7\text{ litres}$ or $100\text{ mL/kg}$).

JBDS Diagnostic Triad for DKA

Diagnosis requires the presence of all three components:

• D (Diabetes / Hyperglycaemia): Blood glucose $> 11.0\text{ mmol/L}$ OR previously known diabetes mellitus.
• K (Ketonaemia): Capillary / venous blood beta-hydroxybutyrate $\ge 3.0\text{ mmol/L}$ (or heavy ketonuria $\ge 2+$ on dipstick if blood ketone testing unavailable). Point-of-care blood ketone meters specifically measure beta-hydroxybutyrate, avoiding the latency and false-negative profile of urine test strips (which measure only acetoacetate via the nitroprusside reaction).
• A (Acidosis): Venous blood gas bicarbonate $< 15.0\text{ mmol/L}$ and/or venous $\text{pH} < 7.30$.

Euglycaemic DKA (euDKA)

Euglycaemic DKA is characterized by significant ketoacidosis ($\text{pH} < 7.30$, $\text{HCO}_3^- < 15\text{ mmol/L}$, blood ketones $\ge 3.0\text{ mmol/L}$) in the presence of normal or near-normal blood glucose ($< 11.0\text{ mmol/L}$):

• Etiological Triggers: SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin), pregnancy (enhanced GFR and fetal glucose utilization), prolonged fasting, low-carbohydrate ketogenic diets, severe chronic liver disease, alcohol abuse.
• SGLT2i Mechanism: SGLT2 inhibition promotes massive renal glycosuria, lowering circulating plasma glucose. The lower glucose dampens endogenous pancreatic insulin secretion while directly stimulating pancreatic alpha-cells to secrete glucagon. The resulting high glucagon-to-insulin ratio stimulates uninhibited hepatic CPT-1 activity and rapid ketogenesis despite euglycaemia.
• Management Rule: Manage identically to standard DKA, but start 10% dextrose concurrently with fixed-rate insulin from the outset to prevent catastrophic hypoglycaemia while clearing ketonaemia.

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2. Joint British Diabetes Societies (JBDS) DKA Management Protocol

Resuscitation focuses on restoring intravascular volume, suppressing lipolysis/ketogenesis with fixed-rate insulin, replacing potassium, and monitoring metabolic clearance targets.

DKA Resuscitation Algorithm (JBDS Guidelines):
[Fluid Protocol: 0.9% NaCl]
- 1st L over 1h → 2nd L over 2h (+KCl) → 3rd L over 2h (+KCl) → 4th L over 4h (+KCl) → 5th L over 4h (+KCl) → 6th L over 8h (+KCl)
- When blood glucose < 14.0 mmol/L → Add 10% Dextrose at 125 mL/h concurrently with 0.9% NaCl

[Insulin Protocol: Fixed-Rate IV Infusion (FRIII)]
- 0.1 units/kg/h based on actual body weight (NO IV bolus!)
- Continue regular subcutaneous basal insulin (glargine/degludec) at normal schedule

[Potassium Replacement Protocol]
- K+ > 5.5 mmol/L → Nil KCl
- K+ 3.5–5.5 mmol/L → Add 40 mmol KCl per litre of IV fluid
- K+ < 3.5 mmol/L → STOP/DELAY insulin, give urgent IV KCl (40–60 mmol/h) until K+ > 3.5 mmol/L

Metabolic Clearance Targets & Monitoring

• Check capillary glucose and capillary blood ketones hourly; venous blood gas (VBG), potassium, and sodium at 2, 4, 8, 12, and 24 hours.
• Clearance Targets:
  1. Reduction in blood ketones by $\ge 0.5\text{ mmol/L/hour}$.
  2. Increase in venous bicarbonate by $\ge 3.0\text{ mmol/L/hour}$.
  3. Reduction in blood glucose by $\ge 3.0\text{ mmol/L/hour}$.
• If clearance targets are not met: check infusion pump and cannula patency; increase insulin infusion rate by $1.0\text{ unit/hour}$ increments until target rates of fall are established.

DKA Resolution & Subcutaneous Transition

• Resolution Criteria (JBDS): Blood beta-hydroxybutyrate $< 0.6\text{ mmol/L}$, venous $\text{pH} > 7.30$, venous bicarbonate $\ge 18.0\text{ mmol/L}$, and patient is alert and tolerating oral intake.
• Transition Rule: Administer subcutaneous rapid-acting prandial insulin with a meal, and continue the IV insulin infusion for 30–60 minutes after the injection before stopping the infusion. Stopping the infusion prematurely without prior subcutaneous cover precipitates rebound ketoacidosis.

Life-Threatening Complications of DKA

• Cerebral Oedema: Occurs predominantly in children and young adults (peak incidence 4–12 hours into resuscitation). Driven by rapid reduction in serum effective osmolality and excessive fluid administration. Features: headache, lethargy, bradycardia, hypertension (Cushing's triad), declining GCS. Treatment: immediate IV mannitol ($0.5\text{–}1.0\text{ g/kg}$ over 20 min) or hypertonic 3% saline ($2.5\text{–}5.0\text{ mL/kg}$), elevate bed head to 30°, restrict fluids, urgent non-contrast CT head.
• Hyperchloraemic Metabolic Acidosis: Non-anion gap metabolic acidosis that routinely appears late during resuscitation. Caused by preferential renal excretion of ketoacids while infused chloride from large volumes of $0.9%$ NaCl ($154\text{ mmol/L } \text{Cl}^-$) is retained. Self-limiting; does not require insulin prolongation once ketonaemia has resolved.

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3. Hyperosmolar Hyperglycaemic State (HHS)

Pathophysiology

HHS occurs predominantly in elderly Type 2 diabetic patients. A small amount of residual endogenous insulin is present—sufficient to suppress adipose lipolysis and prevent ketogenesis (antilipolytic insulin concentration is ~1/10th that needed for glucose disposal), but inadequate to stimulate peripheral glucose uptake or suppress hepatic gluconeogenesis. Unchecked extreme hyperglycaemia causes profound osmotic diuresis, evolving insidiously over days to weeks.

JBDS Diagnostic Criteria for HHS

1. Severe Dehydration & Hypovolaemia: Profound volume deficit ($100\text{–}220\text{ mL/kg}$, average $8\text{–}12\text{ litres}$ in an adult).
2. Marked Hyperglycaemia: Blood glucose typically $\ge 30.0\text{ mmol/L}$.
3. Elevated Serum Effective Osmolality: Calculated effective osmolality $> 320\text{ mOsm/kg}$ ($2 \times [\text{Na}^+] + \text{glucose}$). Total osmolality including urea is not used for management decisions because urea freely permeates cell membranes.
4. Absence of Significant Ketoacidosis: Venous $\text{pH} > 7.30$, venous bicarbonate $> 15.0\text{ mmol/L}$, and blood ketones $< 3.0\text{ mmol/L}$ (mild ketonuria/ketonaemia may occur secondary to starvation).

HHS Management Principles

• Primary Therapy is Fluid Resuscitation: $0.9%$ sodium chloride is the initial crystalloid. Rehydrate slowly, aiming to replace the total fluid deficit over 48 to 72 hours.
• Target Osmolality Fall: Target a gradual fall in serum osmolality of $3.0\text{–}8.0\text{ mOsm/kg/hour}$. Precipitous osmolality drops risk cerebral oedema or central pontine myelinolysis.
• Sodium Dynamics: In severe hyperglycaemia, water shifts from intracellular to extracellular compartments, diluting measured serum sodium. As rehydration proceeds and glucose drops, measured sodium will naturally rise. If measured sodium fails to rise or drops while glucose falls, free water is being administered too rapidly. Only switch to $0.45%$ NaCl if osmolality is not declining despite adequate fluid and corrected sodium is progressively rising.
• Insulin Strategy in HHS: Withhold insulin at presentation! Fluid resuscitation alone restores renal perfusion, lowering blood glucose by $\sim 5\text{ mmol/L/hour}$. Start low-dose fixed-rate insulin ($0.05\text{ units/kg/hour}$) ONLY if blood ketones are $\ge 1.0\text{ mmol/L}$ or blood glucose ceases to fall with fluid resuscitation alone.
• Mandatory Thromboprophylaxis: Extreme hyperviscosity, dehydration, advanced age, and immobility confer a catastrophic risk of arterial and venous thromboembolism. Prophylactic low-molecular-weight heparin (LMWH) is mandatory for all patients unless actively bleeding.

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4. DKA vs. HHS: Comparative Analysis

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5. Severe Hypoglycaemia & Sulfonylurea Toxicity

Clinical Manifestations & Whipple's Triad

Hypoglycaemia is defined clinically by Whipple's Triad:

1. Symptoms and signs consistent with neuroglycopenia or autonomic activation.
2. Measured low plasma glucose ($< 4.0\text{ mmol/L}$ in diabetic patients; $< 3.0\text{ mmol/L}$ in healthy individuals).
3. Prompt resolution of symptoms following carbohydrate administration.

• Autonomic Features (threshold ~3.6 mmol/L): Tremor, palpitations, diaphoresis, pallor, anxiety, hunger, perioral paraesthesia.
• Neuroglycopenic Features (threshold ~2.8 mmol/L): Confusion, drowsiness, bizarre behaviour, speech difficulty, visual disturbances, seizures, focal neurological deficits (mimicking stroke), coma.
• Hypoglycaemia Unawareness: Blunting or loss of sympathetic autonomic warning signs due to repeated episodes of hypoglycaemia inducing central autonomic neuropathy. Markedly increases the risk of severe, catastrophic neuroglycopenia.

Emergency Management Pathways

Hypoglycaemia Emergency Algorithm:
- Conscious / Cooperative Patient:
  → 15–20g fast-acting oral carbohydrate (200 mL fruit juice, 4–5 jelly babies, 170 mL Lucozade)
  → Recheck capillary glucose at 15 minutes; repeat if < 4.0 mmol/L
  → Once glucose > 4.0 mmol/L, give long-acting complex carbohydrate (slice of bread, regular meal)

- Impaired Consciousness / Unconscious Patient:
  • IV Access Available:
    → 100–150 mL of 20% Dextrose IV over 10–15 minutes (or 200 mL 10% Dextrose)
    → Avoid 50% Dextrose (causes severe extravasation injury, chemical phlebitis, rebound hyperinsulinaemia)
  • NO IV Access:
    → 1 mg Intramuscular (IM) Glucagon (or SC)
    → Mobilizes hepatic glycogen; ineffective in starvation, liver cirrhosis, or sulfonylurea toxicity

Sulfonylurea-Induced Refractory Hypoglycaemia

• Sulfonylureas (gliclazide, glimepiride, glibenclamide) bind SUR1 subunits, triggering autonomous insulin exocytosis independent of ambient glucose. Administering boluses of IV dextrose stimulates further endogenous insulin secretion, precipitating vicious cycles of severe rebound hypoglycaemia.
• Patients mandate hospital admission and continuous monitoring for at least 24 to 48 hours.
• Pharmacological Antidote: If hypoglycaemia recurs despite continuous dextrose infusion, administer octreotide ($50\text{–}100\text{ mcg}$ SC or IV every 8–12 hours). Octreotide is a synthetic somatostatin analogue that binds to somatostatin receptor-2 on pancreatic $\beta$-cells, closing voltage-gated calcium channels and shutting down sulfonylurea-stimulated insulin exocytosis.