Hyperglycaemia

Causes of hyperglycaemia

Diabetes
- New-onset DM
- Gestational diabetes (glucose intolerance associated with pregnancy)
- Known DM (type I or II)
  - Poor control (usually poor glucose monitoring and poor compliance with therapy)
  - Inappropriate diet (high in simple sugars)
  - Reduced exercise
  - Change in insulin or oral hypoglycaemic regimen
Acute physiological stress
- Trauma, surgery
- Acute MI, CVA
- Severe illness including infection and sepsis
Endocrine
- Cushing’s syndrome (endogenous glucocorticoids)
- Acromegaly (excessive growth hormone)
Drugs
- Thiazide diuretics, beta-blockers,
- Antipsychotics e.g. olanzepine, clozapine
- Steroid administration (exogenous glucocorticoids)
- Other: antiretrovirals, phenytoin
Exogenous glucose load
- TPN, Peritoneal dialysate
Pancreatic injury (acute or chronic pancreatitis)
Factitious (false)
- Taking blood from a proximal vein containing dextrose
- Taking a fingerprick BGL from fingers covered in sugar.

Clinical manifestations

Diabetic ketoacidosis (DKA) Type I DM with acidosis (i.e. diabetic ketoacidosis)
- Volume depletion with dry skin, tachycardia, ±hypotension manifested with polyuria and polydipsia
- Acidosis:
  - Ketotic breath (sickly sweet, fruity smell)
  - Kussmaul’s breathing (deep, rapid, sighing respirations)
- Abdominal signs and symptoms
  - Anorexia, nausea, vomiting
  - Abdominal pain, ileus, gastric dilatation
  - DKA may mimic an acute surgical abdomen, so always check the urine in these patients (glycosuria)
- Neurological
  - Delirium, coma, hyporeflexia, hypotonia
Hyperosmolar non-ketotic syndrome (HHNS, previously known as HONK) - Type II DM without acidosis
- Volume depletion with dry skin, tachycardia, ±hypotension manifested by polyuria and polydipsia
- Weakness, lethargy, fatigue
- Confusion, convulsions and coma
- Focal neurological deficits.

Investigations

Serum glucose
Serum electrolytes (with calculation of the anion gap), urea, and plasma creatinine
- Sodium – may be low due to dilutional effect of hyperglycemia (osmosis), or high due to hyperglycemia-induced osmotic diuresis causing water loss.
- Total body phosphate depletion occurs – no benefit from replacement in DKA.
FBC with differential
Serum lipase (pancreatitis) – Note: up to 25% of DKA cases have elevated lipase – not actually pancreatitis
Plasma osmolality
Urinalysis and urine ketones by dipstick
Serum ketones (if urine ketones are present)
- Nitroprusside test can be falelsy negative as it does not react with beta-hydroxybutyrate
Arterial blood gas
Electrocardiogram – ECG manifestations
- Hyperkalaemia (usually at presentation)
- Hypokalaemia (secondary to treatment)
Additional testing performed on a case-by-case basis, such as cultures of urine, sputum, and blood, LP, serum lipase and amylase, and chest x-ray to look for precipitating cause

Correction

Correct volume depletion
- Give 500–1000 mL normal saline in IV boluses over the first hour until perfusion has normalised.
- Continue rehydration with 500 mL/h. The rate of subsequent fluid administration is guided by frequent reassessment of volume status, and response to therapy.
- The total body volume deficit in adults is 3–5 L or more, so patients may require saline at rates of 250–500 mL/h for the next 12–24 hours to restore euvolaemia.
- Caution: Patients with a history of CCF, or who weigh <50 kg, or are elderly should have slower fluid replacement to avoid iatrogenic fluid overload.
Begin an insulin infusion
- Actrapid or short-acting insulin 50 U IV in 50 mL normal saline via an infusion pump.
- Start the insulin infusion at 0.1 U/kg/h. Note: Bolus dose insulin is no longer recommended.
- Titrate the infusion rate to allow the blood sugar level to fall at around 10% per hour, and no more than 5 mmol/L/h.
- Continuous low-dose IV insulin remains the safest and most effective way of delivering insulin in a physiological manner to a sick patient.
Replace potassium
- Patients with DKA always have a total body deficit of potassium, even though most patients present with an initial high serum potassium level.
- Serum potassium levels will fall precipitously with volume replacement, insulin therapy and acidosis correction, as glucose is driven intracellularly, taking the extracellular potassium with it.
- After initial resuscitation, if serum potassium levels are <5 mmol/L and a good renal output has been maintained, potassium chloride is added to all replacement fluids at a rate of 10–20 mmol/h.
- Note: Potassium should not be administered if:
  - The patient is anuric
  - The serum potassium level is >6.0 mmol/L
Bicarbonate therapy (rarely if ever indicated)
- There is no evidence that the routine administration of sodium bicarbonate in DKA improves outcomes.
- In fact bicarbonate administration may cause harm, and delay recovery. The best treatment for significant metabolic acidosis is adequate volume resuscitation, insulin therapy and electrolyte replacement.
- Bicarbonate therapy may be considered if the pH remains <7.0 or in the presence of circulatory shock, when cardiac contractility will be compromised.
Commence heparin
- Unfractionated (UF) heparin 5000 units IV bolus, then infusion at 800–1000 units/h OR
- LMWH such as clexane 1.5 mg/kg/day.

Wean the insulin infusion
- Monitor BGL hourly. As it falls, the rate of insulin infusion should be slowed (e.g. 0.025–0.05 U/kg/h).
- When the BGL has fallen to <14 mmol/L, continue the insulin infusion and change the IV rehydration fluid from normal saline to 5% dextrose, until the ketoacidosis is reversed.
- Continue the insulin infusion until the BGL remains stable at 8–10 mmol/L. Monitor the bedside glucose every 4 hours, and commence adding supplemental regular insulin to keep the BGL between 8 and 10 mmol/L, as the insulin infusion is ceased.

Complications

Hypokalaemia
Cerebral oedema (rare) - up to 40% mortality
- Usually in patients <20 years of age
- Onset may be before treatment
- Little evidence base for management. Prevented by:
  - Gradual replacement of sodium and water (osmolality change of <3 mOsm/kg/h)
  - Avoiding over-aggressive correction of BGL (by adding in glucose as BGL falls)

Controversy

Somogyi effect
- The notion that nocturnal hypoglycemia causes hyperglycemia the following morning (the Somogyi hypothesis) has been discredited.
- The opposite is typically found, namely, a direct relation between the overnight blood glucose nadir and the following morning blood glucose value, ie, patients with morning hyperglycemia typically have high, not low, blood glucose concentrations at night. [Reference]
- The most common causes of morning hyperglycemia are nocturnal growth hormone secretion and hypoinsulinemia.
  - Tordjman, KM, Havlin, CE, Levandoski, LA, et al. Failure of nocturnal hypoglycemia to cause fasting hyperglycemia in patients with insulin-dependent diabetes mellitus. N Engl J Med 1987; 317:1552. [Reference]
  - Hirsch, IB, Smith, LJ, Havlin, CE, et al. Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM. Diabetes Care 1990; 13:133. [Reference]

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