Hypoglycaemia

https://www.racgp.org.au/getattachment/e5311638-b32d-4a11-88b3-9a35ee268d83/Hypoglycaemia-in-nondiabetic-patients-an-evidence.aspx

Traditional Classification:

• Postabsorptive (fasting) hypoglycaemia: Occurs when the individual is fasting.
• Postprandial (reactive) hypoglycaemia: Occurs within 4 hours after food ingestion.

Criticisms of Traditional Classification:

• It is diagnostically unhelpful because some conditions (e.g., insulinoma) can present with both postabsorptive and postprandial hypoglycaemia.
• Disorders such as factitious hypoglycaemia can present with symptoms independent of food intake.

Alternative Classification Based on Clinical Characteristics:

• Healthy-looking patients:
  • Accidental, surreptitious, or malicious hypoglycaemia.
  • Endogenous hyperinsulinism.
  • Idiopathic postprandial hypoglycaemia.
• Ill-appearing patients:
  • Hypoglycaemia due to critical illness.
  • Hormone deficiency.
  • Non-islet cell tumours.
• Drug-induced hypoglycaemia: Can occur in both healthy-looking and ill-appearing individuals.

from AustRAliAn FAmily PhysiciAn Vol. 39, no. 6, june 2010 = Hypoglycaemia in nondiabetic patients – an evidence based approach:

Common Causes of Hypoglycaemia:

• Drugs: Insulin and sulphonylureas are the most common drugs causing hypoglycaemia.
• Other drugs with moderate evidence in Australia: Indomethacin, pentamidine, quinine.

Specific Hypoglycaemia Types:

• Accidental Hypoglycaemia: Due to pharmacy or medication errors (e.g., sulphonylurea misdispensing).
• Factitious Hypoglycaemia: Often due to self-administration of insulin or hypoglycaemic agents, presenting with erratic neuroglycopenic symptoms.

Idiopathic Postprandial Hypoglycaemia:

• Mechanisms include:
  • High insulin sensitivity.
  • Exaggerated insulin response due to insulin resistance or increased glucagon-like peptide 1.
  • Renal glycosuria.
  • Defects in glucagon response.
• Dietary recommendations: Low carbohydrate/high protein diets, frequent feeding, and avoiding simple sugars, though efficacy lacks controlled clinical trial support.

Idiopathic Postprandial Syndrome (Pseudohypoglycaemia):

• Autonomic symptoms (tremor, tachycardia, sweating) appear 2–5 hours after a meal with normal plasma glucose.
• Possibly related to enhanced catecholamine release or sensitivity to postprandial noradrenaline/adrenaline.

Biochemical Differentiation of Hyperinsulinaemic Hypoglycaemia:

• Analysis of plasma insulin, C peptide, proinsulin, sulphonylurea, and anti-insulin antibody patterns helps differentiate causes.

common causes

medications

• Insulin:
  • Accidental, suicidal, iatrogenic, factitious.
• Drugs that increase insulin secretion:
  • Sulfonylureas (glimepiride, glipizide, especially glyburide).
  • Meglitinides (repaglinide, nateglinide).
  • Pentamidine.
• Other mechanisms (evidence for many of these drugs is questionable)
  • Diabetes medications not listed above (e.g., SGLT-2 inhibitors, metformin). These usually don’t cause hypoglycemia on their own, but may synergize with other risk factors.
  • Antibiotics (fluoroquinolones, sulfonamides, pentamidine, artemisinin antimalarials).
  • Neurologic: Phenytoin, selegiline, valproate.
  • Psychiatric: doxepin, haloperidol, fluoxetine, lithium.
  • Cardiovascular: Nonselective beta-blockers (propranolol, nadolol), ACE inhibitors.
  • Other:
    • NSAIDs (especially indomethacin).
    • Quinine.
    • Hydroxychloroquine.
    • Salicylate intoxication.

specific diseases

• Adrenal insufficiency.
• Myxedema coma.
• Hepatic failure.
• Sepsis.
• Renal failure (usually not by itself; note that renal dysfunction may cause accumulation of many medications).
• Insulinoma or various malignancies (e.g., mesenchymal tumors, hematologic malignancies).
• Status post gastric bypass surgery
  • Post-prandial hypoglycemia can also occur due to a rapid surge of insulin (‘late dumping’) following rapid entry of food into the small intestine. This may occur after gastric surgery, for instance.

intake/use mismatch

• Starvation, anorexia nervosa.
• Exercise.
• Pregnancy/lactation.
• Alcohol binging.

pseudohypoglycemia

• leukocytosis, thrombocytosis, or erythrocytosis can cause excess consumption of glucose in the collection vial while the sample awaits testing.

Defining Hypoglycemia in Adults and Management Approach

Blood Glucose Levels (BGL) Standards:

• Moderate Hypoglycemia: 2.2-3.9 mmol/L (40-70 mg/dL).
• Severe Hypoglycemia: <2.2 mmol/L (<40 mg/dL); levels <2.8 mmol/L (<50 mg/dL) can cause coma.

Symptom Evaluation:

• Hypoglycemia symptoms are nonspecific, vary among individuals, and may change over time.
• Typically, symptoms develop at plasma glucose levels of ~3.0 mmol/L in healthy individuals.
• Recurrent hypoglycemia lowers the glycemic threshold for symptom response.
• Insulin surges (e.g., post-glucose load) can cause venous glucose to appear significantly lower than arterial glucose, affecting brain glucose metabolism.

• autonomic symptoms
  • pale skin
  • sweating
  • shaking
  • palpitations
  • feeling of anxiety
  • dizziness
• neuroglycopenic symptoms
  • hunger
  • change in intellectual processing
  • confusion and changes in behaviour (eg irritability)
  • paraesthesia
  • coma and seizures.

Whipple’s Triad: Key Criteria for Diagnosing Hypoglycemia

1. Symptoms and/or signs consistent with hypoglycemia.
2. Low plasma glucose concentration.
3. Resolution of symptoms/signs after plasma glucose is raised to normal

Named after the American surgeon Allen Oldfather Whipple (1881-1963) who described the triad indicative of potential hyperinsulinemia secondary to pancreatic insulinoma [The Surgical Therapy of Hyperinsulinism. Journal International de Chirurgie.1938; 3: 237-276]

Key Evaluation for Hypoglycemia

• Medication History: Common causes include insulin and sulfonylureas; consider changes in renal/hepatic function.
• Assess Intake and Other Conditions: Poor intake, alcohol use, sepsis, adrenal insufficiency, or hepatic failure may contribute.

Investigations

No single plasma glucose concentration universally defines hypoglycemia.A normal glucose level during symptoms eliminates the possibility of a hypoglycemic disorder.Diagnosis should be based on laboratory glucose measurement; blood glucose meters are unreliable in hypoglycemic ranges. (from AustRAliAn FAmily PhysiciAn Vol. 39, no. 6, june 2010 = Hypoglycaemia in nondiabetic patients – an evidence based approach)

Additional Laboratory Tests if the Cause Remains Unclear

• Insulin Level: >21 pmol/L suggests excess insulin production or administration.
• C-Peptide Level: >0.6 ng/ml indicates endogenous insulin production.
• Beta-Hydroxybutyrate: Elevated levels suggest starvation, ketoacidosis, or sepsis, arguing against hyperinsulinemia.
• Cortisol Levels: Low cortisol in stressed, hypoglycemic patients indicates possible adrenal insufficiency; consider ACTH stimulation.
• TSH and Liver Function Tests: Evaluate thyroid function and liver health.

Immediate Hypoglycemia Management

1. Conscious Patients:
   • Treat with oral glucose or sucrose (e.g., glucose tablets, sugary drinks).
   • Follow the ‘Rule of 15’:
     • 15 grams of quick-acting carbohydrate: (e.g., ½ can of regular soft drink, ½ glass of fruit juice, 3 teaspoons of sugar or honey, 6–7 jellybeans, or 3 glucose tablets).
     • Wait 15 minutes and recheck BGL. If BGL remains low, provide another 15 grams of carbohydrate.
     • If the next meal is over 15 minutes away, provide a longer-acting carbohydrate (e.g., a sandwich, milk, fruit, or yogurt).
     • Recheck glucose levels during the next 2–4 hours.
2. Unconscious Patients:
   • Administer glucagon 1 mg SC, IM, or IV; a glucagon hypo kit is available through PBS, suitable for home and work.
     • Glucagon may not work, if the patient’s liver glycogen stores are depleted.
     • Glucagon can stimulate vomiting, which may be particularly dangerous if the patient has altered mental status and cannot protect their airway.
     • Glucagon takes 10-15 minutes to work, which seems like a fairly long delay for a patient with severe hypoglycemia.
   • If glucagon fails, give IV 50% glucose (20-30 mL).
3. Severe Hypoglycemia (Hypoglycemic Coma):
   • Commence resuscitation protocols.
   • obtain IV access immediately
   • Once conscious and able to swallow, provide oral carbohydrates.

Management of Severe Hypoglycemia

1. IV Dextrose Bolus:
   • Use 50-100 ml of D50W or 100-200 ml of D10W based on severity; titrate to achieve safe glucose levels (5.6-11.2 mmol/L or 100-200 mg/dL).
2. Dextrose Infusion:
   • Infuse D5W or D10W peripherally or use D20W/D50W centrally if central access exists.
3. Octreotide for Sulfonylurea Toxicity:
   • Load with 100 mcg IV, then 50 mcg SC q6hr.
4. Steroids:
   • IV hydrocortisone 100 mg Q6hr may be used to reduce dextrose requirements in adrenal insufficiency or massive insulin overdose.

POST DISCHARGE

1. Hypoglycemia Awareness and Management

• Education: Patients should be educated on recognizing hypoglycemia symptoms, such as sweating, tremors, dizziness, confusion, and visual disturbances.
• Self-Monitoring: Regular blood glucose monitoring is crucial. Patients should be instructed on when and how often to check glucose levels, especially before driving, exercising, or during illness.
• When to Monitor
  • Typically, BGL should be checked
    • before meals
    • before bedtime
    • before exercising
    • when feeling unwell
    • before critical tasks like driving.
• Hypoglycemia Action Plan:
  • Mild Hypoglycemia: Treat with 15 grams of quick-acting carbohydrate, recheck BGL after 15 minutes, and repeat if necessary (Rule of 15).
  • Severe Hypoglycemia: Administer glucagon (available through PBS) if unconscious, followed by IV glucose if glucagon is ineffective and healthcare access is immediate.

2. Austroads Requirements and Driver’s Licence Authority Notification

• Type 1 and Type 2 Diabetes on Insulin:
  • Notification Requirement: Patients on insulin therapy must inform the Driver’s Licence Authority of their condition.
  • Fitness to Drive: Assessment is required if experiencing frequent hypoglycemia or unawareness. A medical clearance may be necessary.
  • Driving Recommendations:
    • Check BGL before driving and every 2 hours during long trips.
    • Do not drive if BGL is <5.0 mmol/L; treat hypoglycemia first.
    • Always carry fast-acting glucose in the vehicle.
• Type 2 Diabetes Not on Insulin:
  • Notification: Generally not required unless experiencing severe hypoglycemia.
  • Driving Safety: Maintain routine blood glucose checks and avoid driving during hypoglycemic episodes.

3. Emergency Situation Management

• Emergency Kit: Patients should have an emergency kit containing glucagon, glucose tablets, and a medical alert bracelet.
• Family/Friend Training: Ensure family and friends are trained to recognize hypoglycemia and administer glucagon if necessary.
• Ambulance Contact: In cases of severe hypoglycemia, call emergency services (dial 000) and state it’s a ‘diabetic emergency.’
• Educate about the need for a medical ID bracelet and carrying emergency contact information.

4. Sick Day Management for Diabetes on Insulin

• Monitoring: Increase blood glucose checks (every 2-4 hours) and monitor ketones if unwell, especially if BGL >15 mmol/L.
• Medication Adjustments:
  • Continue basal insulin even if not eating to prevent ketoacidosis.
  • Adjust rapid-acting insulin based on blood glucose readings.
• Hydration and Carbohydrate Intake:
  • Stay hydrated with water, sugar-free fluids, and consider carbohydrate intake if unable to eat regular meals (e.g., soup, juice).
• When to Seek Medical Help:
  • Persistent high glucose levels (>15 mmol/L) with ketones.
  • Vomiting, unable to maintain hydration, or severe symptoms.
  • Uncertainty about insulin dosing during illness.

5. Recommendations for Follow-Up Care

• GP/Specialist Review: Arrange follow-up with a GP or endocrinologist to review diabetes management, adjust medications, and ensure proper sick day plans are in place.
• Medication Review: Check for adjustments in insulin doses or any necessary changes to oral medications.
• Continued Education: Reinforce the importance of hypoglycemia prevention strategies, glucose monitoring, and adherence to sick day management protocols.
• Diet and Exercise:
  • Discuss the impact of food choices and physical activity on blood glucose levels.
  • Highlight the need for carbohydrate counting or understanding the glycemic index of foods.
• Insulin
  • Injection Technique:
    • Demonstrate how to inject insulin properly, including site rotation (abdomen, thighs, buttocks, upper arms).
    • Inject at least 1 inch away from the previous site and avoid areas with scars or moles.
    • Ensure proper injection technique (needle length, angle of insertion).
    • Discuss the importance of proper needle disposal.
    • Inform about possible reactions at the injection site and how to manage them.
  • Storage and Handling:
    • Instruct on proper storage of insulin (refrigeration of unused vials/pens, room temperature for in-use insulin).
    • Advise against using insulin past its expiration date or if it appears cloudy (for clear insulins).