What is the recommended acute treatment, diagnostic work‑up, and long‑term management for a patient with confirmed hypoglycaemia (blood glucose ≤3.9 mmol/L)?

Hypoglycaemia Investigations and Management

Acute Treatment Protocol

For any conscious patient with confirmed hypoglycaemia (blood glucose ≤3.9 mmol/L), immediately administer 15-20 grams of oral glucose as first-line treatment. 1, 2

Immediate Treatment Steps:

• Pure glucose tablets or solution are the preferred treatment because the glycemic response correlates more closely with actual glucose content than total carbohydrate content 1, 2
• Any carbohydrate-containing food with glucose can be used if pure glucose is unavailable, though glucose tablets/solution remain most effective 1, 2
• Recheck blood glucose 15 minutes after initial treatment 1, 2
• If hypoglycaemia persists (glucose still ≤3.9 mmol/L), repeat with another 15-20 grams of carbohydrate 1, 2
• Recheck blood glucose again at 60 minutes after initial treatment, as additional intervention may be required 2
• Once glucose normalizes, the patient should consume a meal or snack containing complex carbohydrates and protein to prevent recurrence 1, 2

Critical Treatment Pitfalls to Avoid:

• Do not add fat to the carbohydrate source used for acute treatment, as fat slows and prolongs the glycemic response 1, 2
• Do not use protein-rich foods alone to treat hypoglycaemia, as protein may increase insulin secretion without raising plasma glucose, particularly in type 2 diabetes 1, 2
• Never delay treatment while waiting for blood glucose confirmation if testing is not immediately available 3

Severe Hypoglycaemia (Unconscious or Unable to Take Oral Treatment):

• Administer glucagon immediately via intramuscular, subcutaneous, or intranasal route for patients unable or unwilling to consume oral carbohydrates 1, 4
• Newer intranasal and ready-to-inject glucagon preparations are preferred over traditional reconstitution kits due to ease of administration and more rapid correction 4
• Standard dosing: 1 mg (1000 mcg) for adults and children ≥25 kg or ≥6 years; 0.5 mg (500 mcg) for children <25 kg or <6 years 4
• If no response to glucagon or in hospital settings with IV access, administer 20-40 mL of 50% dextrose solution intravenously 3
• Nausea and vomiting are common side effects of glucagon; ensure airway protection before administration in patients with altered mental status 4

Diagnostic Work-Up

Classification of Hypoglycaemia Severity:

The American Diabetes Association classifies hypoglycaemia into three levels that guide diagnostic evaluation: 1, 3

• Level 1 (Alert Value): Glucose <3.9 mmol/L but ≥3.0 mmol/L - sufficiently low to warrant treatment and medication adjustment
• Level 2 (Clinically Significant): Glucose <3.0 mmol/L - indicates serious hypoglycaemia requiring immediate action
• Level 3 (Severe): Altered mental/physical status requiring external assistance for recovery, regardless of glucose level

Immediate Diagnostic Assessment:

• Document blood glucose level before treatment whenever possible, though treatment should never be delayed 3
• Record all symptoms present: shakiness, irritability, confusion, tachycardia, hunger, and document their resolution with treatment 3
• Determine timing of hypoglycaemia relative to meals, exercise, alcohol consumption, and medication administration 1

Investigation of Underlying Causes:

Any episode of Level 2 hypoglycaemia (<3.0 mmol/L) or Level 3 hypoglycaemia mandates immediate reevaluation of the treatment regimen. 1, 3

Key factors to investigate: 1

• Medication review: Insulin dosing (timing, type, dose), sulfonylureas, meglitinides, or other glucose-lowering agents
• Renal function: Declining renal function increases hypoglycaemia risk and may require medication dose reduction
• Cognitive function: Cognitive impairment is both a risk factor for and consequence of severe hypoglycaemia
• Nutritional factors: Delayed or skipped meals, inadequate carbohydrate intake, alcohol consumption
• Exercise patterns: Intense or prolonged physical activity without appropriate carbohydrate adjustment
• Hypoglycaemia unawareness: Loss of typical warning symptoms indicating impaired counterregulatory responses

Risk Stratification:

High-risk populations requiring enhanced surveillance include: 1

• Adults over 60 years of age
• African American individuals (substantially increased risk)
• Patients with renal impairment or albuminuria
• Those with cognitive impairment or declining cognitive function
• Patients with poor glycemic control (paradoxically at higher risk)
• Insulin users, particularly those on intensive regimens

Long-Term Management

Medication Adjustment Strategy:

For insulin-treated patients with hypoglycaemia unawareness or recurrent Level 2/3 hypoglycaemia, raise glycemic targets to strictly avoid hypoglycaemia for at least several weeks to partially reverse hypoglycaemia unawareness. 1, 3

Specific medication modifications: 1

• Consider deintensifying or switching diabetes medications when risks exceed benefits, particularly insulin, sulfonylureas, or meglitinides
• For patients on basal-bolus insulin with recurrent hypoglycaemia, consider switching to a basal-plus approach (basal insulin with corrective doses only)
• Avoid sliding scale insulin as sole therapy - it is associated with higher hypoglycaemia rates 1
• Sulfonylureas (especially chlorpropamide) carry high risk of prolonged hypoglycaemia; newer agents (gliclazide MR, glimepiride) have lower but still significant risk 1
• Metformin alone carries minimal hypoglycaemia risk and may be continued safely 1

Glycemic Target Adjustment:

The American Diabetes Association changed preprandial targets from 3.9-7.2 mmol/L to 4.4-7.2 mmol/L specifically to provide a safety margin and limit overtreatment 1

• Maintain blood glucose >3.9 mmol/L (70 mg/dL) as the alert threshold for treatment 1, 3
• For high-risk patients, consider raising targets further to prevent recurrent episodes 1, 3
• Postprandial targets <10.0 mmol/L (180 mg/dL) can help achieve A1C goals without excessive hypoglycaemia risk 1

Monitoring and Technology:

• Self-monitoring of blood glucose (SMBG) is essential for all patients at risk of hypoglycaemia 1
• Continuous glucose monitoring (CGM) with automated low glucose suspend is highly effective in reducing hypoglycaemia in type 1 diabetes 1
• CGM detects approximately 17 times more nocturnal asymptomatic hypoglycaemia episodes than SMBG alone 5
• For patients with persistent Level 3 hypoglycaemia and hypoglycaemia unawareness despite medical treatment, human islet transplantation may be considered, though it remains experimental 1

Patient and Caregiver Education:

All patients at risk for clinically significant hypoglycaemia should be prescribed glucagon, and caregivers must be trained in its administration. 1, 4

Essential education components: 1, 4

• Caregivers, family members, school personnel, childcare professionals, and coworkers should know where glucagon is kept, when to administer it, and how to administer it
• Explicit education to never administer insulin to individuals experiencing hypoglycaemia 4
• Patients should understand high-risk situations: fasting for tests/procedures, delayed meals, alcohol consumption, intense exercise, and sleep 1
• Ensure immediate access to glucose tablets or glucose-containing foods at all times 3
• Replace glucagon products when they reach expiration date 1, 4

Prevention Strategies:

• Individualized glucose targets, dietary intervention (bedtime snack when needed), exercise management, and medication adjustment improve outcomes in high-risk populations 1
• For hospitalized patients, implement standardized hypoglycaemia treatment protocols and review treatment regimens when glucose <3.9 mmol/L is documented 3
• Use predictive algorithms to identify patients at high risk for inpatient hypoglycaemia 3
• Balance insulin use with carbohydrate intake and exercise, though these strategies alone are not always sufficient 1

Ongoing Surveillance:

• Assess for symptomatic and asymptomatic hypoglycaemia at every clinical encounter 1
• Monitor cognitive function with increased vigilance for hypoglycaemia if declining cognition is detected 1
• Recognize that severe hypoglycaemia in older adults with type 2 diabetes is associated with increased dementia risk 1
• Any unexplained or recurrent severe hypoglycaemia requires consideration of hospital admission for observation and stabilization 3