What are the new strategies for treating recurrent hypoglycemia?

New Strategies for Treating Recurrent Hypoglycemia

For patients with recurrent hypoglycemia, implement a tiered four-stage algorithm: structured hypoglycemia-specific education (stage 1), add continuous glucose monitoring or insulin pump therapy (stage 2), implement sensor-augmented pumps with low-glucose suspend features (stage 3), and consider islet or pancreas transplantation for refractory cases (stage 4). 1

Immediate Assessment and Risk Stratification

Screen all patients at risk for hypoglycemia at every clinical encounter to document frequency, severity, and timing of episodes 1. Specifically assess for:

• Impaired hypoglycemia awareness using validated tools (Gold, Clarke, or Pedersen-Bjergaard questionnaires), which increases severe hypoglycemia risk 6-20 fold 1
• Problematic hypoglycemia criteria: two or more severe episodes in the past 12 months, or one severe episode associated with impaired awareness, extreme glycemic lability, or major fear and maladaptive behavior 1
• Contributing factors: insulin dosing errors (inappropriate basal/bolus balance, excessive correction doses, inappropriate timing), meal pattern changes, exercise timing, alcohol consumption, and psychological factors including fear of hyperglycemia or depression 1

Stage 1: Structured Education (All Patients)

All patients with recurrent hypoglycemia must undergo structured or hypoglycemia-specific education programs as the foundation of treatment 1. This includes:

• Treat at the hypoglycemia alert value of 70 mg/dL (3.9 mmol/L) or less with 15-20g of fast-acting carbohydrates 1
• Pure glucose is preferred because glycemic response correlates better with glucose content than total carbohydrate content 1
• Recheck glucose after 15 minutes; if hypoglycemia persists, repeat treatment 1
• After recovery, consume a meal or snack to prevent recurrence due to ongoing insulin activity 1

Critical caveat: Protein sources should not be used to treat hypoglycemia as they may increase insulin secretion without raising blood glucose 1. Added fat slows and prolongs glycemic response, delaying recovery 1.

Stage 2: Add One Diabetes Technology

If targets are not met after 3-6 months of structured education, add either continuous glucose monitoring (CGM) or continuous subcutaneous insulin infusion (insulin pump) 1.

Medication Optimization at This Stage:

• Switch from regular and NPH insulins to insulin analogs, which have lower hypoglycemia risk 1
• Avoid premixed insulins 1
• Reduce basal insulin by 10-20% if nocturnal or fasting hypoglycemia occurs 2
• Review insulin-to-carbohydrate ratios and carbohydrate counting accuracy 2
• Temporarily raise glycemic targets for patients with recurrent severe hypoglycemia 1, 2

Important consideration: Changes in injection sites from areas of lipodystrophy to unaffected areas can cause sudden hypoglycemia; closely monitor when making this change 3.

Stage 3: Advanced Technology and Specialized Care

For patients with continued problematic hypoglycemia despite education and one technology, implement sensor-augmented insulin pumps with automated low-glucose suspend features and/or very frequent contact with a specialized hypoglycemia service 1.

Hypoglycemia Unawareness Management:

Implement a 2-3 week period of scrupulous avoidance of hypoglycemia to restore awareness in affected patients 4. This reverses hypoglycemia unawareness in most cases by shifting glycemic thresholds for sympathoadrenal responses back to higher glucose concentrations 4.

Stage 4: Transplantation

For patients whose problematic hypoglycemia persists despite all previous interventions, consider islet or pancreas transplantation 1. This represents the final option for refractory cases where quality of life is severely impaired.

Glucagon Prescription and Training

All individuals treated with insulin or at high risk of hypoglycemia must be prescribed glucagon 1. Current prescribing rates are very low in practice, representing a significant gap in care 1.

• Intranasal and ready-to-inject glucagon preparations are preferred over traditional powder requiring reconstitution due to ease of administration and more rapid correction 1
• Train family members, roommates, school personnel, childcare professionals, and coworkers on glucagon administration, including where it is kept and when/how to administer 1
• Explicitly educate caregivers to never administer insulin to individuals experiencing hypoglycemia 1
• Replace glucagon products at expiration and store according to product-specific instructions 1

Special Populations and Situations

During intercurrent illness, trauma, or surgery, increase glucose monitoring frequency as these conditions increase risk for both hyperglycemia and hypoglycemia 2, 5.

For older adults or those with multiple comorbidities, simplify treatment regimens and use less aggressive glycemic targets (A1C <8.0%) 2.

Alcohol consumption must be moderate and always accompanied by food to reduce hypoglycemia risk 2.

Medication Interaction Considerations

Temporarily decrease or stop sulfonylureas when patients are prescribed interacting medications including fluoroquinolones, clarithromycin, sulfamethoxazole-trimethoprim, metronidazole, and fluconazole 5.

Monitor potassium levels in at-risk patients as all insulins can cause hypokalemia, potentially leading to respiratory paralysis, ventricular arrhythmia, and death 3.

Critical Pitfalls to Avoid

• Do not rely solely on A1C for treatment decisions in patients with recurrent hypoglycemia 2
• Do not overlook the additive effect of multiple glucose-lowering agents when patients are on combination therapy 2
• Avoid treating with carbohydrate sources high in protein as they increase insulin response without raising glucose 1
• For patients using automated insulin delivery systems, ingest only 5-10g carbohydrates for hypoglycemia treatment (not the standard 15g) unless hypoglycemia occurs with exercise or significant meal bolus overestimation 1