From the Guidelines
Persistent hypoglycemia is primarily caused by excess insulin, certain medications, hormonal deficiencies, and severe organ disease, and its management should focus on immediate treatment of acute episodes and long-term strategies to address the underlying cause, with the goal of minimizing morbidity, mortality, and improving quality of life. The causes of persistent hypoglycemia can be multifactorial, including excess insulin from insulinomas or exogenous insulin administration, medications such as sulfonylureas, hormonal deficiencies like adrenal insufficiency or growth hormone deficiency, severe liver or kidney disease, and rare genetic disorders affecting glucose metabolism 1.
Management Strategies
Management begins with immediate treatment of acute episodes using the 15-15 rule: consuming 15 grams of fast-acting carbohydrates and rechecking blood glucose after 15 minutes, as recommended by recent guidelines 1. For unconscious patients, 1 mg of glucagon intramuscularly or 25 grams of D50W intravenously should be administered. Long-term management strategies include:
- Identifying and treating the underlying cause
- Medication adjustments, such as reducing insulin doses or switching from sulfonylureas to other diabetes medications
- Frequent small meals rich in complex carbohydrates
- Continuous glucose monitoring
- Carrying emergency glucose sources
Refractory Cases
For refractory cases, medications like diazoxide (3-8 mg/kg/day divided into three doses), octreotide (25-150 mcg subcutaneously three times daily), or glucocorticoids may be necessary, as they can help address the physiological imbalance between glucose production and utilization, either by increasing glucose availability or reducing excessive insulin action 1.
Key Considerations
It is crucial to prioritize the patient's safety and well-being, ensuring that they are educated on the recognition and treatment of hypoglycemia, and that they have access to emergency glucose sources and glucagon kits, if necessary. The management plan should be tailored to the individual's specific needs and circumstances, taking into account their medical history, lifestyle, and preferences. By adopting a comprehensive and patient-centered approach, healthcare providers can help minimize the risks associated with persistent hypoglycemia and improve the overall quality of life for individuals with diabetes.
From the FDA Drug Label
Diazoxide Oral Suspension is indicated for the management of hypoglycemia due to hyperinsulinism associated with the following conditions: Adults: Inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy. Infants and Children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis Treatment with diazoxide should be initiated under close clinical supervision, with careful monitoring of blood glucose and clinical response until the patient's condition has stabilized.
The causes of persistent hypoglycemia include:
- Hyperinsulinism associated with conditions such as inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy in adults
- Hyperinsulinism associated with conditions such as leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis in infants and children
Management strategies for persistent hypoglycemia include:
- Diazoxide treatment to manage hypoglycemia due to hyperinsulinism
- Close clinical supervision with careful monitoring of blood glucose and clinical response until the patient's condition has stabilized 2
- Regular monitoring of urine glucose and ketones, especially under stress conditions 2
From the Research
Causes of Persistent Hypoglycemia
- Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia 3
- Therapies for diabetes, such as insulins and insulin secretagogues, including glinides and sulfonylureas, increase the risk of hypoglycemia 4
- Increased hypoglycemia risk is observed with the use of insulin and/or sulphonylureas 5
- Vulnerable patients with type 2 diabetes at dual risk of severe hypoglycemia and cardiovascular outcomes show features of "frailty" 5
Management Strategies for Persistent Hypoglycemia
- Rapid-acting glucose is the preferred treatment for a conscious patient regardless of the setting 6
- For an unconscious patient, glucagon is preferred if the patient does not have intravenous (IV) access and dextrose can be used for patients with IV access 6
- Education and regular review are essential between people with diabetes and their caregivers and healthcare professionals about symptoms, prevention, and treatment 4
- Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycemia, impaired hypoglycemia awareness, frequent nocturnal hypoglycemia, and with history of severe hypoglycemia 5
- Optimizing insulin doses and carbohydrate intake, in addition to a short warm-up before or after physical activity sessions, may help avoid hypoglycemia 5
Prevention of Hypoglycemia
- Patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control, can help prevent hypoglycemia 3
- Awareness of the potential dangers of hypoglycemia is fundamental to the optimal management of diabetes 4
- Conversations about hypoglycemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycemia among patients with diabetes and their family members 5