What are the chronic causes of hypoglycemia (low blood sugar)?

From the Guidelines

Chronic hypoglycemia is most commonly caused by medications, particularly insulin, as well as errors in insulin dosing and administration, which can be prevented with proactive surveillance and an interdisciplinary approach to glycemic management, as shown in a recent study 1.

Causes of Chronic Hypoglycemia

The causes of chronic hypoglycemia can be categorized into several groups, including:

• Medications: insulin and sulfonylureas used to treat diabetes, as well as other medications such as quinine, pentamidine, and certain antibiotics
• Endocrine disorders: insulinomas, adrenal insufficiency, and pituitary deficiencies
• Kidney and liver disease: chronic kidney disease and liver failure can lead to impaired glucose metabolism and reduced gluconeogenesis
• Malnutrition: protein deficiency can limit the body's ability to maintain glucose homeostasis
• Autoimmune conditions: insulin autoimmune syndrome and antibodies against insulin receptors
• Genetic disorders: glycogen storage diseases, fatty acid oxidation disorders, and hereditary fructose intolerance

Prevention and Management

Prevention and management of chronic hypoglycemia involve identifying and treating the underlying cause, which may include:

• Medication adjustments
• Tumor removal
• Hormone replacement therapy
• Dietary modifications
• Proactive surveillance of glycemic outliers and an interdisciplinary data-driven approach to glycemic management, as recommended by the Joint Commission 1 Recent studies have shown that hypoglycemic episodes in the hospital can be reduced or prevented with bundled preventive therapies, including proactive surveillance and an interdisciplinary approach to glycemic management, with a decrease in hypoglycemic events of 56-80% compared to baseline 1

From the FDA Drug Label

Hypoglycemia:All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitantly administered medication

The chronic causes of hypoglycemia include:

• Renal or hepatic insufficiency: may cause elevated blood levels of glipizide and diminish gluconeogenic capacity, increasing the risk of serious hypoglycemic reactions 2
• Prolonged use of glucose-lowering drugs: may lead to secondary failure, where the drug is less effective in lowering blood glucose over time 2
• Changes in meal pattern or physical activity: may increase the risk of hypoglycemia 3
• Concomitant administration of other medications: may increase the risk of hypoglycemia 3
• Elderly, debilitated or malnourished patients: are particularly susceptible to the hypoglycemic action of glucose-lowering drugs 2
• Adrenal or pituitary insufficiency: may increase the risk of hypoglycemia 2

From the Research

Chronic Causes of Hypoglycemia

• Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide 4
• Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia 4
• Chronic kidney disease not only is an independent risk factor for hypoglycemia but also augments the risk of hypoglycemia that is already present in people with diabetes 5
• Therapy regimen and a history of hypoglycemia are the most important predictors of future events 6
• Other risk factors include renal insufficiency, older age, and history of hypoglycemia-associated autonomic failure 6

Relationship Between Hypoglycemia and Diabetes

• Hypoglycemia is the most important and common side effect of insulin therapy 7
• A three-fold increased risk of severe hypoglycemia occurs in both type 1 and type 2 diabetes with tight glucose control 7
• Episodes of hypoglycemia are associated with physical and psychological morbidity 4
• The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control 4

Management and Prevention of Hypoglycemia

• Several ways to reduce hypoglycemia risk are recognized and discussed, including frequent monitoring of blood sugars with home blood glucose tests and sometimes continuous glucose monitoring (CGM) 7
• Prompt measured hypoglycemia treatment, attempts to reduce glycemic variability, balancing basal and meal insulin therapy, a pattern therapy approach and use of a physiological mimicry with insulin analogues in a flexible manner can help minimize the risk of hypoglycemia 7
• Patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control, is crucial in preventing hypoglycemia 4