From the Guidelines
Hypoglycemia is primarily caused by an imbalance between glucose consumption and production in the body, resulting in abnormally low blood sugar levels, with the most common cause being medication used to treat diabetes, particularly insulin, as well as other factors such as excessive alcohol consumption, severe liver or kidney disease, and certain hormonal deficiencies. The causes of hypoglycemia can be multifactorial, including:
- Medication used to treat diabetes, such as insulin and sulfonylureas, which can lower blood sugar too much, especially if doses are too high, meals are skipped, or physical activity increases unexpectedly 1
- Excessive alcohol consumption without food
- Severe liver or kidney disease
- Certain hormonal deficiencies, such as adrenal insufficiency
- Prolonged fasting or starvation
- Rare tumors that produce insulin, such as insulinomas
- Critical illness, sepsis, and malnutrition, which can trigger hypoglycemia 1
- Reactive hypoglycemia, which can occur within hours after meals, particularly in people who have had gastric bypass surgery The body normally maintains blood glucose through a balance of insulin and counter-regulatory hormones like glucagon and epinephrine, so any disruption to these regulatory mechanisms can lead to hypoglycemic episodes 1. It is essential to identify and address the underlying cause of hypoglycemia to prevent recurrent episodes and related complications, and to establish a plan for treating and preventing hypoglycemia, including the use of glucagon kits in emergency situations 1.
From the FDA Drug Label
All glinides, including nateglinide, can cause hypoglycemia [see Adverse Reactions (6. 1)]. Factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content), changes in level of physical activity, changes to coadministered medication [see Drug Interactions (7)], and concomitant use with other antidiabetic agents. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6,8.7), Clinical Pharmacology (12. 3)]. 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 2
Hypoglycemia Causes:
- Changes in meal pattern
- Changes in level of physical activity
- Changes to coadministered medication
- Concomitant use with other antidiabetic agents
- Renal or hepatic impairment
- Deficient caloric intake
- Severe or prolonged exercise
- Alcohol ingestion
- Use of multiple glucose-lowering drugs 3 4
From the Research
Causes of Hypoglycemia
- Hypoglycemia can be caused by various factors, including:
- Exogenous or endogenous insulin excess alone 5
- Absolute or relative insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes 5
- Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine 5
- Defective glucose counterregulation and hypoglycemia unawareness due to recent antecedent hypoglycemia 5
- Drug-induced hypoglycemia, with sulfonylureas, alcohol, propranolol, and salicylate being common offenders 6
- Restricted food intake, age, hepatic disease, and renal disease, both individually and in combination 6
Risk Factors for Hypoglycemia
- Risk factors for iatrogenic hypoglycemia include:
- Drug dose, timing, and type 5
- Patterns of food ingestion and exercise 5
- Interactions with alcohol and other drugs 5
- Altered sensitivity to or clearance of insulin 5
- Endogenous insulin deficiency 5
- History of severe hypoglycemia, hypoglycemia unawareness, or both 5
- Aggressive glycemic therapy per se, as evidenced by lower HbA(1c) levels, lower glycemic goals, or both 5