Hypoglycemia Causes and Risk Factors

Introduction to Hypoglycemia

Hypoglycemia is primarily caused by medications, particularly insulin and sulfonylureas, as well as endocrine disorders, critical illness, and nutritional factors, according to the American Diabetes Association 1, 2, 3

Insulin therapy is the most common risk factor for hypoglycemia, especially intensive insulin regimens with multiple daily injections or insulin pumps, as stated by the American Association of Clinical Endocrinologists 4
Sulfonylureas and meglitinides are oral antidiabetic agents that stimulate insulin release and can cause hypoglycemia, as reported by the Endocrine Society 2, 3

Recent history of severe hypoglycemia (within past 3-6 months) is a significant risk factor, according to the American Diabetes Association 4, 5
Impaired hypoglycemia awareness, reduced ability to perceive warning symptoms, is a major risk factor, as stated by the American Association of Clinical Endocrinologists 4
End-stage kidney disease, with decreased renal gluconeogenesis and impaired insulin clearance, is a risk factor, as reported by the National Kidney Foundation 6
Cognitive impairment or dementia, inability to recognize or respond to hypoglycemic symptoms, is a risk factor, according to the Alzheimer's Association 4
Age ≥75 years, elderly patients have reduced counterregulatory hormone responses, is a risk factor, as stated by the American Geriatrics Society 7, 4
Female sex is a risk factor, according to the American Diabetes Association 4
High glycemic variability is a risk factor, as reported by the Endocrine Society 4
Chronic kidney disease (eGFR <60 mL/min/1.73 m²), reduces renal glucose production, is a risk factor, according to the National Kidney Foundation 6
Cardiovascular disease is a risk factor, as stated by the American Heart Association 4
Neuropathy and retinopathy are risk factors, according to the American Diabetes Association 4
Major depressive disorder is a risk factor, as reported by the American Psychiatric Association 4

Food insecurity, irregular access to adequate nutrition, is a risk factor, according to the American Diabetes Association 4
Low-income status, limited resources for proper diabetes management, is a risk factor, as stated by the National Institute of Diabetes and Digestive and Kidney Diseases 4
Housing insecurity, unstable living conditions affecting medication adherence and meal timing, is a risk factor, according to the American Diabetes Association 4
Fasting for religious or cultural reasons, prolonged periods without food, is a risk factor, as reported by the Endocrine Society 4
Alcohol or substance use disorder, alcohol inhibits gluconeogenesis, is a risk factor, according to the American Diabetes Association 4

Interruptions in nutritional intake, NPO status, delayed meals, are risk factors, as stated by the Society of Hospital Medicine 7, 6
Changes in medication regimens, new drugs or altered dosing, are risk factors, according to the American Society of Health-System Pharmacists 6
Critical illness, altered metabolism and increased insulin resistance, is a risk factor, as reported by the Society of Critical Care Medicine 8
Sepsis, dysregulated glucose metabolism, is a risk factor, according to the Infectious Diseases Society of America 6
Low albumin levels, altered drug binding and pharmacokinetics, are a risk factor, as stated by the American Society of Nephrology 6

Hypoglycemia risk assessment should be performed at every clinical encounter for patients on insulin or insulin secretagogues, according to the American Diabetes Association 4
Prior episodes of hypoglycemia are the strongest predictor of future events, as stated by the American Association of Clinical Endocrinologists 4
Understanding these causes is essential for preventing hypoglycemia, which is associated with increased morbidity and mortality, particularly in hospitalized and elderly patients, according to the American Diabetes Association 7, 6