What is the differential diagnosis for a patient experiencing hypoglycemia (low blood sugar) with low total insulin and normal C-peptide (connecting peptide) levels?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 29, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Differential Diagnosis for Hypoglycemia with Low Total Insulin and Normal C-Peptide

Single Most Likely Diagnosis

  • Factitious Hypoglycemia: This condition occurs when a patient intentionally induces hypoglycemia, often by administering insulin or other hypoglycemic agents. The low total insulin level could be due to the body's response to exogenous insulin, and normal C-peptide levels suggest that the patient's own insulin production is not the cause of the hypoglycemia.

Other Likely Diagnoses

  • Insulin Antibody-Mediated Hypoglycemia: In this condition, the patient's immune system produces antibodies against insulin, which can cause hypoglycemia. The low total insulin level may be due to the binding of insulin to these antibodies, and normal C-peptide levels indicate that the patient's own insulin production is intact.
  • Hypoglycemia Due to Oral Hypoglycemic Agents: Certain oral medications, such as sulfonylureas, can cause hypoglycemia by stimulating insulin release from the pancreas. The low total insulin level may be due to the fact that these medications increase insulin secretion, which is then rapidly cleared from the circulation, and normal C-peptide levels suggest that the patient's own insulin production is increased.

Do Not Miss Diagnoses

  • Insulinoma with Insulin Antibodies: Although insulinomas typically present with high insulin levels, the presence of insulin antibodies can bind to the insulin, making it undetectable. Normal C-peptide levels would be expected in this condition, as the tumor produces both insulin and C-peptide.
  • Hepatic or Renal Failure: Both hepatic and renal failure can cause hypoglycemia due to impaired glucose production and clearance. The low total insulin level may be due to decreased insulin clearance, and normal C-peptide levels indicate that the patient's own insulin production is intact.

Rare Diagnoses

  • Non-Insulinoma Pancreatogenous Hypoglycemia Syndrome (NIPHS): This rare condition is characterized by hypoglycemia due to an abnormal pancreatic beta-cell function. The low total insulin level may be due to the fact that the beta-cells are not producing insulin in response to glucose, and normal C-peptide levels suggest that the patient's own insulin production is intact.
  • Autoimmune Hypoglycemia: This condition is caused by the presence of autoantibodies against insulin or the insulin receptor, leading to hypoglycemia. The low total insulin level may be due to the binding of insulin to these antibodies, and normal C-peptide levels indicate that the patient's own insulin production is intact.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.