Differential Diagnosis for Low C-Peptide and Insulin Level with Hyperglycemia

Single Most Likely Diagnosis

• Type 1 Diabetes Mellitus: This condition is characterized by the autoimmune destruction of pancreatic beta cells, leading to a deficiency in insulin production. The low levels of c-peptide and insulin in the presence of hyperglycemia are hallmark findings, as the body's ability to produce insulin is severely impaired.

Other Likely Diagnoses

• Late-Stage Type 2 Diabetes Mellitus: Over time, type 2 diabetes can progress to a point where the pancreatic beta cells are exhausted, leading to a significant decrease in insulin production. Although less common than type 1 diabetes for presenting with very low c-peptide levels, it's a consideration, especially in the context of long-standing disease.
• Pancreatectomy or Pancreatic Disease: Conditions that result in the removal or significant damage to the pancreas (e.g., pancreatic cancer, chronic pancreatitis) can lead to a decrease in insulin production due to the loss of functional pancreatic tissue.

Do Not Miss Diagnoses

• Insulinoma-Associated Diseases with Hypoinsulinemia: Although rare, conditions like insulinoma-associated antigen-2 (IA-2) autoimmune syndrome can present with low insulin and c-peptide levels due to the autoimmune destruction of beta cells, similar to type 1 diabetes but often associated with other autoimmune conditions.
• Factitious Hypoglycemia (if considering the broader differential of low insulin levels): While not directly related to hyperglycemia, factitious hypoglycemia caused by insulin or insulin analog administration can sometimes present with confusing laboratory results, including low c-peptide levels. However, the clinical context would typically involve episodes of hypoglycemia rather than hyperglycemia.

Rare Diagnoses

• Maturity-Onset Diabetes of the Young (MODY): Certain forms of MODY can present with impaired insulin secretion, but they typically have a more gradual onset and may not always present with very low c-peptide levels.
• Wolfram Syndrome: A rare genetic disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The diabetes mellitus component can result from pancreatic beta-cell dysfunction, leading to low insulin and c-peptide levels.
• Mitochondrial Diabetes: Associated with mitochondrial DNA mutations, this form of diabetes can result in impaired insulin secretion due to the critical role of mitochondria in beta-cell function.