C-peptide to insulin ratio (C-peptide/insulin)

Low C-peptide reflects reduced endogenous insulin production — classically type 1 diabetes and LADA (autoimmune beta-cell destruction), and late-stage type 2 diabetes with beta-cell exhaustion.

Other causes: exogenous insulin therapy suppressing pancreatic secretion, pancreatectomy or pancreatic damage, and prolonged fasting or low food intake.

High C-peptide reflects excess endogenous insulin production — most often the compensatory hyperinsulinemia of insulin resistance seen in obesity, metabolic syndrome, and early type 2 diabetes.

Other causes: insulinoma (insulin-secreting tumor), Cushing's syndrome, insulin-stimulating drugs such as sulfonylureas, and reduced renal clearance in kidney insufficiency.

Decreased insulin in a lean, metabolically healthy person means the body needs very little insulin while fasting (very good insulin sensitivity), usually seen in athletes or those on a low carbohydrate diet.

Low fasting insulin reflects reduced pancreatic beta-cell output. Causes include type 1 diabetes (autoimmune beta-cell destruction), advanced type 2 diabetes with beta-cell exhaustion, LADA, pancreatic disease, and hypopituitarism.

Prolonged fasting (beyond the standard 12 hours) can also drive values very low.

High fasting insulin (hyperinsulinemia) most commonly reflects insulin resistance — the pancreas produces more insulin to keep glucose controlled. This can appear before fasting glucose or HbA1c become abnormal.

It is commonly seen with abdominal obesity, metabolic syndrome, fatty liver, early type 2 diabetes, and PCOS. Less common causes include insulinoma, insulin-releasing medications, exogenous insulin, Cushing syndrome, acromegaly, reduced insulin clearance, and assay interference.