Research Blog

April 5, 2022

Biomarkers of Blood Glucose Regulation: C-peptide

Optimal Takeaways

C-peptide is a compound that is released into the blood when proinsulin is cleaved into C-peptide and insulin in the beta cells of the pancreas. C-peptide appears to have its own therapeutic actions including support of blood flow, oxygenation, vasodilation, and nerve and kidney function. Administration of C-peptide may help counteract the negative effects of hyperglycemia on biological tissues and may be therapeutic for those with type 1 diabetes.

Standard Range: 0.8-3.85 ng/mL (0.27-1.27 nmol/L)

The ODX Range: 1.10-2.10 ng/mL (0.37-0.70 nmol/L)  

Low C-peptide is associated with type 1 diabetes, exogenous insulin therapy, pancreatectomy, and factitious hypoglycemia (Pagana 2019).

High C-peptide occurs with insulinoma, type 2 diabetes, insulin-resistant obesity, cardiovascular disease, pancreas transplant, use of oral hypoglycemic medications, and in renal failure where the kidneys fail to degrade it (Pagana 2019).


C-peptide, or “connecting peptide,” is a component of proinsulin and is released from pancreatic beta cells when proinsulin is cleaved into C-peptide and insulin. C-peptide levels parallel those of insulin in the blood and can be used to assess insulin production as well as insulin reserves. It is clinically useful for differentiating type 1 diabetes (insulin deficiency) from type 2 diabetes. C-peptide below 0.6 ng/mL (0.2 nmol/L) is likely an indicator of the need for insulin therapy (Venegopal 2021).

Although C-peptide was initially thought to be biologically inactive, research suggests that C-peptide promotes RBC function and tissue oxygenation; improves blood flow to skeletal muscles and skin; improves kidney function and reduces urinary excretion of albumin; has a vasodilatory effect on the skin, muscles, and kidneys due to stimulation of nitric oxide; and may have therapeutic value in type 1 diabetes (Novac 2019).

C-peptide is also found to reduce the damaging effects of glucose in vital tissues including blood vessels, kidneys, and nerves. Double-blind placebo-controlled research confirmed that C-peptide administration improved neuropathy in type 1 diabetics even though glycemic control was similar in treated patients versus placebo. Research also suggests that C-peptide administration can significantly increase heart rate variability, an action that may reduce risk of cardiac arrhythmias and sudden death. C-peptide also appears to have anti-inflammatory and anti-apoptotic effects. Researchers note that healthy individuals maintain a fasting C-peptide of 0.91-1.81 ng/mL (0.3-0.6 nmol/L) and a post-prandial C-peptide of 3.02-9.06 ng/mL (1.0-3.0 nmol/L) (Yosten 2014).

Elevated fasting C-peptide is also associated with a significantly increased risk of cardiovascular and all-cause mortality in non-diabetics, especially at a level of 2.97 ng/mL (0.984 nmol/L) or above (Patel 2012).


Novac, Carmen et al. “Short Update on C-Peptide and its Clinical Value.” Maedica vol. 14,1 (2019): 53-58. doi:10.26574/maedica.2019.14.1.53

Pagana, Kathleen Deska; Pagana, Timothy J.; Pagana, Theresa N. Mosby's Diagnostic and Laboratory Test Reference. Elsevier Health Sciences. 2019.

Patel, Nileshkumar et al. “Fasting serum C-peptide levels predict cardiovascular and overall death in nondiabetic adults.” Journal of the American Heart Association vol. 1,6 (2012): e003152. doi:10.1161/JAHA.112.003152

Venugopal, Senthil K., et al. “C Peptide.” StatPearls, StatPearls Publishing, 29 May 2021.

Yosten, Gina L C et al. “Physiological effects and therapeutic potential of proinsulin C-peptide.” American journal of physiology. Endocrinology and metabolism vol. 307,11 (2014): E955-68. doi:10.1152/ajpendo.00130.2014

Tag(s): Biomarkers

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