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The 30-amino-acid chain that connects the A and B chains of insulin in proinsulin; removed in the conversion of proinsulin to insulin.
Synonym(s): C chain


Connecting peptide Endocrinology A biologically inactive moiety of proinsulin produced endogenously in the pancreas, and stored in secretory granules in a 1:1 ratio with insulin; unlike factitious hypoglycemia, which is induced by insulin of exogenous origin, an ↑ in C-peptide–≥
0.2 nmol/L, as well as ↑ insulin, ≥ 42 pmol/L is characteristic of insulinoma; C-peptide quantification is used to detect fictitious insulin injection and diagnose insulin-secreting tumors in diabetics, where > 7 ng/ml of C-peptide after induced hypoglycemia supports a diagnosis of insulinoma. See Diabetes, Insulin.


Synonym/acronym: Connecting peptide insulin, insulin C-peptide, proinsulin C-peptide.

Common use

To evaluate hypoglycemia, assess beta cell function, and distinguish between type 1 and type 2 diabetes.


Serum (1 mL) collected in a red-top tube.

Normal findings

(Method: Immunochemiluminometric assay, ICMA)
AgeConventional UnitsSI Units (Conventional Units × 0.333)
9 yr0–3.3 ng/mL0–1.1 nmol/L
10–16 yr0.4–3.3 ng/mL0.1–1.1 nmol/L
Greater than 16 yr0.8–3.5 ng/mL0.3–1.2 nmol/L
1 hr response to glucose2.3–11.8 ng/mL0.8–3.9 nmol/L


C-peptide is a biologically inactive peptide formed when beta cells of the pancreas convert proinsulin to insulin. Most of C-peptide is excreted by the kidneys. C-peptide levels usually correlate with insulin levels and provide a reliable indication of how well the pancreatic beta cells secrete insulin. Release of C-peptide is not affected by exogenous insulin administration. C-peptide values double after stimulation with glucose or glucagon, and measurement of C-peptide levels are very useful in the evaluation of hypoglycemia. An insulin/C-peptide ratio less than 1 indicates endogenous insulin secretion, whereas a ratio greater than 1 indicates an excess of exogenous insulin. An elevated C-peptide level in the presence of plasma glucose less than 40 mg/dL supports a diagnosis of pancreatic islet cell tumor.

This procedure is contraindicated for



  • Assist in the diagnosis of insulinoma: serum levels of insulin and C-peptide are elevated.
  • Detect suspected factitious cause of hypoglycemia (excessive insulin administration): an increase in blood insulin from injection does not increase C-peptide levels.
  • Determine beta cell function when insulin antibodies preclude accurate measurement of serum insulin production.
  • Distinguish between insulin-dependent (type 1) and non–insulin-dependent (type 2) diabetes (with C-peptide–stimulating test): Patients with diabetes whose C-peptide stimulation level is greater than 18 ng/mL can be managed without insulin treatment.
  • Evaluate hypoglycemia.
  • Evaluate viability of pancreatic transplant.

Potential diagnosis

Increased in

  • Islet cell tumor (related to excessive endogenous insulin production)
  • Non–insulin-dependent (type 2) diabetes (related to increased insulin production)
  • Pancreas or beta cell transplants (related to increased insulin production)
  • Renal failure (increase in circulating levels of C-peptide related to decreased renal excretion)

Decreased in

    Factitious hypoglycemia (related to decrease in blood glucose levels in response to insulin injection) Insulin-dependent (type 1) diabetes (evidenced by insufficient production of insulin by the pancreas) Pancreatectomy (evidenced by absence of the pancreas)

Critical findings


Interfering factors

  • Drugs that may increase C-peptide levels include beta-methasone, chloroquine, danazol, deferoxamine, ethinyl estradiol, glibenclamide, glimepiride, indapamide, oral contraceptives, piretanide, prednisone, and rifampin.
  • Drugs that may decrease C-peptide levels include atenolol and calcitonin.
  • C-peptide and endogenous insulin levels do not always correlate in obese patients.
  • Failure to follow dietary restrictions before the procedure may cause the procedure to be canceled or repeated.

Nursing Implications and Procedure


  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assist in assessing for low blood sugar.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s endocrine system, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Instruct the patient to fast for at least 10 hr before specimen collection. Protocols may vary among facilities.
  • Note that there are no fluid or medication restrictions unless by medical direction.


  • Potential complications: N/A
  • Ensure that the patient has complied with dietary restrictions and pretesting preparations; assure that food has been restricted for at least 10 hr prior to the procedure.
  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.


  • Inform the patient that a report of the results will be made available to the requesting health-care provider (HCP), who will discuss the results with the patient.
  • Instruct the patient to resume usual diet as directed by the HCP.
  • Nutritional Considerations: Abnormal C-peptide levels may be associated with diabetes. There is no “diabetic diet”; however, many meal-planning approaches with nutritional goals are endorsed by the American Dietetic Association. Patients who adhere to dietary recommendations report a better general feeling of health, better weight management, greater control of glucose and lipid values, and improved use of insulin. Instruct the patient, as appropriate, in nutritional management of diabetes. The 2013 Guideline on Lifestyle Management to Reduce Cardiovascular Risk published by the American College of Cardiology (ACC) and the American Heart Association (AHA) in conjunction with the National Heart, Lung, and Blood Institute (NHLBI) recommends a “Mediterranean”-style diet rather than a low-fat diet. The new guideline emphasizes inclusion of vegetables, whole grains, fruits, low-fat dairy, nuts, legumes, and nontropical vegetable oils (e.g., olive, canola, peanut, sunflower, flaxseed) along with fish and lean poultry. A similar dietary pattern known as the Dietary Approach to Stop Hypertension (DASH) diet makes additional recommendations for the reduction of dietary sodium. Both dietary styles emphasize a reduction in consumption of red meats, which are high in saturated fats and cholesterol, and other foods containing sugar, saturated fats, trans fats, and sodium. If triglycerides also are elevated, the patient should be advised to eliminate or reduce alcohol. The nutritional needs of each diabetic patient need to be determined individually (especially during pregnancy) with the appropriate health care professionals, particularly professionals trained in nutrition.
  • Instruct the patient and caregiver to report signs and symptoms of hypoglycemia (weakness, confusion, diaphoresis, rapid pulse) or hyperglycemia (thirst, polyuria, hunger, lethargy). Emphasize, as appropriate, that good control of glucose levels delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy.
  • Recognize anxiety related to test results, and be supportive of perceived loss of independence and fear of shortened life expectancy. Discuss the implications of abnormal test results on the patient’s lifestyle. Provide teaching and information regarding the clinical implications of the test results, as appropriate. Emphasize, if indicated, that good glycemic control delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy. Educate the patient regarding access to counseling services, as appropriate. Provide contact information, if desired, for the American Diabetes Association (www.diabetes.org) or the American Heart Association (www.americanheart.org).
  • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Answer any questions or address any concerns voiced by the patient or family.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

  • Related tests include CT cardiac scoring, cortisol, creatinine, creatinine clearance, EMG, ENG, fluorescein angiography, fructose, fundus photography, glucagon, glucose, glucose tolerance tests, glycated hemoglobin, insulin, insulin antibodies, microalbumin, plethysmography, and visual fields test.
  • Refer to the Endocrine System table at the end of the book for related tests by body system.


the central connecting polypeptide which is part of the proinsulin molecule. It is released when the two chains of insulin are cleaved off of the single chain looped polypeptide of proinsulin.