As an endocrinologist, C-peptides can be used a lot in daily diagnosis and treatment. So why should we test for C-peptides? How is C-peptide detected? What do you think of the results?
What is C-Peptide? Why test for C-peptides?
C-peptide, also known as concatenated peptide, is a secretion product of islet β cells, which has a common precursor with insulin - proinsulin. A molecule of proinsulin is cleaved into one molecule of insulin and one molecule of C-peptide under the action of trypsin and carboxypeptidase.
C-peptide and insulin are present in the same granular sac and eventually are secreted and released into the bloodstream. After entering the liver from the portal vein, insulin is partially ingested by the liver in varying amounts; however, C-peptide is taken up very little by the liver, mainly excreted directly through the urine by the kidneys, and the clearance rate is slower; and the half-life of C-peptide is longer than that of insulin, so the concentrations of the two in the blood are not equal.
Detecting C-peptide levels can more stably and comprehensively reflect the insulin secretion function of islet β cells, and C-peptide has no cross-immune response with insulin, and can overcome the interference of insulin receptors.
For diabetic patients who have been treated with exogenous insulin or have produced insulin antibodies, measuring the C-peptide level in the peripheral blood can more accurately and timely respond to the level of endogenous insulin, and can better represent the function of islet β cells and be used to guide the treatment of diabetes.
What is the use of testing C-peptides?
Contributes to the clinical classification of diabetes mellitus and helps to understand the patient's islet function.
Because C peptide is not interfered with by insulin antibodies, the C peptide concentration can be directly determined for patients receiving insulin therapy to determine the function of islet β cells and evaluate the clinical insulin therapy effect.
May differentiate the cause of hypoglycemia. In patients with frequent hypoglycemia, excessive insulin secretion is considered if the C-peptide is outside the normal range, or less than normal, for other reasons.
Determination of C-peptide levels is useful in the diagnosis of insulinoma and the evaluation of the effects of related surgeries. If serum C-peptide levels remain high after surgery, insulin tissue remains, while serum C-peptide levels continue to rise, suggesting a greater likelihood of tumor recurrence or metastasis.
According to the 2020 International Expert Group Consensus, in the management of adult occult autoimmune diabetes "LADA", individualized management of patients based on C-peptide levels is recommended:
"C-peptides are recommended for insulin injections according to the treatment plan for type 1 diabetes.
"0.3 ≤ C-peptide ≤ 0.7 nmol/L" recommends treatment options for metformin, GLP-1RA, or DPP-4i, TZD, and SGLT-2i oral hypoglycemic drug treatment options according to the treatment plan for type 2 diabetes, and prompt insulin therapy if glycosylated hemoglobin is not up to standard.
C-peptide > 0.7 nmol/L recommends that treatment options other than sulfonylureas be considered for treatment with type 2 diabetes, and that C-peptide testing be repeated every 6 months or when blood glucose deteriorates and treatment regimens should be developed again; and care should be taken to differentiate again from patients with type 2 diabetes with false positive autoantibodies.
How is C-peptide detected clinically?
C-Peptide release test: the method is the same as the glucose tolerance test, the insulin release test.
Discontinue drugs that have an effect on the trial.
Discontinue medications that may affect the trial before the test, such as birth control pills, diuretics, or phenytoin, for 3 to 7 days.
Carbohydrate intake should be controlled but not overly restricted.
Patients should consume carbohydrates of at least 150 g per day from 3 days prior to the trial, but should be controlled in the range of 250 to 300 g and maintain normal activity.
Do not overlook the details of sugar water preparation, dosage, and timing.
Starting from 7 to 9 a.m., the patient takes 75 g of anhydrous glucose powder dissolved in 300 mL of warm boiled water on an empty stomach for "8 to 10 h" or 82.5 g with 1 molecule of water glucose. Children are given 1.75 g of body weight per kilogram, for a total of no more than 75 g.
Take the sugar water within 3 to 5 minutes. Starting from the first bite of sugar, blood glucose and C-peptide levels were measured in the forearm before taking sugar and at 0.5 h, 1 h, 2 h, and 3 h after taking sugar.
Stay calm and stable for experiments.
During the trial, the subjects did not drink tea and coffee, did not smoke, did not do strenuous exercise, but did not need to be absolutely bedridden. Blood samples should be sent for testing as soon as possible.
Fasting fingertip blood glucose is less than 10 mmol/L.
The test generally requires the subject to measure fasting fingertip blood glucose less than 10 mmol/L, if the fasting blood glucose exceeds 10 mmol/L, it indicates that the subject has a high glycemic toxicity inhibition effect, and the data at this time do not truly reflect the subject's islet function. In addition, oral sugar water in the case of high fasting blood sugar will make high blood sugar worse and bring unnecessary damage to subjects.
How are C peptide release test results analyzed?
C peptide release curve of patients with normal glucose metabolism: fasting plasma C-peptide is 0.3 to 1.3 nmol/L, and secretion peaks at 0.5 to 1.0 h after oral glucose, with a peak of about 5 to 6 times the fasting value, and gradually returns to the fasting level at 2 to 3 h.
Key points for analyzing c-peptide release tests are as follows:
1. Analyze the relationship between the value of each time point of the C peptide release test and the blood glucose level measured synchronously, and whether there is relative hyperinsulinemia and insulin resistance.
2. Analyze the time of the high peak of the C peptide release test, whether there is a peak delay, and the peak delay is characteristic of type 2 diabetes.
3. When the C peptide release curve is low, whether there is a toxic inhibition of high blood sugar on islet β cells, whether there is serious failure of islet β cells, combined with insulin-related antibodies, disease course, etc., whether it is type 1 diabetes or type 2 diabetes.
What are the common types of C-peptide release curves?
1. The glycotentone test is within the normal range at all points, but elevated C-peptide levels, especially on an empty stomach, indicate fasting insulin resistance, which is more common in overweight and obese patients.
Treatment regimens are primarily for lifestyle management: appropriate diet control, physical activity, weight loss in obese people, and no need for hypoglycemic drug therapy. The glucose tolerance test and C peptide release test are reviewed about 1 year, and if the lifestyle is well controlled, the C-peptide secretion curve can be restored.
Image source: The author draws
2. The sugar tolerance test points are in the normal range, the fasting C-peptide level is elevated, indicating the existence of fasting insulin resistance, the peak after taking sugar is more than 5 times the fasting value, but the peak delay is the early manifestation of type 2 diabetes, suggesting that patients are prone to preprandial hypoglycemia, which is a high-risk group of diabetes.
3. Glucose tolerance test suggests impaired glucose regulation, elevated fasting C-peptide level, peak at 0.5 to 1.0 h, peak is more than 5 times the fasting value, 3 h is still a high level, did not fall back to the fasting level.
Treatment options are mainly for the management of lifestyle: appropriate control of diet, strengthening physical activity, weight loss for obese people, hypoglycemic drugs can choose α glycosidase inhibitors, and obese people can also take metformin orally.
4. Glucose tolerance test suggests that in patients with diabetes mellitus, fasting C-peptide levels can be normal, high, or low, the release curve rises slowly after taking sugar, peak delays, and the release curve still does not fall back to the fasting level at 3 h, which is a characteristic of typical type 2 diabetes.
As the course of diabetes prolongs, the function of islet β cells gradually decreases, the level of fasting C-peptide gradually decreases, the postprandial release curve rises more slowly, and its peak shift is more obvious.
5. The level of C-peptide on an empty stomach is low, and the release curve rises smoothly after taking sugar, almost straight, and has no peak characteristics. After the exclusion of diabetic toxicity, it indicates that the patient's islet β cells are very functionally exhausted, mainly due to insufficient insulin secretion, and long-term insulin replacement therapy is required.
If it is a juvenile patient, accompanied by ketosis, type 1 diabetes is more likely;
If the middle-aged and elderly patient suddenly becomes ill, isting, and the disease progresses rapidly, accompanied by recurrent ketosis, it is necessary to consider adult occult autoimmune diabetes mellitus, combined with islet-related antibodies to confirm the diagnosis;
If the patient has a long history of diabetes and has been treated with adequate amounts of hypoglycemic drugs, which is less effective, islet β cell failure should be considered in patients with type 2 diabetes.
brief summary
Correct analysis of the C peptide release curve of diabetic patients and assessment of islet β cell function of patients have important guiding significance for the classification and treatment of diabetes.
Previous studies have believed that C peptide has no biological activity and is only used to judge the function of islet β cells, but more and more studies have shown that C peptide can relax blood vessels, improve red blood cell deformity, strengthen the function of insulin signaling system, promote the use of muscles in sugars and amino acids, enhance na+K+-ATPase activity, etc., and play an important role in glucose metabolism and the development of diabetic complications such as diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease.
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Planning | Qi Min
This article was first published on Lilac Garden's professional platform: Endocrine Time