C-peptide is a good indicator of how much insulin the body is making. It can be used to differentiate between type 1 and type 2 diabetes. While moderate levels lower inflammation, even slightly higher levels have been linked to insulin resistance, metabolic syndrome, heart disease, and cancer. Read on to learn more about C-peptide and how it can impact your health.
What is C-Peptide?
You probably already know about insulin, the hormone that decreases blood sugar levels. Insulin’s main function is to transport sugar (glucose) from the blood into your cells and tissues. There, glucose can be converted into energy or stored for future use.
The pancreas makes insulin, but not directly. The beta cells in the pancreas first produce a protein called “proinsulin.” Each proinsulin breaks down to one molecule of insulin and one molecule of C–peptide. Both are released when blood sugar levels get high [1, 2].
Insulin and C-peptide are released in equal amounts but broken down differently. The liver breaks down insulin at a variable rate, while the kidneys break down C-peptide at a fairly steady rate. This makes C–peptide a more reliable measure of insulin production and beta cell (pancreas) function [1, 2].
C-peptide was initially considered inactive – a mere byproduct of insulin production. But studies revealed that this peptide actually has both anti-inflammatory and pro-inflammatory effects in the body, depending on its levels [3, 4, 5].
In a nutshell, you’d usually want C–peptide (and insulin production) to be balanced – neither too high nor too low.
C-peptide levels increase with weight (fat mass) and age in healthy, non-diabetic people [6].
In diabetics, on the other hand, C-peptide declines over time [2].
C-Peptide Test
A C-peptide test can be used to [2, 7]:
- Measure the amount of insulin made in the body. It can differentiate between the insulin the body makes and the insulin taken as medication.
- Differentiate between type 1 and type 2 diabetes. Type 1 diabetes is an autoimmune condition in which the pancreas doesn’t produce enough insulin. Type 2 diabetes is a metabolic condition in which the body doesn’t use the insulin that’s produced as well as it should. This test is especially useful in adult-onset autoimmune diabetes (LADA or type 1.5 diabetes), which is often misdiagnosed as type 2 diabetes.
- Monitor diabetes. Doctors can use a C-peptide test to decide whether you need to take insulin or to adjust the dosage if you are already taking it.
- Investigate the reason for your low blood sugar levels (hypoglycemia).
- Help diagnose a tumor of the pancreas or monitor the situation after pancreas removal/transplantation.
Blood C-peptide is a better, more accurate marker than urine C-peptide. Urine levels still offer some advantages. For one, they are less invasive and can be done more frequently. Additionally, they can be used in women with gestational diabetes (diabetes in pregnancy) and in type 1 diabetics with unstable blood sugar levels [8, 9, 10, 11].
However, while healthy kidneys are efficient at breaking down C-peptide, in people with impaired kidney function and kidney disease, blood C-peptide levels will falsely increase and urine levels will falsely decrease [2].
Normal Range
The normal range for fasting blood C-peptide levels is around 0.8 – 3.85 ng/mL or 0.26 – 1.27 nmol/L (260 – 1270 pmol/L). Ranges can vary between laboratories.
Levels below 0.6 ng/mL (0.2 nmol/L) are a sign of possible beta cell failure and type 1 diabetes [2, 1].
Blood levels will increase after a meal to about 3 – 9 ng/mL (1 – 3 nmol/L or 3000 – 9000 pmol/L)) in healthy people. This measurement is referred to as postprandial C-peptide [1, 2].
Values in urine are usually measured over 24h. Normal urine levels are around 14 – 156 ug/24h.
Low C-Peptide Levels
Causes
If your C-peptide levels are low, that may mean your pancreas isn’t working properly and the body is not making enough insulin [2]. Your doctor will interpret this test, taking into account your medical history, signs and symptoms, and other test results.
Low C-peptide can be caused by:
- Type 1 diabetes, an autoimmune condition in which insulin-producing cells of the pancreas get destroyed [2, 12].
- LADA, latent autoimmune diabetes in adults, also known as type 1.5 diabetes [13, 14, 15].
- Type 2 diabetes, insulin dependent. As type 2 diabetes progresses, insulin-producing cells may get damaged and destroyed [16].
- Insulin therapy in people with type 2 diabetes who don’t yet have pancreas damage; in this case, external insulin reduces insulin production in the body [17, 18].
- Low blood glucose (hypoglycemia) in diabetics on insulin [17].
- Fasting for a long period of time or starvation [19, 20].
- Poorly functioning pancreas, in diseases such as pancreatitis (inflamed pancreas) [21].
- Pancreas removal (pancreatectomy) [22].
These causes have been associated with low C-peptide levels. Work with your doctor or another health care professional to get an accurate diagnosis.
Symptoms
Low C-peptide is most often found in people with type 1 diabetes, who may experience the following symptoms [23]:
- Excessive thirst
- Excessive hunger
- Excessive or an abnormally large production or passage of urine
Low blood sugar can also be a cause of low C-peptide. Symptoms of low blood sugar include [24]:
- Hunger
- Nervousness
- Shaking
- Dizziness
- Light-headedness
- Sleepiness
- Confusion
Low blood sugar is common in diabetes, especially in people with type 1 diabetes taking insulin. It’s extremely rare for non-diabetics to experience low blood sugar [24].
Health Effects
1) Inflammation
In type 1 diabetes, C-peptide is beneficial because it signals some insulin-producing pancreas cells still exist. Type 1 diabetics who have detectable C-peptide levels require less insulin and are not as prone to chronic complications, such as heart disease and kidney, nerve, and eye damage [25, 26, 27].
In fact, studies have shown that adding C-peptide to insulin therapy can improve nerve pain, heart, and kidney function in people with type 1 diabetes [28, 29, 30, 31].
This effect may be due to the anti-inflammatory effects of C-peptide. In animals with autoimmune diabetes, C-peptide decreased inflammation (NF-κB, TNF-alpha, IL-1b, IL-2, and IL-6), protected blood vessels from inflammation, and preserved cognitive function [31].
C-peptide injections improved the survival rate of the mice with sepsis, a severe inflammatory response to bloodstream infection [32].
However, these effects are limited to low-normal C-peptide levels. In excess, C-peptide likely worsens inflammation [31].
2) Fragile Bones
Low C-peptide levels may be linked with lower bone density and osteoporosis [33].
Osteoporosis and low bone mineral density are common in people with type 1 diabetes [33].
In a study with 84 postmenopausal women without diabetes, women with lower C-peptide levels tended to have lower bone mineral density [34].
In another similar group of 133 postmenopausal women, low C-peptide levels were linked with a higher risk of fractures [35].
High C-Peptide Levels
Causes
High C-peptide levels indicate that the body is producing too much insulin [36, 37].
Causes shown below are commonly associated with high C-peptide. Work with your doctor or another health care professional to get an accurate diagnosis. Your doctor will interpret this test, taking into account your medical history, signs and symptoms, and other test results.
High C-peptide levels can be caused by:
- Carbs and the resulting increase in blood sugar. After a meal, higher glucose levels in the blood signal the pancreas to release insulin and C-peptide [36, 37].
- Insulin resistance. When cells don’t respond to insulin as well as they used to, blood sugar increases, and insulin and C-peptide increase in response [38].
- Obesity. Many studies have linked weight gain and lack of physical activity to increased insulin resistance and higher insulin and C-peptide levels [39, 40].
- Kidney disease. C-peptide is removed by the kidneys. When kidneys are not working properly, C-peptide levels in the blood increase (they decrease in urine) [41].
- Cushing syndrome. This syndrome is caused by an excess of cortisol, which impairs the response of cells to insulin resulting in insulin resistance [42, 43].
- Insulinomas. Insulinomas are insulin-producing tumors (mostly benign) of the pancreas [44, 45].
Drugs that can increase C-peptide levels include:
- Sulfonylureas, such as chlorpropamide (Diabinese), tolazamide (Tolinase), gliclazide (Diamicron), and glimepiride (Amaryl). These are used to treat type 2 diabetes and work by increasing insulin production [46].
- Glucocorticoids, such as prednisone (Orapred, Pediapred) and dexamethasone (Dexol, Martapan). Long-term use can cause insulin resistance and increases the risk of diabetes [47, 48, 49, 50]
C-peptide levels may normally increase during pregnancy [51].
Symptoms
You can have insulin resistance and elevated C-peptide levels without experiencing any particular symptoms.
You may, however, experience signs and symptoms associated with underlying conditions, such as weight gain (especially belly fat), inflammation, high uric acid, or high blood cholesterol and triglyceride levels – to name a few [52].
Health Effects
1) Insulin Resistance
Higher fasting C-peptide means that the body is producing too much insulin. This happens in insulin resistance, when the body is struggling to keep blood sugar levels at bay. Pancreas increases insulin production in response to higher blood sugar, but the tissues protest – they don’t respond to insulin and become “resistant.”
Studies have found that high C-peptide levels can predict insulin resistance in both healthy people and those with diabetes [53, 54].
2) Metabolic Syndrome
Metabolic syndrome is a group of health problems that often occur together and increase one’s risk of type 2 diabetes and heart disease. You have metabolic syndrome if you have 3 or more of the following [55, 56, 57]:
- High blood pressure
- High blood sugar
- Excess body fat around the waist
- Low HDL cholesterol
- High triglycerides
In a study of 270 people, C-peptide was higher in those with metabolic syndrome. It correlated with all the above-listed components of metabolic syndrome [58].
Another study confirmed the findings: higher C-peptide levels were associated with metabolic syndrome in 77 diabetic patients [59].
Finally, higher C-peptide levels were linked with lower HDL cholesterol levels in a study of over 13k people [60].
3) Hardening of the Arteries and Heart Disease
C-peptide may contribute to the onset of the hardening of the arteries. It deposits in blood vessel walls where it increases local inflammation [61, 62].
In an initial study in 54 patients with rheumatoid arthritis, those with higher C-peptide levels had more artery calcification–a buildup of calcium in the arteries that narrows and stiffens them [63].
In almost 7k adults, those with higher C-peptide levels were more likely to suffer a heart attack and develop heart disease over 3.5 years of follow-up [64].
In addition, higher C-peptide levels were associated with lower HDL cholesterol (“good cholesterol”) levels in a study of over 13k people. A low HDL cholesterol is a well-known risk factor for heart disease [60].
4) Cancer
In a meta-analysis of 9 studies with over 7k people, those with higher C-peptide levels had a 37% higher risk of colon cancer [65].
What’s more, higher C-peptide was linked with a 50% higher risk of invasive breast cancer in over 2.7k women [66].
In another 1k people, higher C-peptide levels were associated with a higher risk of gastric cancer [67].
However, in 528 men, those with higher C-peptide levels were less likely to be diagnosed with prostate cancer. The exact cause is still unclear, though. Higher C-peptide might lower the risk of developing prostate cancer, or it might reduce the accuracy of cancer detection [68].
5) Mortality
In almost 6k people without diabetes, higher C-peptide levels were associated with 80% higher all-cause mortality and more than 3 times higher heart disease mortality [69]!
In a similar study of about 5k people, higher C-peptide levels were linked with a 72% higher risk of all-cause mortality and a 60% higher risk of dying of heart disease [70].
Finally, in 399 patients with newly diagnosed diabetes, the highest C-peptide levels were linked with a 2.75-fold higher risk of death from all causes [71].
Further Reading
We go over lifestyle and dietary modifications that can help improve C peptide levels in this post.
Takeaway
C-peptide points to how well the pancreas is working. Doctors often use it to measure the amount of insulin made in the body, to differentiate between type1 and type 2 diabetes, or to adjust the dose of insulin given as medication. They can also use it to investigate the reason for low blood sugar or to help diagnose a pancreatic tumor.
Low levels usually mean that the body isn’t producing enough insulin, which happens in type 1 diabetes, advanced type 2 diabetes, or after prolonged fasting. High levels, on the other hand, may mean that the body is making too much insulin. This usually happens with insulin resistance and weight gain.
