C-peptide is a good indicator of how much insulin your 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 your 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 Cpeptide. 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 Cpeptide 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 want Cpeptide (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 your body. It can differentiate between the insulin your 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).
  • Diagnose a tumor of the pancreas or monitor the situation after pancreas removal/transplantation.

Healthy kidneys are efficient at breaking down C-peptide. But in people with impaired kidney function and kidney disease, blood C-peptide levels will falsely increase and urine levels will falsely decrease [2].

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].

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 vary between laboratories.

It’s best if your levels fall within the low-normal range, because higher levels (even within the normal range) can signal excessive insulin production and insulin resistance.

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, your pancreas isn’t working properly and your body is not making enough insulin [2].

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, taking insulin reduces its 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].

Symptoms

Low C-peptide is most often found in people with type 1 diabetes, who 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 most 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, adding C-peptide to insulin therapy improves 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 decreases inflammation (NF-κB, TNF-alpha, IL-1b, IL-2, and IL-6), protects blood vessels from inflammation, and preserves cognitive function [31].

C-peptide injections improve 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 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 84 postmenopausal women without diabetes, women with lower C-peptide levels had 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 can be caused by:

  • Carbs and the resulting increase in blood sugar. After a meal, increased glucose levels in the blood signal the pancreas to release insulin and C-peptide [36, 37].
  • Insulin resistance. When your 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

If you have higher fasting C-peptide levels, that means that your body is producing too much insulin. This happens in insulin resistance, when your body is struggling to keep your blood sugar levels at bay. Your pancreas increases insulin production, but your tissues protest – they object to taking insulin in and become “resistant.”

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

C-peptide may contribute to the onset of hardening of the arteries. It deposits in blood vessel walls where it increases local inflammation [61, 62].

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].

4) Heart Disease Risk

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. Low HDL cholesterol is a well-known risk factor for heart disease [60].

5) Cancer Risk

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 almost 3 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].

6) Mortality

In almost 6k people without diabetes, those with the highest C-peptide levels had 80% higher all-cause mortality and more than 3 times higher heart disease mortality [69]!

In a similar study of about 5k people, those with higher C-peptide levels had 72% higher risk of all-cause mortality and 60% higher risk of dying of heart disease [70].

Finally, in 399 patients with newly diagnosed diabetes, those with the highest C-peptide levels had a 2.75-fold higher risk of death from all causes [71].

How to Increase/Decrease C-Peptide Levels

Natural Strategies

The following are all good ways to increase C-peptide levels:

The best natural strategies for lowering your levels include:

We go over how you can naturally increase or decrease your levels in much more detail in the second part of the C-peptide series.

Irregular C-peptide Levels?

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Takeaway

C-peptide points to how much insulin your body is making and how well your pancreas is working.

It’s good to have some C-peptide if you suffer from type 1 diabetes. Normal-low levels reduce diabetic health complications and signal that the pancreas is not completely destroyed.

High levels, on the other hand, indicate insulin resistance, weight gain, and a greater risk of cancer and heart disease.

About the Author

Biljana Novkovic - PHD (ECOLOGICAL GENETICS) - Writer at Selfhacked

Dr. Biljana Novkovic, PhD

PhD (Ecological Genetics)

Biljana received her PhD from Hokkaido University.

Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science & health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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