C-Peptide – The Most Important Blood Test for Diabetes

Have you ever heard of the C-peptide test?

It turns out that your C-peptide is an important indicator of your diabetes health and one of the most important of all diabetes biomarkers.

In this article, we’ll cover the basics of C-peptide biology, understand what it tells you about your body’s ability to secrete insulin, how it helps you understand what type of diabetes you are living with, as well as where and how to get your C-peptide tested easily.

What Exactly is C-Peptide?

When the beta cells in your pancreas secrete insulin, they secrete it as a molecule known as “proinsulin.” Proinsulin is an immature version of insulin comprised of an alpha-chain, a beta-chain, and a C-peptide connector.

C-peptide is a polypeptide (small protein) composed of 31 amino acids that connects the alpha-chain and beta-chain together, as you can see in the following diagram:

C-peptide

Proinsulin is manufactured in the endoplasmic reticulum then passed to the golgi apparatus for processing where the C-peptide connector is removed.

When C-peptide is removed from the proinsulin molecule, the alpha and beta chains become linked, and proinsulin turns into insulin, which has specific and powerful biological activity in your blood.

The C-peptide polypeptide was discovered in 1967, and the first C-peptide test was developed in 1972 (1). At the time, this discovery was a landmark insight into the physiology of diabetes, because they discovered that insulin and C-peptide are made in equal amounts, and that C-peptide remained in the blood for substantially longer periods of time than insulin.

What this means is simple: C-peptide and insulin are present in pancreatic beta cells in equal amounts, however C-peptide has a substantially longer half-life than insulin (20-30 minutes vs. 3-5 minutes).

What this means is very important – C-peptide remains in your blood for approximately 5 times as long as insulin, and is therefore present in your blood at approximately 5 times the concentration (2).

Why is Your C-Peptide Important?

Because C-peptide is directly related to your insulin production, understanding whether beta cells are capable of secreting sufficient amounts of insulin to meet your body’s metabolic needs is an absolutely crucial piece of information.

In fact, understanding your C-peptide value is so important that researchers believe it to be the most suitable measurement for assessing endogenous insulin secretion (3). Therefore, knowing your C-peptide level is crucial in understanding what type of diabetes you have.

Since the treatment of type 1 diabetes, type 1.5 diabetes, prediabetes, type 2 diabetes and gestational diabetes each require different treatment plans, being misdiagnosed with the incorrect type of diabetes can lead to an improper course of treatment, years of frustration, and rapidly declining health.

An accurate C-peptide measurement will provide you and your doctor with a quantitative assessment of the ability of your pancreatic beta cells to secrete insulin. This information allows you to answer the following questions:

  • What type of diabetes are you actually living with?
  • Are you living with autoimmune diabetes (type 1 diabetes or type 1.5 diabe​tes)?
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    How much damage have your beta cells accumulated over time?
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    What are your chances of reversing prediabetes or type 2 diabetes without the need for exogenous insulin?
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    Can you fully reverse prediabetes or type 2 diabetes?

Let’s dive into each of these questions individually, to get a better understanding of how your C-peptide value influences your diabetes treatment (or reversal) regimen.

What Type of Diabetes Are You Actually Living With?

Every year, millions of people are misdiagnosed with type 2 diabetes rather than type 1 diabetes or type 1.5 diabetes because they fail to measure their C-peptide value at an early stage in the disease process.

The C-peptide test will tell you what type of diabetes you are actually living with (4), and help you differentiate between an autoimmune version of diabetes (with extremely low insulin production) and lifestyle-related diabetes (with medium to high insulin production).

Recent guidelines developed by the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) dictate that a C-peptide should be used when there is doubt about what type of diabetes a patient is living with. 

In addition, a recent systematic review suggested that the C-peptide test be used as the principal baseline measure of insulin deficiency (5).

Insulin Deficiency

Knowing your C-peptide value can determine the entire course of your diabetes treatment, and allow you to differentiate between “insulin sufficient” and “insulin deficient.” 

Although it is possible to make an educated guess about what type of diabetes you are living with, a C-peptide test gives you and your doctor much more accurate insight into your diabetes health.

Are You Living with Autoimmune Diabetes (Type 1 or Type 1.5 Diabetes)?

If you are living with an autoimmune version of diabetes (either type 1 or type 1.5 diabetes), then your C-peptide value will most likely be significantly lower than if you are living with prediabetes or type 2 diabetes.

But what exactly is type 1.5 diabetes? Type 1.5 diabetes is increasing in prevalence around the world, and often referred to as Latent Autoimmune Diabetes in Adults (LADA).

Once considered rare conditions, type 1 diabetes and LADA have been on the rise since the 1950’s (6,7).

Living with type 1.5 diabetes (the adult-onset, slow-progressing version of type 1 diabetes) means that your pancreas is still capable of producing insulin, but the presence of one or more autoantibodies against beta cells leads to a slow destruction of beta cells over time.

LADA has characteristics of both type 1 diabetes and type 2 diabetes and is often misdiagnosed as other forms of diabetes, resulting is the wrong treatment (8).

LADA Misdiagnosis

It is currently unknown how many type 1.5 patients are misdiagnosed with other forms of diabetes, but some estimate it could be as many as 1 out of every 10 diabetes patients (9), and some researchers believe that type 1.5 diabetes is the most prevalent form of autoimmune diabetes in general (10).

LADA Prevalence

It’s important to note here that medical scientists are now recognizing that type 1.5 diabetes is not really one type of diabetes. The condition occurs on a spectrum and each patient must be treated as an individual and not as a generic “type.”

The treatment strategy (such as whether or not insulin is used and how much insulin is needed) will likely change over time as type 1.5 diabetes worsens or improves (11,12). C-peptide levels should be monitored routinely in addition to other important diabetes biomarkers.

The Immunology of Diabetes Society has established 3 main criteria for establishing a diagnosis of LADA. These three factors must be present in order for a patient to be diagnosed with LADA:

  • Adult age of onset (greater than 30 years)
  • The presence of at least 1 islet cell autoantibody
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    The absence of insulin requirement for at least 6 months after diagnosis (13)

On the other hand, those living with type 1 diabetes experience a “severe loss of insulin secretion” characterized by multiple autoantibodies and a dangerously low C-peptide value.

Rapid Decline in Insulin

An overwhelming majority of those living with type 1.5 diabetes test positive for only one autoantibody, resulting in a slow-progressing loss of insulin secretion (10).

Evidence of destruction to beta cells is currently accepted as a diagnostic tool for autoimmune diabetes. Those living with type 1 diabetes often require exogenous insulin almost immediately after diagnosis, whereas those with type 1.5 diabetes may not require insulin therapy for between 6 months and 5 years after diagnosis.

It turns out that people with LADA are often misdiagnosed with type 2 diabetes for three main reasons:

  • Diabetes onset occurs after the age of 30
  • Beta cell destruction occurs over the course of time (as opposed to sudden onset type 1 diabetes)
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    They are unaware of their autoimmune status, and are lacking a diabetes antibody panel to test for the autoantibodies GADA, IAA, IA-2A, ICA, and/or ZnT8

Case Study: Type 1.5 Diabetes Misdiagnosis

Anna is a classic example of someone who was misdiagnosed with type 2 diabetes for 11 years. 

Although she diligently reduced her carbohydrate intake and total calorie intake in addition to taking multiple oral diabetes medications, her blood glucose levels were very difficult to control.

She experienced high blood glucose even after eating non-starchy vegetables, and felt shameful that she couldn’t control her blood glucose. She was so desperate to reverse type 2 diabetes that she starved herself with juice fasts. Even this did not help.

Anna joined our small group coaching program and Cyrus asked some poignant questions to gain an understanding of why Anna’s blood glucose was constantly elevated even though she was indeed following a truly low-fat, plant-based, whole-food diet.

When Cyrus asked her a simple question: “What is your C-peptide level?” Anna responded “It is normal.” Cyrus asked “No, what was the actual number?” and Anna replied, “my C-peptide is 0.8.”

Cyrus then explained to her that with a C-peptide value of 0.8 in conjunction with what she had seen when applying a low-fat, plant-based, whole-food diet, her pancreas was not producing sufficient insulin to meet her metabolic needs.

After 11 years of living with the wrong medical diagnosis, Anna is now able to effectively control her blood glucose by discontinuing oral medication and injecting small amounts of basal and bolus insulin. 

She subsequently got a diabetes islet antibody test and tested positive for 1 autoantibody, confirming a new diagnosis of type 1.5 diabetes. Thanks to both the C-peptide and diabetes antibody tests, Anna now lives in full control of her diabetes health.

Type 1.5 diabetes is also likely in patients diagnosed with type 2 diabetes as an adult who are lean and do not have the metabolic syndrome (high blood pressure, high cholesterol or triglycerides, and excess fat around the waist), especially if that patient follows a low-fat, plant-based, whole-food diet and is physically active.

Because a low-fat, plant-based, whole-food lifestyle is so effective at preventing and reversing type 2 diabetes, if you are unable to control your blood glucose after 3 months, then we recommend testing your C-peptide and getting a diabetes antibody panel.

We recommend getting your c-peptide tested first. Once you have that information, you can decide if it’s worth the time and effort to test for diabetes antibodies.

How Much Damage Have Your Beta Cells Accumulated Over Time?

Knowing how much damage has been done to your beta cells over time is an important determinant of whether your body requires exogenous insulin or not.

If your beta cells are still functioning properly, a low fat, plant-based, whole-food diet combined with frequent exercise and adequate sleep can help you achieve non-diabetic blood glucose without the need for medications or insulin injections.

If your C-peptide test reveals significant destruction of your pancreatic beta cells, it is unlikely that you will be able to achieve non-diabetic blood glucose values without the use of exogenous insulin, regardless of how strict you are with your diet and exercise regimen.

If you have been diagnosed with type 2 diabetes on the assumption that you are insulin resistant, even though your C-peptide value was never measured, then taking a C-peptide test can help you avoid unnecessary oral diabetes medications and years of unnecessary side effects.

What Are Your Chances of Reversing Prediabetes or Type 2 Diabetes Without the Need for Diabetes Medications?

If you have been diagnosed with either prediabetes or type 2 diabetes, you may be wondering the answer to a simple question: Can I achieve non-diabetic blood glucose values once again?

Many people ask us if it’s possible to live free of diabetes medications by making consistent changes to their diet and movement patterns. While this is possible, there are a few important things to take into account.

Using conventional treatment, type 2 diabetes is a progressive disease in which approximately 50% of individuals require insulin therapy within 10 years of diagnosis resulting from insulin resistance, the deterioration of beta cell function, and reduced insulin secretion over time (14), (15).

Progressive Disease

Using a low-fat, plant-based, whole-food diet combined with adequate physical exercise, you can reverse prediabetes and type 2 diabetes in 99% of cases, when there is still sufficient insulin production.

In this case, your body is producing plenty of insulin (as measured by a high C-peptide value), but your lifestyle has created a state of insulin resistance. By optimizing your diet and movement patterns, you can reverse insulin resistance and control your blood glucose without diabetes medications.

A high C-peptide value indicates that your beta cells are capable of manufacturing sufficient insulin, and by switching to a low-fat, plant-based, whole-food diet it’s possible to completely reverse insulin resistance and eliminate your need for diabetes medications using your food as medicine (16–19).

A medium C-peptide value indicates that you have adequate insulin production to fully reverse prediabetes or type 2 diabetes, but that it’s imperative to maximize your insulin sensitivity in order to prevent beta cells from becoming exhausted over time.

A low C-peptide test means that your beta cells have been permanently impaired. In this situation, you will likely require exogenous insulin to control your blood glucose for the rest of your life.

If you are living with type 2 diabetes and have been told to inject insulin unaware of your C-peptide value, then you are in the same situation as millions of people around the world. The vast majority of these patients have a medium or high C-peptide value and can fully reverse insulin resistance using lifestyle modification.

However, while it is true that type 2 diabetes can often be fully reversed, this is not always the case.

In the progression towards type 2 diabetes, beta cells in your pancreas can begin hypersecreting insulin as early as 20 years before diabetes is even detected, in an effort to prevent your blood glucose from elevating as a result of increasing insulin resistance.

As you can see in the image below, insulin is not the limiting factor in the early stages of the disease process. As insulin resistance progresses, beta cells increase insulin production – sometimes by as much as 500% of normal – in order to protect against elevated blood glucose.

Hyperinsulinemia

Image courtesy of: This research paper

Over time, if insulin resistance continues to develop due to high-fat feeding, the beta cells in your pancreas become overworked, resulting in beta cell death. When this happens, you develop a state of hypoinsulinemia (impaired insulin production), resulting in high blood glucose in the fasting and post-meal states.

Your C-peptide values follow the same progression as insulin. When you are hyperinsulinemic (producing excess insulin), your C-peptide value increases accordingly, and when beta cells permanently lose their ability to produce sufficient insulin, your C-peptide value falls significantly.

There is strong scientific evidence showing that lifestyle change can help restore beta cell function, however optimal function may never be completely restored (20). By testing your C-peptide level, you and your doctor can find out how much your beta cells are capable of secreting insulin, or if they have been permanently impaired.

High C-peptide levels indicate that your beta cells are still functioning properly, and your likelihood of completely getting off of oral hypoglycemic drugs and/or insulin injections is very high, whereas low C-peptide levels indicate that your beta cell function has been permanently impaired and you may likely require insulin to control your blood glucose.

What is the Difference Between a Fasting and Stimulated C-Peptide Test?

There are two types of C-peptide tests:

  • Fasting C-peptide test, performed after an overnight fast of at least 8 hours, and before any food or non-water beverages are consumed
  • Stimulated C-peptide test, used to measure the amount of insulin your pancreas is capable of manufacturing in response to a high-carbohydrate meal

The fasting C-peptide test is self explanatory. A stimulated C-peptide test can be performed in one of 3 ways:

  • Method #1: Drink a “mixed meal shake,” which is a standardized liquid meal
  • Method #2: The patient receives an injection of glucagon (a hormone produced by the pancreas that stimulates the conversion of glycogen into glucose in the liver)
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    Method #3: Eat a high-carbohydrate meal or drink containing at least 75 grams of carbohydrate energy

The purpose of the stimulated C-peptide test is to measure how much insulin your pancreas produced in the hour after a carbohydrate challenge. The amount of C-peptide in your blood reveals how effective your pancreas is at secreting insulin and C-peptide in response to rising blood glucose.

The Immunology of Diabetes Society currently recommends using both the fasting and stimulated c-peptide tests at diagnosis and annually (21).

Reference ranges for the stimulated C-peptide test are shown below (22).

  • Less than 2 ng/mL indicates severe damage to your pancreas with a 5% chance of controlling blood glucose through lifestyle measures alone; injected insulin likely required
  • 2 - 4 ng/mL indicates some damage to the pancreas with a 50% chance of controlling blood glucose without insulin or diabetes medications
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    Greater than 4 ng/mL indicates that your pancreas is still functioning well with a 95% chance of controlling blood glucose through lifestyle measures alone

Do Doctors Recommend a C-peptide Test?

At Mastering Diabetes, we partner with many doctors, and provide education as well as ongoing support for their patients. We believe that a doctor can be your greatest ally in restoring your health. For this reason, we educate our clients on how they can partner with their doctor to maximize their metabolic health.

Despite the advancements that have been made in the understanding and treatment of diabetes over the past century – including the discovery of C-peptide and subsequent invention of the C-peptide test in 1972 – lifestyle change education for physicians is often lacking in medical school.

Medical School

Because of this, physicians are rarely educated about the importance of a C-peptide test for their patients. In addition, much of medical school education (as well as post-graduate continuing education) is funded by pharmaceutical companies (22,23). 

These companies have a vested interest in ensuring that type 2 diabetes patients remain unaware that their condition is preventable and reversible with a low-fat, plant-based diet.

Always remember one thing – physicians are NOT to blame for a lack of education about lifestyle change (23–25). Until the medical system begins to place a larger emphasis on evidence-based approaches to reversing diabetes, physicians will remain in the dark.

Although this can sound grim, bordering on a conspiracy against public health, the positive side is that most doctors truly want their patients to get well and are willing to work with you when you know how to approach them in the right way.

If you are second-guessing your diagnosis or requesting a different treatment plan, your doctor may become defensive or uncooperative, or even discharge you as a patient. We teach our clients in the Mastering Diabetes Program exactly how to approach their doctor with factual information in a way that will make them more open to the evidence-based science of lifestyle change.

How To Get Your C-Peptide Tested

Here’s the good news – it’s very easy get your c-peptide level tested. It is an inexpensive blood test that you can request from your doctor, or you can order the test for yourself online and schedule to have your blood drawn at a local Labcorp or Quest Diagnostics walk-in facility.

You can usually schedule your blood draw for the same day you place your order, and there is little to no wait time. Most facilities are open on weekends, so paying out of pocket is often more convenient than waiting to see your primary care physician or endocrinologist.

If you are going to use the latter method, we suggest ordering from one of the following online laboratories:

Simply select where you would like to get your blood drawn, enter your credit card information, and then take the order form to your local facility. The results are quick, and often ready in 1-3 days.

Interpreting Your C-Peptide Lab Results

We recommend using the following guidelines to interpret your C-peptide test results. As you can see, your C-peptide results are best interpreted in conjunction with an islet antibody test – interpreting the results of both tests together provides the most accurate information.

*Please note that these guidelines are not considered medical advice and are merely the opinion of Mastering Diabetes. We encourage you to consult your medical professional to interpret your own results.

Your fasting C-peptide is less than 1.0 ng/mL:

Your endogenous insulin production is very low, which means that you fall into one of the 3 categories below:

  • If you test positive for one islet antibody (and are over the age of 30), you are likely living with type 1.5 diabetes, and may require both basal and bolus insulin to control your blood glucose
  • If you test positive for multiple islet antibodies (irrespective of your age), you are likely living with type 1 diabetes, and may require both basal and bolus insulin to control your blood glucose
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    If you test negative for islet antibodies, you are likely living with insulin-dependent type 2 diabetes (low insulin production). You are likely to require both basal and bolus insulin in order to control your blood glucose

Your fasting C-peptide is 1.0 – 2.0 ng/mL:

Your endogenous insulin production is medium, which means that you fall into one of the following 3 categories:

  • If you test positive for one islet antibody (and are over the age of 30), you are likely living with type 1.5 diabetes, and may experience a decline in your insulin production with an increased need for exogenous basal and bolus insulin over time
  • If you test positive for multiple islet antibodies (irrespective of your age), you are likely living with type 1 diabetes and are currently in the “honeymoon” phase in which your endogenous insulin production is declining quickly. You will likely experience an increased need for exogenous basal and bolus insulin over time
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    If you test negative for islet antibodies, you are likely living with type 2 diabetes (impaired insulin production). Adopting a low-fat, plant-based, whole-food diet to maximize your insulin sensitivity is your best chance at remaining free of exogenous insulin

Your fasting C-peptide is 2.0 ng/mL or above:

Your endogenous insulin production is medium-to-high, which means that you fall into one of the following 3 categories:

  • If you test positive for one islet antibody (and are over the age of 30), you are likely living with type 1.5 diabetes, and may experience a decline in your insulin production with an increased need for exogenous basal and bolus insulin over time even though your endogenous insulin production is sufficient now
  • If you test positive for multiple islet antibodies (irrespective of your age), you are likely living with type 1 diabetes and are currently in the “honeymoon” phase in which your endogenous insulin production is declining quickly, even though your endogenous insulin production is sufficient now. You will likely experience an increased need for exogenous basal and bolus insulin over time
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    If you test negative for islet antibodies, you are likely living with type 2 diabetes (high insulin production). You are likely to remain free of exogenous insulin as long as you continually improve your insulin sensitivity

The following table summarizes our C-peptide guidelines:


Low C-Peptide

(<1.0 ng/mL)

Medium C-Peptide

(1.0-2.0 ng/mL)

High C-Peptide

(2.0 ng/mL+)

Negative Antibody Test

Type 2 diabetes with low insulin production

(Insulin likely)

Type 2 diabetes with impaired insulin production

(Insulin unlikely)

Type 2 diabetes with high insulin production

(Insulin unlikely)

Positive

(1 AB)

Type 1.5 diabetes

(Insulin necessary)

Type 1.5 diabetes

(Insulin necessary)

Type 1.5 diabetes

(Insulin necessary over time)

Positive

(2+ ABs)

Type 1 diabetes

(Insulin necessary)

Type 1 diabetes

(Insulin necessary)

Type 1 diabetes

(Insulin necessary over time)

​Take Home Message

We hope this gives you a clear understanding of the importance of your C-peptide value in the course of your diabetes treatment protocol. 

We consider the C-peptide test to be one of the most valuable diagnostic tests available today, because together with an antibody test, they can definitively guide your method of diabetes treatment or reversal.

References

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About the Author

Cyrus Khambatta, PhD, and Robby Barbaro are the co-founders of Mastering Diabetes, a coaching program that reverses insulin resistance via low-fat, plant-based, whole-food nutrition. Cyrus has been living with type 1 diabetes since 2002 and has an undergraduate degree from Stanford University and a PhD in Nutritional Biochemistry from UC Berkeley. Robby was diagnosed with type 1 diabetes in 2000 and has been living a plant-based lifestyle since 2006. He worked at Forks Over Knives for six years, is studying towards a master’s degree in public health, and enjoys sharing his lifestyle on Instagram, YouTube, and Facebook.