An Old Test Teaches Doctors New Tricks: C-peptide Exam Becoming an Accepted Tool for Diabetes Treatment


By: Thomas Connors

If you’re a person with diabetes who suspects your beta cells may still be hard at work, you may be more right than you know. Most people with diabetes, including type 1s, are still producing at least trace amounts of insulin. And while BGs and HbA1cs may be the foundation for any good diabetes treatment, when it comes to showing insulin production, they don’t necessarily paint the full picture.

Fortunately, filling in the blanks is easy. A little-known but valuable part of your health care practitioner’s treatment arsenal is the C-peptide test, a measurement of the body’s natural production of insulin. The C-peptide test’s uses are far from universal, but it has already found acceptance as a way of gauging whether a patient is actually type 1, type 2 or something undefined and in between.

A Familiar Procedure

C-peptides are the byproducts of insulin production. They indicate the body is secreting natural insulin, also known as endogenous insulin. While this procedure may be new ground for many people with diabetes, the actual mechanics of the blood collection will not be unfamiliar territory. In fact, the procedure is in many ways strikingly similar to the fasting blood glucose exam. Eight hours of fasting are required beforehand, and the blood is collected in the doctor’s office, then sent off to a lab for analysis.

The C-peptide provides a snapshot recording of insulin production, which typically ranges between 0.5 and 3 nanograms (ng) per millileter (ml). In people with type 2 diabetes or no diabetes at all, eating anything up to eight hours before the exam can raise blood glucose levels, which makes the body produce more insulin-and can unnaturally alter the C-peptide test’s results. Therefore, for the test to accurately reflect actual insulin production, it is important it be performed on a fasting patient.

“It [the C-peptide test] has to be done fasting,” says Richard Bernstein, MD, FACE, FACN, CWS, director of the Diabetes Center in Mamaroneck, New York. “The amount of C-peptide depends on current insulin production.”

A variety of medications can also affect the results.

Natural Insulin Difficult to Measure

Why can’t the amount of insulin be measured directly? The answer, Bernstein says, is simple.

“We don’t measure insulin levels directly because many people are injecting insulin,” Bernstein says. “How do you tell between the body’s insulin and what’s being injected?”

Insulin measurements are incapable of distinguishing between injected and natural insulin in the bloodstream. C-peptides, however, are only created when endogenous insulin is produced. This means C-peptide levels do not measure injected insulin, and makes them the perfect way to gauge how much the body is secreting on its own.

Making It Easier to Distinguish Between Types

This means that, for most physicians, the C-peptide test’s prime usefulness lies in its ability to help them gauge if a patient is type 1, type 2 or even something in between. Most doctors report the line between the two types of diabetes can sometimes be blurry.

“If you have a case that isn’t clear, that’s when the C-peptide is useful,” says Dr. Robert Kanter, an endocrinologist in private practice in Seattle, Washington. “Is a person late-onset type 1 or a type 2?”

A consistent display of high blood glucose levels may be sufficient proof of diabetes, but elevated C-peptide levels may reveal if the body has grown resistant to the insulin it is producing. Low or absent C-peptide levels may indicate that insulin production is diminished or non-existent. Anything below the normal range of 0.5 to 3.0 ng/ml of blood means that insulin production has slowed down abnormally, and generally indicates type 1 diabetes. Type 2s, on the other hand, will often yield C-peptide results in the normal range, meaning their fluctuating blood sugars must be due to insulin resistance, rather than decreased production.

Correctly assessing what type of diabetes a patient has is a vital first step in treating the disease. An incorrect diagnosis can cause serious problems.

“One of the worst things that can happen is to take somebody with type 1 diabetes and then not treat them adequately,” says Alan Marcus, MD, of Southern Orange County Endocrinology in California. “That has a catastrophic outcome.”

Shaping a Course of Treatment

The C-peptide test was being mentioned in papers written as early as the mid-’70s, but its very specific focus has kept it from becoming a treatment staple. Nonetheless, Marcus, who says he does a C-peptide test on 10 to 15 percent of his patients, says the ever-growing number of treatments for diabetes may increase the C-peptide test’s potential.

“We never had to make any decisions before, because nobody really focused on glucose control until the DCCT [Diabetes Control and Complications Trial],” Marcus says. “Then, in addition, you didn’t really have medicines other than insulin or sulfonylureas. Now, you might want to try a secretagogue [any insulin-secretion-promoting agent] or an insulin sensitizer. In the decision-making process, you could go from failure to failure, a stumbling-step program or you can actually have a systematic-step program which is actually based upon a patient’s disease.”

Not For Some

The C-peptide test, however, still draws its fair share of skepticism from the medical community. Frederick Hom, MD, an endocrinologist with Kaiser Permanente in Fremont, California, says he never uses C-peptide levels in his practice, and knows of no colleagues who do. He cites blood sugar levels as the foundation for a good treatment regimen, and sees no need to factor C-peptide results into the diagnostic equation.

“I’m going to treat my patients as needed to bring blood sugars down, whether they’re type 1 or 2,” Hom says.

Hom points out, however, that the C-peptide test has other uses. He cites it as being particularly useful in detecting insulinoma, when the pancreas secretes more insulin than the glucose load requires.

Doctors who do use the C-peptide test identify it as an exam to be used sparingly.

“I would think that, in the typical day-to-day practice, you could probably do just fine without it,” Kanter says. “It’s just a little extra wrinkle.”

Patients Give Positive Feedback

Overall, most patients with diabetes who have had the test done respond positively, even if it has had no noteworthy effect on their course of treatment.

“I know of a few people who have had their C-peptide levels tested, and do so regularly, so their doctors can modify their treatment if and when it’s necessary,” says Kelly Ellis, of Fort Benning, Georgia. Ellis says that, in her own case, “It didn’t affect my treatment, but it did help me understand a bit more about my diabetes.”

Several readers echo this sentiment, saying the C-peptide helped them understand a little more about their body’s mechanism and the way their diabetes affected them. Others report near-horror stories of incorrect diagnoses being set straight by C-peptide tests.

Bill Whitley of Redlands, California, comments that he was put on oral medications after an initial diagnosis of type 2 diabetes, even though he failed to meet any of the criteria usually associated with type 2. Seven years of steadily rising blood glucose levels and HbA1cs did nothing to change his doctor’s opinion, and it wasn’t until he took the C-peptide test that his official diagnosis was changed to type 1.

“I have to fault the doctors for using statistical probability and costs instead of using all the tools available to make their diagnosis,” says Whitley. “The C-peptide test would appear to be one of those tools that should have been used and wasn’t until quite late in the game.”

Test Establishes Criteria

The C-peptide test is also used to dictate who will get their insulin pump paid for by Medicare. The government HMO requires two things to cover 80 percent of insulin pump costs: a doctor’s recommendation and a reading of 0.5 ng./ml or less (see sidebar “Interpreting Your C-peptide Values”) on the C-peptide test.

The C-peptide test finds its strongest support base, however, in the world of clinical trials. In many clinical trials, its use is almost routine, and over 80 studies at this year’s ADA conference in San Antonio, Texas, used C-peptide levels as a means of measuring their treatment’s effects on diabetes. Which means that, even if most physicians are slow to embrace the test, it will still contribute to diabetes research out of the public eye.



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