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DRI Answers C-peptide Question    

by Diabetes Research Institute on Thursday, March 24, 2011 at 9:48am on T1 Diabetes Cure - Global Headquarters and Diabetes Research Institute Facebook pages.

Happy DRI Thursday!  Yesterday Vincent Antoine Solez posted a question about Lantus and Humalog and whether or not they contain C-peptide.  Julie made a good suggestion - that this is something DRI could answer today - and we’re happy to do so. 

Below you will find a response from Diabetes Research Institute Sr. Director of Medical Development Gary Kleiman.  (Below that is an additional note from DRI's Dr. Jay Skyler.)

The quick answer is “no”.

C-peptide is the “chain” or link that connects pro-insulin to insulin and is a sort of by-product of natural insulin release from the beta cells. The ability to measure C-peptide in the blood has helped determine if a person is making any of his or her own insulin—as opposed to measuring insulin levels which won’t differentiate between injected insulin and one’s own. Levels of C-peptide can fluctuate greatly depending on how hard the beta cells are working and how many there are.

The question of the beneficial role of C-peptide has been raised and debated for as long as I can remember. There is still no clear evidence showing what or how it may help. One of the earliest findings in the landmark Diabetes Control and Complications Trial (DCCT), a seven year study that concluded in 1992, noted people with sustained C-peptide had less severe hypoglycemia and few long term complications. However, the question still remains whether the inherent benefit is from the C-peptide itself OR from a small but sustained beta cell mass OR both.

With respect to C-peptide and its relationship to type 1 or type 2, clearly, type 2’s would have C-peptide, probably fairly high levels. In Type 1’s, while most would have virtually no C-peptide, this is not always the case. Tests for auto-antibodies are available to determine the type of diabetes if there are questions. You can check with TrialNet to get more information about this.

There are suggestions by some that C-peptide may play a role in reducing long-term micro-vascular complications- but nothing has been confirmed. There are studies that suggest that C-peptide might help with neuropathy or nephropathy but I know of nothing conclusive.

Just as an FYI -  In islet transplant trials, candidates are screened for C-peptide to determine if they have any detectable levels. The absence of C-peptide is part of the criteria for participation in these clinical trials and is important for comparing the effects of islet transplantation vs. exogenous insulin injections.

C-peptide measurements are taken during a mixed-meal challenge and levels are drawn at standard time intervals and can be assessed if there is any natural insulin production in response to a rise in blood sugar. After islet transplantation, the same tests are performed and monitored over time.

Additional note from Dr. Jay Skyler, DRI's Associate Director for Academic Programs:

The issue is complicated.

First, the DCCT and other studies have demonstrated that preservation of pancreatic beta cell function – as measured by continued C-peptide production – is associated with a decreased risk of complications (eye and kidney) and a decreased risk of severe hypoglycemia.

Second, after islet or pancreas transplantation, persistent pancreatic beta cell function – as measured by continued C-peptide production – is associated with a decreased risk of severe hypoglycemia.  Thus, pancreatic beta cell function – as measured by continued C-peptide production is a good thing.

The question then becomes whether administration of C-peptide itself has beneficial effects.  For many years, John Wahren in Stockholm Sweden has argued that C-peptide treatment would have beneficial effects, based on reduction of complications in some rodent models of diabetes.  He formed a company - Creative Peptides Sweden Inc – to test this in human beings and about 5 years ago they did a study of the effects of C-peptide on diabetic neuropathy.  I cannot find the results of that study published.  I have found a symposium issue of Reviews of Diabetes Studies devoted to C-peptide’s role in diabetes but no human controlled clinical trials.


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