The Continued Hope of Beta Cell Production in People With Type 1 Diabetes

Dr. Fran Cogen Health Pro
  • We have talked about the "Gold Medalists" of Joslin Clinic--those people with diabetes who lived long lives and passed away from natural causes. The beta cells of those gold medalists were examined, and much to the surprise of all, a small percentage were still producing insulin! This is a very exciting paradigm insofar as that for many years it was believed that once the beta cells were attacked by the autoimmune response, eventually all would be destroyed with the eventual loss of an insulin response.


    In a paper by Drs. Wang, Lovejoy, and Faustman of Harvard University, published in Diabetes Care, Volume 35, March 2012, pages 465-470, "Persistence of Prolonged C-peptide Production in Type 1 Diabetes as Measured with an Ultrasensitive c-peptide assay," the authors demonstrated that c-peptide production persists for "decades after disease onset and remains functionally responsive."

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    What does this mean?
    A brief review of c-peptide is in order. Proinsulin is first produced and then the c-peptide is cleaved with the alpha and B chains remaining to form insulin. C-peptide is an indirect marker or by-product of endogenous insulin (insulin that is produced by the body's beta cells as opposed to exogenous insulin which is injected into the body). The presence of c-peptide indicates insulin production and therefore surviving beta cells.


    By application of an extremely sensitive assay (22 times more sensitive than standard assays), the authors were able to measure c-peptide many years after the onset of type 1 diabetes. They also looked at factors associated with the preservation of B cell function. There were 182 subjects where c-peptide was measured along with duration of disease, age at onset, age, sex, and antibody titers. Another group of four individuals was studied for up to 20 weeks to evaluate c-peptide levels and functioning beta cells.


    What were the results?
    1. The supersensitive assay detected c-peptide in 10 percent of people with diabetes 31 to 40 years after disease onset, indicating residual beta cell function.
    2. Other analyses demonstrated that beta cells, with formally undetectable c-peptide levels by standard assay, were capable of producing insulin.
    3. Statistical analysis revealed that disease duration (p=0.005) and level of a specific type of antibody (zinc transporter 8 autoantibodies (p=0.015) were significantly associated with c-peptide production.
    4. Type 1 Diabetes onset greater than 40 years of age was associated with a low c-peptide production despite shorter disease duration (this was unexpected).


    How may we interpret this information for our patients and families with type 1 diabetes?
    There continues to be production of insulin from beta cells as measured by sensitive assays even after many years of autoimmune destruction of beta cells. Perhaps this may help explain some of the fluctuations in blood sugars that are simply "unexplainable." Everyone has experienced a time period wherein blood sugars are consistently lower despite the usual eating pattern, exercise routine, and daily living. WHY? Is it possible that there is some production of insulin from beta cells that remain accounting for the hypoglycemia? If so, perhaps frustration in regard to labile blood sugars will be viewed in a more positive light?


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    What about different approaches to preserve insulin function? Will the awareness that c-peptide continues to be present in people with long-standing diabetes stimulate new research directions? The monoclonal antibody studies appeared to be going in the correct direction-stopping the immune response and allowing beta cells to survive. However, insulin production eventually stopped despite the presence of the monoclonal antibodies and the study failed to reach efficacy. What if we could measure the presence of c-peptide in the subjects who enrolled in the monoclonal antibody trials using the supersensitive assay as developed by Wang et. al? Would the results indicate the presence of microscopic amounts of endogenous insulin as measured by c-peptide? Would there be any clinical significance of the presence of tiny amounts of insulin production by remaining beta cells? These are just some of the questions that arise after new information is revealed via "bench to bedside" research. It is my hope that the results of these studies will provide the building blocks for future innovations that will ultimately improve the quality of care and outcomes of those with type 1 diabetes.

Published On: April 27, 2012