Latest Studies on Type 1 Diabetes and Insulin Production

Dr. Fran Cogen Health Pro
  • As we have been told for many years, type 1 diabetes is an autoimmune disease resulting in the destruction of insulin-producing beta cells by killer T-cells. Our previous conception was that all beta cells would be gone as a result of the mass destruction of these cells. Recently, there have been hints to the contrary based on the following information:

    • Joslin Diabetes Center gold medal survivors (those with type 1 diabetes for over 50 years) who died from natural causes were found to have evidence of active beta islet cells and microscopic amounts of insulin secretion. (Keenan, Sun, Levine et al, Residual insulin production and pancreatic B-cell turnover after 50 years of diabetes: Joslin Medalist Study: Diabetes 2010; 59: 2846-2853.)
    • Unexplained changes in insulin requirements. For example, the fact that certain periodswith type 1 diabetes need less insulin or have increased insulin sensitivity that is otherwise unexplained.  Indeed, a period of decreased insulin requirement is not uncommon for many of my patients, often without any particular changes in usual routines.

    According to Andrew Hattersley, (Oram, McDonald, Shields, Hudson, Shepherd, Hammersely, Pearson and Hattersley, Diabetes Care- DOI: 2337/dc14-0871)), “most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors.”

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    What does this mean?


    People with long-standing diabetes are producing small amounts of insulin, thus indicating that they still have functioning beta islet cells.


    According to Dr. Hattersley, “previous small studies using ultrasensitive C-peptide assays suggest insulin secretion is frequently detectable in patients with long-standing type 1 diabetes, but these studies do not use representative samples.” His research team decided to perform a large cross-sectional, population-based study of people with type 1 diabetes.  The team recruited 924 patients with type 1 diabetes from the United Kingdom for the study. Criteria included participants must be under 30 years of age at diagnosis with a diabetes duration of over 5 years. The median age at diagnosis was 11 years, and median duration was 19 years. Study participants collected urine to measure stimulated urine C-peptide-to-creatinine ratio (UCPCR) to measure c-peptide levels (c-peptide is a reflection of the amount of endogenous insulin that is produced).


    What were the results?

    • 80 percent of patients (740/924) had detectable endogenous c-peptide levels
    • 52 percent  (483/924) had historically very low undetectable levels previously
    • Eight percent  (70/924) had a UCPCR that was “equivalent to serum levels associated with reduced complications and hypoglycemia”
    • Absolute UCPCR levels fell with duration of diabetes
    • Ages at diagnosis and disease duration were independent predictors of c-peptide level in multivariate modeling. However, according to Hattersley, age at diagnosis is associated with HLA risk and may reflect “the strength and intensity of the underlying autoimmune process”
    • No association of persistent c-peptide secretion with either insulin dosage or Hb A1c level was noted

    One significant limitation was that the participants in the study where from U.K. and so mainly white Europeans. Hence, the results may not be generalizable to ethnic groups or other locations around the world.


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    What may we conclude?

    “The majority of long-duration type 1 diabetes patients have detectable urine c-peptide levels and some maintain clinically relevant endogenous insulin secretion for many years after the diagnosis of diabetes.


    Thus, complete beta cell loss does not develop in most people with type 1 diabetes, and they will continue to secrete low levels of insulin for many years after diagnosis. However, it is still not known why some patients with type 1 diabetes are able to produce endogenous insulin for long periods of time.  It is speculated that these people with diabetes have a less aggressive autoimmune response resulting in a slower process of destruction of beta cells or that beta cells in those individuals have the ability to regenerate.


    Next steps: now that we know some individuals with long-standing type 1 diabetes produce endogenous insulin, how do we enhance production? Efforts have been made without efficacy to stop the killer cells through various monoclonal antibody studies. Perhaps an alternative treatment will be to find a strategy to enhance production of insulin from the remaining beta cells.


    Further studies are underway.

Published On: December 23, 2014