Assessing Genetic and Immunological Predictors of Endogenous Insulin Production in Type 1 Diabetes

Background & Introduction:

Type 1 Diabetes (T1D) is a disease caused by the autoimmune destruction of pancreatic beta cells. It commonly presents in childhood with elevated blood sugars and long-term insulin treatment is required. People diagnosed with T1D have some pancreatic beta cells remaining at diagnosis and these remaining insulin producing cells were thought to be lost within the first few months or years after diagnosis. The underlying mechanism for destruction of beta cells is T-cell driven autoimmunity with genetic, environmental and immune associations that point towards the immune system as being the key to pancreatic beta cells loss. Extensive research has focussed on trying to prevent, halt or reverse immune attack in T1D using immunosuppression or immunomodulation with a variety of drugs and vaccines. These efforts have been largely unsuccessful and demonstrate that although we know that autoimmunity is critical to the development of T1D we still do not know enough about specific mechanisms to successfully stop this process. By better understanding the role of the immune system in T1D, this may ultimately lead to better treatments or reversal of T1D.

Contrary to conventional understanding, not all people with T1D lose insulin production soon after diagnosis. Modern assays that can detect low levels of endogenous insulin have shown that many people with T1D make low levels of insulin for many years after diagnosis. There are also a smaller group of patients who make significant amounts of insulin despite having T1D for many years. Conversely, there are some patients who seem to lose all endogenous insulin very quickly after diagnosis.

Urine C-peptide Creatinine ratio is a new technique that allows assessment of endogenous insulin production in a urine sample that is posted from home. This has allowed the assessment of insulin production in over 1000 patients with T1D in the South West of England with identification of patients still making significant amounts of insulin after years of T1D, and other patients who have lost insulin production very rapidly.

Retained endogenous insulin production may represent a slower autoimmune process, with a dampening of the immune response by regulation within the autoimmune system (tolerance), or a "burning out" of the process of autoimmunity as can happen in some other autoimmune diseases. Similarly, very rapid loss of insulin production may represent the opposite, more aggressive end of the spectrum.