Functioning beta cells survive in type 1 diabetes in some

There are more than just attacks on the immune system.

Type 1 diabetes is a disease characterized by the destruction of the patient's immune system by his own beta cells. But a previous study has shown that not all beta cells are completely eliminated. The Diabetes Control and Complication (DCCT) trial showed that "11% of adult participants with type 1 diabetes for more than 5 years had a measurable C-peptide on an empty stomach and after stimulation of a mixed meal" . Peptide C was lower in volunteers who had been intensively treated with insulin after one year. And after only two weeks of intensive insulin therapy in adolescents, their beta-cell function improved after one year (blood glucose levels also dropped).

Apart from peptide C, it has been found that proinsulin (prohormone precursor insulin) still circulates in patients with type 1 diabetes, even after 30 months (since diagnosis). This is proof that in patients with type 1 diabetes, beta cells are still able to produce proinsulin. In many people with type 1 diabetes, proinsulin can also be converted into C-peptide and insulin.

In this Diabetic treatments Three groups of volunteers were tested for their C-peptide response. The three different C-peptide responses were "absent", "intermediate" and "high" responses. The "high" response to peptide C was still not as high as in healthy individuals (it was only named "high" as a category of differentiation). In the absent group, C-peptide responses were undetectable. Only the intermediate and upper groups were tested (with mixed meal tests) at years 1, 2 and 4 after their initial testing, as both categories had measurable responses to peptide C. The high-response category had response to peptide C (both fasting and stimulated) seven times higher than those in the intermediate response group. Glucose management was also better in the high-response group.

Although type 1 diabetes was diagnosed at about the same time in the high- and intermediate-response groups, "those in the high-response group were significantly older (mean 29 years) at the time of diagnosis than those in the high-response group. with type 1 diabetes intermediate responses (19 years), "found researchers. So, it seems that those who were diagnosed later in life may have had more functional beta cells. The levels of proinsulin relative to peptide C were abnormally increased in both groups during their initial visit, which revealed beta cell dysfunction. "In addition, the proinsulin-C-peptide ratio was higher in patients with the weakest C-peptide responses, consistent with those with lower B-cell function." Therefore, patients in the high C peptide response group had a better cell than the intermediate response group.

We know that type 1 diabetes is heterogeneous. This may include the involvement of the HLA genotype, the age of onset, the number of autoantibodies and the differences in mbad and survival of beta cells. In addition, some people with type 2 diabetes have genes that have contributed to the disease (activation of antibodies and / or T cells). Most people with chronic type 1 diabetes have a proinsulin present in the blood, whereas it is harder to detect C peptide in the majority of patients with type 1 diabetes. So, we know that They still have beta cells. We do not know if they are old cells (before diabetes disease) or new cells. Therefore, we do not know the extent of the function of these persistent beta cells in the treatment of proinsulin, but we know that there are more functional beta cells in patients who have been diagnosed older.

In conclusion, the duration of type 1 diabetes is not the major factor in the worsening of beta cell function, given the age of study volunteers and their better ability to treat proinsulin. However, further research is needed, for example, to determine the amount of insulin needed to obtain lower A1C hemoglobin and to identify factors that affect beta cell function, for example if beta cells have been affected by the Immune system of the body whether they are previous or not to diabetes, or if they are new beta cells. Changes in the expression of proinsulin have been suggested in previous studies. It would be useful to know if there are differences in the treatment of proinsulin in type 1 and type 2 diabetes. Another hypothesis on which further research is needed is whether the expression or the Prohormone convertase action has been lost in type 1 diabetics. Amyloid deposits may also play a role. The "localization of amyloid deposits is consistent with the IAPP (islet amyloid polypeptide), their unique peptide component, being a secretory product of cell b that typically needs to be exocytized for amyloid to occur. form, "according to the researchers. The formation of amyloid should also be examined. There must be so much more than just destruction in type 1 diabetes.

Pearls of practice:

• Genetics and the immune system are very involved in type 1 diabetes, but not all beta cells are destroyed in the disease. All the operation can not be lost either. Peptide C and proinsulin are still being treated in many of these patients.
• A longer duration of the disease does not lead to the progression of beta cell dysfunction.
• People who had been diagnosed with type 1 diabetes when they were older had more functioning beta cells than people who had been diagnosed when they were young.

References:

Hull, Rebecca L .; Kahn, Steven E.; Templin, Andrew T .; Verchere, C. Bruce. "Exploring the meaning of the persistent release of prepopeptide in type 1 diabetes". Diabetes Care 2019. http://care.diabetesjournals.org/content/42/2/183. January 31, 2019.

Annahita Forghan, Pharm.D. Candidate 2019, College of Pharmacy LECOM