Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Anoptchenko, V.
Persistence of proinsulin secretion in type 1 diabetes –
what is really measured?
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2021. pp. 98
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Sourij Harald
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- Abstract:
- Background: Type 1 diabetes is an autoimmune disease that is characterized by specific immune destruction of the insulin-producing ß-cells. There is increasing evidence supporting the notion that in individuals with long-standing T1DM, a sustained or minimal C-peptide production can be found. Interestingly, researchers recently claimed that proinsulin, a precursor molecule of insulin, is detectable in up to 90% of individuals with long-standing type 1 diabetes, despite C-peptide levels below the limit of detection. In this study, a radioimmunoassay with high sensitivity and specificity was used. It could be hypothesized that incomplete insulin production still occurs and the capacity to secrete proinsulin seems to persist in those subjects. This could enable potential new treatment options. We aimed to validate those findings shown by Sims et al. by using two different assays and to investigate whether this high percentage of proinsulin-positive subjects is due to unspecific assays or if this finding can be reproduced in a large cohort of patients with type 1 diabetes. Methods: We analyzed proinsulin levels of 69 subjects (28 females) with T1DM, a mean age of 39.1 ± 16.0 years and a mean diabetes duration of 19.9 ± 14.3 years, from the Graz Diabetes Registry for Biomarker Research using two different proinsulin assays: a radioimmunoassay (RIA, catalog number HPI-15 K, Millipore, Burlington, MA, USA) and a sandwich enzyme-linked immunosorbent assay (ELISA, Mercodia,Uppsala, Sweden). Results: Using the RIA method, 60.3% of subjects were proinsulin-positive (with a sensitivity of 3.1 pmol/L), whereas the ELISA classified only 31.9% as proinsulin-positive (with a sensitivity of 0.5 pmol/L). In the C-peptide negative group, defined as fasting Cpeptide below 0.08 nmol/L(4), the RIA measurement classified 54,4% as proinsulinpositive, whereas only 20.7% were proinsulin-positive according to ELISA measurement. Overall, proinsulin levels measured by both assays decreased with increasing diabetes duration. Discussion: Taking into account this considerable difference between the proinsulinpositivity rates observed with the two assays, the significance of these proinsulin results remains to be elucidated. Further research is needed to clarify what is really measured with which assay in this cohort, among other things, the possibility of the interference of autoimmune antibodies such as glutamic acid decarboxylase antibodies or islet cell antibodies with the proinsulin assay in subjects with type 1 diabetes needs to be acknowledged.