Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Reintar, S.
C-peptide to creatinine ratio (UCPCR) as urinary biomarker for metabolic risk and monitoring and the development of UCPCR self-testing
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2024. pp. 160
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Haudum Christoph
- Obermayer-Pietsch Barbara
- Sourij Harald
- Altmetrics:
- Abstract:
- Human C-peptide consists of 31 amino acids (molecular weight 3 kilo Dalton). C-peptide mirrors the endogenous pancreatic beta cell secretory pattern of insulin, which is clinically significant in diabetes management. C-peptide measurement has extensive radiation for other applications, such as the determination of hyperinsulinemia, e.g., in women with polycystic ovarian syndrome, obesity, preeclampsia, and gestational diabetes mellitus. A urinary biomarker, such as urinary C-peptide-to-creatinine ratio (UCPCR) is useful to monitor insulin secretion, aiding in assessing diabetes and other metabolic-related conditions. The predictive capabilities of UCPCR to determine people at risk of prediabetes among healthy individuals with normal glucose metabolism are to be elucidated. We investigated the predictive value and characterized guiding values of UCPCR in apparently healthy individuals with normal glucose metabolism based on American Diabetes Association criteria to predict the risk of prediabetes. We further evaluated the metabolic outcomes of the apparently healthy individuals over time. A cohort study from Biomarkers in Personalized Medicine including 1022 participants was screened. A total of 317 control group with normal glucose metabolism, 87 prediabetic, and 43 diabetic group were included. Statistical Package for Social Sciences (IBM SPSS) was used for statistical analysis. R software 4.1.3 (package MatchIt) was used for propensity score matching studies. The prediabetic group showed higher UCPCR median values than control group. Following the dysglycemic state of the baseline of the control group over 4.5 ± 0.9 years, at least 30% have developed preDM during follow-ups, which was predicted by UCPCR (p < 0.05). This is in accordance with the negative predictive UCPCR value of 60.2% based on logistic regression. UCPCR were nearly similar between women and men due to the adjustment for individual urinary creatinine. This study suggests that UCPCR measurements can support the prevention and monitoring of impaired insulin metabolism. Several diagnostic assays were developed for C-peptide detection; however, it is rather costly, and limited use in a laboratory or in a clinical setting. We further aim to describe a proof-of-concept of an immunosensor for urinary C-peptide detection. The C-peptide immunosensor relies on a competition format. The C-peptide is covalently linked onto the gold electrode via the self-assembled monolayer formation of 11-mercaptoundecanoic acid and 11-amino undecanethiol hydrochloride. The two immobilization approaches with its corresponding blocking agents and incubation times were compared for its analytical performance (e.g., sensitivity). An enzyme-labeled C-peptide antibody was used as a detection label for both colorimetric and electrochemical detection. We found that it is crucial to optimize different immobilization techniques, parameters (concentrations of labeled antibodies and coating antigen), and conditions (e.g., incubation times) as it can influence the analytical performance of the assay. Antibodies are susceptible under some harsh environmental conditions (e.g., temperature), an alternative bioreceptors such as aptamers are explored. No aptamer against C-peptide were known yet. We aim to generate C-peptide aptamer for future C-peptide aptasensor developments. A Systematic Evolution of Ligands by Exponential Enrichments (SELEX) was performed to generate aptamer against C-peptide. An aptamer against C-peptide was chemically synthesized using the SELEX. Further work should be carried out for C-peptide aptasensor development, providing a more stable bioelements for point-of-care device. UCPCR is a promising predictive biomarker for prediabetes. A normalized UCPCR enables spot urine specimen, a more convenient, non-invasive approach to assess and monitor metabolic disturbances especially when frequent monitoring is required. UCPCR is independent to muscle mass variations between g