Abstract

The current diagnostic tools are insufficient for the early detection of many diseases, including type 1 diabetes mellitus. The disease is accompanied not only by a permanently elevated level of blood glucose and altered levels of other biomarkers, but also by changes in the conformation of blood plasma proteins and other biomolecules associated with the pathogenesis of diabetes. However, the observation of these structural changes by conventional Raman and infrared spectroscopy is limited. Therefore, we used chiroptical spectroscopy which is inherently sensitive to the 3D structure of chiral molecules and able to detect any possible structural changes. We investigated the blood plasma samples of diabetic patients and healthy controls by Raman optical activity and electronic circular dichroism. The measurements were combined with conventional methods of molecular spectroscopy, i.e. Raman and infrared spectroscopy. The obtained data sets were statistically evaluated using linear discriminant analysis focusing on the spectral ranges that correspond to the structure and conformation of proteins and other plasmatic biomolecules. Our results suggest that chiroptical spectroscopy gives more detailed information about the 3D structure of biomolecules; and therefore, might be a promising complement to conventional diagnostic methods.

Highlights

  • In this pilot study, we propose the utilization of Raman optical activity (ROA) and electronic circular dichroism (ECD) of human blood plasma for the diagnostics of type 1 diabetes mellitus (T1DM)

  • The disease is accompanied by a permanently elevated level of blood glucose and altered levels of other biomarkers, and by changes in the conformation of blood plasma proteins and other biomolecules associated with the pathogenesis of diabetes

  • Our results suggest that chiroptical spectroscopy gives more detailed information about the 3D structure of biomolecules; and might be a promising complement to conventional diagnostic methods

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Summary

Introduction

We propose the utilization of Raman optical activity (ROA) and electronic circular dichroism (ECD) of human blood plasma for the diagnostics of type 1 diabetes mellitus (T1DM). Blood glucose is routinely measured by placing a drop of blood on a diagnostic strip and using an enzymatic reaction.[18] Many experiments have been conducted in search of a reliable non-invasive diagnostic method based mainly on Raman and IR spectroscopy.[19,20] dealing primarily with glucose or glycated hemoglobin, the research focus is narrow and does not affect all pathological changes within plasma biomolecules that might be worth following Some of these changes appear before the disease onset.[17] For example, the production of altered antigens begins shortly after the virus attacks the β-cells but before the blood glucose level starts to increase and clinical symptoms occur.[16] We believe that focusing on these pre-diabetic alterations in the structure of proteins, carbohydrates and other essential biomolecules in blood plasma might lead to a diagnosis early enough to prevent children and adolescents from life-threatening sudden collapses and severe complications that are inevitably connected with the outbreak of T1DM

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