Searching for the Mechanical Fingerprint of Pre-diabetes in T1DM: A Case Report Study

Abstract

We report the case of a 38 year-old Caucasian man enrolled in a study aimed at investigating the physical properties of red blood cells (RBCs) using advanced microscopy techniques, including Atomic Force Microscopy (AFM). At the time of his first enrolment in the study, he had normal Fasting Plasma Glucose (FPG) values, a BMI of 24.1, and no other symptoms of diabetes, including fatigue, high triglycerides, low HDL cholesterol, and altered inflammatory and corpuscular RBC indices. The subject reported no family history of diabetes, obesity, and cardiovascular diseases. Despite his apparently healthy conditions, the biomechanics of his RBCs was altered, showing increased values of stiffness and viscosity. More than 1 year after the mechanical measurements, the subject was admitted to the Operational Unit of Diabetology of the Policlinico Gemelli Hospital with high blood glucose and glycosylated hemoglobin (HbA1c) levels and diagnosed with type 1 diabetes (T1DM). Here, we show these data, and we discuss the hypothesis that RBC mechanical properties could be sensitive to changes occurring during the pre-diabetic phase of T1DM.

Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer’s disease

“…In the last decades, a large body of evidence has emerged that—along with biochemical and genetic cues—mechanical stimuli are critical regulators in human physiology, as well as fundamental players in the onset and the progression of many pathological states ( Kumar and Weaver, 2009 ; Lu et al, 2011 ; Van Zwieten et al, 2014 ; Ciasca et al, 2016a , 2019 ; Vielmuth et al, 2016 ; Weaver, 2017 ; Perini et al, 2019 ; De-Giorgio et al, 2020 ; Di Giacinto et al, 2020 ; Mazzini et al, 2020 ). A wide range of diseases that bring patients to the doctor’s office can be, indeed, associated with significant alterations in the mechanical properties of cells, tissues, and organs.…”

Machine Learning-Assisted FTIR Analysis of Circulating Extracellular Vesicles for Cancer Liquid Biopsy

“…Additionally, PCA-LDA has been widely employed in other FTIR-based classification problems in different fields, including diagnostics and forensic sciences [ 17 , 18 , 19 , 20 , 21 ]. More specifically, PCA is an unsupervised statistical learning technique and was used here to find a low-dimensional representation of spectra that retains as much as possible of the variation in the original dataset [ 22 ]. Mathematically, this is achieved by computing the covariance matrix of the whole dataset and finding the matrix eigenvalues with the corresponding eigenvectors.…”

“…In this regard, Fourier-transform infrared spectroscopy (FTIR), especially in the Attenuated Total Reflection (ATR) mode, is emerging as a promising tool for label-free molecular profiling of EVs, with several papers published on the subject [ 4 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Most of these works involve in vitro experiments aimed at assessing sample composition and purity [ 15 , 16 ], distinguishing different EV classes [ 18 ] or EVs derived from cells under different states/phenotypes/culture conditions [ 4 , 8 , 10 , 12 , 21 , 22 , 23 ]. So far, very few FTIR papers have focused on EVs purified from biofluids of subjects enrolled in clinical studies.…”

Recent Advances in the Label-Free Characterization of Exosomes for Cancer Liquid Biopsy: From Scattering and Spectroscopy to Nanoindentation and Nanodevices

“…Cantilever deflection is recorded thanks to an optical setup coupled with high-precision piezoelectric actuators (Figure 6a). Aside from imaging purposes, the same cantilever can be used as a sensitive mechanical probe to indent the sample, acquiring spatially resolved images of its mechanical properties [168][169][170][171][172][173][174]. This operation mode is often referred to as force spectroscopy, and it is remarkably flexible, allowing scientists to measure a wide range of mechanical parameters, such as stiffness, Young's modulus, adhesion force, work adhesion, hysteresis, dissipation, and relaxation times [113,[175][176][177][178][179][180].…”

“…This operation mode is often referred to as force spectroscopy, and it is remarkably flexible, allowing scientists to measure a wide range of mechanical parameters, such as stiffness, Young's modulus, adhesion force, work adhesion, hysteresis, dissipation, and relaxation times [113,[175][176][177][178][179][180]. As a further degree of freedom, different types of tips and cantilevers can be chosen [181], and custom relaxation curves can be designed to monitor the mechanical response of the sample over time [171,173,176,182]. Interestingly, AFM can be coupled to nanoscale IR spectroscopy (nano-IR), exploiting tipenhanced plasmonic effects [183].…”