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Non-invasive measurement of skin autofluorescence to evaluate diabetic complications.

ABSTRACT: Although the accumulation of advanced glycation end-products (AGEs) of the Maillard reaction in our body is reported to increase with aging and is enhanced by the pathogenesis of lifestyle-related diseases such as diabetes, routine measurement of AGEs is not applied to regular clinical diagnoses due to the lack of conventional and reliable techniques for AGEs analyses. In the present study, a non-invasive AGEs measuring device was developed and the association between skin AGEs and diabetic complications was evaluated. To clarify the association between the duration of hyperglycemia and accumulation of skin fluorophores, diabetes was induced in mice by streptozotocin. As a result, the fluorophore in the auricle of live mice was increased by the induction of diabetes. Subsequent studies revealed that the fingertip of the middle finger in the non-dominant hand is suitable for the measurement of the fluorescence intensity by the standard deviation value. Furthermore, the fluorescence intensity was increased by the presence of diabetic microvascular complications. This study provides the first evidence that the accumulation of fluorophore in the fingertip increases with an increasing number of microvascular complications, demonstrating that the presence of diabetic microvascular complications may be predicted by measuring the fluorophore concentration in the fingertip.

SUBMITTER: Yamanaka M

PROVIDER: S-EPMC4788401 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Non-invasive measurement of skin autofluorescence to evaluate diabetic complications.

Yamanaka Mikihiro M Matsumura Takeshi T Ohno Rei-Ichi R Fujiwara Yukio Y Shinagawa Masatoshi M Sugawa Hikari H Hatano Kota K Shirakawa Jun-Ichi J Kinoshita Hiroyuki H Ito Kenji K Sakata Noriyuki N Araki Eiichi E Nagai Ryoji R

Journal of clinical biochemistry and nutrition 20160120 2

Although the accumulation of advanced glycation end-products (AGEs) of the Maillard reaction in our body is reported to increase with aging and is enhanced by the pathogenesis of lifestyle-related diseases such as diabetes, routine measurement of AGEs is not applied to regular clinical diagnoses due to the lack of conventional and reliable techniques for AGEs analyses. In the present study, a non-invasive AGEs measuring device was developed and the association between skin AGEs and diabetic comp ...[more]

PMID: 27013780

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Project description:BackgroundAdvanced glycation end products (AGE), one of the main factors causing diabetic end-organ damage, accumulate in long half-life proteins, such as skin and cartilage collagen. AGE measurement may offer additional evidence to predict diabetic vascular complications. Skin autofluorescence (SAF) is suggested as a non-invasive, quick, and reliable method to measure tissue AGE level. The aim of this study was to review and evaluate evidence on the clinical validation of SAF measurement in diabetes mellitus (DM) patients.MethodsIn this systematic review and meta-analysis, we searched "PubMed" (MEDLINE) and "Cochrane" databases from their inception to 10 August 2021 for observational studies concerning SAF measurement in diabetic patients. The following key terms were used in advanced searching: "Diabetes", "Diabetes Mellitus"," DM", "Glycation ", "Advanced Glycation End product", "AGE", "skin autofluorescence", "SAF". Published studies that included DM patients and estimated their AGE using SAF were considered eligible for meta-analysis. Articles that were editorials, study proposals, congress posters, or case reports and were not on human subjects were excluded. We used a random-effect models for meta-analyzing the clinical validation of SAF in DM with particular emphasis on chronic diabetes complications.FindingsWe identified 881 records and twenty-nine records fulfilled our eligibility criteria and were included in the systematic review and meta-analysis. A statistically significant correlation was found between SAF and diabetes last HbA1c 0.21(0.13,0.28) in studies with substantial heterogeneity (I2=77.99%, p<0.05). Nevertheless, a significant positive association between SAF level and diabetic retinopathy (DR) [(OR= 1.05, 95% CI=1.03,1.08), (I2=63.78%, p<0.05)], diabetic peripheral neuropathy (DPN) [(OR= 1.11, 95%CI= 1.06,1.16), (I2=79.17%, p<0.05)], diabetic nephropathy (DNP) [(OR= 1.08, 95%CI: 1.05,1.11), (I 2 =65.36%, p<0.05)] and diabetic macrovascular events (D-MVE) [(OR=1.08, 95%CI=1.05,1.11) (I2=67.32, p<0.05)] were found.InterpretationOur study confirmed the significance of SAF measurement as a non-invasive surrogate marker of DM micro and macrovascular complications. Skin AGE estimation may be a useful factor for the prediction and early detection of irreversible DM complications. More studies with larger populations and longer follow-up periods are required.

Project description:IntroductionMicrovascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques.MethodChanges in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi.ResultsIontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p<0.001) and RBC concentration (TiVi: baseline 119±18; 10-min 150±41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0±4.4 PU; 10-min 38.9±5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6±11.8 AU; 10-min 54.4±13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8±3.6 PU; max 112±55 PU; p<0.001, LSCI: baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses.ConclusionLSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses.

Project description:Vitiligo is a multifaceted autoimmune depigmenting disorder affecting around 0.5 to 2.0% of individuals globally. Standardizing diagnosis and therapy tracking can be arduous, as numerous clinical evaluation methods are subject to interobserver variability and may not be validated. Therefore, there is a need for diagnostic tools that are objective, dependable, and preferably non-invasive.AimsThis systematic review provides a comprehensive overview of the non-invasive objective skin measurement methods that are currently used to evaluate the diagnosis, severity, and progression of vitiligo, as well as the advantages and limitations of each technique.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was used for the systematic review. Scopus, Embase, Cochrane Library, and Web of Science databases were comprehensively searched for non-invasive imaging and biophysical skin measuring methods to diagnose, evaluate the severity of, or monitor the effects of vitiligo treatment. The risk of bias in included articles was assessed using the QUADAS-2 quality assessment scale.ResultsAn extensive literature search resulted in 64 studies for analysis, describing eight imaging techniques (reflectance confocal microscopy, computer-aided imaging analysis, optical coherence tomography, infrared photography, third-harmonic generation microscopy, multiphoton microscopy, ultraviolet light photography, and visible light/digital photograph), and three biophysical approaches (dermoscopy, colorimetry, spectrometry) used in diagnosing and assessing vitiligo. Pertinent information about functionality, mechanisms of action, sensitivity, and specificity was obtained for all studies, and insights into the strengths and limitations of each diagnostic technique were addressed. Methodological study quality was adequate; however, statistical analysis was not achievable because of the variety of methods evaluated and the non-standardized reporting of diagnostic accuracy results.ConclusionsThe results of this systematic review can enhance clinical practice and research by providing a comprehensive overview of the spectrum of non-invasive imaging and biophysical techniques in vitiligo assessment. Studies with larger sample sizes and sound methodology are required to develop verified methods for use in future practice and research.Systematic review registration(PROSPERO) database, (CRD42023395996).

Project description:The metabolic syndrome (MetS) comprises several cardiometabolic risk factors associated with increased risk for both type 2 diabetes and cardiovascular disease. Skin autofluorescence (SAF), a non-invasive biomarker of advanced glycation end products accumulation, is associated with cardiovascular complications in subjects with diabetes. The aim of the present study was to examine the association between SAF and the presence of MetS as well as its individual components in a general population.For this cross-sectional analysis, we included 78,671 non-diabetic subjects between 18 and 80 years of age who participated in the LifeLines Cohort Study and had SAF measurement obtained non-invasively using the AGE Reader. MetS was defined according to the revised NCEP ATP III criteria. Students unpaired t test was used to test differences between groups. Both logistic and linear regression analyses were performed in order to test associations between the individual MetS components and SAF.Subjects with MetS had higher SAF (2.07 ± 0.45 arbitrary units, AU) compared to individuals without MetS (1.89 ± 0.42 AU) (p < 0.001). There was a positive association between the number of MetS components and higher SAF Z-scores (p < 0.001). Individuals in the highest SAF tertile had a higher presence of MetS (OR 2.61; 95% CI 2.48-2.75) and some of the individual components compared to subjects in the lowest SAF tertile. After correction for age, gender, creatinine clearance, HbA1c and smoking status, only elevated blood pressure and low HDL cholesterol remained significantly associated with higher SAF (p = 0.002 and p = 0.001 respectively).Skin autofluorescence was associated with the presence of MetS and some of its individual components. In addition, increasing SAF Z-scores were observed with a higher number of MetS components. Prospective studies are needed to establish whether SAF can be used as an (additional) screening tool to predict both cardiovascular disease and type 2 diabetes in high-risk populations.

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Non-invasive measurement of skin autofluorescence to evaluate diabetic complications.

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Non-invasive measurement of skin autofluorescence to evaluate diabetic complications.

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