Purpose: The purpose of this study was to verify the relationship between glycative stress and skin stiffness and fluorescence derived from advanced glycation end products (AGEs), N^ε-(carboxymethyl) lysine (CML) content in corneum or blood oxidative stress (OS), and the skin stiffness were measured in healthy men and women. Methods: The subjects were 58 healthy men and women in their 20s to 80s. The intensity of skin AGEs fluorescence (SAF) was measured using three devices, AGE Reader su, AGE Reader mu, and AGEs sensor. The measuring site tested by theAGE Reader su was the inside of the upper arm, and that by the AGE Reader mu were on the inside of the forearm, and that by the AGEs sensor was the middle finger. The CML content in corneum, which was from the inside of the upper arm using the tape stripping method, was measured by ELISA. Skin stiffness was evaluated on the inside of the upper arm using MyotonPRO, and the biomechanical parameters, Tone, Stiffness, D value (logarithmic decrement), were obtained. The oxidative stress (OS) was evaluated using a Spotchem i-Pack Oxystress test. The correlation analysis of the measured values were verified between the biomechanical parameters for skin stiffness and the SAF, the CML content in corneum or OS.This study was carried out with the approval of the Ethics Review Committee of the Society of Glycative Stress Research. Results: A significant positive correlation was noted between the subjects’ age and the biomechanical parameters of Tone, Stiffness and D value. The SAF of the forearm measured by AGE Reader mu were significantly correlated with Tone and Stiffness, and had a correlation tendancy with D value. No correlation was observed between the SAF of the middle finger measured by AGEs sensor and the biomechanical parameters. CML content in the corneum was negatively correlated with Tone and Stiffness, while not correlated with the D value. The OS did not show any correlation with the biomechanical parameters. Conclusion: An elevation of the skin AGEs as well as aging were associated with higher Tone and Stiffness. In contrast, the increase of the CML content in the corneum was associated with lower Tone and Stiffness. The OS of the blood, an index of oxidative stress, was not associated with the biomechanical properties. These findings suggested that the skin AGEs and the CML content in the corneum accumulation due to glycative stress may influence the elasticity and viscoelasticity of skin.

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Purpose: In HPLC-fluorescence measurement of pentosidine in blood, multiple-speciemen measurement has problems such as complexity of sample pretreatment, and measurement time. In this study, a sample pretreatment method using a spin column was verified for the purpose of simplifying sample processing. Methods: The blood sample (specimen) used was plasma provided by healthy men and women between the age of 20 to 100 years. For verification of the pretreatment method of the sample, plasma provided by 40 men and women in their 50s to 80s was mixed and used after homogenization. The sample was hydrolyzed under 6 N hydrochloric acid, added to a spin column (Monospin AG) having a mixed group consisting of a cation exchange group and a hydrophobic group as a carrier, followed by elution. Pentosidine was fluorescently detected by HPLC using a reverse phase column. Targeting 72 subjects aged between 20 and 80, a correlation analysis of plasma pentosidine was performed with subject age and age-related physical markers. This study was carried out under the deliberation and approval of the Ethics Review Committee of Doshisha University and the Society for Glycative Stress Research. Results: The recovery rate of pentosidine in the sample was 116% on average by this pretreatment method. The time required for pretreatment after hydrolysis was within 10 minutes. There was a positive correlation between the measured plasma pentosidine levels and age, and a weak positive correlation with HbA1c. Regarding the value of skin autofluorescence (AF) resulting from AGEs and the plasma pentosidine level, the value measured by AGE Reader mu was positively correlated, while by AGEs Sensor was weakly positively correlated. Conclusion: The pretreatment time of the blood sample was shortened from about 12 hours in the ion pair-HPLC method to approximately 10 minutes by using the spin column. Furthermore, this pretreatment could reduce contaminants, and the HPLC measurement time could be shortened to one-third that of the citric acid-HPLC method. It was verified that this method is useful as a multi-specimen assay for pentosidine in blood.

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Purpose: One of the methods for reducing glycative stress is suppression of postprandial hyperglycemia (PPHG). In this study, we picked up food materials with nutrition, i.e., protein, lipids, acetic acid, and dietary fiber, which were reported to have the suppressing effect on PPHG, and their effects were verified. Methods: The subjects were 20 healthy young men and women (8 men, 12 women, 23.3±1.8 years). As the standard food, 200 g of cooked rice (carbohydrate: 67.8 g) + 2.5 g of seasoning was used. The model food, rich in specific nutrition, included A: Salad chicken (protein: low dose (L) 11.5 g/ high dose (H) 23.0 g), B: olive oil (lipid: 14 g/28 g), C: grain vinegar (acetic acid: 0.63 g/1.26 g), D: indigestible dextrin (dietary fiber: 4.2 g/8.4 g), and E: cabbage (dietary fiber: 0.9 g/1.8 g). The complex foods include F: vinegar rice, G: fried chicken, H: fried chicken + lemon juice, and I: Japanese dumplings (gyoza) + ponzu soy sauce. The test food was ingested for 10 min after starting the test, and in the cases of rice + the model food or rice + complex food, these were ingested prior to rice. FreeStyle Libre Pro (Abbott) was used to continuously measure blood glucose levels in the tissue interstitial fluid. The effect on PPHG was evaluated by the maximum blood glucose change (ΔCmax) and the incremental area under the curve (iAUC). This study was approved by the Ethics Review Committee of Doshisha University. Results: When the model foods A, B, C, and E were ingested in high doses (H), the iAUC tended to be lower than that of the standard food. In particular, the ΔCmax and iAUC in test food C were significantly decreased (p < 0.05) and the effect was in a dose dependent manner. On the other hand, the model food D did not have a suppressing effect on PPHG. As compared to the standard food, the complex food F tended to lower ΔCmax and iAUC, while the complex foods G, H, and I significantly reduced the ΔCmax and iAUC (p < 0.05). Conclusion: The suppression of PPHG was strongly influenced by protein and acetic acid in food, and weakly influenced by lipids and dietary fiber in the young subjects. It was suggested that the content of protein and acetic acid in complex foods may be important when expecting side dishes to suppress PPHG.

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People with Diabetes show an increased susceptibility to infection by SARS-CoV-2, greater incidence of pneumonia, and worse clinical outcomes. As diabetes involves high glycative stress, here we present a review of the literature regarding the potential interactions of glycative stress and COVID-19 that may help to explain some of the observed differences in outcomes of diabetic patients. Glycative stress directly suppresses immune function, leaving the body less able to deal with infection. Increased colonization of potentially pathogenic bacteria, mediated by glycative stress, such as Staphylococcus aureus, may also lead to negative outcomes during infection. The presence of S. aureus on the skin may weaken its barrier function and increase the risk of infection through the skin. Proteolytic activity necessary for the virus to enter cells may be enhanced in tissue exposed to S. aureus as well as by the bacteria’s own secreted proteases. Finally, S. aureus carriage could be a risk factor for the development of secondary bacterial pneumonia during primary COVID-19 infection. In order to avoid infection and severe disease outcomes, it is important for those suspected of having diabetes to maintain strict glycemic control and take measures to avoid exposure to the virus.

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Sensorineural hearing loss is reported to be frequently associated with diabetic patients; however, it has not been widely recognized as a complication. Renal disorders are well known as one of the three major complications of diabetes, and the renal glomerulus has a histological similarity to the cochlear stria vascularis of the inner ear. It is well known that ototoxicity and nephrotoxicity are common adverse events in administration of aminoglycoside antibiotics and platinum-based antineoplastic agents. As just described, the relationship between inner ear disease and renal disease has been pointed out before. In order to elucidate the mechanism of the onset of hearing loss in diabetes, we conducted a study using Tsumura Suzuki Obese Diabetes (TSOD) mouse, a type 2 diabetes mellitus (T2DM) model. It was confirmed that TSOD mice developed deafness earlier than those of the control, and histopathologically, a significant reduction in the capillary distribution density was observed in the stria vascularis. This is considered to be a finding of diabetic microangiopathy in the inner ear. In order to prevent hearing loss caused by diabetes, caloric restriction and Kampo administration (Bofutsushosan and Daisaikoto) were conducted with TSOD mice, resulting in the hearing loss being significantly ameliorated and the cochlear blood flow being maintained. On the other hand, the administration of metformin, drawing attention in the field of anti-aging medicine, was not effective in TSOD mice, while, in the presbycusis model DBA/2, the hearing loss was suppressed from the early stage in an interesting issue. The background of T2DM is often associated with the metabolic syndrome caused by excessive accumulation of visceral fat. Various factors are involved in its pathogenesis in a complicated manner. Further studies are needed to clarify the mechanism of diabetic inner ear disorder.

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Purpose: In this study, we compared the subjective symptoms and changes in skin condition of university students that consumed sub-aleurone layer residual rinse-free rice (SARFR; Kinmemai rice) for one month, with polished rice free intake group. Method: The 59 subjects analyzed consisted of 37 in the SARFR group (24 males, 13 females 21.0 ± 1.5 years), and 22 in the control group (13 males, 9 females, 22.0 ± 1.2 years). In the SARFR group, 150 g or more of the test meal was ingested once a day for one month. In the control group, normal ingestion of polished rice was freely decided by participants. Before and after the test, the questionnaire, skin function by Clreo-Pro (Fujitex), and skin AGEs fluorescence by AGEs sensor (Sharp) were evaluated. Results: SARFR intake compliance was 84%, and no adverse events due to dyspepsia were observed. Skin age was significantly improved in the SARFR group compared to the control. This effect was remarkable for males and home students, and was not observed in boarding house students. There was no significant difference in skin AGEs fluorescence. Conclusion: It was suggested that SARFR contributes to health promotion, including skin condition, by reducing the indigestibility of brown rice and ensuring nutrition, which facilitates continuous intake.

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Purpose: Postprandial hyperglycemia induces a chain reaction of aldehyde production, thus causing vascular endothelial cell damage which greatly increases the risk of cerebral cardiovascular disease. In this study, we verified the postprandial hyperglycemia improvement effect of a resistance exercise using a rubber band after eating. Methods: 66 men and women with no regular exercise habits were recruited, followed by selecting in the order of high fasting blood glucose, 12 subjects (7 males, 5 females, 55.3 ± 5.2 years old) were analyzed. After ingesting cooked rice (200 g), three types of resistance exercises using a super soft rubber band (large or small size) were performed, and blood glucose and insulin levels were measured. The test was non-cross-over, and every week, control (no exercise), GB10 (large, 10 min, 35 kcal), GS10 (small, 10 min, 35 kcal), GS6 (small, 16 min, 21 kcal) of each group was performed. Results: Compared with the control, GS10 showed significantly lower blood glucose levels at 30 min, while GS6 at 30 and 90 min (p < 0.05). There were no differences between groups in glucose AUC, iAUC, Cmax, Tmax, HOMA-IR. The insulin levels of GB10, GS10, and GS6 were significantly higher than those of the control at 60 min (p < 0.05). The low order of fasting blood glucose, Cmax and the high order of insulin AUC were GS6 group (4th), GS10 group (3rd), GB10 group (2nd), control (1st), and indicating accumulative effect of the exercise. There were no adverse events. Conclusion: Middle-aged people with insufficient physical activity performed resistance exercises with this band for 6 to 10 min after eating, leading to reduced postprandial hyperglycemia and an increase in glucose-responsive insulin secretion. In addition, an accumulation effect was observed, suggesting that glycative stress may be improved by continuing this exercise.

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