Cross-sectional association of continuous glucose monitoring-derived metrics with cerebral small vessel disease in older adults with type 2 diabetes.

AIM: To examine cross-sectional associations between continuous glucose monitoring (CGM)-derived metrics and cerebral small vessel disease (SVD) in older adults with type 2 diabetes. MATERIALS AND METHODS: In total, 80 patients with type 2 diabetes aged ≥70 years were analysed. Participants underwent CGM for 14 days. From the CGM data, we derived mean sensor glucose, percentage glucose coefficient of variation, mean amplitude of glucose excursion, time in range (TIR, 70-180 mg/dl), time above range (TAR) and time below range metrics, glycaemia risk index and high/low blood glucose index. The presence of cerebral SVD, including lacunes, microbleeds, enlarged perivascular spaces and white matter hyperintensities, was assessed, and the total number of these findings comprised the total cerebral SVD score (0-4). Ordinal logistic regression analyses were performed to examine the association of CGM-derived metrics with the total SVD score. RESULTS: The median SVD score was 1 (interquartile range 0-2). Higher hyperglycaemic metrics, including mean sensor glucose, TAR >180 mg/dl, TAR >250 mg/dl, and high blood glucose index and glycaemia risk index, were associated with a higher total SVD score. In contrast, a higher TIR (per 10% increase) was associated with a lower total SVD score (odds ratio 0.73, 95% confidence interval 0.56-0.95). Glycated haemoglobin, percentage glucose coefficient of variation, mean amplitude of glucose excursions, time below range and low blood glucose index were not associated with total cerebral SVD scores. CONCLUSIONS: The hyperglycaemia metrics and TIR, derived from CGM, were associated with cerebral SVD in older adults with type 2 diabetes.

Differences in Iron Kinetics during Cardiac Load between Patients with Atrial Fibrillation and Those with Sinus Rhythm.

INTRODUCTION: The prevalence of atrial fibrillation (AF) increases with age. Although most AF cases are caused by irregular electrical impulses near the pulmonary vein, not all elderly individuals develop AF. Moreover, risk factors such as hypertension and diabetes do not always lead to AF, even in severe conditions such as pneumonia. We aimed to examine iron kinetics, including ferritin, in patients with AF and individuals in normal sinus rhythm (NSR) using peripheral blood samples. METHODS: This case-control study included 178 patients who visited the outpatient clinic of a cardiovascular and arrhythmia specialist at the National Center for Geriatrics and Gerontology between August and October 2023. Patients with missing iron-related blood tests and those with pacemaker implantation were excluded. Iron parameters (ferritin, free iron, transferrin saturation) were compared between AF (n = 53) and NSR (n = 125) groups. RESULTS: The AF group had higher log brain natriuretic peptide (BNP) levels, indicating increased cardiac load (AF 2.18 vs. NSR 1.53). However, there were no significant differences in iron parameters between the AF and NSR groups. After matching for age, sex, and coronary artery disease, the AF group showed an increasing trend in ferritin and a decreasing trend in free iron with BNP elevation, suggesting chronic inflammation. In contrast, the NSR group showed no significant changes in iron parameters with BNP elevation. CONCLUSION: Patients with AF are more likely to have elevated ferritin levels and decreased free iron levels during cardiac overload. Thus, they are more likely to present with chronic inflammation associated with cardiac overload in AF. Future studies should investigate the mechanisms underlying this phenomenon and its implications for AF treatment.

Effects of Radio-Taiso on Health-related Quality of Life in Older Adults With Frailty: a Randomized Controlled Trial.

BACKGROUND: Radio-Taiso, a long-standing exercise program in Japan, could be a sustainable public health strategy for maintaining quality of life (QoL) in older adults with frailty. This study aimed to investigate whether Radio-Taiso provided greater benefits for health-related quality of life (HRQoL) and to identify the mechanisms underlying the effectiveness in this population. METHODS: A 12-week randomized controlled trial enrolled 226 older Japanese adults with pre-frailty or frailty, assessed using the modified frailty phenotype. Participants were randomly allocated to the intervention (Radio-Taiso + nutrition program) or control (nutrition program) groups. The Radio-Taiso program comprised five 60-min group sessions and daily practice at the participants' homes. The primary outcome was the change in the mental domain of HRQoL, assessed using the SF-36®. The secondary outcomes included six physical fitness items and exercise self-efficacy. RESULTS: Overall, 104 and 105 participants in the intervention and control groups, respectively, were analyzed based on the intention-to-treat principle. The median daily practice rate of Radio-Taiso was 94.1% (interquartile range, 73.2-98.8%). Although general linear models adjusted for baseline values and allocation stratification factors showed that the intervention group obtained greater benefits (adjusted mean differences) in the up-and-go (0.3; 95% confidence interval [CI], 0.1 to 0.6 s), 2-min step-in-place (-3.2; 95% CI, -6.2 to -0.2 steps) tests, and exercise self-efficacy scale (-1.4; 95% CI, -2.6 to -0.1 points) than the control group, there were no group differences in changes in the mental domain score of HRQoL. CONCLUSION: Radio-Taiso provided greater benefits for agility/dynamic balance, aerobic endurance, and exercise self-efficacy in older adults with frailty; however, these changes do not improve HRQoL.

High-resolution 3D display using time-division light ray quadruplexing technology.

We propose a flicker-reduced time-division light ray quadruplexing technology to improve both the spatial and angular resolutions of three-dimensional (3D) images. The proposed method uses an image-shift optical device with polarization gratings. By optimizing the design of the image-shift optical device and incorporating it into the display system, we confirmed that the resolution characteristics of 3D images displayed at a depth of 30 mm or more can be improved by up to 1.58 times. Furthermore, by developing the display system using a 120 Hz 8K projector with wobbling device and a wavelength-selective λ/2 plate for reducing flicker, we achieved high-resolution 3D image display with deeper depth.

Muscle fiber type specific alterations of mitochondrial respiratory function and morphology in aged female mice.

Mitochondrial dysfunction is considered to be a major cause of sarcopenia, defined as age-related muscle fiber atrophy and muscle weakness, as reduced mitochondrial respiration and morphological changes such as ragged red fibers (RRFs) are observed in aging muscles. However, the role of mitochondrial dysfunction in sarcopenia is not fully elucidated. Although previous studies have suggested that aging has a fiber type-specific effect on mitochondrial function, little is known about mitochondrial changes in individual fiber types. Here, we used C57BL/6NCr female mice to identify fiber type-specific pathological changes, examine the significance of pathological changes in sarcopenia, and identify possible mechanisms behind mitochondrial changes in slow-twitch soleus muscle (SOL) and fast-twitch extensor digitorum longus muscle (EDL). We observed reduced type I fiber-specific mitochondrial respiratory enzyme activity, impaired respiration, and subsarcolemmal mitochondrial accumulation in aged SOL, which was different from RRFs. These pathological alterations were not directly associated with fiber atrophy. Additionally, we found increased oxidative stress markers in aged SOL, suggesting that oxidative stress is involved in the pathological and functional changes in mitochondria. Meanwhile, obvious mitochondrial changes were not seen in aged EDL. Thus, age-related mitochondrial dysfunction is specific to the fiber type and may correlate with the muscle quality rather than the muscle mass.

Does atrial fibrillation occur exclusively in the elderly?

Although atrial fibrillation is a prevalent condition, it is crucial to recognize that it can be effectively addressed by identifying the underlying disease and not merely assuming that it is caused by aging.

Enhancing Diabetes Management for Older Patients: The Potential Role of ChatGPT.

Artificial intelligence (AI) technology has the potential to improve diabetes education for older individuals with diabetes. However, as AI becomes integrated into healthcare, it will be important to ensure even greater accuracy and establish a framework. The significance of direct communication between patients and healthcare providers will remain unchanged, regardless of the level of technological advancement.

Tirzepatide and Glycemic Control Metrics Using Continuous Glucose Monitoring in Older Patients with Type 2 Diabetes Mellitus: An Observational Pilot Study.

This observational pilot study aimed to investigate continuous glucose monitoring (CGM) metrics in older Japanese patients with type 2 diabetes mellitus (T2DM) using a CGM system (FreeStyle Libre Pro) during the first tirzepatide administration and compare the glycemic control measures before and after the initial injection. The four patients had a mean age of 79.5 years (standard deviation [SD]: 5.8), a mean body mass index of 24.6 kg/m2 (SD: 4.7), a mean glycated hemoglobin level of 9.1% (SD: 2.1), and a mean measurement period of 10.5 days (SD: 3.5). After the inclusion of tirzepatide treatment, the mean of time in range, time above range, and time below range changed from 53.2% to 78.9% (p = 0.041), 45.8% to 19.7% (p = 0.038), and 1.0% to 1.5% (p = 0.206), respectively. Improved hyperglycemia reduced the oral hypoglycemic medication in two cases and decreased the frequency of insulin injections in two cases. To elucidate the potential benefits of tirzepatide, future studies should investigate the long-term impact on functional prognosis, safety, and tolerability and distinguish between the use of other weekly agonists, especially in nonobese older Asian patients. However, tirzepatide-associated robust glycemic improvement may simplify diabetes treatment regimens in older patients with T2DM.

Evolution of a Large Language Model for Preoperative Assessment Based on the Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery.

Background: The Japanese Circulation Society 2022 Guideline on Perioperative Cardiovascular Assessment and Management for Non-Cardiac Surgery standardizes preoperative cardiovascular assessments. The present study investigated the efficacy of a large language model (LLM) in providing accurate responses meeting the JCS 2022 Guideline. Methods and Results: Data on consultation requests, physicians' cardiovascular records, and patients' response content were analyzed. Virtual scenarios were created using real-world clinical data, and a LLM was then consulted for such scenarios. Conclusions: Google BARD could accurately provide responses in accordance with the JCS 2022 Guideline in low-risk cases. Google Gemini has significantly improved its accuracy in intermediate- and high-risk cases.

Exploratory bibliometric analysis and text mining to reveal research trends in cardiac aging.

Objectives: We conducted a text mining analysis of 40 years of literature on cardiac aging from PubMed to investigate the current understanding on cardiac aging and its mechanisms. This study aimed to embody what most researchers consider cardiac aging to be. Methods: We used multiple text mining and machine learning tools to extract important information from a large amount of text. Results: Analysis revealed that the terms most frequently associated with cardiac aging include "diastolic," "hypertrophy," "fibrosis," "apoptosis," "mitochondrial," "oxidative," and "autophagy." These terms suggest that cardiac aging is characterized by mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. We also revealed an increase in the frequency of occurrence of "autophagy" in recent years, suggesting that research on autophagy has made a breakthrough in the field of cardiac aging. Additionally, the frequency of occurrence of "mitophagy" has increased significantly since 2019, suggesting that mitophagy is an important factor in cardiac aging. Conclusions: Cardiac aging is a complex process that involves mitochondrial dysfunction, oxidative stress, and impairment of autophagy, especially mitophagy. Further research is warranted to elucidate the mechanisms of cardiac aging and develop strategies to mitigate its detrimental effects.

Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts: Amplification of osteoprotegerin/interleukin-6 by gallein.

Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gßγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and d-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD2, is expressed on osteoblasts. We previously reported that prostaglandin D2 (PGD2) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD2 in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gßɤ subunits, on the syntheses of OPG and IL-6 induced by PGD2 in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gßɤ subunits, and subsequently stimulated with PGD2. Not fluorescein but gallein amplified the PGD2-stimulated releases of OPG and IL-6. Gallein enhanced the PGD2-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD2-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD2-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gßγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.

Impact of Type 2 Diabetes and Glycated Hemoglobin Levels Within the Recommended Target Range on Mortality in Older Adults With Cognitive Impairment Receiving Care at a Memory Clinic: NCGG-STORIES.

OBJECTIVE: To determine the impact of type 2 diabetes and glycated hemoglobin (HbA1c) levels within the recommended target range according to the Japan Diabetes Society/Japan Geriatrics Society Joint Committee on mortality in older adults with cognitive impairment. RESEARCH DESIGN AND METHODS: This retrospective cohort study included 1,528 and 468 patients aged ≥65 years without and with type 2 diabetes, respectively, who were visiting a memory clinic. The 468 patients with type 2 diabetes were divided into three groups (within, above, and below the target range) based on their HbA1c levels, cognitive function, ability to perform activities of daily living, and medications associated with a high risk of hypoglycemia. The impact of diabetes and HbA1c levels on mortality was evaluated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 3.8 years, 353 patients (17.7%) died. Compared with individuals without type 2 diabetes, HbA1c levels above (hazard ratio [HR] 1.70, 95% CI 1.08-2.69) and below (HR 2.15, 95% CI 1.33-3.48) the target range were associated with a higher risk of death; however, HbA1c levels within the target range were not (HR 1.02, 95% CI 0.77-1.36). CONCLUSIONS: HbA1c levels above and below the target range were associated with a higher risk of mortality, whereas patients with HbA1c levels within the target range did not exhibit a higher risk of mortality than individuals without type 2 diabetes. These results provide empirical support for the current target ranges among older adults with cognitive impairment.

Prolonged COVID-19 Infection in a Patient with Complete Remission from Follicular Lymphoma with Hyperosmolar Hyperglycemic Syndrome.

An 81-year-old woman undergoing B-cell depletion therapy developed COVID-19 and a hyperglycemic hyperosmotic state. She had a history of multiple vaccinations against coronaviruses but had persistent antigen positivity. Strategies to prevent the development of COVID-19 in immunosuppressed patients have not been established. Moreover, there is no standard treatment for prolonged antigen positivity. In this case, we were able to follow IgG antibodies during the course of treatment. The absence of N-IgG antibody titer elevation despite an effective immune response triggered by the vaccine is of great interest. The impaired humoral response observed in patients with lymphoma after anti-CD20 treatment implies the need for a justified different vaccination strategy for these patients. Furthermore, negative N-IgG titers in the immunosuppressed state may serve as an indicator of resistance to therapy.

Proteolytic ectodomain shedding of muscle-specific tyrosine kinase in myasthenia gravis.

Autoantibodies to muscle-specific tyrosine kinase (MuSK) proteins at the neuromuscular junction (NMJ) cause refractory generalized myasthenia gravis (MG) with dyspnea more frequently than other MG subtypes. However, the mechanisms via which MuSK, a membrane protein locally expressed on the NMJ of skeletal muscle, is supplied to the immune system as an autoantigen remains unknown. Here, we identified MuSK in both mouse and human serum, with the amount of MuSK dramatically increasing in mice with motor nerve denervation and in MG model mice. Peptide analysis by liquid chromatography-tandem-mass spectrometry (LC-MS/MS) confirmed the presence of MuSK in both human and mouse serum. Furthermore, some patients with MG have significantly higher amounts of MuSK in serum than healthy controls. Our results indicated that the secretion of MuSK proteins from muscles into the bloodstream was induced by ectodomain shedding triggered by neuromuscular junction failure. The results may explain why MuSK-MG is refractory to treatments and causes rapid muscle atrophy in some patients due to the denervation associated with Ab-induced disruption of neuromuscular transmission at the NMJ. Such discoveries pave the way for new MG treatments, and MuSK may be used as a biomarker for other neuromuscular diseases in preclinical studies, clinical diagnostics, therapeutics, and drug discovery.

Skeletal muscle as a treatment target for older adults with diabetes mellitus: The importance of a multimodal intervention based on functional category.

Although the lifespan of people with diabetes has increased in many countries, the age-related increase in comorbidities (sarcopenia, frailty and disabilities) and diabetic complications has become a major issue. Diabetes accelerates the aging of skeletal muscles and blood vessels through mechanisms, such as increased oxidative stress, chronic inflammation, insulin resistance, mitochondrial dysfunction, genetic polymorphism (fat mass and obesity-associated genes) and accumulation of advanced glycation end-products. Diabetes is associated with early onset, and progression of muscle weakness and sarcopenia, thus resulting in diminished daily life function. The type and duration of diabetes, insulin section/resistance, hyperglycemia, diabetic neuropathy, malnutrition and low physical activity might affect muscular loss and weakness. To prevent the decline in daily activities in older adults with diabetes, resistance training or multicomponent exercise should be recommended. To maintain muscle function, optimal energy and sufficient protein intake are necessary. Although no specific drug enhances muscle mass and function, antidiabetic drugs that increase insulin sensitivity or secretion could be candidates for improvement of sarcopenia. The goals of glycemic control for older patients are determined based on three functional categories through an assessment of cognitive function and activities of daily living, and the presence or absence of medications that pose a hypoglycemic risk. As these functional categories are associated with muscle weakness, frailty and mortality risk, providing multimodal interventions (exercise, nutrition, social network or support and optimal medical treatment) is important, starting at the category II stage for maintenance or improvement in daily life functions. Geriatr Gerontol Int 2022; 22: 110-120.

Effects of a home-based Radio-Taiso exercise programme on health-related quality of life in older adults with frailty: protocol for an assessor-blind randomised controlled trial.

INTRODUCTION: Few clinical trials have examined the effects of home-based exercise programmes on health-related quality of life (HR-QoL) in older adults with frailty. Radio-Taiso is the most famous exercise programme in Japan. A home-based Radio-Taiso exercise programme may serve as an accessible, scalable and sustainable care intervention for older adults with frailty. The primary aim of this trial is to test whether older adults with frailty who are prescribed our home-based Radio-Taiso exercise programme will receive greater benefits for HR-QoL compared with those who are not prescribed the exercise programme. Potential mechanisms underlying the effectiveness of the programme and the effects of the programme on daily lifestyle will also be investigated. METHODS AND ANALYSIS: This assessor-blind randomised controlled trial will be conducted at the Tokyo Metropolitan Institute of Gerontology (TMIG) in Itabashi-ku, Tokyo, Japan. From April to May 2022, 226 older adults with prefrailty or frailty according to the revised Japanese version of the Cardiovascular Health Study criteria will be included from a large database. After a baseline assessment in June 2022, participants will be randomly assigned to the intervention (home-based Radio-Taiso exercise and nutrition programme) or control (nutrition programme) groups at a 1:1 ratio. After intervention completion, a follow-up assessment will be conducted in September 2022. The primary outcome is the change in the mental domain of HR-QoL assessed using SF-36. Secondary outcomes include physical and role/social domains and subscales of HR-QoL, frailty phenotype, physical fitness, posture, cognition, exercise self-efficacy, depressive symptoms, brain-derived neurotrophic factor, social network, habitual energy intake, physical activity and sleep conditions. ETHICS AND DISSEMINATION: The Research Ethics Committee of TMIG has approved the research protocol. This trial will be conducted in accordance with the principles of the Declaration of Helsinki. The findings will be presented at international academic conferences and published in peer-reviewed international journals. TRIAL REGISTRATION NUMBER: UMIN000047229.

Exploring the capability of mayenite (12CaO·7Al2O3) as hydrogen storage material.

We utilized nanoporous mayenite (12CaO·7Al2O3), a cost-effective material, in the hydride state (H-) to explore the possibility of its use for hydrogen storage and transportation. Hydrogen desorption occurs by a simple reaction of mayenite with water, and the nanocage structure transforms into a calcium aluminate hydrate. This reaction enables easy desorption of H- ions trapped in the structure, which could allow the use of this material in future portable applications. Additionally, this material is 100% recyclable because the cage structure can be recovered by heat treatment after hydrogen desorption. The presence of hydrogen molecules as H- ions was confirmed by 1H-NMR, gas chromatography, and neutron diffraction analyses. We confirmed the hydrogen state stability inside the mayenite cage by the first-principles calculations to understand the adsorption mechanism and storage capacity and to provide a key for the use of mayenite as a portable hydrogen storage material. Further, we succeeded in introducing H- directly from OH- by a simple process compared with previous studies that used long treatment durations and required careful control of humidity and oxygen gas to form O2 species before the introduction of H-.

Functional categories based on cognition and activities of daily living predict all-cause mortality in older adults with diabetes mellitus: The Japanese Elderly Diabetes Intervention Trial.

AIM: Although the glycemic target in older diabetes patients is based on cognition, activities of daily living and multimorbidity in the Japanese guideline, evidence of the relationships is limited. Thus, we aimed to assess the relationship between functional category and mortality in older people with diabetes. METHODS: We evaluated the data of 843 older diabetes patients in a 6-year prospective study, and the association between functional categories and all-cause mortality. The patients were divided into three functional categories based on cognition, instrumental activities of daily living and basic activities of daily living using the Mini-Mental State Examination, Tokyo Metropolitan Institute of Gerontology Index of Competence and Barthel Index at baseline, respectively (model 1). Those with multimorbidity (≥4 of 8 morbidities) were classified into category III (model 2). The functional category assessed using eight items from the Tokyo Metropolitan Institute of Gerontology Index of Competence and Barthel Index was also constructed (model 3). Hazard ratios and 95% confidence intervals were calculated in the Cox regression analysis using age, sex, body mass index, glycated hemoglobin level, total cholesterol level, estimated glomerular filtration rate and frequency of severe hypoglycemia as covariates. RESULTS: During the 6-year follow up, 64 incident mortalities occurred. The hazard ratios for mortality in categories II and III (as the reference of category I) were 1.83 (95% confidence interval 1.06-3.14, P = 0.030) and 3.05 (95% confidence interval 1.12-8.26, P = 0.029) after adjustment for covariates, respectively (model 1). Models 2 and 3 showed similar associations between functional category and mortality. CONCLUSIONS: The functional categories predicted all-cause mortality in older adults with diabetes. Geriatr Gerontol Int 2021; 21: 512-518.

Subclinical Atherosclerosis, Vascular Risk Factors, and White Matter Alterations in Diffusion Tensor Imaging Findings of Older Adults With Cardiometabolic Diseases.

White matter abnormalities may reflect cerebral microvessel disease. Diffusion tensor imaging (DTI) can help detect early changes in white matter integrity in each tract. However, studies investigating the relationship between subclinical atherosclerosis markers and white matter alterations in DTI findings are limited. This study aimed to examine associations between cardiovascular risk factors and indices of subclinical atherosclerosis-ankle brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and carotid artery intima-media thickness (IMT)-and altered white matter integrity in older patients. A total of 224 patients (aged ≥65 years) with cardiometabolic disease who underwent magnetic resonance imaging (MRI) and either plethysmography or cervical ultrasound at the start of the 3-year observational study period were included in this study. We measured fractional anisotropy (FA) and mean diffusivity (MD), which are indices of white matter integrity in seven white matter tracts. In a univariate analysis, lower ABI and higher baPWV values were associated with FA or MD abnormalities in several tracts, whereas IMT was scarcely associated with such change. In addition, high blood pressure and glycoalbumin/glycohemoglobin ratio (GA/HbA1c) and low body mass index (BMI) and triglyceride (TG) levels were associated with FA or MD abnormalities. In a multivariate analysis adjusted for age, sex, BMI, diastolic blood pressure, TG, and GA/HbA1c, the associations between ABI and FA or MD remained in all of either side of the following tracts: anterior thalamic radiation, forceps minor, inferior frontooccipital fasciculus (p < 0.001 for all) and superior longitudinal fasciculus (SLF; p < 0.05), whereas most of those between baPWV and FA or MD disappeared except for SLF (p < 0.05). These results indicate that low ABI could be an indicator of white matter abnormalities.