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Background: Vildagliptin/Metformin (EquMet) and imeglimin (Twymeeg) are effective oral hypoglycemic agents (OHAs) for patients with type 2 diabetes (T2D). Case Presentation: The patient was a 68-year-old male with T2D and fatty liver for several years. In November 2022, his HbA1c had increased to 8.2%, and he was started on Twymeeg, followed by EquMet. Results: Over the course of four months, the patient’s HbA1c value successfully decreased from 8.2% to 6.7%, and he did not experience any gastrointestinal adverse effects (GIAEs). Discussion and Conclusion: The combined treatment of EquMet and Twymeeg demonstrated clinical efficacy without any adverse effects. The Trials of IMeglimin for Efficacy and Safety (TIMES) provided various evidence of imeglimin’s effectiveness.

Background: Among oral hypoglycemic agents (OHAs), imeglimin (Twymeeg) would be in focus. Case Presentation: The patient in this case is a 58-year-old female with a history of obesity and previous operations for posterior longitudinal ligament ossification. In early September 2022, she developed dizziness and a general feeling of unwellness, leading to a diagnosis of Type 2 Diabetes (T2D) with an HbA1c level of 11.1%. Result: The patient was treated with a low carbohydrate diet (LCD) and Twymeeg, resulting in a significant decrease in HbA1c levels from 11.1% to 9.0%, 6.7%, and 5.9% over the course of three months. Pre-prandial and post-prandial blood glucose levels were measured with great accuracy. Discussion and Conclusion: The administration of Twymeeg was found to be effective in reducing the patient’s HbA1c levels, and the relationship between HbA1c and glucose variability could be further investigated based on these results.

Background: Recent diabetic focus includes imeglimin (Twymeeg). Case Presentation: The case was an 83-year-old female with 19 years of type 2 diabetes (T2D) associated with recent treatment for dementia. Result: HbA1c decreased from 10.0% to 6.6% for 4 months by Twymeeg 2000 mg/day. For neuropsychiatric symptoms in dementia, memantine and tiapride were provided and controlled. Furthermore, zinc acetate hydrate (Novelzin) was continued for T2D and dementia. Discussion and Conclusion: Twymeeg administration was effective as the results of Trials of IMeglimin for Efficacy and Safety (TIMES) 2 and 3. Perspectives on the efficacy of zinc were discussed including Alzheimer’s-Plus with low zinc (APLZ).

Clinical effectiveness of sedative music on sleep quality was investigated. Subjects were 14 females aged 40s to 70s, and methods included listening to music during going to sleep using by sound sleep support sound player “Lullaby reverberation (Komoriuta-no-Hibiki)”, which was evaluated by Pittsburgh Sleep Quality Index (PSQI) in 0,4,8 weeks. Thirteen cases showed decreased points of PQSI. Time to sleep and sleep duration were almost the same. The relationship figure for PSQI and time until sleeping showed general tendency of left and horizontal/lower directional arrows. These results suggest positive beneficial effect of music for sleep quality evaluated by PSQI.

As a reliable psychological test, Tokyo University Egogram (TEG) 2nd has been used widely. TEG was recently revised to TEG 3rd. Authors continued TEG research on university students for long, in which results of 2018 by TEG 2nd and results of 2019-2022 by TEG 3rd were compared. For the 3rd revision, FC dominant and AC dominant increased markedly, whereas CP dominant and NP dominant decreased. C dominant pattern showed remarkable increase, which is due to increase of AC dominant and FC dominant. This is a characteristic tendency for late teenagers. Further, mixed types of N-shaped and reverse N-shaped patterns were found.

For the latest development for anti-diabetic agents, nanoparticles (NPs) have been in focus. Permeation enhancers (PEs) are known to increase the oral absorption of various kinds of macromolecules. One of PEs would be sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC), which has been used for glucagon-like peptide-1 receptor agonist (GLP-1RA) as oral semaglutide (Rybelsus). For insulin encapsulation, polyelectrolyte nanocomplex (PEC) have been the promising carriers. Furthermore, spray drying technique has been an adequate and well-known industrial method for developing pharmaceutical industries, and aqueous polymer dispersions (APDs) have been applied. Consequently, self-nanoemulsifying drug delivery systems (SNEDDS) can be expected to improve future diabetic treatment.

In the current changing society, the elderly need the zest for living. For acquiring satisfactory health care and management, an adequate degree of health literacy would be required. From the research of Health Literacy Questionnaire (HLQ) and Short Test of Functional Health Literacy Assessment (S-TOFHLA), significant differences were found in living in urban areas, regular exercise, medical service-seeking behavior, occupation, self-care ability and others. For higher health literacy, the significance of cultural and recreational activities would be advocated, such as sports and music. This continuation would bring appropriate long-term care services and support (LTSS), leading to well-being, satisfaction and happiness.

Background: Seasonal variation of HbA1c has been in focus. Patients and Methods: The protocol included type 2 diabetes (T2D) patients (n=26, 71.4±10.2 years) on vildagliptin and metformin (EquMet) and HbA1c changes in 4 seasons for 6 years. Results: HbA1c values ranged 6.9-7.5%, and tend to show highest in winter, and rather lower in autumn. Discussion & Conclusion: Rather elderly T2D cases can tolerate EquMet with fair control. Previous reports showed a similar tendency. Some factors may be involved in the variation, such as temperature, climate, carbohydrate intake, Ramadan, and others. Furthermore, blood pressure and cardiovascular disease (CVD) can also influence them.

Authors and collaborators have investigated the subjective health and life satisfaction of elderly male Masters’ athletes. Subjects were 97 cases with 63.9 years in average, who participated in Masters track and field competition event, and they are asked to answer the questionnaire concerning healthy lifestyle habits. It had the inquiries about subjective health, satisfaction of daily life, spending leisure time and others. Two groups were categorized as non-elderly and elderly people (n=46/51), and compared for the detail such as frailty. As a result, no significant difference was found between two age groups for several aspects including daily lifestyle situation.

Sodium–glucose cotransporter 2 inhibitor (SGLT2i) has been attracting attention for novel agent for patients with diabetes and also heart failure (HF), in which the left ventricular ejection fraction (LVEF) has decreased. For standard cardiovascular treatment, 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure is recently presented. Some important perspectives were found, which are HF with mildly reduced EF (HFmrEF), HF with improved EF (HFimpEF) and HF with preserved EF (HFpEF). For patients with HFmrEF, SGLT2i can contribute reducing HF hospitalizations and cardiovascular death. From now, the guideline-directed medical therapy (GDMT) will contribute the standard and beneficial therapy.

Background: Recent pharmacological studies reveal imeglimin (Twymeeg) including dual mechanisms for stimulating insulin secretion and reducing insulin resistance. Case Presentation: The case is a 62-year-old male with type 2 diabetes (T2D). He showed HbA1c 6.4% and started imeglimin. After 5 weeks, a 75g oral glucose tolerance test (75gOGTT) was conducted, and the biomarkers were compared with that of 6 months ago. Insulinogenic index (IGI) 0-30min was stable, but insulin secretion was increased during 30-60min and 60-120min. Discussion: Previous studies of imeglimin revealed improved insulin secretion for GTT. Clinical progress will be followed up with detailed investigation of glucose and insulin variability.

Background: Oral semaglutide (Rybelsus) has been in focus for type 2 diabetes (T2D). Case Presentation: The patient is a 73-year-old male with T2D treated with metformin, Ipragliflozin, and rosuvastatin. He was diagnosed with depression by the Geriatric depression scale (GDS) with a stable condition by mirtazapine. His diabetic control was exacerbated to HbA1c 8.8% and weight 63.5kg in Feb 2022. Results: He started to take Rybelsus, and then clinical improvement was found as HbA1c 6.9% and weight 57.5kg for 4 months. Discussion: Remarkable effect of HbA1c and weight may be from longer fasting time after post-med, and regular lifestyle from the stable psychosomatic situation.

The discussion of chronic kidney disease (CKD), kidney replacement therapy (KRT), and end-stage kidney disease (ESKD) has been important. Recently, a useful predictive model of CKD progression to renal failure was reported by the German CKD study group. They include a novel 6-variable risk score (Z6), composed of creatinine, albumin, cystatin C, urea, hemoglobin, and urinary alb/cre ratio (UACR). CKD patients were studied in 3 groups based on educational attainment. Hazard ratios compared to low vs high groups showed mortality of 1.48, MACE 1.37, and renal failure 1.54, respectively. For the prediction of CKD progression, UACR and estimated glomerular filtration rate (eGFR) are useful.

Music has beneficial power physically and psychologically. Among Integrative Medicine (IM), music therapy (MT) has been useful, and authors have continued research for IM, MT, and piano-playing. Most pianists do not consider the movement of their fingers, because the memorized process is transformed into automatic action. The function may involve the neural signals from the superior parietal lobule to the primary motor area and dorsal premotor cortex, which is called the sensory-motor transformations. The supplementary motor area (SMA) in the frontal lobe seems to be involved in the function of beat-based timing, expression, and activity of musical behavior.

As recommended pharmacological agents for type 2 diabetes mellitus (T2DM), Glucagon-Like Peptide 1 receptor agonist (GLP-1Ra) is highly evaluated for its various beneficial effects. Among them, semaglutide (Rybelsus) has been in focus for useful oral formation with useful oral hypoglycemic agent (OHA). Administration per os is possible due to the developed technique of absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate. Clinical efficacy was shown by a series of Peptide Innovation for Early Diabetes Treatment (PIONEER) with enough weight reduction and decreased HbA1c. From the results of several PIONEER programs, oral semaglutide 14 mg/day had reduced HbA1c values by approximately 1.0-1.4%.

Background: As an oral hypoglycaemic agent (OHA), imeglimin (Twymeeg) has been recently introduced to clinical practice for patients with type 2 diabetes mellitus (T2DM) as Twymeeg. It has beneficial pharmacological mechanisms, which are improving insulin secretion, increasing insulin sensitivity, and decreasing insulin resistance. Case Presentation: The case is 84-year-old man with mild cognitive impairment (MCI) for 3 years. He visited late August, 2021 our clinic for general malaise and was pointed out to have post-prandial blood glucose 336 mg/dL and HbA1c 8.6%. He was diagnosed with T2DM. Results: He was started to be given imeglimin 1000mg twice a day, and then HbA1c value was decreased to 7.3% in 4 weeks and 5.7% in 8 weeks. During 9-12 weeks, he felt loss of appetite and reduced food intake. Biochemical examination on 12 weeks showed decreased values of TP, Alb, HbA1c, glucose, free T3, and normal values of TSH, free T4. Doses of imeglimin were 500 mg twice a day for 9-12 weeks and discontinued after 12 weeks. Discussion: Regarding appetite loss, possible causes may include MCI, previous history of gallbladder dyskinesia, adverse effect of imeglimin, and so on. Further development of research will be expected for imeglimin in the future.

The authors and collaborators have continued practice of hospital art in the university and community hospitals and various research with experts. The material for hospital art is masking tape which is easily made and attached for everyone. Formerly, we have conducted artwork in front of the wall, which took a long time. Currently, we have tried to take the most advantage of the thin-film sheet. Our staff can prepare artwork with a size of 20 cm square in advance. Many square parts with double-sided attachment tape can be gathered together, which is completed and useful in a short time.

The impact of COVID-19 can be shown by life expectancy, excess death and total years of life lost (YLL). United States showed life expectancy minus 1.67 years, excess deaths 375,235 and total YLL 7,362,555. The excess death of Japan has remained minus value for long, in which long-term care facilities (LTCF) may contribute. LTCF has characteristic points as i) mutual interrelationships between hospitals, medical societies and prefectural offices, ii) rapid communication channels for regulatory official authorities, iii) high degree of citizenship and cooperation of all Japanese people for daily life and iv) mild lockdown without any punishment with declaration.

Recent topic concerning weather-related pain or meteoropathy is described. Such symptoms are observed in patients with rheumatoid arthritis (RA), fibromyalgia, osteoarthritis, or headache, neck pain, stiff shoulder, back pain. Patients often feel pain when atmospheric pressure showed lower pressure of 1003-1007 hPa or decrease of 6-10 hPa. From psychosomatic point of view, decreased self-efficacy or higher catastrophic thinking are involved. Several questionnaires are useful for the evaluation, such as Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale (HADS), Pain Self–Efficacy Questionnaire (PSEQ), and Pain Catastrophizing Scale (PCS). For treatment, exercise–induced hypoalgesia (EIH) would be effective.

Transactional Analysis (TA) has been a personality theory beneficial to mutual communication associated with the research of egogram. Tokyo University Egogram (TEG) has been a reliable psychological battery. TEG ver3 was recently introduced, which was applied to 98 university students. The results for 5 egogram factors were compared to previous standard values. Similar data were observed in Critical Parent(CP), Nurturing Parent(NP), and Adult(A). Higher tendency values (vs standard value) were found in male Free Child (FC) 12.3 vs 10.6, male Adapted Child (AC) 13.6 vs 10.0, and female AC 14.8 vs 10.8. Further study for TEG will be expected in the future.

Recently, the importance of mental health has been emphasized, and clinical practice and research for egogram has been attracted attention. Tokyo University Egogram (TEG) has been a reliable and useful battery for psychological evaluation. Authors and colleagues have continued several reports of TEG so far. Egogram has 5 egos, which are Critical Parent (CP), Nurturing Parent (NP), Adult (A), Free Child (FC) and Adapted Child (AC). Each factor can be calculated by the points from 0 to 20. Subjects were 98 university students and the results were analyzed in comparison with previous standard data of TEG. The results were as follows: i) CP; the average value tended to be slightly lower, but the shape of the distribution was similar, ii) NP; it showed almost the same results as general people, iii) A; average value is similar, but the distribution was different, and no case was found with less than 5 points, iv) FC; average value was higher than general public, and distribution was deviated to high level, v) AC; mean value was higher compared with general people, and distribution was deviated to high level. Several characteristic points were found, which will be worthwhile to psychological development in the future.

Pandemic COVID-19 has been crucial problem worldwide, and authors have reported less prevalence and excess death in Japan. The Ministry of Health, Labour and Welfare of Japan presented COVID-report of July 2021 Edition. Among them, the number of people diagnosed with COVID-19 in Japan was 796,835 until July 1, 2021, which is equivalent to 0.6% of the total population. Aggravation rate of COVID-19 increases remarkably with aging. The result shows 1, 4, 10, 25, 47, 70< in 30s, 40s, 50s, 60, 70s, 80s< years old, respectively. In contrast, it shows 0.5, 0.2, 0.3 in

The case was 71-year-old male patient with type 2 diabetes mellitus (T2DM). He was diagnosed T2DM at the age of 61 associated with thirsty, polydipsia and fatigue. HbA1c value was 12.5% and blood glucose profile was 150-300 mg/dL. Just after starting low carbohydrate diet (LCD), his blood glucose kept under 150 mg/dL all day long. He continued good diabetic control as HbA1c 5.8-6.8% for 10 years. Some beneficial points are found: i) keeping LCD with the feeling not stressful but pleasant for observing the normal glucose level, ii) walking daily for 2 hours, iii) continuing educational activity in the walking association for DM and health care. iv) writing the diary for years every day, including exercise, meal, medicine, activities and so on, v) checking post-prandial hyperglycemia by meal tolerance test (MTT). For details of v), HbA1c was 6.5% in May 2021 and fasting glucose was 107mg/dL. Glucose values 45-min and 60-min after 3 meals showed 210-201-177mg/dL and 195-213-172mg/dL, respectively. His various continuing behaviors contributed satisfactory glycemic control. This article becomes reference in the diabetic practice and research.

The relationship among sarcopenia, protein intake, elderly, and diabetes has been in discussion. The Asian Working Group for Sarcopenia (AWGS) 2019 has revised the content by emphasizing the 5-time chair stand test. For prevention and treatment of sarcopenia and frailty, continuous protein intake is required such as meat, eggs, tofu, and so on. Elderly aged >65 is recommended to take at least >1.0 g/kg weight of protein per day for preventing sarcopenia and frailty. Sodium/glucose cotransporter-2 inhibitors (SGLT2i) have been widely used. However, SGLT2i are advised not to provide the subjects who are elderly and/or with sarcopenia or senile syndrome. As to sarcopenia, clinical and research interest has burgeoned internationally [1]. The Asian Working Group for Sarcopenia (AWGS) 2019 has revised the diagnosis, protocols, and criteria to some degree. It emphasized the evaluation of the 5 time chair stand test and possible sarcopenia in primary health care for earlier lifestyle interventions [1]. Regarding the severity of sarcopenia, physical performance can be determined by several kinds of assessments. Among them, the gait speed or 5 times chair stand test seems to be practically simple and useful for actual evaluation [2]. For sarcopenia and/or pre sarcopenia, the efficacy for multi component exercise programs was evaluated on muscle mass and physical function in elderly people [3]. Subjects included 72 elderly and the exercise group tended to prevent the decrease of muscle mass. By exercise program for 12 weeks, physical function was improved in the intervention group [3]. Sarcopenia has been associated with cognitive impairment in the elderly, and their relationship was studied [4]. Participants were 61.9± 8.0 years (n=3810) and evaluated by AWGS 2019, Short Portable Mental Status Questionnaire (SPMSQ), and Mini Nutritional Assessment Short Form (MNA SF). The results showed that i) the relationship was significantly mediated by the nutritional situation and ii) early nutritional interventions may be effective for preventing cognitive decline. Regarding the prevention and treatment of sarcopenia and frailty, a clinically important matter is continuous protein intake [5]. The general public may think that most of the components of meat are proteins. However, it is different and far from the fact. The standard values for the protein content per 100 g of edible portion are shown as follows: chicken 19.7g, beef red meat 16.8g, pork rose meat 12.8g, wiener sausage 10.5g, ribs 16.4g, bigeye tuna 21.9g, chicken egg 11.3g, natto 14.5g, tofu 6.7g, and so on [6]. In recent years, the concept of a low carbohydrate diet (LCD) has been widespread, and the clinical significance for taking protein has been more emphasized [7]. Ministry of Health, Labor, and Welfare of Japan has announced dietary intake standards (2020 edition). Among them, for the purpose of preventing frailty and sarcopenia, it was recommended to take at least 1.0 g/kg body weight or more of protein per day for people aged 65 and over [8]. In other words, it is estimated to be about >60g every day and >20g per meal. If the subject is undernourished, more intake of protein is required. Low fat meats contain about 20g of protein per 100g such as fish, chicken fillet, and lean beef. On the other hand, the protein content is lower in meats with many fats and oils such as ribs and processed meats. Some important points are found to get enough protein. Firstly, it is recommended to eat three times a day, and do not miss a meal. Secondly, be sure to take protein containing foods with each meal. Do not increase your staple food, and be a little careful with meat containing too much fat. With this diet, one will not gain weight unless taking much carbohydrate. Thirdly, eggs are easy to use [9]. One piece (50g) contains 76 kcal, protein 6.2g, fat 5.2g, carbohydrate 0.2g, and the protein score 100, and then it is no problem to take several eggs a day. Soy and dairy products are available to those who have difficulty eating meat. To get 20g of protein from tofu, a 300g intake is needed [9]. Therefore, it is recommended to take it together with meat and fish. One can also add dairy and egg proteins with gratin, cream stew, piccata, etc., rather than single dishes. It is also possible to add tofu or fried tofu to Japanese miso soup. When taking noodles, some protein materials as a topping would be added such as eggs, tuna cans, and natto [10]. Vitamin D is also important for protein synthesis and is abundant in fish such as mushrooms, sardines, saury, and salmon. Several debates have been found as to whether protein intake should be recommended for patients with impaired renal function. There is evidence that protein restriction prevents progression to end stage renal disease (ESRD) in chronic kidney disease (CKD) [11]. On the other hand, protein restriction may increase mortality in patients with older CKD. This mechanism involves the presence or absence of sarcopenia. Based on the above situation, the Japanese Society of Nephrology published “Recommendations for Diet for Conservative CKD with Sarcopenia Frail” in 2019 [12]. Among them, protein intake should be set flexibly by examining whether to emphasize the prevention of ESRD or the risk of death [13]. In cases of high risk of death or severe sarcopenia, it is recommended to loosen protein intake restrictions. However, in the case of CKD 4 5 stage, it seems appropriate to set an upper limit of 0.8 g/kg body weight per day for protein intake. Sarcopenia and frailty are important clinical issues in elderly diabetes. How should we evaluate, intervene, and treat these problems? [14] Our group has been involved in diabetes treatment for many years [15]. Among them, a low carbohydrate diet (LCD) was initiated for the first time in Japan, and LCDs have been performed for thousands of obese and diabetic patients [16]. A study examining the effects of Sodium/glucose cotransporter 2 inhibitors (SGLT2i) on body composition in T2DM patients was recently reported [17]. In a sub analysis aged 65 74 years, SGLT2 inhibitors did not bring a decrease in muscle mass or strength compared to metformin. However, these subjects were slightly obese with a BMI of ≥22 and an average BMI of 27 associated with maintained muscle mass and strength. On the other hand, the effect of SGLT2i has not been clear on muscle mass and strength of elderly people >75 years and/or lean patients. As to the proper use of SGLT2i, recommended comments are presented [18,19]. It indicates that caution should be required when the subject is aged >75, or 65 74 years associated with sarcopenia or senile syndrome. In such patients, it is important to carefully determine the administration of SGLT2i and to ensure that protein intake and exercise are adequate when used [18]. Furthermore, it recommends observing weight, muscle strength, and motor function on a regular basis, and choosing the option to refrain or discontinue if those factors show a clear decrease [19]. In summary, several topics are introduced here concerning the relationship between sarcopenia, protein intake, the elderly, and diabetes. These descriptions will hopefully become one of the references for future development of clinical practice and research.

From Integrative Medicine point of view, people tend to exercise less, leading to decreased physical, nutritional and cognitive function. Authors have been involved in rehabilitation and workshop for various subjects with masters’ athletes. Previous walking methods have some problems, such as stretching the chest, large movement of arm swing, heel touchdown with extended knees and push backward with thumb-ball. In contrast, our recommended methods include walking with the concept of centered position, using the gravity center and reflection power by flat grounding, adjusting speed and striding with forward leaning angle and creating some effective image in the mind.

Several trials for the COVID-19 pandemic are found. Prof. Shunji Nakamura, Tokushima University was awarded the 2014 Nobel prize in Physics for light-emitting diodes (LEDs). Deep ultraviolet LED (DUV-LED) causes SARS-CoV-2 inactivation as 99.9% by 265 nm. Gc protein-derived macrophage-activating factor (GcMAF)-based immunotherapy has a wider application for serious infection, chronic fatigue syndrome, and cancers. Covid center in Naples submitted a phase II report concerning GcMAF and COVID-19 in Feb 2021. 5-aminolevulinic acid (5-ALA) and its metabolite protoporphyrin IX (PpIX) show anti-inflammatory and antiviral effects for Zika, Dengue, influenza A viruses, and SARS-CoV-2. These results hopefully contribute to the research development for COVID-19.

Diabetes mellitus (DM) has wider neurological complications. They include upper gastrointestinal (GI) symptoms, impaired motility, impaired gastric emptying (GE) and diabetic gastroparesis (DG), which are usually found. The patient was a 64-year-old man with type 2 diabetes (T2D) for 22-years. The patient weighed 74 kg with body mass index (BMI) 23.6 kg/m2, hemoglobin A1C (HbA1c) 9.2%, ankle brachial index (ABI) 1.19/1.23, AST 25 U/L(7-38), ALT 23 U/L(4-44), GGT 48 U/L(

The patient was a 74-year-old female with type 2 diabetes mellitus (T2DM) treated on Humalog mix 25 twice a day. As social history, she has worked long years for growing and harvesting lotus roots. It gives physically heavy loading, which brings unstable glycemic daily control. She had to titrate minute regulation every time. For stable glucose variability, the treatment was changed to Xultophy, which is a specific combined agent of Insulin Degludec and Liraglutide (IDeg/Lira) once a day. Then, detailed glucose monitoring showed a better daily profile of blood glucose, irrespective of heavy or light work. It showed the bio-psycho-social benefit of Xultophy.

The patient was an 85-year-old female who has been treated for hypertension and atrial fibrillation (Af). She has visited outpatient clinic and has received regularly general blood tests for every six months. Hemoglobin (Hb) level was stable as 11.2-12.3 g/dL and MCV 88fL from 2017, but it decreased suddenly to 5.2 g/dL and 64 fL in Sept 2020. She did not feel any symptoms or signs. Further evaluations revealed that occult blood in stool and upper and endoscopic exams were negative. About 40 days after starting sodium ferrous citrate, she developed edema anasarca, bilateral pleural effusion and heart failure. Laboratory test showed hypothyroidism, and then the administration of thyroid hormone and diuretics brought her early improvement. As to this impressive case report, general clinical progress and some discussion of the relationship among anemia, edema anasarca, heart failure and hypothyroidism would be described.

The problems among obesity, diabetes mellitus (DM), fatty liver, metabolic dysfunction have been prevalent, and diagnostic criteria as non-alcoholic fatty liver disease (NAFLD) has been used in practice. When diagnosing NAFLD, to exclude other related liver diseases was necessary, including excessive alcohol intake. The international experts proposed the proper term from NAFLD to metabolic associated fatty liver disease (MAFLD). MAFLD criteria include the evidence of the presence of hepatic steatosis associated with three situations. They are obesity/overweight, presence of Type 2 DM (T2DM), or metabolic impaired function, which were studied in the light of pathophysiology, epidemiology, diagnosis and pharmacotherapy.

Hyperuricemia is a clinical important problem and its prevalence has been increased. Latest topics are described. The guideline adequately managing gout was published from American College of Rheumatology (ACR). Various optimal uses of urate-lowering therapy (ULT) were presented. The cardiorenal effects of hyperuricemia have been investigated for years. Regarding the patients on chronic kidney disease (CKD) and high risk of progression, ULT with allopurinol did not show the decline in eGFR compared to the control. Recently, dotinurad that is a new selective urate reabsorption inhibitor (SURI) would be applied to medical practice. Low-dose dotinurad showed satisfactory pharmacological efficacy.

The case is an 82-year-old female patient with Type 2 Diabetes Mellitus (T2DM) for 22 years. She developed right empyema in early January, 2021 and was treated by antibiotics and CT-guided drainage. After improving the status, she was transferred to Hayashi hospital, Tokushima, Japan. Treatment for T2DM was initially multiple daily insulin injection (MDI), but it could not continue because of injection several times a day by the family. Then, Xultophy was started once a day, which brought satisfactory glucose variability with lower doses. Consequently, Xultophy would be effective and useful agent from bio-psycho-social points of view.

The patient is a 56-year old (yo) female with type 2 diabetes mellitus (T2DM). Medical histories include persisting T2DM from 35yo, renal stone at 43yo, hypertension from 45yo, photocoagulation for retinopathy on 54yo. An incidentaloma was found in the left adrenal gland, where endocrinological exams were negative for functional tumor. Her diabetic control situation became worse with HbA1c > 10%, then the treatment has been changed from multiple daily injection (MDI), Dulaglutide to Xultophy which is combined agents of degludec and liraglutide (IDegLira). It was provided 10-18 doses daily, and then glucose variability profile was improved satisfactory, suggesting the dual synergistic effects.

The excess mortality would be adequate objective indicator for COVID-19 research, and was reported in 77 countries for 2020. Several representative data are: United States 420,000, Mexico 270,000, Russia 270,000, Brazil 170,000, Japan -15,000, Taiwan -4,800, Australia -4,700 and New Zealand -2,100. From demographics in Japan, the number of deaths increased by 18 thousand each year during 2015-2019. However, death in 2020 decreased by 9,373 from 2019, which indicated 27 thousand difference. A meaningful perspective showed that focusing on human life saves the economy. Future crucial factors would be new ways of working with the ability of human resources.

Background: Transactional Analysis (TA) and egogram have been in focus for medical and educational fields. There has been a reliable personality battery, Tokyo University Egogram (TEG). Recent topic includes TEG new version 3 for clinical introduction. Using TEG ver.3, university students were investigated for their egogram pattern. Subjects & Methods: Subjects were 99 late teenagers. They were given lectures of TEG and their data was analyzed three months after the admission of the university. Results: TEG ver3 presents 33 egogram types which are related to the personality of Japanese people. Among them, there were four higher prevalence of egogram types, which were Free Child (FC) dominant, Adapted Child (AC) dominant, Critical Parent (CP) inferior and Child (C) Dominant. The percentage datum of current study vs previous standard value in each type was 10 vs 6.8%, 26 vs 6.1%, 8 vs 2.1% 9 vs 1.1%, respectively. Discussion & Conclusion: These four types are estimated as free-spirit, dependent, loose and selfishness. Elevated FC and AC would be probably due to the influence of educational and social environment in Japan. Among them, high school students must study hard for entrance exams without meaningful social experiences. Further investigation will be required for TEG.

Two patients with Type 2 Diabetes Mellitus (T2DM) were treated with Xultophy. Xultophy consists of degludec and liraglutide (IDegLira). It is the combination of long-acting insulin and Glucagon like Peptide-1 Receptor Agonist (GLP-1RA) and is characteristic for effective agent for improving glucose variability for patients with T2DM. However, clinical responses are not always satisfactory due to different complication and background of each patient. We have experienced two impressive T2DM cases. Case 1 was 59-year-old male with hypertension for 20 years and T2DM for 3 years. He was treated on Novolin 30R 30/21 units twice a day, and after that Xultophy 32 doses brought him successful glucose profile. Case 2 was 78-year-old male with hypertension, bronchial asthma, hyperuricemia, and others with heavy alcohol drinking for 50 years. He was formerly treated by Insulin detemir, Liraglutide, exenatide and Degludec/NovoRapid, but has been recently unstable in glucose control. Xultophy up to 40 doses could not successfully improve glucose variability. One of the less responsiveness to Xultophy would be due to impaired liver function. Clinical progress of both cases associated with several perspectives from various points of view are discussed in this article.

Background: The authors and colleagues have been involved in treatment and care for the elderly with rehabilitation, Integrative Medicine (IM), art in hospitals for artworks using masking tape. Combined together, we conducted a pilot study for medical application of masking tape art-work for elderly subjects. Subjects and Methods: Subjects enrolled were 12 elderly patients with dementia regularly coming to day care center for rehabilitation (M/F 3/9, 78-100 years, 88.3±6.0 years). As methods, masking tape has been known as Washi Tape (wa=Japanese and shi=paper), which is adhesive tape easily to stick and peel off for decorative work. Protocol included i) working 2-3 times a week, ii) sticking masking tape on a rough sketch paper, iii) evaluation of several biomarkers before and after the intervention. Results: i) Artworks were performed satisfactory for each case, ii) grasping power (right) showed increasing tendency from 13.5±7.7kg to 14.8±6.8kg (p=0.11), iii) vitality test showed significantly increase (p=0.02). Discussion and Conclusion: Artworks of masking tape seem to be beneficial for improving grasping power and psychological condition. This study included other biomarkers such as Mini-Mental State Examination (MMSE), pinch power, language word test and Barthel index. We plan to develop further detail analyses in the future research.

American Diabetes Association (ADA) has announced the new version of the standards of Medical Care in Diabetes-2021. The guideline of the diabetic patients with Older Adults seems to be used for a wide range of clinical practice. Among them, several impressive comments were found, where “Once-daily basal insulin injection therapy is associated with minimal side effects and maybe a reasonable option in many elder patients”. Recent topic includes Dual Action of Liraglutide and insulin degludec (DUAL) studies, and Xultophy has shown beneficial efficacy. Consequently, the trend would be developed from multiple daily injection (MDI) method to once daily injection.

Whether saturated fatty acid (SFA) has a clinical influence on atherosclerotic cardiovascular disease (ASCVD) or not has been disputed. Prospective Urban Rural Epidemiology (PURE) study was recently summarized from 21 countries with about 150 thousand data. Dairy intake was negatively correlated with the prevalence of metabolic syndrome and the incidence of diabetes and hypertension. To increase the intake of dairy products would be easy and inexpensive to continue for treatment. Polyunsaturated fatty acid (PUFA) and monounsaturated fatty acid (MUFA) may reduce atherosclerotic diseases with beneficial effects. Clinical evidence of SFA will be hopefully accumulated for practice and research in the future.

Regarding the diet treatment of diabetic nephropathy, protein restriction has been recommended. American Diabetes Association (ADA) proposed protein restriction guidelines in the 2008 edition. However, this comment was deleted in the 2013/2019 edition, because of insufficient evidence. A recent report showed that the intake of plant protein has a protective effect on the decrease of estimated glomerular filtration rate (eGFR), and the intake of animal protein has neither protection nor deterioration. There are controversies about the relationship between protein intake and the reduction of renal function. Further research will be expected for diabetic nephropathy, diabetic kidney disease (DKD), and chronic kidney disease (CKD).

Authors and collaborators have continued clinical practice and research on rehabilitation and self-training, in which various problems were found. Protocol: The author himself tried home self-training exercise of push-up for 2 months, which was successfully achieved. Results: Positive changes were 94 to 96.5cm in chest circumference, and 45 to 100 times in continuous push-up, respectively. Discussion: From the viewpoint of sport psychology, close relationship among motivation, self-efficacy and performance has been observed. Self-efficacy can influence one’s beliefs concerning accomplishing and continuing the task, activities and effort. This report will hopefully become the reference for future practice and research development.

Authors’ and collaborators have continued research concerning stretching, the flexibility of thoracic spine. In this study, author himself continued our stretching protocol for 4 months. The changes were i) the spreading degree of open legs, ii) bridge posture bending the whole body backward, iii) finger floor distance (FFD) with 3 to 18cm. The purpose was self-verification by habituation training, and clinical efficacy was found. For other effects, he has not been injured for the period as soccer player at all, and has felt comfortable operation subjectively. This process will be beneficial for managing various patients and athletes from now.

Case: The case is 86-year-old male hypertensive patient with anti-hypertensive drug for 5 years. He has been provided Amlodipine besilate 5mg at 0800h and doxazosin mesylate 2mg at 2300h for long. In June 2020, he noticed unstable fluctuation of Blood Pressure (BP) during morning, afternoon and night. Results: Then, he checked the circadian rhythm of BP, which showed higher BP in early morning, decreasing BP 0800-1000h, minimum BP during 1000-1400h, increasing BP during 1400-1800h and stable BP during 1800-2400h. Due to the result, he changed to take amlodipine at 2300h. Consequently, his BP gradually became stable during 24 hours after 2 weeks. Discussion: Some factors may exist for contributing improved BP fluctuation. They include a) pathophysiological characteristics of BP circadian rhythm, b) effective time for anti-hypertensive drug, c) accuracy of the obtained BP data and d) the social and psychological reliability of the patient. Regarding d) he was engaged in research and development work as a senior researcher at a chemical company. He has been also a member of New Elderly Association (NEA), which was established by Shigeaki Hinohara. He lives on the philosophy of Hinohara-ism for long, associated with stable mind and body.

Diabetes includes various heterogeneous factors. Similar to subtypes of type 1 diabetes, type 2 diabetes may show four subtype clusters. They are cluster A: severe insulin-deficient diabetes, B: severe insulin-resistant diabetes, C: mild obesity-related diabetes, and D: mild age-related diabetes. Comparing them, the prevalence of nephropathy and cardiovascular events was highest in the cluster A. Reference data are i) the ratio of cluster A-D is 18.7%, 23.7%, 21.1%, 36.4%, ii) HbA1c for A-D is 11.05%, 8.17%, 8.49%, 7.95%, iii) event ratio of MACE is 14.4%, 10.6%, 11.4%, 9.1%. Future diabetic treatment is hopefully provided suitable for each subtype.

The daily profile of blood glucose can be detected by continuous glucose monitoring (CGM) using FreeStyle Libre. The case was a 51-year-old female with type 2 diabetes mellitus (T2DM) for uncontrolled glucose variability as HbA1c 10.3%. During CGM measurement, diabetic treatment was changed from multiple daily insulin injections (MDI) to Xultophy (insulin degludec and liraglutide). Xultophy starting from 10 to 18 doses has brought the improvement of glucose variability, such as decreased pre-prandial glucose from 268 mg/dL to 101 mg/dL. Consequently, detailed data of glucose variability on Xultophy using CGM would be beneficial and become some reference for further clinical diabetic research.

Due to current pandemic of Coronavirus disease-2019 (COVID-19), elderly people tend to show deterioration of physical and cognitive function and exacerbation of nutritional status, leading to the progression of sarcopenia and frailty. Recent topic includes the National Center for Geriatrics and Gerontology-Home Exercise Program for Older People (NCGG-HEPOP) 2020. It has six packs for health maintenance, such as balance improvement, strengthening, inactivity prevention, feeding/swallowing improvement, nutrition improvement and cognition. The pandemic may bring decreased social interaction, decreased physical activity, and increased physical stress of viral infection. NCGG-HEPOP will hopefully prevent such exacerbation in the light of geriatrics and rehabilitation medicine.

Diabetes mellitus has become a medical and social problem. For better diabetic management and improvement of the health care system, the concept of social determinants of health (SDOH) and socioeconomic status (SES) would be required. SES includes adequate diabetes care, medical cost, health condition, and regular access to care and cure. World Health Organization (WHO) has continued the prevention and management of diabetes and proposed the Global Diabetes Compact in last 2020 [1]. The purpose of the Compact includes several items, such as i) to leverage present capacities in the healthcare system, ii) to meet people’s needs more holistic way, iii) to promote efforts to prevent diabetes especially the young generation, and others. A successful key would be the combined action among public, private, and philanthropic associations. Diabetes mellitus has been a growing medical and social problem in all countries and districts worldwide [2]. The socio economic gradient for diabetic prevalence is shown in high income countries [3]. Further, this gradient seems to be continued for a long despite the improvement of the health care system in those countries [4,5]. In this paper, we describe the social determinants of health (SDOH) and socioeconomic status (SES), among other axes of symmetry for diabetes. In medical practice and health care, population based and value based care have been emphasized. Then, the concept of social determinants of health (SDOH) has been gradually known for an intervention target for estimating health equity [6]. Recently, some comments for SDOH were proposed from medical associations, such as the Society of General Internal Medicine, the American College of Physicians, and other organizations [7]. Moreover, the action perspectives tend to focus on the determinants for individuals and policy [8,9]. In diabetic practice, some basic matters exist including prevalence, incidence, adequate therapy, and economic problems [10]. ADA presented a comment about socio ecological determinants of diabetes. Successively, ADA had an advanced health improvement project for the diabetes writing committee. It has the goal of clarifying diabetic risk and outcomes, academic literature for SDOH [11]. From previous literature, SDOH covers certain areas as follows [6]: i) social context (social support, relationship, and capital, social relationship), ii) health care (quality, accessibility, affordability), iii) local and physical circumstance (residence condition, building environment), iv) food environment (insecurity for food, accessibility for food) and v) socio economic condition (occupation, education, income). According to academic reports, the health disparities for diabetes have been present in the light of adverse influence [12]. Social and environmental factors have been summarized as SDOH in WHO [13]. Among them, social environments seem to be rather main factors. They include societal and community context [14], social capital, social cohesion, and social elements [15]. Health care has been found as an SDOH in the Healthy People 2020, WHO, County health rankings models, associated with accessible factors. WHO regards the health system as one of the SDOH which can give a message of determinants of several health outcomes [15]. On the other hand, it is socioeconomic status (SES) that may influence all related aspects of diabetic treatment in the clinical practice [16]. Actually, lower SES diabetic cases are likely to have some barriers to adequate diabetes care, including medical cost, unsatisfactory health condition, and regular access to care and cure [17]. SES has revealed the multidimensional construct, associated with the occupational, economic, and educational situation [18]. SES has been related to all factors of SDOH [13]. They include medical care, health care, nutrition, social resources, housing, transportation, and so on. The factors of SES and diabetes were investigated for observational studies [19]. It included 28 investigations including diabetic complications, retinopathy, cardiopathy, and others. In summary, SDOH and SES concerning diabetes were introduced. This information will be hopefully useful for developing a bio psycho social perspective in clinical practice.