Association between variation in hemoglobin A1c levels and diabetes therapy-related quality of life in patients with diabetes.

AIMS/INTRODUCTION: We aimed to investigate the association between glycemic variability and quality of life (QOL) in patients with diabetes, which has not been studied previously. MATERIALS AND METHODS: Patients who were undergoing treatment at the Kyoto Prefectural University of Medicine Hospital and Kameoka City Hospital participated in the KAMOGAWA-DM study, and completed the diabetes therapy-related (DTR)-QOL questionnaire from January 2016 to July 2020 were included in this study. We used linear regression analyses to compare the association between DTR-QOL scores and glycemic variability. RESULTS: We included a total of 635 patients in this analysis. The hemoglobin A1c (HbA1c) levels of these patients were measured at least four times during the 9-month period, before and after answering the questionnaire. Results showed that HbA1c variability, HbA1c mean and duration of diabetes were negatively associated with the total DTR-QOL score. Conversely, the body mass index and total DTR-QOL score were positively associated with HbA1c variability. CONCLUSIONS: A small variation in HbA1c level was associated with higher total DTR-QOL scores and the scores for each factor. Reducing blood glucose variability is significant when we treat diabetes.

IL-33 Reduces Saturated Fatty Acid Accumulation in Mouse Atherosclerotic Foci.

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

Relationship between diabetes diet-related quality of life and dietary fiber intake among people with type 2 diabetes: a cross-sectional study.

Diet therapy is one of the most important treatments for people with type 2 diabetes (T2D). However, dietary restrictions due to diet therapy may reduce quality of life (QOL). This cross-sectional study aimed to investigate the association between diabetes diet-related QOL and dietary fiber intake in 238 people with T2D. The Diabetes Diet-related Quality of Life-Revised version (DDRQOL-9-R) and the brief-type self-administered diet history questionnaire were used to evaluate diabetes diet-related QOL and nutritional intake, respectively. Higher scores of each DDRQOL-9-R subscale means greater satisfaction with diet, perceived merits of diet therapy, and lower burden of diet therapy, which indicates good QOL. The median scores for perceived merits of diet therapy, satisfaction with diet, and burden of diet therapy were 58.3 [41.7-75.0], 75.0 [66.7-91.7], and 66.7 [50.0-75.0] points, respectively. HbA1c levels in people with high perceived merits of diet therapy (7.3 [6.7-7.8] vs. 7.5 [7.1-8.2] %, p = 0.007) and people with high satisfaction with diet (7.3 [6.8-7.8] vs. 7.5 [7.1-8.4] %, p = 0.010) were lower than those without. Dietary fiber intake was higher in people with high perceived merits of diet therapy (11.6 [8.8-16.7] vs. 10.0 [7.9-13.8] g/day, p = 0.010), high satisfaction with diet (11.4 [8.8-16.1] vs. 9.7 [7.8-13.2] g/day, p = 0.007), and low burden of diet therapy (11.8 [8.7-16.5] vs. 9.7 [7.8-12.6] g/day, p = 0.004) than in those without. Dietary fiber intake was related to perceived merits of diet therapy (Odds ratio [OR]1.07 [95%CI: 1.00-1.15], p = 0.049), burden of diet therapy (OR 0.90 [95%CI: 0.82-0.98], p = 0.022), and satisfaction with diet (OR 1.18 [95%CI: 1.09-1.27], p < 0.001) after adjusting for covariates. Dietary fiber intake is associated with diabetes diet-related QOL in people with T2D.

Association between gastrointestinal symptoms and insomnia in patients with type 2 diabetes: The KAMOGAWA-DM cohort study.

AIMS/INTRODUCTION: Gastrointestinal disturbances and insomnia affect the quality of life of patients with diabetes. However, the relationship between gastrointestinal symptoms and insomnia in patients with diabetes has rarely been analyzed. Thus, aim of this study was to investigate the association between gastrointestinal symptoms and insomnia in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: This cross-sectional study of patients with type 2 diabetes was carried out from January 2014 to April 2022 using the database of the KAMOGAWA-DM cohort study. Patient data were collected using a self-administered questionnaire, and the Izumo Scale and the Athens Insomnia Scale were used to assess gastrointestinal symptoms and insomnia, respectively. Multivariate logistic regression analysis was carried out to determine the association between gastrointestinal symptoms and insomnia. RESULTS: A total of 175 patients with type 2 diabetes were included in this study. Patients with insomnia had higher Izumo scores than those without insomnia (P < 0.0001). Izumo scale score was significantly associated with insomnia in patients with type 2 diabetes, even after adjustment for age, body mass index, systolic blood pressure, glycated hemoglobin level, neuropathy, insulin therapy and nocturia (odds ratio 1.10, 95% confidence interval [CI] 1.06-1.16). Each gastrointestinal symptom assessed using the Izumo scale was associated with insomnia. The odds ratios of heartburn, stomach pain, lethargy, constipation and diarrhea for insomnia were 1.32 (95% CI 1.13-1.55), 1.38 (95% CI 1.16-1.63), 1.33 (95% CI 1.13-1.56), 1.21 (95% CI 1.08-1.36) and 1.29 (95% CI 1.12-1.47), respectively. CONCLUSIONS: Gastrointestinal symptoms are strongly associated with sleep disturbances in patients with type 2 diabetes.

Impact of an online nutrition management application service on glycaemic management in individuals with diabetes: A propensity-score-matched retrospective cohort study.

AIMS: To assess the impact of 'Oishi Kenko', a nutrition management application (app), on glycaemic control in patients with diabetes. MATERIALS AND METHODS: A propensity-score-matched retrospective cohort study was performed using data from the KAMOGAWA-DM cohort study conducted between January and June 2022 in Japan. We analysed data from patients with type 1 and type 2 diabetes, comparing users who used the Oishi Kenko app (app group) with non-users (control group) over 3 months. RESULTS: Among the 50 participants who actively used it, 47 participants in both the app and control cohorts were selected from the KAMOGAWA-DM cohort according to propensity-score matching. Within the app group, the median glycated haemoglobin (HbA1c) level was 51 mmol/mol (6.9%) at baseline, which slightly decreased to 50 mmol/mol (6.8%) at the 3-month mark (median change 0.0%). Conversely, in the control group, the baseline HbA1c level of 51 mmol/mol (6.9%) exhibited a marginal increase of 52 mmol/mol (7.0%) after 3 months (median change 0.20%). The median HbA1c level change between the groups was statistically significant, with the app group showing a significant positive change compared with the control group (p = 0.012). CONCLUSION: The Oishi Kenko app effectively improved glycaemic control in patients with diabetes; hence, it may be a promising tool for patient-driven dietary management.

Postoperative Insulin Dose for Cardiac Artery Bypass Graft and Other Cardiac Surgeries in Patients with Type 2 Diabetes: A Retrospective Study.

Purpose: Recommendations on perioperative glycemic control in cardiac surgery are based on coronary artery bypass graft surgery (CABG), though coronary artery disease and valvular disease are pathologically distinct. We aimed to compare the postoperative insulin requirement between CABG and other cardiac surgeries in type 2 diabetic patients and identify predictive factors for the maximum postoperative insulin dose. Patients and Methods: We retrospectively included 60 Japanese patients with diabetes/glucose intolerance (HbA1c > 37 mmol/mol [5.6%]) who were hospitalized for cardiovascular surgery between April 2017 and March 2019. We categorized the subjects into the CABG and non-CABG groups, and performed subgroup analysis on patients who received postoperative insulin therapy. Results: The CABG group required a significantly higher insulin dose on postoperative days 2, 5, 6, and 7, and a significantly higher maximum postoperative insulin dose (24.6 U vs 9.7 U, P < 0.001) than the non-CABG group. Multivariate linear regression analyses showed that the independent determinants of the maximum postoperative insulin dose were HbA1c and duration of diabetes in the non-CABG group, and HbA1c in the CABG group. Conclusion: CABG had a higher postoperative insulin requirement than other cardiovascular surgeries; early aggressive insulin therapy is indicated, especially for patients with higher HbA1c levels/longer duration of diabetes.

Associations between thyroid hormones and appendicular skeletal muscle index, and hand grip strength in people with diabetes: The KAMOGAWA-A study.

AIM: To assess the effects of thyroid hormones on appendicular skeletal muscle index (SMI) and hand grip strength (HGS) in people with diabetes. METHODS: This cross-sectional cohort included 1,135 participants with diabetes admitted to 3 hospitals in Japan. Multiple regression analysis was performed to determine the associations among thyroid hormone levels, SMI, and HGS. RESULTS: Of the 1,135 participants, 480 were female. Their median (interquartile range) age, body mass index, durations of diabetes, and glycated haemoglobin levels were 68 years, 24.3 kg/m2, 10 years, and 7.6 %, respectively. The median (interquartile range) SMI (kg/m2) and hand grip strength of the cohort were 7.1 kg/m2 and 28.2 kg, respectively. Positive correlations between FT3 and the FT3/FT4 ratio with SMI and HGS was observed after adjusting for covariates in males. A negative correlation was found between the FT3/FT4 ratio and sarcopenia as a result of low SMI and low HGS in the male participants but not in females (p for interaction = 0.02). CONCLUSIONS: FT3/FT4 ratios may impact skeletal muscles in people with diabetes-particularly in males. Assessments of FT3/FT4 ratios may represent key indicators of muscle mass and strength in males.

Miso, fermented soybean paste, suppresses high-fat/high-sucrose diet-induced muscle atrophy in mice.

This study investigated the effects of miso, a traditional fermented soybean food in Japan, on muscle mass atrophy. Eight week old male C57BL/6J mice were fed high fat/high sucrose diet with or without miso for 12 weeks. A miso diet increased soleus muscle weights (p<0.05) and reduced intraperitoneal glucose tolerance and insulin tolerance (p<0.05). The miso diet downregulated the Tnfα and Ccl2 expression, related to inflammation, and Trim63 and Fbxo32 expression, related to muscle atrophy, in the soleus muscle (p<0.05). The miso diet increased short-chain fatty acids levels, including acetic, propanoic, and butanoic acids, in the feces, serum, and soleus muscle (p<0.05). According to the LEfSe analysis, the miso diet increased family Prevotellaceae, family Christensenellaceae, family Dehalobacterium, family Desulfitibacter; family Deferribacteraceae, order Deferribacterales, class Deferribacteres; and family Gemmatimonadaceae, order Gemmatimonadetes, and class Gemmatimonadales, whereas the miso diet decreased family Microbacteriaceae, order Micrococcales, class Actinobacteria, and family Lactobacillaceae. Miso suppressed high fat/high sucrose diet induced impaired glucose tolerance, low muscle strength, and muscle atrophy by improving dysbiosis and increasing short-chain fatty acids production and provides new insights into the preventive effects of fermented foods on sarcopenia.

Effects of weight loss on metabolic dysfunction-associated fatty liver disease in Japanese people: Non-alcoholic fatty liver disease in the Gifu area, longitudinal analysis study.

AIM: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major health concern. This cohort study aimed to evaluate the association between weight loss and remission of MAFLD in the Japanese population to aid the development of efficient treatment strategies. METHODS: This retrospective cohort study was conducted at a Japanese health screening center. Participants included 3309 individuals diagnosed with baseline MAFLD between 2004 and 2016. Logistic regression analysis was used to assess the association between MAFLD remission from baseline to 5 years and weight change. RESULTS: After 5 years, 671 participants achieved MAFLD remission. Weight loss was associated with MAFLD remission for every 1 kg of weight loss over 5 years; the odds ratio for MAFLD remission was 1.24 (95% CI 1.15-1.34) for participants with type 2 diabetes, 1.40 (95% CI 1.35-1.45) for overweight participants, and 1.51 (95% CI 1.33-1.72) for non-overweight participants with metabolic dysfunctions. The cutoff values for weight loss for MAFLD remission were 1.9 kg for all participants, 3.0 kg for participants with type 2 diabetes, 1.9 kg for overweight participants, and 0.8 kg for non-overweight participants with metabolic dysfunctions. CONCLUSIONS: Among participants diagnosed with MAFLD, weight loss was associated with MAFLD remission regardless of the type of metabolic dysfunction in MAFLD. The results of this study may contribute to the development of novel approaches to achieve MAFLD remission.

Predictive power of isolated high home systolic blood pressure for cardiovascular outcomes in individuals with type 2 diabetes mellitus: KAMOGAWA-HBP study.

AIMS/INTRODUCTION: Isolated high home systolic blood pressure (IHHSBP) is a risk for cardiovascular disease (CVD). However, no study has shown an association between IHHSBP and CVD in diabetes. We examined the association between IHHSBP and CVD in type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study included 1082 individuals with type 2 diabetes, aged 20 to 90 years, without a history of macrovascular complications. Home blood pressure (HBP) was measured three times every morning and evening for 14 days. Cox proportional hazards models were used to examine the relationship between IHHSBP and CVD incidence. RESULTS: With the normal HBP group as the reference, the adjusted hazard ratio (HR) (95% confidence interval [CI]) for CVD was 1.58 (1.02-2.43) in the IHHSBP group. Correcting for antihypertensive medication use did not change HR. Based on sex, the adjusted HR (95% CI) for CVD was 1.25 (0.74-2.13) in males and 2.28 (1.01-5.15) in females. CONCLUSIONS: In individuals with type 2 diabetes, those with IHHSBP had a higher HR for cardiovascular disease than those with normal HBP. But, Isolated high home diastolic blood pressure and high HBP were not. The association between IHHSBP and CVD was stronger in females than in males.

Reasons for Discontinuing Treatment with Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Diabetes in Real-World Settings: The KAMOGAWA-A Study.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are a class of antidiabetic agents known to exert cardioprotective, renoprotective, and hypoglycemic effects. However, these agents have been associated with adverse effects, such as genital infection, volume depletion, hypoglycemia, and diabetic ketoacidosis, resulting in drug discontinuation. Herein, we aimed to determine the reasons for discontinuing treatment with SGLT2is among Japanese patients with diabetes. This retrospective cohort study enrolled 766 patients with diabetes who had initiated SGLT2is between January 2014 and September 2021. The follow-up period was 2 years from the initiation of the SGLT2is. Overall, 97 patients (12.7%) discontinued the SGLT2is during the follow-up period. The most common reasons for discontinuing the SGLT2is were frequent urination (19.6%), followed by genital infection (11.3%), improved glycemic control (10.6%), and renal dysfunction (8.2%). A comparison of the characteristics between the continuation and the discontinuation group was conducted, excluding those who discontinued the SGLT2is because of improved glycemic control. The patients in the discontinuation group (68 [55-75] years) were older than those in the continuation group (64 [53-71] years; p = 0.003). Importantly, we found no significant association between diabetes duration, diabetic control, renal function, or complications of diabetes in both groups. This real-world study revealed that frequent urination was the most common reason underlying SGLT2i discontinuation among Japanese patients with diabetes. To avoid discontinuation, precautions against various factors that may cause frequent urination must be implemented.

Younger patients and low c-peptide immunoreactivity index but not nutritional states affect fasting blood ketone levels in Japanese with type 1 diabetes after sodium-glucose cotransporter 2 inhibitor administration.

AIM: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are available for individuals with type 1 diabetes, but appropriate use is recommended to prevent ketosis or ketoacidosis. This study aimed to evaluate the risk of ketosis in people with type 1 diabetes, focusing on the relationship between nutritional assessment, glycaemic status, c-peptide immunoreactivity (CPR) index and body composition. MATERIALS AND METHODS: In total, 46 Japanese patients with type 1 diabetes were included, and dietary assessment from food photographs and ketone levels were evaluated before and after taking SGLT2is. The effect of diet on morning ketone levels was also investigated. RESULTS: All patients had an increase in mean ketone concentrations after taking SGLT2is (before 0.12 ± 0.06 mmol/L, after 0.23 ± 0.16 mmol/L). A significant negative correlation was found between average morning ketone levels and age (r = -0.514, p < .001) and the CPR index (r = -0.523, p = .038) after taking SGLT2is. Using a mixed-effects model based on the results before starting the inhibitors, it was noted that both patient-to-patient and age, or patient-to-patient and capacity of insulin secretion, influenced the ketone levels. Multiple regression analysis showed that factors associated with the risk of increasing ketone levels after taking SGLT2is were younger age (ß = -0.504, p = .003) and a low ratio of basal to bolus insulin (ß = -0.420, p = .005). CONCLUSIONS: When administering SGLT2is to patients with a low CPR index or younger patients with type 1 diabetes, adequate instructions to prevent ketosis should be given.

Factors associated with bleeding complications in patients with coronavirus disease 2019 admitted to intensive care units: A multicenter retrospective cohort study.

AIMS/INTRODUCTION: Diabetes is a major risk factor for coronavirus disease 2019 (COVID-19) severity. We aimed to retrospectively investigate the rates of patients with no diabetes, untreated diabetes, treated diabetes, COVID-19-related diabetes and the factors associated with bleeding complications in a cohort of patients with severe COVID-19. MATERIALS AND METHODS: This was a multicenter, retrospective, observational study. Participants were COVID-19 patients enrolled in the Cross-sectional ICU Information Search System (CRISIS) from February 2020 to March 2022. Patients were classified into four groups according to diabetes status and treatment status. Hemorrhagic complications were defined as bleeding requiring transfusion of four or more red blood cell units, a drop of hemoglobin of ≥2 g in 24 h and retroperitoneal, airway or intracranial bleeding. Logistic regression analysis was carried out to examine factors associated with bleeding complications. RESULTS: A total of 1,076 patients were included in the analysis. The rates of patients in the no diabetes, untreated diabetes, treated diabetes and COVID-19-related diabetes groups were 17.4, 23.0, 23.9 and 35.7%, respectively. Bleeding complications were observed in 7.5% of all patients. Glycated hemoglobin level and renal failure were significantly correlated with bleeding complications (odds ratio 1.16, 95% confidence interval 1.02-1.33 and 2.77, 95% confidence interval 1.16-6.63, respectively). Patients with diabetes, including those with COVID-19-related diabetes, accounted for approximately 83% of all cases. CONCLUSIONS: In patients with severe COVID-19 with high glycated hemoglobin and renal failure, we recommend additional attention to the course of COVID-19, given the risk of bleeding complications.

Comparison of Diet, Sleep, and Stress During the Emergency Coronavirus Disease Curfew in Men and Women with Hemodialysis.

OBJECTIVE: To investigate the effect of coronavirus disease 2019 (COVID-19) on diet, stress, and sleep in Japanese patients with hemodialysis. METHODS: Data on nutritional intake, frequency of food intake by cuisine, dietary behavior, and frequency of food use before and during the declaration of the state of emergency due to COVID-19, were collected. RESULTS: For the 81 participants (47 men), changes were observed in the following diet-related items: nutrition and nutrient content (one item for men, three for women), eating behavior, and frequency of food use (1 item for men, six for women), and the total number of items was two for men and nine for women. Nine out of 12 questions addressed stress and six out of eight questions addressed sleep, with a higher percentage of women adversely affected and no item with a higher percentage of men adversely affected. The mean score for stress was 25.3 ± 5.1 for men and 29.5 ± 5.0 for women, P < .001, and for sleep disturbance was 11.6 ± 3.0 for men and 14.4 ± 4.4 for women, P < .001. CONCLUSIONS: In patients with hemodialysis, the effect of refraining from going out due to the spread of COVID-19 on diet, sleep, and stress was suggested to be more significant in women than in men.

Effects of Royal Jelly on Gut Dysbiosis and NAFLD in db/db Mice.

Royal jelly (RJ) is a naturally occurring substance synthesized by honeybees and has various health benefits. Herein, we focused on the medium-chain fatty acids (MCFAs) unique to RJ and evaluated their therapeutic efficacy in treating non-alcoholic fatty liver disease (NAFLD). We examined db/m mice that were exclusively fed a normal diet, db/db mice exclusively fed a normal diet, and db/db mice fed varying RJ quantities (0.2, 1, and 5%). RJ improved NAFLD activity scores and decreased gene expression related to fatty acid metabolism, fibrosis, and inflammation in the liver. RJ regulated innate immunity-related inflammatory responses in the small intestine and decreased the expression of genes associated with inflammation and nutrient absorption transporters. RJ increased the number of operational taxonomic units, the abundance of Bacteroides, and seven taxa, including bacteria that produce short-chain fatty acids. RJ increased the concentrations of RJ-related MCFAs (10-hidroxy-2-decenoic acid, 10-hydroxydecanoic acid, 2-decenedioic acid, and sebacic acid) in the serum and liver. These RJ-related MCFAs decreased saturated fatty acid deposition in HepG2 cells and decreased the gene expression associated with fibrosis and fatty acid metabolism. RJ and RJ-related MCFAs improved dysbiosis and regulated the expression of inflammation-, fibrosis-, and nutrient absorption transporter-related genes, thereby preventing NAFLD.

Leucine and Glutamic Acid as a Biomarker of Sarcopenic Risk in Japanese People with Type 2 Diabetes.

This study aimed to identify the serum metabolites associated with sarcopenic risk in Japanese patients with type 2 diabetes, determine the effect of dietary protein intake on the serum metabolic profile, and examine its association with sarcopenia. Ninety-nine Japanese patients with type 2 diabetes were included, and sarcopenic risk was defined as low muscle mass or strength. Seventeen serum metabolites were quantified after gas chromatography-mass spectrometry analysis. The relationship between dietary protein intake and the metabolites concerning sarcopenia was analyzed, and the factors affecting sarcopenic risk were clarified. Twenty-seven patients were classified as being at risk of sarcopenia, the same as the general risk, which was associated with older age, a longer duration of the disease, and a lower body mass index. Low levels of leucine and glutamic acid were significantly associated with low muscle strength (p = 0.002 and p < 0.001, respectively), and leucine was also associated with muscle mass (p = 0.001). Lower levels of glutamic acid had higher odds of sarcopenic risk after being adjusted for age and HbA1c (adjusted OR 4.27, 95% CI 1.07-17.11, p = 0.041), but not for leucine. Leucine and glutamic acid can serve as useful biomarkers for sarcopenia, highlighting potential targets for its prevention.

Milk protects against sarcopenic obesity due to increase in the genus Akkermansia in faeces of db/db mice.

BACKGROUND: Sarcopenic obesity, a combination of sarcopenia and obesity, is a pathological feature of type 2 diabetes. Several human studies have shown that milk is useful in the prevention of sarcopenia. This study was aimed at clarifying the effect of milk on the prevention of sarcopenic obesity in db/db mice. METHODS: A randomized and investigator-blinded study was conducted using male db/db mice. Eight-week-old db/db mice were housed for 8 weeks and fed milk (100 µL/day) using a sonde. The faecal microbiota transplantation (FMT) group received antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. RESULTS: Milk administration to db/db mice increased grip strength (Milk-: 164.2 ± 4.7 g, Milk+: 230.2 ± 56.0 g, P = 0.017), muscle mass (soleus muscle, Milk-: 164.2 ± 4.7 mg, Milk+: 230.2 ± 56.0 mg, P < 0.001; plantaris muscle, Milk-: 13.3 ± 1.2 mg, Milk+: 16.0 ± 1.7 mg, P < 0.001) and decreased visceral fat mass (Milk-: 2.39 ± 0.08 g, Milk+: 1.98 ± 0.04 mg, P < 0.001), resulting in a significant increase in physical activity (light: P = 0.013, dark: P = 0.034). FMT from mice fed milk not only improved sarcopenic obesity but also significantly improved glucose intolerance. Microarray analysis of gene expression in the small intestine revealed that the expression of amino acid absorption transporter genes, namely, SIc7a5 (P = 0.010), SIc7a1 (P = 0.015), Ppp1r15a (P = 0.041) and SIc7a11 (P = 0.029), was elevated in mice fed milk. In 16S rRNA sequencing of gut microbiota, the genus Akkermansia was increased in both the mice fed milk and the FMT group from the mice fed milk. CONCLUSIONS: The findings of this study suggest that besides increasing the intake of nutrients, such as amino acids, milk consumption also changes the intestinal environment, which might contribute to the mechanism of milk-induced improvement of sarcopenic obesity.

Metabolic outcomes and changes in innate immunity induced by diesel exhaust particles airway exposure and high-fat high-sucrose diet.

AIMS: Epidemiological studies have shown that exposure to diesel exhaust particles (DEP) is associated with metabolic diseases. We used mice with nonalcoholic fatty liver disease (NAFLD) caused by a high-fat, high-sucrose diet (HFHSD), which mimics a Western diet, to investigate the mechanism of NAFLD exacerbation via changes in innate immunity in the lungs by airway exposure to DEP. MAIN METHODS: Six-week-old C57BL6/J male mice were fed HFHSD, and DEP was administered endotracheally once a week for eight weeks. The histology, gene expression, innate immunity cells in the lung and liver, and the serum inflammatory cytokine levels, were investigated. KEY FINDINGS: Under the HFHSD, DEP increased blood glucose levels, serum lipid levels, and NAFLD activity scores, and also the expression of genes associated with inflammation in the lungs and liver. DEP caused an increase in ILC1s, ILC2s, ILC3s, and M1 macrophages in the lungs and a marked increase in ILC1s, ILC3s, M1 macrophages, and natural killer cells in the liver, while ILC2 levels were not changed. Furthermore, DEP caused high levels of inflammatory cytokines in the serum. SIGNIFICANCE: Chronic exposure to DEP in HFHSD-fed mice increased inflammatory cells involved in innate immunity in the lungs and raised local inflammatory cytokine levels. This inflammation spread throughout the body, suggesting the association with the progression of NAFLD via increased inflammatory cells involved in innate immunity and inflammatory cytokine levels in the liver. These findings contribute to a better understanding of the role of innate immunity in air pollution-related systemic diseases, especially metabolic diseases.

Dental care and oral conditions are associated with the prevalence of sarcopenia in people with type 2 diabetes: a cross-sectional study.

BACKGROUND: Insulin resistance, which is closely associated with type 2 diabetes mellitus (T2DM), is a cause of sarcopenia and people with T2DM have a high risk of sarcopenia. Keeping good oral condition by dental care is important for people with T2DM. Keeping good oral condition by dental care is important for people with T2DM. This study has investigated the association between dental care or oral conditions and sarcopenia in people with T2DM. METHODS: Dental care and oral conditions were evaluated based on a self-reported questionnaire. Individuals with both low handgrip strength and low skeletal muscle mass index were diagnosed with sarcopenia. RESULTS: Among 266 people with T2DM, the proportions of sarcopenia, not having a family dentist, not having a toothbrushing behavior, poor chewing ability, and use of complete dentures were 18.0%, 30.5%, 33.1%, 25.2%, and 14.3%, respectively. The proportions of sarcopenia in people not having a family dentist (27.2% vs. 14.1%, p = 0.017), those with poor chewing ability (26.9% vs. 15.1%, p = 0.047), and use of complete dentures (36.8% vs. 14.9%, p = 0.002) were higher than those in people without. The proportion of sarcopenia in people without toothbrushing behavior tended to be higher than that in people with toothbrushing behavior (25.0% vs. 14.6%, p = 0.057). Not having a family dentist (adjusted odds ratio [OR] 2.48 [95% confidence interval (CI): 1.21-5.09], p = 0.013), poor chewing ability (adjusted OR 2.12 [95% CI: 1.01-4.46], p = 0.048), and use of complete dentures (adjusted OR 2.38 [95% CI: 1.01-5.99], p = 0.046) were related to the prevalence of sarcopenia. CONCLUSIONS: This study revealed that dental care and oral conditions were associated with the prevalence of sarcopenia.

Oral Exposure to Polystyrene Microplastics of Mice on a Normal or High-Fat Diet and Intestinal and Metabolic Outcomes.

BACKGROUND: Microplastics (MPs) are small particles of plastic (≤5mm in diameter). In recent years, oral exposure to MPs in living organisms has been a cause of concern. Leaky gut syndrome (LGS), associated with a high-fat diet (HFD) in mice, can increase the entry of foreign substances into the body through the intestinal mucosa. OBJECTIVES: We aimed to evaluate the pathophysiology of intestinal outcomes associated with consuming a high-fat diet and simultaneous intake of MPs, focusing on endocrine and metabolic systems. METHODS: C57BL6/J mice were fed a normal diet (ND) or HFD with or without polystyrene MP for 4 wk to investigate differences in glucose tolerance, intestinal permeability, gut microbiota, as well as metabolites in serum, feces, and liver. RESULTS: In comparison with HFD mice, mice fed the HFD with MPs had higher blood glucose, serum lipid concentrations, and nonalcoholic fatty liver disease (NAFLD) activity scores. Permeability and goblet cell count of the small intestine (SI) in HFD-fed mice were higher and lower, respectively, than in ND-fed mice. There was no obvious difference in the number of inflammatory cells in the SI lamina propria between mice fed the ND and mice fed the ND with MP, but there were more inflammatory cells and fewer anti-inflammatory cells in mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. The expression of genes related to inflammation, long-chain fatty acid transporter, and Na+/glucose cotransporter was significantly higher in mice fed the HFD with MPs than in mice fed the HFD without MPs. Furthermore, the genus Desulfovibrio was significantly more abundant in the intestines of mice fed the HFD with MPs in comparison with mice fed the HFD without MPs. Muc2 gene expression was decreased when palmitic acid and microplastics were added to the murine intestinal epithelial cell line MODE-K cells, and Muc2 gene expression was increased when IL-22 was added. DISCUSSION: Our findings suggest that in this study, MP induced metabolic disturbances, such as diabetes and NAFLD, only in mice fed a high-fat diet. These findings suggest that LGS might have been triggered by HFD, causing MPs to be deposited in the intestinal mucosa, resulting in inflammation of the intestinal mucosal intrinsic layer and thereby altering nutrient absorption. These results highlight the need for reducing oral exposure to MPs through remedial environmental measures to improve metabolic disturbance under high-fat diet conditions. https://doi.org/10.1289/EHP11072.