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.

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.

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.

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.

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.

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.

Insulin dose reduction in dapagliflozin combination therapy for type 1 diabetes mellitus: the RISING-STAR study.

To clarify the frequency of hypoglycemia in patients with type 1 diabetes mellitus receiving dapagliflozin combination therapy to reduce their basal insulin dose. Sixty subjects were assigned to two groups according to their basal insulin-to-total daily dose (TDD) ratio: group A (basal insulin/TDD <40%) and group B (≥40%). Reduction of the basal insulin dose was instituted in group B, but not in group A. The number of hypoglycemic events per day and ketosis frequency were the primary and secondary endpoints, respectively. The hypoglycemia frequency before and after the intervention was 0.23 and 0.26 times/day in group A and 0.19 and 0.23 times/day in group B, respectively, with no significant difference between the groups. The total insulin dose reduction was approximately 10% in both groups. Ketosis frequency increased significantly after the intervention (from 0.013 to 0.086 times/day in group A and 0.013 to 0.059 times/day in group B). Time-in-range, mean amplitude of glycemic excursion, and glycated hemoglobin A1c improved in both groups. No significant difference in hypoglycemia frequency was observed between patients with and without reduction of the basal insulin dose. The combination therapy improved glycemic control and patient satisfaction regarding hyperglycemia. Nevertheless, adequate attention to ketosis is crucial.

Relative low muscle mass and muscle strength is associated with the prevalence of metabolic syndrome in patients with type 2 diabetes.

This cross-sectional study investigated the association of metabolic syndrome (MetS) with sarcopenia defined by absolute low muscle mass (aLMM) and absolute low muscle strength (aLMS), or sarcopenia defined by relative low muscle mass (rLMM) and relative low muscle strength (rLMS). The cut-off values for men and women were as follows: aLMM, appendicular muscle mass in kg/height|2 was <7.0 kg/m|2 and <5.7 kg/m|2; rLMM, appendicular muscle mass/body weight ×100 was <28.64% and <24.12%; aLMS, handgrip strength was <28 kg and <18 kg; and rLMS, handgrip strength/body weight ×100 was 51.26% and 35.38%. Among 207 men and 164 women, 41.5% men and 57.3% women had MetS, 14.0% men and 6.1% women had sarcopenia as defined by aLMM and aLMS, and 14.0% men and 22.0% women had sarcopenia defined by rLMM and rLMS. Compared with non-sarcopenia, adjusted OR of sarcopenia defined by aLMM and aLMS for the prevalence of MetS was 0.79 (95% CI 0.38-1.67), whereas that of sarcopenia defined by rLMM and rLMS for the prevalence of MetS was 20.6 (95% CI 7.81-54.3). Sarcopenia defined by rLMM and rLMS was associated with the risk of prevalence of MetS, whereas sarcopenia defined by aLMM and aLMS was not.

Brazilian green propolis improves gut microbiota dysbiosis and protects against sarcopenic obesity.

INTRODUCTION: Brazilian green propolis is an important honeybee product that is considered beneficial for health. Here, we examined the therapeutic potential of dietary supplementation with propolis against sarcopenic obesity using Db/Db mice. METHODS: Db/m mice fed a normal diet alone and Db/Db mice fed normal diet alone, or supplemented with different amounts of propolis (0.08, 0.4 and 2%), were examined for effects on sarcopenic obesity. RESULTS: Propolis improved the glucose tolerance (P < 0.001), increased the grip strength (P < 0.001) and the weight of soleus (P = 0.006) and plantaris muscles (P = 0.008). Moreover, propolis improved the non-alcoholic fatty liver disease activity score (P < 0.001) and decreased the expression of genes related to inflammation, liver fibrosis and fatty acid metabolism. Propolis decreased the accumulation of saturated fatty acids in the liver and increased their excretion in faeces. With regard to the innate immunity, propolis decreased the ratio of M1 macrophages (P = 0.008) and Type 1 and 3 innate lymphoid cells to CD45-positive cells (P < 0.001) and increased the ratio of M2 macrophages (P = 0.002) and ILC2s (P = 0.007) in the liver. Additionally, propolis decreased the expression of genes related to muscle atrophy and inflammation and the concentration of saturated fatty acids in the soleus muscle. 16S rRNA phylogenetic sequencing revealed that propolis increased the Bacteroidetes/Firmicutes ratio, and the abundance of Butyricicoccus and Acetivibrio genera. Gut microbiota related to the pentose phosphatase pathway and glycerolipid metabolism was more prevalent after the administration of propolis. CONCLUSIONS: This is the first study to demonstrate that propolis can improve sarcopenic obesity by improving dysbiosis due to overeating and provides new insights into diet-microbiota interactions during sarcopenic obesity.

Gut Microbiota Changes by an SGLT2 Inhibitor, Luseogliflozin, Alters Metabolites Compared with Those in a Low Carbohydrate Diet in db/db Mice.

In recent years, sarcopenic obesity has been considered central pathological factors in diabetes. This study aimed to compare the effect of luseogliflozin, a sodium-glucose co-transporter-2 inhibitor (SGLT2i), on sarcopenic obesity in comparison to that of a low-carbohydrate diet (LCD). Twenty-week-old male db/db mice were fed a normal diet (Ctrl), LCD, and normal diet with 0.01% w/w luseogliflozin (SGLT2i) for eight weeks. Skeletal muscle mass and grip strength decreased in the LCD group mice compared to those in the control group, while they increased in the SGLT2i group mice. The amino acid content in the liver, skeletal muscle, and serum were lower in the LCD group than those in the Ctrl group but increased in the SGLT2i group mice. Short-chain fatty acids in rectal feces were lower in the LCD group mice than those in the Ctrl group, whereas they were higher in the SGLT2i group mice. The abundance of Gammaproteobacteria, Enterobacteriaceae, Escherichia, Enterobacterales, and Bacteroides caccae species increased in the LCD group compared to the other two groups, whereas the abundance of Syntrophothermus lipocalidus, Syntrophomonadaceae family, Parabacteroidesdistasonis distasonis, and the genus Anaerotignum increased in the SGLT2i group. Luseogliflozin could prevent sarcopenic obesity by improving amino acid metabolism.

The Association of Salt Intake and Non-alcoholic Fatty Liver Disease in People With Type 2 Diabetes: A Cross-Sectional Study.

Objectives: Non-alcoholic fatty liver disease (NAFLD), which has a close relationship with type 2 diabetes (T2D), is related to salt intake in the general population. In contrast, the relationship between salt intake and the presence of NAFLD in patients with T2D has not been clarified. Methods: Salt intake (g/day) was assessed using urinary sodium excretion, and a high salt intake was defined as an intake greater than the median amount of 9.5 g/day. Hepatic steatosis index (HSI) ≥ 36 points was used to diagnosed NAFLD. Odds ratios of high salt intake to the presence of NAFLD were evaluated by logistic regression analysis. Results: The frequency of NAFLD was 36.5% in 310 patients with T2D (66.7 ± 10.7 years old and 148 men). The patients with high salt intake had a higher body mass index (25.0 ± 4.0 vs. 23.4 ± 3.8 kg/m2, p < 0.001) than those with low salt intake. HSI in patients with high salt intake was higher than that in patients with low salt intake (36.2 ± 6.2 vs. 34.3 ± 5.5 points, p = 0.005). In addition, the presence of NALFD in patients with high salt intake was higher than that in patients with low salt intake (44.5% vs. 28.4%, p = 0.005). High salt intake was associated with the prevalence of NAFLD [adjusted odds ratio, 1.76 (95% confidence interval: 1.02-3.03), p = 0.043]. Conclusion: This cross-sectional study revealed that salt intake is related to the prevalence of NAFLD in patients with T2D.

Household Income Is Related to Dietary Fiber Intake and Dietary Acid Load in People with Type 2 Diabetes: A Cross-Sectional Study.

Household income was related to habitual dietary intake in general Japanese people. This cross-sectional study investigated the relationship between household income and habitual dietary intake in people with type 2 diabetes mellitus (T2DM). Household income was evaluated using a self-reported questionnaire and categorized into high and low household income. Nutritional status was assessed using a brief-type self-administered diet history questionnaire. Among 128 men and 73 women, the proportions of participants with low household income were 67.2% (n = 86/128) in men and 83.6% (n = 61/73) in women. Dietary fiber intake (11.3 ± 4.2 vs. 13.8 ± 6.0 g/day, p = 0.006) was lower, and dietary acid load, net endogenous aid production score (NEAP) (51.7 ± 10.5 vs. 46.8 ± 10.4 mEq/day, p = 0.014) and potential renal acid load score (PRAL) (9.5 ± 10.7 vs. 3.7 ± 14.1 mEq/day, p = 0.011) were higher in men with low household income than in those without. Multivariable linear regression analyses demonstrated that log (dietary fiber intake) in men with low household income was lower than that in those with high household income after adjusting for covariates (2.35 [2.26−2.44] vs. 2.52 [2.41−2.62], p = 0.010). Furthermore, NEAP (54.6 [51.7−57.4] vs. 45.8 [42.5−49.2], p <0.001) in men with low household income were higher than in those with high household income after adjusting for covariates. Contrastingly, household income was not related to diet quality in women. This study showed that household income was related to dietary fiber intake and dietary acid load in men but not in women.

Impact of Eating Speed on Muscle Mass in Older Patients With Type 2 Diabetes: A Prospective Study of KAMOGAWA-DM Cohort.

Background and Aims: Maintenance of muscle mass is important for sarcopenia prevention. However, the effect of eating speed, especially fast, normal, or slow speed, on muscle mass changes remains unclear. Therefore, the purpose of this prospective study was to investigate the effect of eating speed on muscle mass changes in patients with type 2 diabetes (T2DM). Methods: This study included 284 patients with T2DM. Based on a self-reported questionnaire, participants were classified into three groups: fast-, normal-, and slow-speed eating. Muscle mass was assessed using a multifrequency impedance body composition analyzer, and skeletal muscle mass (SMI) decrease (kg/m2/year) was defined as [baseline SMI (kg/m2)-follow-up SMI (kg/m2)] ÷ follow-up duration (year). The rate of SMI decrease (%) was defined as [SMI decrease (kg/m2/year) ÷ baseline SMI (kg/m2)] × 100. Results: The proportions of patients with fast-, normal-, and slow-speed eating were, respectively, 50.5%, 42.9%, and 6.6% among those aged <65 years and 40.4%, 38.3%, and 21.3% among those aged ≥65 years. In patients aged ≥65 years, the rate of SMI decrease in the normal (0.85 [95% confidence interval, CI: -0.66 to 2.35]) and slow (0.93 [95% CI -0.61 to 2.46]) speed eating groups was higher than that in the fast speed eating group (-1.08 [95% CI -2.52 to 0.36]). On the contrary, there was no difference in the rate of SMI decrease among the groups in patients aged <65 years. Compared with slow speed eating, the adjusted odds ratios of incident muscle loss [defined as rate of SMI decrease (%) ≥0.5%] due to fast- and normal-speed eating were 0.42 (95% CI 0.18 to 0.98) and 0.82 (95% CI 0.36 to 2.03), respectively. Conclusion: Slow-speed eating is associated with a higher risk of muscle mass loss in older patients with T2DM.

Inulin reduces visceral adipose tissue mass and improves glucose tolerance through altering gut metabolites.

AIM: Inulin, a soluble dietary fiber, is a source of energy for the host while the metabolites, such as short-chain fatty acids (SCFAs), produced in the gut through bacterial fermentation exerts the anti-obesity effect. In this study, we aimed to apply a metabolomics approach and clarify the role of this soluble dietary fiber on glucose and lipid metabolism under the calorie-matched condition. MATERIALS AND METHODS: Eight-week-old male C57BL/6J mice were fed a high-fat/high-sucrose based diet containing maltodextrin or inulin for 12 weeks through calorie-matched pair feeding. We evaluated glucose tolerance, and energy expenditure using indirect calorimetry, comprehensive metabolites in the content of jejunum, feces, and portal vein serum using gas chromatography-mass spectrometry, and histological changes in the adipose tissue. RESULTS: The inulin group exhibited reduced visceral adipose tissue and smaller size of visceral adipocyte. It also exhibited improved glucose tolerance and an increase in energy expenditure. Reflecting the results of fermentation, the metabolomics analysis revealed an increase in the succinic acid and SCFA contents in both feces and portal vein serum in the inulin group. CONCLUSIONS: Inulin altered the gut metabolites and reduced visceral adipose tissue, thereby resulting in improved glucose tolerance.