Low-carbohydrate diets in East Asians with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

AIMS: Despite the reported success of low-carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of low-carbohydrate diets on glycemic control in East Asian adults. MATERIALS AND METHODS: We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low-carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low-carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile. RESULTS: Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low-carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low. CONCLUSIONS: Low-carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months.

Associations between anthropometric indices as complementary predictors and incidence of type 2 diabetes; Panasonic Cohort Study 21.

AIMS: To compare the predictive abilities of body mass index (BMI), waist circumference (WC), waist-corrected BMI (wBMI), a body shape index (ABSI), and waist-to-height ratio (WHtR) for the incidence of type 2 diabetes and determine the practical cut-off values for the Japanese population. METHODS: This study used data from 155,623 participants who had medical checkups with Panasonic Corporation between 2008 and 2021. Predictive abilities of anthropometric indices were evaluated at 13 years using time-dependent receiver operating characteristic (ROC) curve analyses. RESULTS: 8,800 developed type 2 diabetes during the study period. The area under the ROC curve for the WHtR was high (0.717, 95 % confidence interval [CI]: 0.710-0.724), with cut-off value of 0.497 in men, while those for wBMI (0.829, 95 % CI: 0.808-0.848) and WHtR (0.826, 95 % CI: 0.806-0.845) were high in women, with cut-off values of 18.6 kg/m and 0.510, respectively. It was also showed WHtR was the most effective in men, while WHtR and wBMI outperformed WC and were comparable to BMI in women for predicting type 2 diabetes. CONCLUSIONS: WHtR demonstrated superior effectiveness in predicting type 2 diabetes in men, while both WHtR and wBMI showed higher effectiveness than WC and were almost equivalent to BMI in women.

Effect of Isoflavone on Muscle Atrophy in Ovariectomized Mice.

BACKGROUND: Sarcopenia, characterized by muscle mass decline due to aging or other causes, is exacerbated by decreased estrogen levels after menopause in women. Isoflavones, a class of flavonoids acting on estrogen receptors, may have beneficial effects on metabolic disorders. We examined these effects in ovariectomized mice fed a high-fat, high-sucrose diet (HFHSD). METHODS: At 7 weeks old, female C57BL6/J mice (18-20 g, n = 12) underwent bilateral ovariectomy (OVX), and were then fed a high-fat, high-sucrose diet starting at 8 weeks of age. Half of the mice received isoflavone water (0.1%). Metabolic analyses, including glucose and insulin tolerance tests, were conducted. Muscle analysis involved grip strength assays, next-generation sequencing, quantitative RT-PCR, and western blotting of skeletal muscle after euthanizing the mice at 14 weeks old. Additionally, 16S rRNA gene sequence analysis of the gut microbiota was performed. RESULTS: The results demonstrated that isoflavone administration did not affect body weight, glucose tolerance, or lipid metabolism. In contrast, isoflavone-treated mice had higher grip strength. Gene expression analysis of the soleus muscle revealed decreased Trim63 expression, and western blotting showed inactivation of muscle-specific RING finger protein 1 in isoflavone-treated mice. Gut microbiota analysis indicated higher Bacteroidetes and lower Firmicutes abundance in the isoflavone group, along with increased microbiota diversity. Gene sets related to TNF-α signaling via NF-κB and unfolded protein response were negatively associated with isoflavones. CONCLUSIONS: Isoflavone intake alters gut microbiota and increases muscle strength, suggesting a potential role in improving sarcopenia in menopausal women.

Daidzein Inhibits Muscle Atrophy by Suppressing Inflammatory Cytokine- and Muscle Atrophy-Related Gene Expression.

BACKGROUND: Sarcopenic obesity, which is associated with a poorer prognosis than that of sarcopenia alone, may be positively affected by soy isoflavones, known inhibitors of muscle atrophy. Herein, we hypothesize that these compounds may prevent sarcopenic obesity by upregulating the gut metabolites with anti-inflammatory effects. METHODS: To explore the effects of soy isoflavones on sarcopenic obesity and its mechanisms, we employed both in vivo and in vitro experiments. Mice were fed a high-fat, high-sucrose diet with or without soy isoflavone supplementation. Additionally, the mouse C2C12 myotube cells were treated with palmitic acid and daidzein in vitro. RESULTS: The isoflavone considerably reduced muscle atrophy and the expression of the muscle atrophy genes in the treated group compared to the control group (Fbxo32, p = 0.0012; Trim63, p < 0.0001; Foxo1, p < 0.0001; Tnfa, p = 0.1343). Elevated levels of daidzein were found in the muscles and feces of the experimental group compared to the control group (feces, p = 0.0122; muscle, p = 0.0020). The real-time PCR results demonstrated that the daidzein decreased the expression of the palmitate-induced inflammation and muscle atrophy genes in the C2C12 myotube cells (Tnfa, p = 0.0201; Il6, p = 0.0008; Fbxo32, p < 0.0001; Hdac4, p = 0.0002; Trim63, p = 0.0114; Foxo1, p < 0.0001). Additionally, it reduced the palmitate-induced protein expression related to the muscle atrophy in the C2C12 myotube cells (Foxo1, p = 0.0078; MuRF1, p = 0.0119). CONCLUSIONS: The daidzein suppressed inflammatory cytokine- and muscle atrophy-related gene expression in the C2C12 myotubes, thereby inhibiting muscle atrophy.

Multicenter, open label, randomized controlled superiority trial for availability to reduce nocturnal urination frequency: The TOP-STAR study.

AIM: Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co-transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. MATERIALS AND METHODS: This multicenter, open-label, randomized, parallel-group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half-life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. RESULTS: At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time-shift effect of the short half-life tofogliflozin and salt restriction on urinary time. CONCLUSIONS: The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half-life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

Efficacy of long-term low carbohydrate diets for patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS/INTRODUCTION: Efficacy of long-term low-carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long-term LCD and glycemic control in individuals with type 2 diabetes. MATERIALS AND METHODS: We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long-term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and weight between long-term LCD and control groups. RESULTS: Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long-term LCD and control diets (standardized mean difference -0.11, 95% confidence interval -0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low-density lipoprotein cholesterol between long-term LCD and control diets. However, long-term LCD were associated with greater elevation in high-density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04-0.41; P = 0.02) and decrease in triglyceride (standardized mean difference -0.19; 95% confidence interval -0.37 to 0.02; P = 0.03) than that in control diets. CONCLUSIONS: Our findings suggest efficacy of long-term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long-term LCD for glycemic control in the individuals.

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.

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.

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.

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.

Changes in glycemic control and skeletal muscle mass indices after dapagliflozin treatment in individuals with type 1 diabetes mellitus.

AIMS/INTRODUCTION: Dapagliflozin is used for individuals with type 1 diabetes, although the effect of this medication on skeletal muscle mass is not well established. In addition, there are few studies examining the effects of good glycemic control on skeletal muscle mass in type 1 diabetes patients. We investigated changes in glycemic control and skeletal muscle mass with dapagliflozin in individuals with type 1 diabetes, and the association between these changes. MATERIALS AND METHODS: This was a post-hoc analysis of a multicenter, open-label, non-randomized, prospective, interventional study in individuals with type 1 diabetes. The participants received dapagliflozin at 5 mg/day for 4 weeks, and were reviewed before and after treatment. Weight- and height-corrected appendicular skeletal muscle mass (ASM) were calculated as indices of skeletal muscle mass using bioelectrical impedance analysis. RESULTS: A total of 36 individuals were included in the analysis. After the 4 weeks of dapagliflozin treatment, ASM/height2 decreased in the body mass index <23 group (P = 0.004). ASM / weight decreased in all men aged >60 years. The change in ASM / weight (%) was negatively correlated with the change in glycated hemoglobin (%;P = 0.023). The change in ASM / height2 (kg/m2 ) was also positively correlated with the change in time within the glucose range of 70-180 mg/dL (P = 0.036). CONCLUSION: Dapagliflozin treatment of individuals with type 1 diabetes, particularly non-obese individuals and older men, might result in loss of skeletal muscle mass. However, good glycemic control during treatment might prevent the onset and progression of sarcopenia.

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.

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.

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.

Effect of Activation Methods of Molecular Sieves on Ketimine Synthesis.

Although the use of molecular sieves for imine synthesis is a common protocol, there have been no comprehensive studies on heat-drying methods. This can be crucial for reproducibility. It was found that molecular sieve 5A dried at 160 °C for 5 h under vacuum efficiently promoted the condensation of various ketones and amines to afford even relatively bulky ketimines. Several control experiments and analyses revealed that only a small amount of Brønsted acid sites was important for the activity, rather than dehydration ability. Other types of molecular sieves could be utilized for the reaction after treatment with water followed by heat drying. A continuous-flow acetalization reaction of alcohols using the activated molecular sieve 5A was also demonstrated.

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.