Metabolic dysfunction-associated steatotic liver disease: A superior predictor for incident type 2 diabetes over traditional criteria - NAGALA study.

AIMS/INTRODUCTION: The 2023 Delphi consensus recommended the use of new term, metabolic dysfunction-associated steatotic liver disease (MASLD), aiming conceptual shift from the conventional non-alcoholic fatty liver disease (NAFLD). The association between NAFLD and type 2 diabetes mellitus (T2DM) development is well known. This study aimed to examine the correlation between MASLD and T2DM development, comparing their utility as predictors. MATERIALS AND METHODS: This retrospective cohort study obtained data from a medical health checkup program conducted at Asahi University Hospital, Japan, between 2004 and 2021. Logistic regression analysis was used to assess the association between MASLD and incident T2DM over 5 years. To compare the predictive utility of NAFLD and MASLD, receiver operating characteristic curves were drawn, followed by area under the curve (AUC) comparisons. RESULTS: In total, 15,039 participants (59.6% males; median [interquartile range {IQR}] age, 44 [38, 50] years) were included. Out of 2,682 participants meeting the criteria for MASLD, 234 individuals (8.7%) developed T2DM. Multivariate analysis revealed a significantly elevated risk of T2DM in MASLD compared with the reference healthy group (without steatotic liver disease or cardiometabolic risk), presenting an OR of 127.00 (95% CI 40.40-399.00, P < 0.001). The concordance rate of diagnosis between NAFLD and MASLD was 98.7%. The AUC values were 0.799 for NAFLD and 0.807 for MASLD, respectively. Comparative analysis of the AUC showed a statistical difference between NAFLD and MASLD (P < 0.001). CONCLUSIONS: MASLD was shown to be a significant risk factor for incident T2DM, exhibiting a potentially higher predictive capacity than conventional NAFLD.

A Study of Small Intestinal Epigenomic Changes Induced by Royal Jelly.

This study explores the impact of royal jelly (RJ) on small intestinal epigenomic changes. RJ, produced by honeybees, is known for its effects on metabolic diseases. The hypothesis is that RJ induces epigenomic modifications in small intestinal epithelial cells, affecting gene expression and contributing to metabolic health. Male db/m and db/db mice were used to examine RJ's effects through mRNA sequencing and CUT&Tag methods. This study focused on histone modifications and gene expression changes, with statistical significance set at p < 0.05. RJ administration improved insulin sensitivity and lipid metabolism without affecting body weight. GO and KEGG pathway analyses showed significant enrichment in metabolic processes, cellular components, and molecular functions. RJ altered histone modifications, increasing H3K27me3 and decreasing H3K23Ac in genes associated with the G2M checkpoint. These genes, including Smc2, Mcm3, Ccnd1, Rasal2, Mcm6, and Mad2l1, are linked to cancer progression and metabolic regulation. RJ induces beneficial epigenomic changes in small intestinal epithelial cells, improving metabolic health and reducing cancer-associated gene expression. These findings highlight RJ's potential as a therapeutic agent for metabolic disorders. Further research is needed to fully understand the mechanisms behind these effects and their implications for human health.

A multi-omics approach to overeating and inactivity-induced muscle atrophy in db/db mice.

BACKGROUND: Overeating and inactivity are associated with type 2 diabetes. This study aimed to investigate its pathological basis using integrated omics and db/db/mice, a model representing this condition. METHODS: The study involved housing 8-week-old db/m and db/db mice for 8 weeks. Various analyses were conducted, including gene expression in skeletal muscle and small intestine using next-generation sequencing; cytokine arrays of serum; assessment of metabolites in skeletal muscle, stool, and serum; and analysis of the gut microbiota. Histone modifications in small intestinal epithelial cells were profiled using CUT&Tag. RESULTS: Compared with db/m mice, db/db mice had 22.4% lower grip strength and approximately five times the visceral fat weight (P < 0.0001). Serum cytokine arrays showed a 2.8-fold relative concentration of VEGF-A in db/db mice (P < 0.0001) and lower concentrations of several other cytokines. mRNA sequencing revealed downregulation of Myh expression in skeletal muscle, upregulation of lipid and glucose transporters, and downregulation of amino acid transporters in the small intestine of db/db/mice. The concentrations of saturated fatty acids in skeletal muscle were significantly higher, and the levels of essential amino acids were lower in db/db mice. Analysis of the gut microbiota, 16S rRNA sequencing, revealed lower levels of the phylum Bacteroidetes (59.7% vs. 44.9%) and higher levels of the phylum Firmicutes (20.9% vs. 31.4%) in db/db mice (P = 0.003). The integrated signal of histone modifications of lipid and glucose transporters was higher, while the integrated signal of histone modifications of amino acid transporters was lower in the db/db mice. CONCLUSIONS: The multi-omics approach provided insights into the epigenomic alterations in the small intestine, suggesting their involvement in the pathogenesis of inactivity-induced muscle atrophy in obese mice.

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.

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.

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.

Association of Elevated Serum Branched-chain Amino Acid Levels With Longitudinal Skeletal Muscle Loss.

Context: Branched-chain amino acids (BCAA) are substrates for protein synthesis. Although their intake may contribute to an increase in skeletal muscle mass, elevated serum BCAA levels have been reported to be associated with insulin resistance, potentially resulting in decreased skeletal muscle mass. Objective: This study aimed to explore the association between elevated serum BCAA levels and longitudinal skeletal muscle loss. Design and Setting: A cohort analysis was conducted, in which serum amino acids were analyzed in healthy individuals who underwent a medical health checkup at Kameoka Municipal Hospital (HOZUGAWA study), Japan. Patients: Seventy-one participants (37 men and 34 women) underwent follow-up checkups after the baseline visit. The follow-up duration was 1.2 ± .4 years. Main Outcome Measures: The relationship between fasting baseline serum BCAA levels and lifestyle factors, body composition, blood test results, dietary history, and changes in skeletal muscle mass was evaluated. Results: In both men and women, serum BCAA levels were positively correlated with body weight, body mass index, skeletal muscle mass index (SMI), and serum triglycerides but inversely correlated with serum high-density lipoprotein cholesterol. In men, fasting serum BCAA levels were inversely associated with the rate of change in SMI (adjusted ß = -.529, P = .006), and elevated BCAA levels were independently associated with a longitudinal decrease in skeletal muscle mass (odds ratio: 1.740; 95% confidence interval: 1.023-2.960 per 50 nmol/mL serum BCAAs increase). Conclusion: Increased circulating BCAAs could be an indicator of skeletal muscle loss in men.

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.

The role of chicken eggs in modulating sarcopenic obesity and gut microbiota in db/db mice.

Background: Sarcopenia obesity, in which loss of muscle mass and fat accumulation occur simultaneously, is the pathological basis of type 2 diabetes mellitus. The usefulness of chicken eggs in sarcopenia prevention has been reported in several previous studies. The purpose of this study was to determine the beneficial effects of chicken eggs in the prevention of sarcopenic obesity in db/db mice. Methods: We raised 8-week-old db/db male mice, a model of sarcopenia obesity, for 8 weeks and fed them a diet mixed with dried whole eggs. The fecal microbiota transplant (FMT) group was treated with antibiotics for 2 weeks, starting at 6 weeks of age, followed by FMT twice a week until 16 weeks of age. Results: Eggs administered to db/db mice showed increased grip strength (p = 0.022) and muscle mass (p = 0.013), decreased visceral fat mass (p = 0.005), and significantly increased physical activity (p < 0.001). The FMT group of egg-fed mice showed a significant improvement in glucose intolerance and sarcopenic obesity. Sequencing of gene expression in the small intestine showed that the gene expression of amino acid transporters such as Slc6a18, Slc6a19, and Slc38a6 was increased in egg-fed mice. 16S rRNA sequencing of the gut microbiota showed an increase in the genus Vampirovibrio in both the egg-fed and FMT groups compared to that in egg-fed mice. Conclusion: The results of this study indicate that egg consumption not only increases the intake of amino acids and other nutrients but also alters the intestinal microbiota and increases amino acid absorption from the intestinal tract, suggesting that eggs might contribute to the ameliorative mechanism of sarcopenic obesity.

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.

U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.

Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.

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.

The Impact of Nutritional Markers and Dietary Habits on the Bioimpedance Phase Angle in Older Individuals.

Low phase angle (PhA), as determined via bioelectrical impedance analysis, reflects unhealthy aging and mortality. In this study, we assessed whether nutritional status, including serum nutritional markers and dietary habits, is related to PhA in older individuals. We recruited 212 participants (aged ≥ 65 years) who underwent medical health checkups. PhA was measured using a multi-frequency impedance body composition analyzer. Habitual food and nutrient intake was evaluated using a brief, self-administered diet history questionnaire. Low PhA values were defined as ≤4.95 in males and ≤4.35 in females. Males with low PhA had poor exercise habits (p = 0.0429) and a lower body mass index (p = 0.0024). PhA was significantly correlated with serum cholinesterase levels, a nutritional status marker (r = 0.3313, p = 0.0004 in males; r = 0.3221, p = 0.0070 in females). The low-PhA group had significantly lower total energy and carbohydrate intake per ideal body weight (IBW) than the high-PhA group in males (total energy intake:30.2 ± 9.8 and 34.5 ± 9.3 kcal/kg/day, p = 0.0307; carbohydrate intake:15.2 ± 4.9 and 18.0 ± 5.8 kcal/kg/day, p = 0.0157). Total energy intake per IBW (adjusted odds ratio [95% confidence interval], 0.94 [0.89-1.00] per 1 kcal/kg/day increase) was independently associated with a low PhA in males. Our study revealed that lower total energy intake independently impacted low PhA in older males.

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.

Diet, exercise, and pharmacotherapy for sarcopenia in people with diabetes.

Diabetes prevalence is increasing rapidly in older people, and sarcopenia is prevalent as a novel complication, particularly in patients with type 2 diabetes mellitus (T2DM). Therefore, sarcopenia prevention and treatment in these people is necessary. Diabetes accelerates sarcopenia through several mechanisms, such as hyperglycemia, chronic inflammation and oxidative stress. The effects of diet, exercise, and pharmacotherapy on sarcopenia in patients with T2DM need to be considered. In diet, low intake of energy, protein, vitamin D, and ω-3 fatty acid are associated with sarcopenia risk. In exercises, although intervention studies in people, especially older and non-obese patients with diabetes, are few, accumulating evidence shows the usefulness of exercise, particularly resistance exercise for muscle mass and strength, and aerobic exercise for physical performance in sarcopenia. In pharmacotherapy, certain classes of anti-diabetes compounds have possibility of preventing sarcopenia. However, much data on diet, exercise, and pharmacotherapy were obtained in obese and non-elderly patients with T2DM, demanding actual clinical data on non-obese and older patients with diabetes.