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Abstract 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

ABSTRACT 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.

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.

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.

Abstract 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

Abstract 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.

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.

Abstract 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

Abstract 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.

ABSTRACT Aims/Introduction Metformin is associated with the risk of gastrointestinal complications, and probiotic Bifidobacterium bifidum G9‐1 (BBG9‐1) can improve the symptoms of diarrhea. This study aimed to clarify the effects of probiotic BBG9‐1 on the gastrointestinal symptoms of type 2 diabetes mellitus patients using metformin. Materials and methods In this open‐label single‐arm exploratory study, 40 patients (mean age 64.0 ± 9.4 years) were given probiotic BBG9‐1 for 10 weeks. Changes in the gastrointestinal symptom rating scale total score, which was the primary end‐point, gastrointestinal symptom rating scale subscale scores, glycated hemoglobin levels and gut microbiota after the administration of probiotic BBG9‐1 were evaluated by the Student's t‐test. Results The gastrointestinal symptom rating scale total score significantly improved (from 2.02 ± 0.51 to 1.59 ± 0.43, change, −0.43 ± 0.49, P

Abstract Background Diabetes mellitus increases the excretion of urinary glucose from the renal glomeruli due to elevated blood glucose levels. In the renal tubules, SGLT2 is expressed and reabsorbs the excreted urinary glucose. In the pathogenesis of diabetes mellitus, glucose reabsorption by SGLT2 is increased, and SGLT2 inhibitors improve hyperglycaemia by inhibiting this reabsorption. When urinary glucose excretion is enhanced, glucose supply to skeletal muscle may be insufficient and muscle protein catabolism may be accelerated. On the other hand, SGLT2 inhibitors not only ameliorate hyperglycaemia but also improve fatty acid metabolism in muscle, which may prevent muscle atrophy. Methods Eight‐week‐old male db/m mice or db/db mice were fed a standard diet with or without the SGLT2i luseogliflozin (0.01% w/w in chow) for 8 weeks. Mice were sacrificed at 16 weeks of age, and skeletal muscle and serum lipidomes, as well as skeletal muscle transcriptome, were analysed. Results Administration of SGLT2i led to not only decreased visceral fat accumulation (P = 0.004) but also increased soleus muscle weight (P = 0.010) and grip strength (P = 0.0001). The levels of saturated fatty acids, especially palmitic acid, decreased in both muscles (P = 0.017) and sera (P = 0.041) upon administration of SGLT2i, while the content of monosaturated fatty acids, especially oleic acid, increased in both muscle (P

ObjectivesNon-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.MethodsSalt 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.ResultsThe 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].ConclusionThis cross-sectional study revealed that salt intake is related to the prevalence of NAFLD in patients with T2D.

Background and AimsMaintenance 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).MethodsThis 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.ResultsThe proportions of patients with fast–, normal–, and slow–speed eating were, respectively, 50.5%, 42.9%, and 6.6% among those aged

Abstract Aims/Introduction Postprandial hypotension (PPH) refers to a decrease in systolic blood pressure by ≥20 or to

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.

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.

Abstract Background Diabetic nephropathy, a major complication of diabetes, is the primary risk factor for dialysis, cardiovascular diseases, and mortality. Dietary fatty acids (FAs) have been revealed to be related with cardiovascular diseases in the general populations. The aim of this study was to investigate the association of circulating FAs with diabetic nephropathy. Methods In this cross-sectional study, 190 Japanese patients with type 2 diabetes were included. Circulating FAs were measured by gas chromatography-mass spectrometry. Spearman rank correlation coefficients were used to investigate the association between the logarithm of FAs and the logarithm of urinary albumin excretion (UAE). We have performed logistic regression analysis to determine the effect of FAs on the presence of macroalbuminuria, defined as UAE value ≥300 mg/g creatinine. Results Mean age, body mass index, and duration of diabetes were 62.7 ± 12.1 years, 25.0 ± 4.5 kg/m2, and 9.8 ± 8.7 years, respectively. In total, 26 patients were diagnosed with macroalbuminuria. The logarithm of circulating arachidonic acid (AA) was negatively associated with the logarithm of UAE (r = − 0.221, p = 0.002). Additionally, circulating AA in patients with macroalbuminuria was lower than that in patients without macroalbuminuria (112.3 ± 75.3 mg/day vs. 164.8 ± 66.0 mg/day, p

ObjectivesTo investigate the relationship between dietary fiber intake and skeletal muscle mass, body fat mass, and muscle-to-fat ratio (MFR) among men and women with type 2 diabetes (T2D).MethodsThis cross-sectional study involved 260 men and 200 women with T2D. Percent skeletal muscle mass (%) or percent body fat mass (%) was calculated as (appendicular muscle mass [kg] or body fat mass [kg]/body weight [kg]) × 100. MFR was calculated as appendicular muscle mass divided by body fat mass. Information about dietary fiber intake (g/day) was obtained from a brief-type self-administered diet history questionnaire.ResultsDietary fiber intake was correlated with percent body fat mass (r = –0.163, p = 0.021), percent skeletal muscle mass (r = 0.176, p = 0.013), and MFR (r = 0.157, p = 0.026) in women. However, dietary fiber intake was not correlated with percent body fat mass (r = –0.100, p = 0.108), percent skeletal muscle mass (r = 0.055, p = 0.376), and MFR (r = 0.065, p = 0.295) in men. After adjusting for covariates, dietary fiber intake was correlated with percent body fat mass (β = 0.229, p = 0.009), percent skeletal muscle mass (β = 0.364, p < 0.001), and MFR (β = 0.245, p = 0.006) in women. Further, dietary fiber intake was related to percent skeletal muscle mass (β = 0.221, p = 0.008) and tended to be correlated with percent body fat mass (β = 0.148, p = 0.071) in men.ConclusionDietary fiber intake was correlated with skeletal muscle mass, body fat mass, and MFR among women with T2D.

Background and AimsTo understand the role of microRNAs in muscle atrophy caused by androgen-depletion, we performed microarray analysis of microRNA expression in the skeletal muscles of Sham, orchiectomized (ORX), and androgen-treated ORX mice.MethodsTo clarify role and mechanisms of let-7e-5p in the muscle, the effect of let-7e-5p overexpression or knockdown on the expression of myosin heavy chain, glucose uptake, and mitochondrial function was investigated in C2C12 myotube cells. Moreover, we examined serum let-7e-5p levels among male subjects with type 2 diabetes.ResultsWe found that the expression of the miRNA, lethal (let)-7e-5p was significantly lower in ORX mice than that in Sham mice (p = 0.027); however, let-7e-5p expression in androgen-treated ORX mice was higher (p = 0.047). Suppression of let-7e-5p significantly upregulated the expression of myosin heavy chain, glucose uptake, and mitochondrial function. Real-time PCR revealed a possible regulation involving let-7e-5p and Igf2bp2 mRNA and protein in C2C12 cells. The serum let-7e-5p levels were significantly lower, which might be in compensation, in subjects with decreased muscle mass compared to subjects without decreased muscle mass. Let-7e-5p downregulates the expression of Igf2bp2 in myotube cells and inhibits the growth of the myosin heavy chain.ConclusionsBased on our study, serum level of let-7e-5p may be used as a potential diagnostic marker for muscle atrophy.

BackgroundSarcopenia has reportedly been associated with increased risk of mortality in general populations. However, few studies have investigated the association between sarcopenia and mortality in older people with type 2 diabetes mellitus (T2D). This study aimed to investigate the effect of sarcopenia on incident all-cause mortality in older people with T2D.MethodsLow muscle strength were set at handgrip strength

Background and aimsGroup 2 innate lymphoid cells (ILC2s) have been implicated in the regulation of metabolic homeostasis in mice.MethodsIn this study, the role of ILC2s in white adipose tissue (WAT) was investigated using ST2, an IL-33 receptor that is expressed on ILC2 knockout mice.ResultsThe deficiency of ST2 decreased ILC2s in WAT, whereas ex-ILC2, which acquired group 1 innate lymphoid cell (ILC1)-like traits, was increased. This led to significant metabolic disorders such as visceral fat obesity, decreased browning in WAT, reduction of energy metabolism, and impaired glucose tolerance, compared to wild type (WT) mice. Those metabolic abnormalities of ST2-knockout (ST2KO) mice were not ameliorated by IL-33 administration, but impaired glucose tolerance and visceral fat obesity were significantly improved by transplantation of ILCs from the bone marrow of WT mice. The relative expression of Cd36 in WAT increased due to the deficiency of ST2, and the storage of saturated fatty acids in WAT of ST2KO mice was significantly higher than that of WT mice. Moreover, saturated fatty acids aggravated the chronic inflammation in adipocytes, promoted the differentiation of M1-like macrophages, and inhibited that of M2-like macrophages.ConclusionsOur results indicated that ILC2 regulates diet-induced obesity and chronic inflammation through the regulation of saturated fatty acid absorption in visceral adipose tissue.

Abstract Whole‐exome sequencing is a new technology. We used it to explore the gene responsible for early‐onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188‐31G>A mutation in the proband – a 43‐year‐old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes.

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

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.

Background and AimsMany nutritional and epidemiological studies have shown that high consumption of trans fatty acids can cause several adverse effects on human health, including cardiovascular disease, diabetes, and cancer. In the present study, we investigated the effect of trans fatty acids on innate immunity in the gut by observing mice fed with a diet high in trans fatty acids, which have been reported to cause dysbiosis.MethodsWe used C57BL6/J mice and fed them with normal diet (ND) or high-fat, high-sucrose diet (HFHSD) or high-trans fatty acid, high-sucrose diet (HTHSD) for 12 weeks. 16S rRNA gene sequencing was performed on the mice stool samples, in addition to flow cytometry, real-time PCR, and lipidomics analysis of the mice serum and liver samples. RAW264.7 cells were used for the in vitro studies.ResultsMice fed with HTHSD displayed significantly higher blood glucose levels and advanced fatty liver and intestinal inflammation, as compared to mice fed with HFHSD. Furthermore, compared to mice fed with HFHSD, mice fed with HTHSD displayed a significant elevation in the expression of CD36 in the small intestine, along with a reduction in the expression of IL-22. Furthermore, there was a significant increase in the populations of ILC1s and T-bet-positive ILC3s in the lamina propria in mice fed with HTHSD. Finally, the relative abundance of the family Desulfovibrionaceae, which belongs to the phylum Proteobacteria, was significantly higher in mice fed with HFHSD or HTHSD, than in mice fed with ND; between the HFHSD and HTHSD groups, the abundance was slightly higher in the HTHSD group.ConclusionsThis study revealed that compared to saturated fatty acid intake, trans fatty acid intake significantly exacerbated metabolic diseases such as diabetes and fatty liver.

The sequence of complementarity-determining region 3 of the T-cell receptor (TCR) varies widely due to the insertion of random bases during V-(D)-J recombination. In this study, we used single-cell VDJ sequencing using the latest technology, BD Rhapsody, to identify the TCR sequences of autoreactive T-cells characteristic of Japanese type 1 diabetes mellitus (T1DM) and to clarify the pairing of TCR of peripheral blood mononuclear cells from four patients with T1DM at the single-cell level. The expression levels of the TCR alpha variable (TRAV) 17 and TRAV21 in T1DM patients were higher than those in healthy Japanese subjects. Furthermore, the Shannon index of CD8+ T cells and FOXP3+ cells in T1DM patients was lower than that of healthy subjects. The gene expression of PRF1, GZMH, ITGB2, NKG7, CTSW, and CST7 was increased, while the expression of CD4, CD7, CD5, HLA-A, CD27, and IL-32 was decreased in the CD8+ T cells of T1DM patients. The upregulated gene expression was IL4R and TNFRSF4 in FOXP3+ cells of T1DM patients. Overall, these findings demonstrate that TCR diversity and gene expression of CD8+ and FOXP3+ cells are different in patients with T1DM and healthy subjects.

ObjectiveReduction of muscle mass and strength is an important treatment target for patients with type 2 diabetes. Recent studies have reported that high-intensity resistance training improves physical function; however, all patients found it difficult to perform high-intensity resistance training. Radio calisthenics, considered as therapeutic exercises to promote health in Japan, are simple exercises that can be performed regardless of age and help move the muscles and joints of the whole body effectively according to the rhythm of radio. We investigated the efficacy of radio calisthenics for muscle mass in patients with type 2 diabetes in this retrospective cohort study.Research design and methodsA total of 42 hospitalized patients with type 2 diabetes were recruited. The skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). We defined the change of SMI as the difference of SMI between the beginning and end of hospitalization.ResultsAmong 42 patients, 15 (11 men and 4 women) performed radio calisthenics. Body weights of both radio calisthenics exercisers and non-exercisers decreased during hospitalization. The change of SMI was significantly lesser in radio calisthenics exercisers than in non-exercisers (7.1±1.4 to 7.1±1.3, –0.01±0.09 vs 6.8±1.1 to 6.5±1.2, –0.27±0.06 kg/m2, p=0.016). The proportion of decreased SMI was 85.2% (23/27 patients) in non-radio calisthenics exercisers, whereas that in radio calisthenics exercisers was 46.7% (7/15 patients).ConclusionsRadio calisthenics prevent the reduction of skeletal muscle mass. Thus, radio calisthenics can be considered effective for patients with type 2 diabetes.

To determine the relationship between eating speed and the presence of sarcopenia in older patients with type 2 diabetes (T2D), in this cross-sectional study, patient eating speeds were classified as “fast-”, “normal-” and “slow-speed eating.” A multifrequency impedance analyzer was used to evaluate patient body compositions. Sarcopenia was defined as having both low muscle strength, a handgrip strength 2 for men and 2 for women. Among 239 individuals, the frequencies of fast-, normal-, and slow-speed eating were 47.3%, 32.2%, and 20.5%, respectively; and the prevalence of sarcopenia was 15.9%. Patients with a slow eating speed had greater prevalence of low skeletal muscle mass, low muscle strength, and sarcopenia than those with a fast or normal eating speed. After adjusting for covariates, compared to slow eaters, the odds ratio of having sarcopenia among fast- and normal-speed eaters was 0.31 [95% CI: 0.12–0.80] and 0.18 [95% CI: 0.06–0.53], respectively. Having a slow eating speed is associated with a heightened risk of sarcopenia in older patients with T2D.

The aim of this cross-sectional study was to examine the association between the geriatric nutritional risk index (GNRI) and the prevalence of sarcopenia in people with type 2 diabetes (T2DM). Having both low handgrip strength (2 for men and 2 for women) was diagnosed as sarcopenia. GNRI was estimated by the formula as below: GNRI = (1.489 × serum albumin level [g/L]) + (41.7 × [current body weight (kg)/ideal body weight (kg)]). Participants were dichotomized on the basis of their GNRI scores (GNRI < 98, low; or GNRI ≥ 98, high). Among 526 people (301 men and 225 women) with T2DM, the proportions of participants with sarcopenia and low GNRI were 12.7% (n = 67/526) and 5.1% (n = 27/526), respectively. The proportion of sarcopenia in participants with low-GNRI was higher than that with high GNRI (44.4% [n = 12/27] vs. 11.0% [n = 55/499], p < 0.001). The GNRI showed positive correlations with handgrip strength (r = 0.232, p < 0.001) and skeletal muscle mass index (r = 0.514, p < 0.001). Moreover, low GNRI was related to the prevalence of sarcopenia (adjusted odds ratio, 4.88 [95% confidence interval: 1.88–12.7], p = 0.001). The GNRI, as a continuous variable, was also related to the prevalence of sarcopenia (adjusted odds ratio, 0.89 [95% confidence interval: 0.86–0.93], p < 0.001). The present study revealed that low GNRI was related to the prevalence of sarcopenia.

Salt intake is often estimated by the amount of sodium excreted in urine, and miso has been reported to increase it. This cross-sectional study investigated the relationship between obesity and high estimated salt intake with and without habitual miso consumption. Estimates of salt intake (g/day) were calculated using urinary sodium excretion, and a high estimated intake was defined as greater than the median amount of 9.5 g/day. Participants were divided into four groups based on estimated salt intake and miso consumption. Among 300 people, the proportions of obesity were 77.8% (n = 14/18), 40.2% (n = 53/132), 26.0% (n = 33/127), and 34.8% (n = 8/23) in the (+/−), (+/+), (−/+), and (−/−) groups of high estimated salt intake/habitual miso consumption, respectively. Compared with the (+/−) group, the adjusted odds ratios for obesity were 0.07 (95% confidence interval (CI): 0.02–0.26, p < 0.001), 0.16 (95% CI: 0.03–0.76, p = 0.022), and 0.14 (95% CI: 0.04–0.51, p = 0.003) in the (−/+), (−/−), and (+/+) groups, respectively. The presence of obesity was not much higher in people with high estimated salt intake with habitual miso consumption than that in people without. Clinicians should be aware that miso consumption promotes salt excretion, which may lead to an apparently higher estimated salt intake than actual.

The aim of this prospective cohort study was to examine the relationships between the intakes of various vitamins and the loss of muscle mass in older people with type 2 diabetes (T2DM). The change in skeletal muscle mass index (SMI, kg/m2) (kg/m2/year) was defined as follows: (SMI at baseline (kg/m2) − SMI at follow-up (kg/m2))/follow-up period (year). The rate of SMI reduction (%) was calculated as follows (the change in SMI (kg/m2/year)/SMI at baseline (kg/m2)) × 100. The rate of SMI reduction ≥ 1.2% was considered as the loss of muscle mass. Among 197 people with T2DM, 47.2% of them experienced the loss of muscle mass at the 13.7 ± 5.2 month follow-up. Vitamin B1 (0.8 ± 0.3 vs. 0.8 ± 0.3 mg/day, p = 0.031), vitamin B12 (11.2 ± 8.3 vs. 13.4 ± 7.5 μg/day, p = 0.049), and vitamin D (16.5 ± 12.2 vs. 21.6 ± 13.0 μg/day, p = 0.004) intakes in people with the loss of muscle mass were significantly lower than those without. Vitamin D intake was related to the loss of muscle mass after adjusting for sex, age, exercise, alcohol, smoking, body mass index, SMI, glucagon-like peptide-1 agonist, sodium glucose cotransporter-2 inhibitor, insulin, HbA1c, creatinine, energy intake, and protein intake (adjusted odds ratio 0.93, 95% confidence interval: 0.88–0.97, p = 0.003). This study showed that vitamin D intake was related to the loss of muscle mass in older people with T2DM. Vitamin B12 intake tended to be related to the loss of muscle mass, although vitamin A, vitamin B2, vitamin B6, vitamin C, and vitamin E intake were not related.

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.

Background: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. Methods: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. Results: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. Conclusions: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.

Glycemic control, including glycemic variability, is important for the prevention of diabetic vascular complications in patients with type 2 diabetes mellitus (T2DM). There was an association between miso soup intake and insulin resistance. However, the relationship between habitual miso consumption and glycemic control, including glycemic variability, in patients with T2DM remains unknown. We defined people without habitual miso consumption if they did not consume miso soup at all in a day. The average, standard deviation (SD), and coefficient of variation (CV), calculated as CV = (SD/average HbA1c) × 100 (%), of hemoglobin (Hb) A1c levels were evaluated. The proportions of habitual miso consumption of male and female were 88.1% and 82.3%, respectively. The average (7.0 [6.4–7.5] vs. 7.3 [6.8–8.4] %, p = 0.009), SD (0.21 [0.12–0.32] vs. 0.37 [0.20–0.72], p = 0.004), and CV (0.03 [0.02–0.04] vs. 0.05 [0.03–0.09], p = 0.005) of HbA1c levels in female with habitual miso consumption were lower than those of female without. Moreover, habitual miso consumption correlated with average (β = −0.251, p = 0.009), SD (β = −0.175, p = 0.016), and CV (β = −0.185, p = 0.022) of HbA1c levels after adjusting for covariates. However, no association between habitual miso consumption and any glycemic parameters was shown among male. This study clarified the association between habitual miso consumption and good glycemic control, including glycemic variability, in female, but not in male.

Insulin resistance is a risk of sarcopenia, and the presence of sarcopenia is high in patients with type 2 diabetes (T2DM). It has been reported that habitual miso soup consumption was associated with lower insulin resistance. However, the association between habitual miso consumption and the presence of sarcopenia in patients with T2DM, especially sex difference, was unclear. In this cross-sectional study, 192 men and 159 women with T2DM were included. Habitual miso consumption was defined as consuming miso soup regularly. Having both low skeletal muscle mass index (p = 0.018); however, there was no association between habitual miso consumption and the presence of sarcopenia in men. Habitual miso consumption was negatively associated with the presence of sarcopenia in women (adjusted odds ratio (OR), 0.20 (95% confidence interval (CI): 0.06–0.62), p = 0.005) but not in men. This study indicated that habitual miso consumption was associated with the presence of sarcopenia in women but not in men.

Metformin is reported to affect human gut microbiota; however, the nature of this association in Japanese patients with type 2 diabetes mellitus (T2DM) is unknown. We enrolled 31 patients with T2DM who took metformin for the first time in this study. We compared them before and after four weeks of taking metformin. Fecal samples were collected and 16S rDNA sequences were performed to identify the gut microbiota. Blood samples and Gastrointestinal Symptom Rating Scale (GSRS) questionnaire results, denoting gastro-intestinal symptoms, were also collected. In the whole-group analysis, no significant differences were found at the phylum level. In a subgroup of 21 patients that excluding those using medications affecting gut microbiota, there was a significant decrease of the phylum Firmicutes (p = 0.042) and of the ratio of the Firmicutes and Bacteroidetes abundances (p = 0.04) after taking metformin. Changes in abdominal pain (r = −0.56, p = 0.008) and regurgitation (r = −0.53, p = 0.01) were associated with Parabacteroides. Despite there being no direct association with abdominal symptoms, our study revealed that the composition of gut microbiota in Japanese individuals with T2DM partially changed after starting metformin.

BACKGROUND/AIMS: The senescence marker protein-30 (SMP30) is a 34 kDa protein originally identified in rat liver that shows decreased levels with age. Several functional studies using SMP30 knockout (Smp30(Y/-) ) mice established that SMP30 functions as an antioxidant and protects against apoptosis. To address the potential role of SMP30 in nonalcoholic fatty liver disease (NAFLD) pathogenesis, we established Smp30(Y/-) mice on a Lepr(db/db) background (Lepr(db/db)Smp30(Y/-) mice). RESEARCH DESIGN/PRINCIPAL FINDINGS: Male Lepr(db/db)Smp30(Y/-) mice were fed a standard diet (340 kcal/100 g, fat 5.6%) for 16 weeks whereupon the lipid/lipoprotein profiles, hepatic expression of genes related to lipid metabolism and endoplasmic reticulum stress markers were analyzed by HPLC, quantitative RT-PCR and western blotting, respectively. Changes in the liver at a histological level were also investigated. The amount of SMP30 mRNA and protein in livers was decreased in Lepr(db/db)Smp30(Y/+) mice compared with Lepr(db/+)Smp30(Y/+) mice. Compared with Lepr(db/db)Smp30(Y/+) mice, 24 week old Lepr(db/db)Smp30(Y/-) mice showed: i) increased small dense LDL-cho and decreased HDL-cho levels; ii) fatty liver accompanied by numerous inflammatory cells and increased oxidative stress; iii) decreased mRNA expression of genes involved in fatty acid oxidation (PPARα) and lipoprotein uptake (LDLR and VLDLR) but increased CD36 levels; and iv) increased endoplasmic reticulum stress. CONCLUSION: Our data strongly suggest that SMP30 is closely associated with NAFLD pathogenesis, and might be a possible therapeutic target for NAFLD.