Liver autophagy-induced valine and leucine in plasma reflect the metabolic effect of sodium glucose co-transporter 2 inhibitor dapagliflozin.

BACKGROUND: Sodium glucose co-transporter 2 (SGLT2) inhibitors are anti-diabetic drugs for type 2 diabetes that lower blood glucose levels and body weight. It is of special interest that SGLT2 inhibitors also improve liver metabolism and fatty liver. Liver is an important organ in regulation of energy metabolism, but the metabolic action of SGLT inhibitors in liver remains unclear. METHODS: We investigated the factors associated with the beneficial effects of dapagliflozin, a SGLT2 inhibitor, in the liver after confirming its glucose-lowering and weight loss effects using an obesity and diabetes mouse model. We also performed clinical study of patients with type 2 diabetes to explore candidate biomarkers that reflect the beneficial action of dapagliflozin in the liver. FINDINGS: In animal study, dapagliflozin induced autophagy in the liver (LC3-II to LC3-I expression ratio: P < 0·05 vs. control), and valine and leucine levels were increased in plasma (P < 0·01 vs. control) as well as in liver (P < 0·05 vs. control). Thus, increased plasma valine and leucine levels are potential biomarkers for improved liver metabolism. Clinical study found that valine and leucine levels were markedly higher in patients treated with dapagliflozin (valine: P < 0·05 vs. control, leucine: P < 0·01 vs. control) than those not treated after one week intervention. INTERPRETATION: Dapagliflozin improves liver metabolism via hepatic autophagy, and plasma valine and leucine levels may reflect its metabolic effect. FUNDING: AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan Society for the Promotion of Science (JSPS), Japan Agency for Medical Research and Development (AMED), Novo Nordisk Pharma Ltd., and Japan Foundation for Applied Enzymology, and MSD Life Science Foundation International.

Novel psychosocial factor involved in diabetes self-care in the Japanese cultural context.

AIMS/INTRODUCTION: Recent evidence shows that cultural context can influence the management of diabetes mellitus. The aim of the present study was to examine the relationship between interdependence, which is valued in the Eastern cultural context, and diabetes self-care behavior in Japanese patients with type 2 diabetes mellitus. MATERIAL AND METHODS: We carried out a cross-sectional survey of 161 Japanese adults with type 2 diabetes mellitus using well-established questionnaires. The association of an interdependent tendency with diabetes self-care activities was analyzed using multiple regression analysis. RESULTS: Diabetes self-care activities had a negative correlation with interdependent tendency (r = -0.16, P = 0.047), and they had positive correlations with age (r = 0.42, P < 0.001), emotional support (r = 0.25, P = 0.001) and diabetes self-care support (r = 0.36, P < 0.001). When patients were divided into two groups at the median age (68 years), multiple regressions showed that interdependent tendency (ß = -0.20, P = 0.048), male sex (ß = -0.24, P = 0.023), emotional support (ß = 0.22, P = 0.028) and diabetes self-care support (ß = 0.39, P < 0.001) were significant determinants of diabetes self-care activities only in the younger group. CONCLUSIONS: Interdependence might influence diabetes self-care behavior, and intervention focusing on support from close others might lead patients to more successful care among Japanese adults with type 2 diabetes mellitus, especially those aged <68 years.

Reduction in Gastroesophageal Reflux Disease Symptoms Is Associated with Miso Soup Intake in a Population-Based Cross-Sectional Study: The Nagahama Study.

Dietary habits and lifestyles are considered to affect the frequency of epigastric symptoms. In our previous study, we found that three amino acids in Japanese broth promoted gastric emptying. We hypothesized that a higher consumption of miso soup which was mainly composed of Japanese broth and miso paste would be associated with a lower frequency of epigastric symptoms. We conducted a cross-sectional study of the association between frequency of miso soup intake and reflux or dyspepsia symptoms in a general Japanese population. Sixteen items of dietary habits were assessed using a self-reported questionnaire, and epigastric symptoms were evaluated using the Frequency Scale for Symptoms of Gastroesophageal Reflux Disease (FSSG). We fitted generalized linear models to analyze the association between miso soup intake and FSSG, reflux, or dyspepsia scores adjusted by age, sex, body mass index (BMI), another 15 dietary habits, smoking, drinking alcohol, and unfavorable dietary behaviors. A total of 9,364 subjects were included in the analysis. Trend analysis revealed that higher frequency of miso soup intake was associated with lower FSSG scores (p<0.001). In a generalized linear model, daily intake of miso soup was associated with lower FSSG, reflux, and dyspepsia scores independent of age, sex, BMI, other 15 dietary habits, smoking, drinking alcohol, and unfavorable dietary behaviors (estimate=-0.46, -0.22, and -0.27, respectively; 95% CI=-0.83, -0.12; -0.38, -0.07; and -0.47, and -0.08, respectively). Dairy intake of miso soup was associated with lower epigastric symptoms.

The Effect of White Rice and White Bread as Staple Foods on Gut Microbiota and Host Metabolism.

The purpose of this study was to examine the influence of two kinds of major Japanese staple foods, white rice and white bread, on gut microbiota against the background in which participants eat common side dishes. Seven healthy subjects completed the dietary intervention with two 1-week test periods with a 1-week wash-out period in cross-over design (UMIN registration UMIN000023142). White bread or white rice and 21 frozen prepared side dishes were consumed during the test periods. At baseline and at the end of each period, fasting blood samples, breath samples, and fecal samples were collected. For fecal samples, 16S rRNA gene sequencing was used to analyze the gut microbiota. After the bread period, the abundance of fecal Bifidobacterium genus (19.2 ± 14.5 vs. 6.2 ± 6.6 (%), p = 0.03), fasting glucagon-like peptide 1 (GLP-1) (13.6 ± 2.0 vs. 10.5 ± 2.9 (pg/mL), p = 0.03), and breath hydrogen (23.4 ± 9.9 vs. 8.2 ± 5.5 (ppm), p = 0.02) were significantly higher than those of after the rice period. Plasma SCFAs also tended to be higher after the bread period. White bread contains more dietary fiber than refined short grain rice. These findings suggest that indigestible carbohydrate intake from short grain rice as a staple food may be smaller than that of white bread.

Characteristics of the Japanese Diet Described in Epidemiologic Publications: A Qualitative Systematic Review.

CONTEXT: International interest in the Japanese diet has grown in recent years. OBJECTIVE: The aim of this systematic review was to evaluate and organize the Japanese diet and dietary characteristics from an epidemiological perspective, mainly focusing on the nutritional and dietary elements. DATA SOURCES: PubMed, Web of Science, Japan Medical Abstracts Society, JDream III, and CiNii databases were searched. STUDY SELECTION: The eligibility criteria included research with an epidemiological study design that was either cross-sectional, cohort, or case-control-based that defined the dietary patterns of the Japanese diet using dietary pattern analysis. A total of 39 research articles that described the Japanese diet were included. DATA EXTRACTION: The data that were extracted included the following: implementing country, location, study design, participant characteristics, key outcomes, methods used in the analysis of dietary patterns, and descriptions of the Japanese diet. DATA SYNTHESIS: As a result of the systematic review analyzing the descriptions of the Japanese diet from 39 selected articles, we were able to aggregate the descriptions into 16 categories from 33 factors. After performing a content analysis using a further aggregation of categories, we found that the top three applicable categories were soybeans/soybean-derived products, seafood, and vegetables; these were followed by rice and miso soup. CONCLUSION: The Japanese dietary content was found to be diverse based on an examination of epidemiological studies; however, we were able to aggregate the content into 16 categories. The Japanese diet is considered to be a dietary pattern that contains a combination of factors: the dietary staple, side dishes, and soup.

Dietary habits associated with reduced insulin resistance: The Nagahama study.

AIMS: To investigate the association between insulin resistance assessed by a homeostasis model and dietary habits. METHODS: Cross-sectional analysis using a community-based cohort, the Nagahama Prospective Cohort for Comprehensive Human Bioscience. Multiple linear regression analysis was performed with log HOMA-IR or log HOMA-ß as the dependent variable and 20 dietary habits, tobacco smoking, medical history, family medical history of diabetes, age and BMI as the simultaneous independent variables in each sex separately. RESULTS: Females (n = 2956) eating fish dishes every day had a HOMA-IR 0.90 times that of the reference group (P = 0.043). Females eating miso-soup every day had a HOMA-IR 0.95 times that of the reference group (P = 0.038). Males (n = 1371) eating vegetable dishes every day had a HOMA-IR 0.91 times that of the reference group (P = 0.003). Males eating egg dishes 4 to 5 times per week had a HOMA-IR 1.14 times that of the reference group (P = 0.011). Males eating fruits every day had a HOMA-IR 1.13 that of the reference group (P = 0.008). CONCLUSIONS: Dietary habits associated with lower insulin resistance were eating fish dishes, miso soup or vegetable dishes every day and eating staple foods for dinner, egg dishes or fruits less frequently.

Effects of three major amino acids found in Japanese broth on glucose metabolism and gastric emptying.

OBJECTIVES: To our knowledge, the effect of the broth of dried kelp and dried bonito, dashi, on glucose metabolism and digestion has rarely been studied. Based on the component analysis of three actual broths served in traditional restaurants, a chemically synthesized broth with three free amino acids (histidine, glutamate, aspartate) and salt was prepared to investigate their effect on glucose metabolism, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) secretion, and digestion. METHODS: In study 1, seven healthy individuals were enrolled in a four-period crossover study. Participants drank or ate hot water, synthesized broth, hot water with rice, and synthesized broth with rice. Plasma glucose, serum insulin, plasma glucagon, plasma GIP, and plasma GLP-1 were measured at baseline and after ingestion. In study 2, 6 of the 7 individuals ingested rice steamed with 13C-labeled sodium acetate with hot water or synthesized broth to estimate gastric emptying by the 13C-labeled acetate breath test in a two-period crossover trial. RESULTS: Ingesting water or synthesized broth alone elicited no change in plasma glucose or serum insulin levels. Ingesting synthesized broth with rice resulted in a rapid rise in plasma glucose and GLP-1 (P = 0.01 and 0.02, respectively) in an early postprandial phase compared with that by ingesting water with rice, but the area under the curve of those showed no significant differences. Ingesting synthesized broth with rice resulted in a significantly higher gastric emptying coefficient than that after rice with water (P = 0.03). CONCLUSIONS: Three amino acids and sodium chloride corresponding to those found in actual broth promoted gastric emptying and led to a rapid response of plasma glucose. Our findings suggest that ingestion of the broth of dried kelp and dried bonito may improve gastric motility.