Associations between dietary diversity and dyslipidemia among Japanese workers: cross-sectional study and longitudinal study findings.

OBJECTIVE: The aim of this study was to determine the associations between dietary diversity and risk of dyslipidemia in Japanese workers. METHODS: The cross-sectional study included 1399 participants aged 20-63 years and the longitudinal study included 751 participants aged 20-60 years in 2012-2013 (baseline) who participated at least once from 2013 to 2017 with cumulative participation times of 4.9 times. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity score (DDS) was determined using the Quantitative Index for Dietary Diversity. Dyslipidemia was diagnosed when at least one of the following conditions was met: hypertriglyceridemia, high LDL-cholesterol, low HDL-cholesterol, high non-HDL-cholesterol, and a history of dyslipidemia. Multivariable logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for dyslipidemia with control of confounding factors in cross-sectional analysis. Generalized estimating equations were used for calculating the ORs (95% CI) for dyslipidemia in the follow-up period according to the DDS at baseline with control of confounding factors in longitudinal analysis. RESULTS: Cross-sectional analysis showed that the highest DDS reduced the odds of dyslipidemia in men (OR [95% CI] in Tertile 3: 0.67 [0.48-0.95], p value = 0.023). In longitudinal analysis, a moderate DDS reduced the risk of dyslipidemia (OR [95% CI] in Tertile 2: 0.21 [0.07-0.60], p value = 0.003) in women. CONCLUSIONS: The results of cross-sectional analysis in this study suggest that the higher diversity of diet might reduce the presence of dyslipidemia in men and the results of longitudinal analysis suggest that a moderate DDS might reduce the risk of dyslipidemia in women. Further studies are needed since the results of cross-sectional and longitudinal analyses in this study were inconsistent.

Associations between dietary diversity and high sensitive C-reactive protein among Japanese workers: findings of a cross-sectional and longitudinal study.

PURPOSE: To clarify the association between dietary diversity and inflammatory status in Japanese workers. METHODS: Of 1,460 men and women aged 20-64 years in 2010 (baseline), those who were followed-up at least once between 2011 and 2018 were included in this study; 1,433 participants and 745 participants were included in the cross-sectional and longitudinal analyses, respectively. Dietary intake was assessed using a food frequency questionnaire at baseline, and the dietary diversity score was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). High-sensitivity C-reactive protein (hs-CRP) was taken to indicate inflammatory status at the baseline and follow-up surveys. In the cross-sectional analysis using baseline data, a generalized linear model was used to calculate adjusted means and 95% confidence intervals (CIs) for hs-CRP according to the QUANTIDD score. In the longitudinal analysis, generalized estimating equations were used to calculate the adjusted mean (95% CI) for hs-CRP in follow-up according to the QUANTIDD score at baseline. RESULTS: In the cross-sectional analysis, the hs-CRP concentration in male participants was significantly lower in those who had a high QUANTIDD score (adjusted mean [95% CI]: 0.074 [0.009-0.140] mg/dL in the lower group vs. 0.038 [-0.029-0.105] mg/dL in the higher group, p-value = 0.034). In the longitudinal analysis, the hs-CRP concentration of male participants also tended to be lower in those with higher QUANTIDD scores (p-value = 0.103). In both the cross-sectional and longitudinal analyses in women, there was no significant difference between the lower and higher QUANTIDD score groups. CONCLUSION: These findings suggest that, in male Japanese workers, higher dietary diversity might be important for maintaining a low inflammatory status.

Associations of dietary diversity with allergic diseases in Japanese workers: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the associations of dietary diversity with prevalences of allergic diseases. METHODS AND STUDY DESIGN: The participants were 1,317 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics and current medical histories of allergic diseases using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The ORs and 95% CIs for each of the allergic diseases with a 1 standard deviation (SD) increase in the QUANTIDD score were estimated, controlling for age, family history of allergic diseases, education, smoking, drinking, physical activity, energy intake and BMI. RESULTS: Higher dietary diversity showed significant inverse dose-response relationships with allergic diseases and allergic rhinitis in women. Multivariate-adjusted ORs (95% CI) for allergic diseases and allergic rhinitis with 1 SD increase in the QUANTIDD score were 0.77 (95% CI: 0.60-0.98, p=0.037) and 0.69 (95% CI: 0.53-0.90, p=0.007), respectively, in women. There were no significant associations between dietary diversity and allergic diseases in men. CONCLUSIONS: The results indicate that there is an inverse association between higher dietary diversity and allergic rhinitis in Japanese female workers.

Palmitate-stimulated monocytes induce adhesion molecule expression in endothelial cells via IL-1 signaling pathway.

Increased intake of saturated fatty acids (SFAs), such as palmitate (Pal), is linked to a higher risk of type 2 diabetes and cardiovascular disease. Although recent studies have investigated the direct effects of SFAs on inflammatory responses in vascular endothelial cells, it remains unknown whether SFAs also induce these responses mediated by circulating cells. In this study, especially focused on adhesion molecules and monocytes, we investigated the indirect effects of Pal on expression and release of ICAM-1 and E-selectin in vascular endothelial cells. Phorbol 12-myristate 13-acetate (PMA)-treated THP-1 (pTHP-1) cells and human monocytes were stimulated with various free fatty acids (FFAs). SFAs, but not unsaturated fatty acids (UFAs), increased interleukin (IL)-1ß secretion and decreased IL-1 receptor antagonist (IL-1Ra) secretion, resulting in an increase in the IL-1ß/IL-1Ra secretion ratio. UFAs dose-dependently inhibited the increase in IL-1ß secretion and decrease in IL-1Ra secretion induced by Pal. Moreover, in human aortic and vein endothelial cells, expression and release of ICAM-1 and E-selectin were induced by treatment with conditioned medium collected from Pal-stimulated pTHP-1 cells and human monocytes, but not by Pal itself. The up-regulated expression and release of adhesion molecules by the conditioned medium were mostly abolished by recombinant human IL-1Ra supplementation. These results suggest that the Pal-induced increase in the ratio of IL-1ß/IL-1Ra secretion in monocytes up-regulates endothelial adhesion molecules, which could enhance leukocyte adhesion to endothelium. This study provides further evidence that IL-1ß neutralization through receptor antagonism may be useful for preventing the onset and development of cardiovascular disease.

Insulin receptor cleavage induced by estrogen impairs insulin signaling.

INTRODUCTION: Soluble insulin receptor (sIR), which is the ectodomain of insulin receptor (IR), is present in human plasma. Plasma sIR levels are positively correlated with blood glucose levels and negatively correlated with insulin sensitivity. An in vitro model of IR cleavage shows that extracellular calpain 2 directly cleaves IR, which generates sIR, and sequential cleavage of the IRß subunit by γ-secretase impairs insulin signaling in a glucose concentration-dependent manner. Nevertheless, sIR levels vary among subjects with normal glucose levels. RESEARCH DESIGN AND METHODS: We examined sIR levels of pregnant women throughout gestation. Using an in vitro model, we also investigated the molecular mechanisms of IR cleavage induced by estradiol. RESULTS: In pregnant women, sIR levels were positively correlated with estrogen levels and significantly increased at late pregnancy independent of glucose levels. Using an in vitro model, estrogen elicited IR cleavage and impaired cellular insulin signaling. Estradiol-induced IR cleavage was inhibited by targeting of calpain 2 and γ-secretase. Estrogen exerted these biological effects via G protein-coupled estrogen receptor, and its selective ligand upregulated calpain 2 expression and promoted exosome secretion, which significantly increased extracellular calpain 2. Simultaneous stimulation of estrogen and high glucose levels had a synergic effect on IR cleavage. Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen. CONCLUSIONS: Estradiol-induced IR cleavage causes cellular insulin resistance, and its molecular mechanisms are shared with those by high glucose levels. sIR levels at late pregnancy are significantly elevated along with estrogen levels. Therefore, estradiol-induced IR cleavage is preserved in pregnant women and could be part of the etiology of insulin resistance in gestational diabetes mellitus and overt diabetes during pregnancy.

Dietary diversity and characteristics of lifestyle and awareness of health in Japanese workers†:†a cross-sectional study.

The aim of this study was to clarify the characteristics of lifestyle and health awareness according to dietary diversity in a Japanese worksite population. The participants were 1,312 men and women aged 20 to 63 years who were living in Tokushima Prefecture, Japan during the period 2012-2013. We obtained anthropometric data and information on lifestyle characteristics using a self-administered questionnaire. Dietary intake was assessed using a food frequency questionnaire, and dietary diversity was determined using the Quantitative Index for Dietary Diversity (QUANTIDD). The characteristics of lifestyle and health awareness according to quartiles of the QUANTIDD score were assessed using the chi-square test and a general linear model. The higher the QUANTIDD score was, the larger were the proportions of participants who knew the appropriate amount of dietary intake and participants who referred to nutritional component information when choosing and / or buying food. Among participants with higher QUANTIDD scores, the proportion of participants who considered their current diet was good was high in women, whereas the proportion of participants who wanted to improve their diet in the future was high in men. Those results indicate that higher dietary diversity was related to better characteristics of lifestyle and awareness of health. J. Med. Invest. 67 : 255-264, August, 2020.

Soy product and isoflavone intake associations with allergic diseases in Japanese workers: rhinitis, dermatitis and asthma.

BACKGROUND AND OBJECTIVES: The aim of this study was to determine the associations of intake of soy products and isoflavones with allergic diseases. METHODS AND STUDY DESIGN: We conducted a cross-sectional study in 1437 participants (aged 20-64 years) who were living in Tokushima Prefecture, Japan during the period 2010- 2011. We obtained anthropometric data and information on life style characteristics including dietary intake and current medical histories of allergic diseases using a structural self-administered questionnaire. Multiple logistic regression models were used to assess the associations of soy products and isoflavones with allergic diseases after controlling for age, family history of allergic diseases, smoking, drinking, physical activity, energy intake, BMI and dietary factors. RESULTS: Intake of soy products showed significant inverse dose-response relationships with allergic rhinitis. The third quartile for soy products had an adjusted OR of 0.56 (95% CI: 0.35-0.91) compared to the reference group (first quartile), though intake of soy products showed no dose-response relationship with atopic dermatitis. Intake of soy isoflavones showed a significant inverse dose-response relationship with atopic dermatitis, though the association between intake of soy isoflavones and atopic dermatitis was U-shaped after adjustments for potential confounders. On the other hand, the associations between intake of soy isoflavones and other allergic diseases were not significant. CONCLUSIONS: The results indicate that higher intake of soy products is associated with reduced risk of allergic rhinitis in Japanese workers. Furthermore, moderate intake amounts of soy products and soy isoflavones are associated with inverse risk of atopic dermatitis.

Associations between intake of dietary fermented soy food and concentrations of inflammatory markers: a cross-sectional study in Japanese workers.

Epidemiological investigations have shown that consumption of soybeans or soy foods reduces the risk of the development of cardiovascular disease, cancer and osteoporosis. The aim of this study was to determine the associations between different soy foods and inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, and IL-18, in Japanese workers. The cross-sectional study included 1,426 Japanese workers (1,053 men and 373 women) aged 20 to 64 years. Intake of 12 soy foods was estimated by a validated food frequency questionnaire. Associations of total soy foods, fermented soy food, non-fermented soy food, soy isoflavone with hs-CRP, IL-6, and IL-18 levels were examined by general linear model regression analysis. We found that total fermented soy food intake was inversely associated with multivariable-adjusted geometric concentration of IL-6 in men (Q1:1.03 pg/mL, Q5:0.94 pg /mL;P for trend = 0.031). Furthermore, it was shown that IL-6 concentrations were inversely associated with miso intake (ß = -0.068;p = 0.034) and soy sauce intake in men (ß = -0.074;p = 0.018). This study suggests that intake of total fermented soy food, miso and soy sauce be associated with IL-6 concentrations in Japanese men. J. Med. Invest. 65:74-80, February, 2018.

A pilot study comparing the CGM-assessed glycemic profiles of patients with type 1 diabetes on insulin degludec and insulin glargine.

AIMS: To compare the diurnal glycemic profiles obtained with basal insulin degludec (InsDeg) and basal insulin glargine (InsGla) in patients with type 1 diabetes using continuous glucose monitoring (CGM) in an outpatient setting. METHODS: Twenty Japanese patients with type 1 diabetes who were using once-daily InsGla before supper as part of their multiple daily insulin injections were consecutively recruited. CGM was initiated before supper on day 1, and InsGla was switched to InsDeg at the same dose on day 3. The average CGM glucose profile obtained on days 1 and 2 was compared with the corresponding profile for days 5 and 6. The bolus insulin regimen was not changed during the study period. RESULTS: CGM glucose was significantly higher (p < 0.05) from 19:30 to 22:30 and significantly lower (p < 0.05) from 6:30 to 8:00 with basal InsDeg than with basal InsGla. The duration of hypoglycemia (<70 mg/dl) was the same regardless of whether basal InsDeg or basal InsGla was used. CONCLUSIONS: The peak in the action profile of InsDeg lasts longer and is possibly stronger than that of InsGla.

Cut-off value of total adiponectin for managing risk of developing metabolic syndrome in male Japanese workers.

AIM: To determine the optimal cut-off value of serum total adiponectin for managing the risk of developing metabolic syndrome (MetS) in male Japanese workers. METHODS: A total of 365 subjects without MetS aged 20-60 years were followed up prospectively for a mean of 3.1 years. The accelerated failure-time model was used to estimate time ratio (TR) and cut-off value for developing MetS. RESULTS: During follow-up, 45 subjects developed MetS. Age-adjusted TR significantly declined with decreasing total adiponectin level (≤ 4.9, 5.0-6.6, 6.7-8.8 and ≥ 8.9 µg/ml, P for trend = 0.003). In multivariate analyses, TR of MetS was 0.12 (95% CI 0.02-0.78; P = 0.03) in subjects with total adiponectin level of 5.0-6.6 µg/ml, and 0.15 (95% CI 0.02-0.97; P = 0.047) in subjects with total adiponectin level ≤ 4.9 µg/ml compared with those with total adiponectin level ≥ 8.9 µg/ml. The accelerated failure-time model showed that the optimal cut-off value of total adiponectin for managing the risk of developing MetS was 6.2 µg/ml. In the multivariate-adjusted model, the mean time to the development of MetS was 78% shorter for total adiponectin level ≤ 6.2 µg/ml compared with > 6.2 µg/ml (TR 0.22, 95% CI: 0.08-0.64, P = 0.005). CONCLUSION: Our findings suggest that the cut-off value for managing the risk of developing MetS is 6.2 µg/ml in male Japanese workers. Subjects with total adiponectin level ≤ 6.2 µg/ml developed MetS more rapidly than did those with total adiponectin level > 6.2 µg/ml.

Correlation of fibroblast growth factor 21 serum levels with metabolic parameters in Japanese subjects.

OBJECTS: Since serum level of fibroblast growth factor 21 (FGF21) has been implicated as a potential biomarker for the early detection of the metabolic syndrome and type 2 diabetes, we examined how FGF21 serum levels are correlated with metabolic parameters in Japanese subjects. METHODS: FGF21 levels were analyzed by enzyme-linked immunosorbent assays. Spearman's correlation and multiple stepwise regression analyses were used to examine the relationship between serum FGF21 and other factors. A Mann-Whitney U test was performed between the normal and high groups for triglycerides and systolic blood pressure (BP) respectively. RESULTS: By univariate correlation analysis, serum FGF21 levels were significantly associated with triglyceride levels, systolic BP, diastolic BP, pulse pressure, body mass index (BMI), age, fasting plasma glucose (FPG) levels, and total cholesterol levels. Multiple regression analysis (adjusted for age, gender, and BMI) showed that serum FGF21 levels were independently and significantly associated with triglyceride levels and systolic BP. Serum FGF21 levels were significantly higher in subjects with high triglyceride levels and high systolic BP compared with those who had normal triglyceride levels and normal systolic BP respectively. CONCLUSIONS: This study found that FGF21 levels might be a biomarker for some metabolic disorders associated with metabolic syndrome.

Diabetic conditions differentially affect the endothelial function, arterial stiffness and carotid atherosclerosis.

AIM: The levels of fasting and postprandial plasma glucose, HbA1c and other risk factors for atherosclerosis have distinct effects in patients with and those without diabetes mellitus. The aim of this study was to determine the impact of diabetic surrogate markers on the endothelial function, arterial stiffness and carotid atherosclerosis in individuals with and without diabetes. METHODS: A total of 320 Japanese subjects(mean age: 61.2 ± 12.1 years) were recruited in this study. Demographic, clinical and laboratory parameters, including 75 g OGTT(155 subjects) results, were examined. The endothelial function was evaluated according to the flow-mediated vasodilation of the brachial artery(%FMD). In addition, arterial stiffness was evaluated according to the brachial-ankle pulse wave velocity(baPWV), and carotid atherosclerotic changes were estimated according to the maximum intima-media thickness(max-IMT) and resistive index of the common carotid artery(CCA-RI). A multiple regression analysis was performed to identify independent determinants of these vascular surrogate markers. RESULTS: None of the glucose-related parameters were associated with the %FMD. In contrast, the presence of T2DM, the HbA1c level and an increased plasma glucose level at 60 minutes during 75 g OGTT were associated with an increased baPWV. The HbA1c level was also correlated with an increased max-IMT. The fasting plasma glucose(FPG) level and the presence of T2DM correlated with an increased CCA-RI. In the subjects with T2DM, the protective effects of high-density lipoprotein cholesterol(HDL-C) on the %FMD and baPWV were abolished. CONCLUSIONS: Various glucose metabolism parameters have different effects the degree of arterial stiffness and presence of carotid atherosclerosis, but not the endothelial function, suggesting that pharmacological intervention has the potential to preserve the endothelial function in diabetic individuals. In addition, the presence of T2DM blunts the vascular protective effects of HDL-C on the endothelial function and progression of arterial stiffness.

Singlet oxygen induced products of linoleates, 10- and 12-(Z,E)-hydroxyoctadecadienoic acids (HODE), can be potential biomarkers for early detection of type 2 diabetes.

Current diagnostic tests such as glycemic indicators have limitations for early detection of impaired glucose tolerance (IGT), which leads to diabetes. Oxidative stress induced by various oxidants in a random and destructive manner is considered to play an important role in the pathophysiology of a number of human disorders and diseases such as impaired glucose tolerance. We have developed an improved method for the measurement of in vivo lipid peroxidation, where the presence of 8-iso-prostaglandin F2α (8-iso-PGF2α), hydroxyoctadecadienoic acids (HODEs), hydroxyeicosatetraenoic acids (HETEs), and 7-hydroxycholesterol (7-OHCh), as well as their parent molecules, linoleic acid (LA) and cholesterol (Ch), was determined by performing LC-MS/MS (for 8-iso-PGF2α, HODE, and HETE) and GC-MS (for 7-OHCh, LA, and Ch) after reduction with triphenyl phosphine and saponification by potassium hydroxide. We then applied this method to volunteers (n = 57), including normal type (n = 43), "high-normal" (fasting plasma glucose, 100-109 mg/dL, n = 7), pre-diabetic type (IGT, n = 5), and diabetic type (n = 2) subjects who are diagnosed by performing oral glucose tolerance tests (OGTTs). Several biomarkers in plasma, such as insulin, leptin, adiponectin, interleukin-6, tumor necrosis factor-α, high sensitivity-C-reactive protein, HbA1c, and glucose levels were measured during OGTT. We found that the fasting levels of (10- and 12-(Z,E)- HODE)/LA increased significantly with increasing levels of HbA1c and glucose during OGTT and with insulin secretion and resistance index. In conclusion, 10- and 12-(Z,E)-HODE may be prominent biomarkers for the early detection of IGT and "high-normal" type without OGTT.