Prospective association of daily ambulatory activity with metabolic syndrome in middle-aged and older Japanese adults: the Toon Health Study.

BACKGROUND: This cohort study aimed to examine the relationship between objectively measured daily ambulatory activity (AA) variables and the onset of metabolic syndrome (MetS) in middle-aged and older Japanese individuals. METHODS: A total of 1,034 participants (women, 76.8%; mean age, 56.9 years) who were initially free from MetS, underwent objective assessment of daily AA using a uniaxial accelerometer at baseline. The number of steps, time accumulated in light-intensity AA (LIAA), moderate-to-vigorous intensity AA (MVAA), and total AA (LIAA + MVAA) were calculated. The diagnostic criteria outlined by the Japanese standards were employed to define the presence of MetS. To explore the association between AA variables and MetS onset, both multivariate logistic regression and a restricted cubic spline model were used while controlling for variables such as age, sex, education, alcohol habit, smoking habit, energy intake, and the number of MetS components present at baseline. RESULTS: Over the course of the 5-year follow-up period, 116 participants (11.2%) developed MetS. In terms of the number of steps, LIAA, and total AA, the third quartile had significantly lower multivariate adjusted odds ratios for MetS onset than the first quartile. The odds ratios (95% confidence intervals) were 0.386 (0.197-0.755), 0.527 (0.285-0.975), and 0.392 (0.206-0.745), respectively. In the spline model, an L-shaped association with MetS was observed for the number of steps (p for nonlinearity = 0.066), LIAA (p for nonlinearity = 0.034), and total AA (p for nonlinearity = 0.040). CONCLUSIONS: Among the variables related to AA, the index of daily amount AA, in particular, may be linked to the onset of MetS.

Effect of high-amylose rice "Hoshinishiki" on postprandial glucose levels measured by continuous glucose monitoring in patients with diabetes.

We examined the effect of consuming Hoshinishiki, a type of high-amylose rice, on postprandial glucose as measured by continuous glucose monitoring in diabetes patients. A single-blinded clinical trial involving 11 hospitalized patients diagnosed with type 1 or type 2 diabetes was performed. The patients consumed high-amylose rice for 2 days (days 2 and 4 of the study) and control rice for 2 days (days 1 and 3 of the study). Linear mixed models were used to test the effects on the 24-h mean glucose levels, time in range (TIR), incremental area under the curve of glucose levels at 2 h after meals, the average glucose levels at 1, 2, and 3 h after meals, and the maximum glucose levels within 3 h. The results showed that the consumption of high-amylose rice led to significantly lower 24-h mean glucose levels, levels at 2 and 3 h after a meal, and postprandial glucose peak levels within 3 h, as well as significantly higher TIR. A similar trend was observed when the analysis was restricted to patients with type 2 diabetes. These results suggest that high-amylose rice may be a more beneficial staple food for glycemic control than regular rice.

Serum microRNA-501-3p is a potential diagnostic tool for detecting mild cognitive impairment: Ehime genome study.

Tight junction disruption and dysfunction are involved in the progression of blood-brain barrier (BBB) breakdown. Recent investigations have revealed BBB disruption in patients with vascular cognitive decline. Our previous studies showed that miR-501-3p negatively regulates cerebral endothelial tight junction protein-1, resulting in the disruption of the BBB, and playing an important role in the development of vascular cognitive impairment. BBB breakdown in white matter lesions is often seen in the patients with vascular mild cognitive impairment (MCI). We therefore hypothesize that most early-phase MCI patients may demonstrate elevated expression of miR-501-3p and sought to investigate whether serum exosome miR-501-3p levels could be a clinical indicator for detecting mild cognitive impairment. One hundred and seventy-eight subjects (aged 73 [68-75] years, 53% male) were recruited for this study. The Japanese version of the Montreal Cognitive Assessment (MoCA-J) was used for detecting MCI. Serum exosome miR-501-3p expression levels were measured by qPCR methods. Patients were divided into two groups depending on whether their miR-501-3p ∆Ct values were above ("High"; n = 74) or below ("Low"; n = 104) cutoff levels determined by ROC curve. MCI was detected significantly more often in the miR-501-3p-High group (vs. -Low group, 63.5% vs. 47.1%, respectively; p < 0.05). Multivariate logistic regression analysis showed a significant association between MCI status and High miR-501-3p (odds ratio 2.662; p < 0.01), improved vs. known risk factors. In non-diabetic patients, High miR-501-3p was positively associated with MCI status (odds ratio 3.633; p < 0.01) and also positively associated with MCI status in those with atherosclerosis (odds ratio 3.219; p < 0.01). The present study demonstrates that elevated expression of blood exosomal miR-501-3p can indicate the presence of MCI in human patients. Early detection of vascular injuries may allow a reduction in progressive dementia through the management of vascular risk factors.

Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study.

Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.

Latent profile analysis approach to the relationship between daily ambulatory activity patterns and metabolic syndrome in middle-aged and elderly Japanese individuals: The Toon Health Study.

BACKGROUND: This cross-sectional study aimed to identify the accumulation patterns of objectively measured ambulatory activity (AA) variables in the Japanese middle-aged and elderly individuals and examine the relationship of these derivative patterns with metabolic syndrome (MetS). METHODS: A total of 1850 participants (66.1% women, mean age: 57.7 years) provided objectively assessed AA data using a uniaxial accelerometer. The number of steps, time accumulated in light-intensity AA (LIAA) and moderate-to-vigorous intensity AA (MVAA), and the ratio of MVAA to total AA (LIAA + MVAA) were calculated. Latent profile analysis was used to identify groups of participants based on their distinct AA patterns. Logistic regression models were used to assess the association of groups with MetS after adjusting for age, sex, alcohol intake, and cigarette smoking. RESULTS: Four distinct groups were identified: Group A had few steps and low levels of LIAA and MVAA; group B had a certain number of steps and recommended level of MVAA but low level of LIAA; group C had a certain number or more of steps, high level of LIAA, and recommended level of MVAA; group D had an extremely high number of steps and high levels of both LIAA and MVAA. The multivariate-adjusted odds ratio (95% CI) for MetS in groups B, C, and D relative to group A were 0.857 (0.611-1.201), 0.679 (0.500-0.922), and 0.434 (0.259-0.730), respectively. Groups C and D had significantly lower odds ratio of MetS compared to group A. CONCLUSION: AA pattern involving a certain number or greater of steps accumulated through not only MVAA but also LIAA may help reduce the risk of MetS compared to inactive AA pattern.

[The association between alcohol consumption and Mild Cognitive Impairment: the Toon Health Study].

AIM: The effects of alcohol consumption on Mild Cognitive Impairment (MCI) among the Japanese population had not been fully examined. Therefore, the objective of this study was to examine the association between alcohol consumption and MCI among the Japanese elderly population. METHODS: In total, 421 men and 700 women aged 60-84 years participated in this cross-sectional study. Alcohol consumption was estimated according to frequency and amount of major alcoholic beverages (i.e., beer, Japanese sake, shochu, and wine) consumed by each individual using a self-administered questionnaire. MCI was assessed using the Japanese version of the Montreal Cognitive Assessment. Multivariable odds ratio (OR) and 95% confidence intervals (CIs) of MCI according to alcohol consumption were calculated using logistic models. We further analyzed the associations of the major alcoholic beverages with MCI. RESULTS: The prevalence of MCI was 50.4% among the male participants and 31.4% among the females. A positive association between alcohol consumption and MCI was observed in men, but not in women. The multivariable OR (95% CI) of MCI for ≥ 2 go (46 g ethanol) /day vs. non-drinkers was 1.78 (0.93-3.40, p for trend = 0.045) in men and for ≥ 1 go (23 g ethanol) /day was 0.96 (0.39-2.38, p for trend = 0.92) in women, respectively. We also observed an association between shochu consumption and MCI in men, whereby the multivariable OR (95% CI) of MCI for each 1 go increment was 1.57 (1.18-2.07). CONCLUSION: Our findings suggest that alcohol consumption in moderation may contribute to the prevention of MCI development in men.

An inverse association between serum resistin levels and n-3 polyunsaturated fatty acids intake was strongest in the SNP-420 G/G genotype in the Japanese cohort: The Toon Genome Study.

OBJECTIVE: Resistin is secreted by monocytes/macrophages and is associated with insulin resistance, inflammation and cardiovascular diseases. In the Japanese cohort, serum resistin is tightly associated with a single-nucleotide polymorphism (SNP) at -420 (rs1862513) in the promoter region of the human resistin gene. However, interactions between SNP-420 and environmental factors remain to be elucidated. The aim of this study was to investigate the association between serum resistin levels and nutrient intake, and the effect of SNP-420 on this association. DESIGN, PARTICIPANTS AND MEASUREMENTS: The Toon Genome Study is a cohort study of Japanese community-dwelling subjects. A total of 1981 participants were cross-sectionally analysed. Each nutrient intake was assessed using the semiquantitative food frequency questionnaire and categorized into the quartiles (Q1-Q4). Serum resistin was measured by ELISA. RESULTS: Serum resistin tended to be inversely associated with fish intake and positively associated with meat intake after adjustment for age, sex, BMI and energy intake. Serum resistin was inversely associated with n-3 polyunsaturated fatty acids (PUFA) intake after adjustment for age, sex, BMI and energy intake (Q1 12.5, Q2 12.5, Q3 12.2, Q4 11.5 ng/mL; P for trend = .007). This inverse association was strongest in the G/G genotype of SNP-420, followed by C/G and C/C (G/G, Q1 18.9, Q2 19.5, Q3 18.4, Q4 14.5 ng/mL, P = .001; C/G, 14.4, 13.3, 13.1, 12.9, P = .015; C/C, 9.5, 9.5, 9.2, 8.8, P = .020; P for interaction = .004). CONCLUSIONS: The inverse association between serum resistin and n-3 PUFA intake was strongest in SNP-420 G/G genotype in the Japanese cohort.

Low Heart Rate Variability and Sympathetic Dominance Modifies the Association Between Insulin Resistance and Metabolic Syndrome　- The Toon Health Study.

BACKGROUND: Insulin resistance is strongly associated with metabolic syndrome (MetS), but it is not known how this association is influenced by the autonomic nervous system, which controls insulin secretion.Methods and Results:The subjects were 2,016 individuals aged 30-79 years enrolled between 2009 and 2012. MetS was determined using the harmonized MetS definition, which includes waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting glucose. The homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt's insulin sensitivity index (ISI) were calculated based on fasting and 2 h-post-load glucose and insulin concentrations in a 75-g oral glucose tolerance test. The 5-min heart rate variability (HRV) was evaluated using time-domain indices of standard deviations of NN intervals (SDNN) and root mean square of successive differences (RMSSD). Power spectral analysis yielded frequency-domain measures for HRV: high-frequency (HF) power, low-frequency (LF) power and LF/HF. Multivariable adjusted logistic models showed that the highest quartiles for SDNN, RMSSD, LF, and HF vs. the lowest quartiles had a significant association with MetS. RMSSD, HF, and LF/HF remained significantly associated with MetS after adjustment for HOMA-IR (or ISI). Additive interactions between the levels of high LF/HF and high HOMA-IR (or low ISI) were significantly positive. CONCLUSIONS: Sympathovagal imbalance as evidenced by low HF and high LF/HF modified the association of insulin resistance or low insulin sensitivity with MetS.

Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population.

Resistin is a cytokine inducing insulin resistance in mice. We previously identified single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and -358 (rs3219175) located in the human resistin gene (RETN) promoter as strong determinants for circulating resistin in the Japanese population. The objective was to identify additional functional variants for circulating resistin. We conducted a genome-wide association study in 448 Japanese subjects. A peak association signal was found on chromosome 19 where RETN is located. The top-hit SNP was SNP -358 G>A, followed by rs1423096 C>T, SNP -420 C>G, and rs10401670 C>T (P = 5.39×10-47, 1.81×10-22, 2.09×10-16, and 9.25×10-15, respectively). Meta-analysis including another two independent general Japanese populations showed that circulating resistin was most strongly associated with SNP-358, followed by SNP-420, rs1423096, and rs10401670. Rs1423096 and rs10401670 were located in the 3'-region of RETN and were in strong linkage disequilibrium. Although these SNPs were also in linkage disequilibrium with the promoter SNPs, conditional and haplotype association analyses identified rs1423096 and rs10401670 as independent determinants for circulating resistin. Functionally, nuclear proteins specifically recognized T but not C at rs10401670 as evidenced by an electrophoretic mobility shift assay. The promoter activity of a luciferase reporter with T at either rs1423096 or rs10401670 was lower than that with C in THP-1 human monocytes. Therefore, rs1423096 and rs10401670, in addition to SNP-420 and SNP-358, were identified as possible functional variants affecting circulating resistin by the genome-wide search in the Japanese population.

Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study.

BACKGROUND: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. METHODS: Between 2009-2012, the Toon Health Study recruited 1899 individuals aged 30-79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR) and Gutt's insulin sensitivity index (ISI). Pulse was recorded for 5 min, and time-domain heart rate variability (HRV) indices were calculated: the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive difference (RMSSD). Power spectral analysis provided frequency domain measures of HRV: high frequency (HF) power, low frequency (LF) power, and the LF:HF ratio. RESULTS: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41-3.10). CONCLUSIONS: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

Fulminant type 1 diabetes caused by DIHS could be affected by the reactivation of HHV-6.

CONTEXT: In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear. OBJECTIVE: We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6. METHODS: We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases, and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D. RESULTS: The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In one case, HHV-6 DNA was also identified shortly before the onset of FT1D. CONCLUSION: These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS.　.

Interaction effect between low birthweight and resistin gene rs1862513 variant on insulin resistance and type 2 diabetes mellitus in adulthood: Toon Genome Study.

AIMS/INTRODUCTION: Gene-environment interactions are considered to critically influence type 2 diabetes mellitus development; however, the underlying mechanisms and specific interactions remain unclear. Given the increasing prevalence of low birthweight (LBW) influenced by the intrauterine environment, we sought to investigate genetic factors related to type 2 diabetes development in individuals with LBW. MATERIALS AND METHODS: The interaction between 20 reported type 2 diabetes susceptibility genes and the development of type 2 diabetes in LBW (<2,500 g) individuals in a population-based Japanese cohort (n = 1,021) was examined by logistic regression and stratified analyses. RESULTS: Logistic regression analyses showed that only the G/G genotype at the rs1862513 locus of the resistin gene (RETN), an established initiator of insulin resistance, was closely related to the prevalence of type 2 diabetes in individuals with LBW. Age, sex and current body mass index-adjusted stratified analyses showed a significant interaction effect of LBW and the RETN G/G genotype on fasting insulin, homeostatic model assessment 2-insulin resistance, Matsuda index and the prevalence of type 2 diabetes (all P-values for interaction <0.05). The adjusted odds ratio for type 2 diabetes in the LBW + G/G genotype group was 7.33 (95% confidence interval 2.43-22.11; P = 0.002) compared with the non-LBW + non-G/G genotype group. Similar results were obtained after excluding the influence of malnutrition due to World War II. CONCLUSIONS: Simultaneous assessment of LBW and the RETN G/G genotype can more accurately predict the risk of future type 2 diabetes than assessing each of these factors alone, and provide management strategies, including early lifestyle intervention in LBW population.

Pulse rate variability and health-related quality of life assessment with the Short Form-8 Japanese version in the general Japanese population.

We aimed to investigate the association between pulse rate variability (PRV) and health-related quality of life (HRQOL) in the general population. A cross-sectional study was conducted with 5908 Japanese men and women aged 30-79 years. PRV was assessed at rest using 5-min recordings of pulse waves with a photoplethysmographic signal from a fingertip sensor, and the time and frequency domains of PRV were determined. HRQOL was assessed with the Short Form-8 (SF-8) Japanese version, and poor HRQOL was defined as an SF-8 sub-scale score < 50. A test for nonlinear trends was performed with the generalized additive model with a smoothing spline adjusted for confounders. The lowest multivariable-adjusted odds ratios for poor physical component score were found in those who had second or third quartile levels of standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive difference (RMSSD), and high-frequency (HF) power and trended slightly upward in the higher levels. PRV-derived parameters were nonlinearly associated with poor physical component scores. In conclusion, reduced PRV-derived SDNN, RMSSD and HF power were associated with poor HRQOL in the domain of physical function. Higher levels of these parameters did not necessarily translate into better HRQOL.

Longitudinal Changes in Arterial Stiffness Associated with Physical Activity Intensity: The Toon Health Study.

AIMS: Several studies have revealed an association between moderate-to-vigorous physical activity (MVPA) and arterial stiffness, which is a known risk factor for cardiovascular disease. However, a few studies have considered the difference in the longitudinal effect of its intensity in a large general population. Therefore, we examined the effect of MVPA intensity on longitudinal changes in arterial stiffness. METHODS: We conducted a prospective cohort study involving 1,982 Japanese men and women. Arterial stiffness was measured using the cardio-ankle vascular index (CAVI) at baseline and 5-year follow-up. Physical activity was quantified using the Japan Arteriosclerosis Longitudinal Study Physical Activity Questionnaire and categorized into quartiles as MVPA levels. Linear mixed models were used to examine the differences at baseline and the rate of changes in CAVI associated with MVPA levels for over 5 years. RESULTS: The multivariable-adjusted mean differences in CAVI at baseline were significantly lower in the third (ß=-0.019 [95% confidence interval {CI}=-0.033 to -0.005]) and fourth (ß=-0.018 [95% CI=-0.035 to -0.001]) quartiles of the MVPA group compared with those in the lowest quartile of MVPA, and the significant effect persisted 5 years later. CONCLUSIONS: In summary, this study provides evidence to support the existence of a threshold for beneficial levels of MVPA in the prevention of arterial stiffness. Furthermore, this study suggests that exceeding this threshold may exert similar effects on arterial stiffness. These findings suggest that an optimal level of MVPA exists for preventing arterial stiffness, and exceeding this threshold may not engender additional benefits.

A prediction model for estimating NT-proBNP in a general Japanese population: the Toon Health Study.

AIMS: As part of the Toon Health Study, which is an ongoing population-based cohort study, we aimed to develop a prediction model for N-terminal pro-brain natriuretic peptide (NT-proBNP) in a general Japanese population. We sought to explore the influence of various demographic and clinical factors on NT-proBNP levels and assess the model's performance. In addition, our objectives included internal validation and investigation of the diagnostic potential of the observed-to-predicted NT-proBNP ratio (OPR) at baseline for predicting the risk of heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: In this prospective cohort study, participants were recruited from Toon City, Japan, as part of the larger Toon Health Study, focusing on cardiovascular risk factors. We measured the NT-proBNP levels and used linear regression with penalization (ridge regression) to develop the model. The model incorporated 10 prespecified predictors (age, gender, body mass index, diastolic blood pressure, heart rate, haemoglobin, albumin, total cholesterol, haemoglobin A1c, and estimated glomerular filtration rate) and underwent assessment using R2 and root mean squared error (RMSE). Internal validation was conducted through bootstrapping. In a post hoc analysis, we explored the OPR's diagnostic potential using 5 year follow-up data (n = 636) to predict the elevation of NT-proBNP > 125 pg/mL at the 5 year follow-up as the risk of HFpEF. A total of 2505 participants (age: 60.4 ± 12.9 years, men: 35%) were enrolled in this study. There was a linear relationship between the observed and predicted values of NT-proBNP in which the logarithm of observed NT-proBNP was <6, which corresponds to 403 pg/mL in NT-proBNP. The prediction model demonstrated satisfactory performance (R2: 0.291, RMSE: 0.688), with age identified as a dominant predictor. The stability of the model was underscored by the internal validation. The OPR at baseline predicted NT-proBNP > 125 pg/mL at the 5 year follow-up with an area under the curve of 0.793. CONCLUSIONS: This study introduces the first prediction model for NT-proBNP in a general Japanese population. Although the model has acceptable performance, ongoing refinement is essential. Our transparent approach to model development, alongside a web-based interactive tool, lays the groundwork for further improvements and external validation. The OPR holds potential for predicting the future risk of HFpEF. This research contributes to understanding the nuanced influence of patient backgrounds on levels of NT-proBNP in asymptomatic individuals within the context of a broader population-based cohort study.

Resistin G-A haplotype at SNP-420/-358 is associated with the latent sarcopenic obesity index in the toon genome study.

AIM/INTRODUCTION: Resistin, which induces insulin resistance, is mainly expressed in monocytes/macrophages in humans. We reported previously that serum resistin was highest in the G-A haplotype defined by resistin single nucleotide polymorphisms (SNPs) at -420 (rs1862513) and - 358 (rs3219175). As sarcopenic obesity is associated with insulin resistance, we aimed to examine whether serum resistin and its haplotypes were associated with sarcopenic obesity at a latent stage. MATERIALS AND METHODS: We cross-sectionally analyzed 567 community-dwelling Japanese participants attending annual medical check-ups in which the sarcopenic obesity index was evaluated. The age- and gender-matched normal glucose tolerance subjects with G-A homozygotes and those with C-G homozygotes were examined via RNA-sequencing and pathway analysis (each n = 3), and RT-PCR (each n = 8). RESULTS: In multivariate logistic regression analyses, the fourth quartile (Q4) of serum resistin and G-A homozygotes were both associated with the latent sarcopenic obesity index defined by a visceral fat area of ≥ 100 cm2 and grip strength Q1 after adjustment for age and gender, with or without other confounding factors. RNA sequencing and pathway analysis showed that tumor necrosis factor (TNF) was involved in the top five pathways in the whole blood cells of G-A homozygotes compared with C-G homozygotes. RT-PCR revealed that TNF mRNA was higher in G-A homozygotes than in C-G homozygotes. CONCLUSIONS: The G-A haplotype was associated with the latent sarcopenic obesity index defined by grip strength in the Japanese cohort, could be mediated by TNF-α.

The association between masticatory ability and lower Timed Up & Go Test performance among community-dwelling Japanese aging men and women: The Toon Health Study.

Objectives: Few studies examined the association between deterioration of masticatory ability assessed by objective marker and physical function. Therefore, we examined the association between salivary flow rate which is one of the objective and surrogate marker of masticatory ability and lower Timed Up & Go (TUG) performance which is one of major measurement of physical function among aging Japanese. Methods: This cross-sectional study enrolled 464 Japanese aged 60-84 years old. Participants chewed tasteless and odorless gum for 5 min, calculated stimulated salivary flow rate (g/min) during all chews. The 3 m TUG was conducted, and 75th percentile value (6.8 s for men and 7.0 s for women) or higher was defined as lower TUG performance. Logistic regression analysis was used to examine the association between stimulated salivary flow rate and lower TUG performance. Results: We found that the stimulated salivary flow rate tended to be negatively associated with the TUG time. We also observed significant negative association between stimulated salivary flow rate and lower TUG performance; the multivariable-adjusted OR (95% confidence interval, CIs) of lower TUG performance for the highest quartile of stimulated salivary flow rate compared with the lowest quartile was 0.34 (0.16-0.69, P for trend = 0.02). Further adjusting for BMI, the association was attenuated but remaind significant; the OR (95% CIs) in highest quartile was 0.37 (0.18-0.76, P for trend = 0.04). Conclusions: Higher stimulated salivary flow, which means well masticatory ability, was inversely associated with lower TUG performance in the aging Japanese population.

Role of insulin resistance in the association between resting heart rate and type 2 diabetes: A prospective study.

BACKGROUND: Elevated resting heart rate (RHR) is a predictor of incident type 2 diabetes (T2D). Insulin resistance is thought to play a role in this association; however, the extent to which insulin resistance mediates this association is unclear. METHODS: 1309 Japanese individuals without diabetes were recruited during 2009-2012 and followed for 5 years, of whom 78 developed T2D, as diagnosed by the 75 g oral glucose tolerance test. Supine RHR was measured by electrocardiography. Using logistic regression analysis, we examined the association between RHR and incident T2D, and interaction with the homeostasis model assessment of insulin resistance (HOMA-IR) index. Causal mediation analysis was applied to decompose the effect of RHR on the outcome and estimate the proportion mediated by the HOMA-IR index. RESULTS: The sex- and age-adjusted cumulative incidence rate of T2D increased with increasing RHR. After adjustment for sex, age, waist circumference, current smoking status, alcohol use, habitual exercise, and cardiovascular disease medications, individuals with a RHR ≥80 bpm, compared with <60 bpm, showed an increased risk of incident T2D [odds ratio (OR), 2.89; 95 % confidence interval (CI), 1.07 to 7.80]. Multivariate adjusted OR for the total effect per 1 SD increase in RHR on incident T2D was 1.37 (95 % CI, 1.01 to 1.74) in the mediation analysis, and the proportion of the total indirect effect mediated by the HOMA-IR index was 27.5 % (95 % CI, 1.5 to 53.5). CONCLUSIONS: Approximately 30 % of the effect of RHR on incident T2D was explained by the indirect effect of insulin resistance.

Poor glycemic control rather than types of diabetes is a risk factor for sarcopenia in diabetes mellitus: The MUSCLES-DM study.

AIMS/INTRODUCTION: Though poor glycemic control and insulin treatment are reported to be associated with sarcopenia in type 2 diabetes, type 1 diabetes may be a stronger risk for sarcopenia. We therefore studied the effect of the type of diabetes, glycemic control, and insulin therapy on the prevalence and characteristics of sarcopenia. MATERIALS AND METHODS: A total of 812 Japanese patients with diabetes (type 1: n = 57; type 2: n = 755) were enrolled in this study. Sarcopenia was defined as low handgrip strength or slow gait speed and low appendicular skeletal muscle mass. RESULTS: Among participants aged ≥65 years, the sarcopenia prevalence rate was higher among patients with type 1 diabetes (20.0%) than among those with type 2 diabetes (8.1%). The prevalence rate of low handgrip strength was higher in type 1 diabetes (50.0%) than in type 2 diabetes (28.7%). In logistic regression analysis, type 1 diabetes was significantly associated with the prevalence of low handgrip strength. In logistic regression analysis, medication with insulin was significantly associated with the prevalence of sarcopenia; this association was not retained after adjusting for HbA1c. CONCLUSIONS: The prevalence of sarcopenia in older adult patients was higher in those with type 1 diabetes than in those with type 2 diabetes. Among the components of sarcopenia, the difference was most prominent in the frequency of low handgrip strength. Poor glycemic control rather than type of diabetes or insulin treatment was revealed to be a primary risk factor for sarcopenia in diabetes mellitus.

Association of Fish and Omega-3 Fatty Acid Intake with Carotid Intima-Media Thickness in Middle-Aged to Elderly Japanese Men and Women: The Toon Health Study.

Fish and omega-3 fatty acid consumption is known to be beneficial for cardiometabolic health. However, the related evidence for individuals with a relatively higher intake of fish or omega-3 unsaturated fatty acids, e.g., Japanese individuals, is scarce. Therefore, this study aimed to examine the association of fish and omega-3 fatty acid intakes with the carotid intima-media thickness (C-IMT) in the Japanese population. In total, 1803 Japanese men and women aged 30-84 years without a history of myocardial infarction or angina pectoris were included in the study. The fish and omega-3 fatty acid intakes were estimated using food frequency questionnaires. The C-IMT was measured using ultrasound imaging, and the participants were classified into three groups: normal, moderate (1.1 to 1.4 mm of maximum C-IMT), and severely increased C-IMT (≥1.5 mm). Multinomial logistic regression models were used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI) of the presence of moderately and severely increased C-IMT. The omega-3 fatty acid intake was shown to be associated with lower odds of severely increased C-IMT. The multivariable-adjusted OR (95%CI) was 0.55 (0.31-0.97; p for trend = 0.04). We also found a borderline significant negative association between fish intake and the presence of severely increased C-IMT. In conclusion, omega-3 fatty acid intake might protect against the development of atherosclerosis in the Japanese population.