Neuromuscular electrical stimulation increases serum brain-derived neurotrophic factor in humans.

Brain-derived neurotrophic factor (BDNF) plays several important roles in nervous system function including neuronal growth and plasticity. The purpose of the present study was to clarify whether neuromuscular electrical stimulation (NMES) and voluntary exercise to the same integrated force as by the NMES-induced exercise would enhance serum BDNF. Eleven healthy male subjects completed three interventions (NMES, voluntary exercise, and resting interventions) for 20 min on different days. In the NMES intervention, NMES was applied to the quadriceps femoris muscles. The stimulus intensity of NMES was progressively increased to the highest tolerated intensity during the experiment. In the voluntary exercise intervention, subjects performed an isometric knee-extension task; in this intervention, the target torque was calculated in accordance with the integrated force of knee extension obtained during the NMES intervention. In the resting intervention, subjects relaxed in a sitting posture. We measured serum BDNF, blood lactate, heart rate, oxygen uptake, respiratory ratio, and blood pressure. Serum BDNF was increased in the NMES (p = 0.003) and voluntary exercise interventions (p = 0.004) after each intervention. At the post-timepoint, serum BDNF in the NMES intervention was highest among all interventions (p = 0.038) and significantly higher than in the voluntary exercise (p = 0.036) and resting (p = 0.037) interventions. Our results showed that NMES was more effective for enhancing serum BDNF than voluntary exercise at least when employing the same method and integrated force.

Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight.

Xanthine oxidoreductase (XOR), an enzyme of uric acid formation from hypoxanthine and xanthine, is recognized as a source of oxidative stress. Plasma activity of XOR has been reported to be a biomarker of metabolic disorders associated with obesity, liver dysfunction, insulin resistance, hyperuricemia and adipokines. We investigated longitudinal change in plasma XOR activity, which was determined by using mass spectrometry and liquid chromatography to detect [13C2, 15N2]-uric acid using [13C2, 15N2]-xanthine as a substrate, in 511 subjects (male/female: 244/267) of the Tanno-Sobetsu Study in the years 2016 and 2017. Plasma XOR activity in a basal state was significantly higher in men than in women, but no significant sex difference was observed in annual change in plasma XOR activity. Annual change in plasma activity of XOR was positively correlated with changes in each parameter, including body weight (r = 0.203, p < 0.001), body mass index, diastolic blood pressure, aspartate transaminase (AST) (r = 0.772, p < 0.001), alanine transaminase (r = 0.647, p < 0.001), γ-glutamyl transpeptidase, total cholesterol, triglycerides, uric acid, fasting glucose and HbA1c. Multivariate regression analysis demonstrated that change in AST and that in body weight were independent predictors of change in plasma XOR activity after adjustment of age, sex and changes in each variable with a significant correlation without multicollinearity. In conclusion, annual change in plasma XOR activity is independently associated with changes in liver enzymes and body weight in a general population. Improvement of liver function and reduction of body weight would decrease plasma XOR activity and its related oxidative stress as a therapeutic strategy.

Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population.

BACKGROUND: Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR promotes oxidative stress-related tissue injury. We investigated the associations between metabolic parameters and plasma XOR activity measured by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry to detect [13C2,15N2]-uric acid using [13C2,15N2]-xanthine as a substrate.Methods and Results:A total of 627 Japanese subjects (M/F, 292/335) from the Tanno-Sobetsu Study, a population-based cohort, were recruited. Plasma XOR activity was significantly higher in males than in females, and habitual smoking was associated with elevation of activity. Plasma XOR activity was positively correlated with body mass index (BMI; r=0.323, P<0.001), waist circumference, blood pressure, and levels of liver enzymes including alanine transaminase (r=0.694, P<0.001), uric acid (r=0.249, P<0.001), triglycerides (r=0.312, P<0.001), hemoglobin A1c, fasting glucose, insulin and HOMA-R (r=0.238, P<0.001) as a marker of insulin resistance and was negatively correlated with high-density lipoprotein cholesterol level. On stepwise and multivariate regression analyses, BMI, smoking and levels of alanine transaminase, uric acid, triglycerides and HOMA-R were independent predictors of plasma XOR activity after adjustment for age and gender. CONCLUSIONS: Plasma XOR activity is a novel biomarker of metabolic disorders in a general population.

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication.

BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.Methods and Results:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.

Associations of High-Density Lipoprotein Particle and High-Density Lipoprotein Cholesterol With Alcohol Intake, Smoking, and Body Mass Index　- The INTERLIPID Study.

BACKGROUND: Recently, high-density lipoprotein particles (HDL-P) have been found to be more strongly inversely associated with coronary artery disease (CAD) risk than their counterpart, HDL cholesterol (HDL-C). Given that lifestyle is among the first targets in CAD prevention, we compared the associations of HDL-P and HDL-C with selected lifestyle factors. Methods and Results: We examined 789 Japanese participants of the INTERLIPID Study: men (n=386) and women (n=403) aged 40-59 years in 1996-1998. Participants treated for dyslipidemias were excluded. Lifestyle factors included alcohol intake, smoking amount, and body mass index (BMI). Multivariable linear regression was used for cross-sectional analyses of these factors with HDL-P, HDL-C, HDL-P size subclasses (small, medium and large) and mean HDL-P size. In men, higher alcohol intake was associated with higher HDL-P and higher HDL-C. The associations of alcohol, however, were strongest with HDL-P. A higher smoking amount tended to be associated with lower HDL-P and HDL-C. In contrast, BMI was not associated with HDL-P, but was strongly inversely associated with HDL-C. While alcohol intake favored larger mean HDL-P size, smoking and BMI favored a lipid profile with smaller HDL-P subclasses and overall smaller mean HDL-P size. Similar, but generally weaker results were observed in women. CONCLUSIONS: Although both HDL-P and HDL-C are parameters of HDL, they have different associations with alcohol, smoking and BMI.

Relationship Between Socioeconomic Status and the Prevalence of Underweight, Overweight or Obesity in a General Japanese Population: NIPPON DATA2010.

BACKGROUND: Socioeconomic status (SES) imbalances in developed and developing countries may result in individuals being overweight and obese. However, few studies have investigated this issue in Japan. We herein examined the relationship between SES and being underweight, overweight or obese according to sex and age groups (20-64 or ≥65 years) in Japan. METHODS: In 2010, we established a cohort of participants in the National Health and Nutrition Survey of Japan. We divided 2,491 participants (1,081 men and 1,410 women) according to the WHO definitions of underweight, overweight or obesity and performed multinomial logistic analyses using BMI <18.5 kg/m2 (underweight), BMI 25.0-29.9 kg/m2 (overweight), and BMI ≥30.0 kg/m2 (obese) versus BMI 18.5-24.9 kg/m2 (normal) as the outcome, with SES groups as the main explanatory variables. RESULTS: In adult men, a lower education level relative to a higher education level was inversely associated with obesity after adjustments for other SESs (odds ratio [OR] 0.41; 95% confidence interval [CI], 0.18-0.96). However, in adult women, lower education level was positively associated with being overweight and obese (OR 1.67; 95% CI, 1.07-2.49 for overweight and OR 2.66; 95% CI, 1.01-7.01 for obese). In adult women, a lower household income was positively associated with being overweight and obese (obese: OR 4.84; 95% CI, 1.36-17.18 for those with a household income <2 million JPY relative to those with ≥6 million JPY). CONCLUSIONS: In adult women, a lower education level and lower household income were positively associated with being overweight or obese. In contrast, in adult men, a lower education level was inversely associated with obesity. Gender and age differences in SESs affect the prevalence of being overweight or obese.

Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid.

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.

A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Age-specific impact of diabetes mellitus on the risk of cardiovascular mortality: An overview from the evidence for Cardiovascular Prevention from Observational Cohorts in the Japan Research Group (EPOCH-JAPAN).

BACKGROUND: Diabetes mellitus is a strong risk factor for cardiovascular disease. However, the age-specific association of diabetes with cardiovascular risk, especially in the elderly, remains unclear in non-Western populations. METHODS: A pooled analysis was conducted using 8 cohort studies (mean follow-up period, 10.3 years) in Japan, combining the data from 38,854 individual participants without history of cardiovascular disease. In all, 1867 of the participants had diabetes, defined based on the 1998 World Health Organization criteria. The association between diabetes and the risk of death from cardiovascular disease, coronary heart disease (CHD), and stroke was estimated using a stratified Cox model, accounting for variability of baseline hazard functions among cohorts. RESULTS: During the follow-up, 1376 subjects died of cardiovascular disease (including 268 of coronary heart disease and 621 of stroke). Diabetes was associated with an increased risk of cardiovascular death after multivariable adjustment (hazard ratio [HR] 1.62; 95% confidence interval [CI], 1.35-1.94). Similarly, diabetes was a risk factor for CHD (HR 2.13; 95% CI, 1.47-3.09) and stroke (HR 1.40; 95% CI, 1.05-1.85). In the age-stratified analysis of the risk of cardiovascular death, the relative effects of diabetes were consistent across age groups (p for heterogeneity = 0.18), whereas the excess absolute risks of diabetes were greater in participants in their 70s and 80s than in younger subjects. CONCLUSIONS: The management of diabetes is important to reduce the risk of death from cardiovascular disease, not only in midlife but also in late life, in the Japanese population.

Relationship of three different types of low-carbohydrate diet to cardiometabolic risk factors in a Japanese population: the INTERMAP/INTERLIPID Study.

PURPOSE: Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations. METHODS: We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40-59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA). RESULTS: In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = -0.010, P = 0.018). CONCLUSIONS: All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.

Physical activity changes in the winter in older persons living in northern Japan: a prospective study.

BACKGROUND: Physical activity affects physical and mental health, prevents disease, and improves quality of life. However, physical activity also decreases with age in older persons, and is affected by adverse climatic periods. This study examined changes in physical activity during the winter season in older persons (≥75 years of age) who were living in northern Japan, and evaluated the factors that were associated with this decline. METHODS: A total of 201 older persons (83 men and 118 women; mean age, 79.7 ± 3.8 years) participated in two separate tests that were conducted in November 2012 and February 2013. Physical activity was monitored using the Kenz Lifecorder, and mean step counts and moderate-vigorous physical activity (MVPA) times were calculated over a 1-week period. We also measured body mass index, handgrip strength, normal walking speed, functional capacity, exercise habits, snow-shovelling habits, a change in frequency (between early winter and midwinter) of outdoor excursions, the length of outdoor excursions, social support, and morbidity. RESULTS: In the group that maintained their frequency of outdoor excursions, step counts significantly increased during midwinter compared with early winter (p < 0.01). In the group with a lower frequency of outdoor excursions, MVPA was significantly decreased during midwinter compared with early winter (p < 0.05). After adjusting for other variables, logistic regression analysis showed that weakness (odds ratio [OR]: 2.89, p < 0.05) was independently associated with a decline in step counts. Age (OR: 1.12, p < 0.05) and a change in frequency of outdoor excursions (OR: 0.75, p < 0.01) were independently associated with a decline in MVPA. CONCLUSIONS: Older persons should be supported in their attempts to go outdoors during midwinter. They should be provided with intervention programs to increase their physical activity at home.

Subjective physical and cognitive age among community-dwelling older people aged 75 years and older: differences with chronological age and its associated factors.

OBJECTIVE: The aim of this cross-sectional study was to determine the associations between self-reported subjective physical and cognitive age, and actual physical and cognitive functions among community-dwelling older people aged 75 years and older. METHOD: The sample comprised 275 older adults aged 75-91 years. Two questions were asked regarding subjective age: 'How old do you feel physically?' and 'How old do you feel cognitively?' To assess physical functions, we measured handgrip strength, knee extension strength, standing balance and walking speed. Tests of attention, executive function, processing speed and memory were performed to assess actual cognitive function. RESULTS: Subjective physical and cognitive age was associated with performance on all of the physical and cognitive tests, respectively (p < 0.01). We also found that older adults who reported themselves as feeling older than their chronological age had a slower walking speed and lower scores for word-list memory recall than those who did not report themselves as feeling older than their actual age. CONCLUSION: These findings suggest that promoting a fast walking speed and good memory function may help to maintain a younger subjective physical and cognitive age in older adults aged 75 years and older.

Does glycemic control reverse dispersion of ventricular repolarization in type 2 diabetes?

BACKGROUND: Abnormal ventricular repolarization is a predictor of cardiovascular mortality. In this study, we tested the hypothesis that glycemic control reverses abnormal ventricular repolarization in patients with type 2 diabetes. METHODS: We analyzed longitudinal changes in repolarization indices of electrocardiograms in retrospectively enrolled 44 patients with type 2 diabetes and 44 age-matched healthy subjects. RESULTS: In the diabetic group, BMI was greater, levels of HbA1c (10.0 ± 1.6 vs. 5.6 ± 0.3%) and triglyceride were higher and level of HDL cholesterol was lower than those in the control group. Although mean QTc intervals were similar (413.6 ± 18.5 vs. 408.3 ± 22.7 ms), QT dispersion (41.8 ± 15.4 vs. 28.7 ± 7.7 ms) and Tpeak-Tend in lead V5 (83.6 ± 13.6 vs. 71.3 ± 10.3 ms) were significantly longer in the diabetic group than in the control group, indicating increased heterogeneity of ventricular repolarization in type 2 diabetes. During follow-up of 36 patients in the diabetic group for 787 ± 301 days, HbA1c level decreased to 7.3 ± 1.6%, while BMI did not significantly change. In contrast to HbA1c, QT dispersion (45.8 ± 15.0 ms) and Tpeak-Tend in lead V5 (83.6 ± 10.6 ms) were not significantly reduced during the follow-up period. There was no correlation between the change in HbA1c and the change in QT dispersion or Tpeak-Tend. CONCLUSIONS: Increased heterogeneity of ventricular repolarization in type 2 diabetic patients was not reduced during the relatively short follow-up period despite significantly improved glycemic control.

Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. METHODS: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. RESULTS: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. CONCLUSIONS: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

The Contributions of Knee Extension Strength and Hand Grip Strength to Factors Relevant to Physical Frailty: The Tanno-Sobetsu Study.

Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Consumption of dairy products and death from cardiovascular disease in the Japanese general population: the NIPPON DATA80.

BACKGROUND: Recent Western studies show an inverse association between milk and dairy product intake and cardiovascular disease (CVD). We studied the association between consumption of milk and dairy products and CVD death in Japan. METHODS: Men and women aged 30 years or older were followed for 24 years. All had participated in a national nutrition survey in 300 health districts throughout Japan in 1980. The Cox proportional hazards model was used to assess mortality risk according to tertiles of milk and dairy product intake, with the high consumption group as reference. Hazard ratios (HRs) per 100-g/day increase in consumption were also estimated. RESULTS: During the 24-year follow-up period, there were 893 CVD deaths, 174 deaths from coronary heart disease (CHD), and 417 stroke deaths among 9243 participants. For women, the HRs for death from CVD, CHD, and stroke in the low consumption group were 1.27 (95% CI: 0.99-1.58; P for trend = 0.045), 1.67 (0.99-2.80; P = 0.02), and 1.34 (0.94-1.90; P = 0.08), respectively, after adjustment for age, body mass index, smoking status, alcohol drinking habits, history of diabetes, use of antihypertensives, work category, and total energy intake. With each 100-g/day increase in consumption of milk and dairy products, HRs tended to decrease for deaths from CVD (HR, 0.86; 95% CI, 0.74-0.99), CHD (0.73; 0.52-1.03), and stroke (0.81; 0.65-1.01) in women. No significant association was observed in men. CONCLUSIONS: Consumption of milk and dairy products was inversely associated with CVD death among women in Japan.

[Hypertension].

As the population of obesity increases by the change of living habits, hypertensive prevalence increases in particularly middle-aged Japanese men. Obesity affects the development of hypertension and other metabolic risk factors. And the mechanism of development hypertension has been investigated from adipocyte standpoints. Recently, physiology or pathophysiology functions of adipocyte including TNF-alpha or leptin have been elucidated. Leptin makes sympathetic nerve activity by effects of the central nerve system. TNF-alpha induces insulin resistance. These effects cause hypertension. In particular, knowledge of insulin resistance has been clear by epidemiologic studies. Hypertension with obesity is often refractory, and it is poor prognosis. We have to develop an effective prevention and therapy in hypertension with obese subjects.

Preserved Lower Limb Muscle Mass Prevents Insulin Resistance Development in Nondiabetic Older Adults.

OBJECTIVE: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults. DESIGN: A 2-year follow-up cohort. SETTING AND PARTICIPANTS: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019. METHODS: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated. RESULTS: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline. CONCLUSIONS AND IMPLICATIONS: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults.

Small High-Density Lipoprotein and Omega-3 Fatty Acid Intake Differentiates Japanese and Japanese-Americans: The INTERLIPID Study.

AIM: To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors. METHODS: Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's 1H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis. RESULTS: Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI. CONCLUSIONS: Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.

Circulating plasma phospholipid fatty acid levels as a biomarker of habitual dietary fat intake: The INTERMAP/INTERLIPID Study.

BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.