Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project.

Purpose: Dairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults. Methods: This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P < 0.05. Results: In multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment. Conclusions: Dairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure. Clinical trial registry number and website where it was obtained: The Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.

Tryptophan metabolism and small fibre neuropathy: a correlation study.

Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (ß = -0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.

Association between Gut Microbiota and Muscle Strength in Japanese General Population of the Iwaki Health Promotion Project.

The association between the gut microbiota and muscle strength has garnered attention in the context of mitigating muscle decline. However, many study subjects have been individuals with existing illnesses or the elderly only. This study aims to elucidate the association between the gut microbiota and muscle strength indicators using grip strength/BMI in a large-scale study of community residents. The mean age of men (n = 442) and women (n = 588) was 50.5 (15.3) and 51.2 (15.9) years, respectively. The muscle strength indicator used was grip/BMI. The association between total read count and genus-level gut microbiota and muscle strength was analyzed. The mean grip/BMI was 1.8 (0.3) for men and 1.2 (0.2) for women. The genus of the gut microbiota that showed an association in both sexes was Eggerthella (men: ß = 0.18, CI: 0.04-0.31, p = 0.009; women: ß = 0.07, CI: 0.00-0.12, p = 0.028). Blautia, Eggerthella and Faecalibacterium were found to be significantly associated with grip/BMI in both the multiple regression analysis and Spearman's correlation analysis after the multiple comparison adjustment. These results suggest that an increase in Blautia and Eggerthella, coupled with a decrease in Faecalibacterium, may contribute to muscle strengthening or the suppression of muscle weakness.

Reduction in all-cause medical and caregiving costs through innovative health awareness projects in a rural area in Japan: a retrospective cohort study.

BACKGROUND: This study evaluates cost reduction in participants of a health awareness program (the Center of Healthy Aging Program, CHAP) in a Japanese rural area, characterized by an annual check-up and personalized interview on health issues and related risks immediately after the check-up. METHODS: This is a cross-sectional study using medical and caregiving costs and Japan-specific health check-up results in Hirosaki residents stored by the local government, which were individually-based linked to the CHAP information collected by Hirosaki University. This is the first study that used anonymized data with individually-based linkages to both a research institute and a local government in Japan under a strict limitation regarding linking to third-party data. We included residents who had been continuously enrolled for > 6 months as of 1 July 2015. We compared 5-year all-cause costs between three groups (with CHAP, with Japan-specific health check-up, and no check-up) using a multivariate negative binomial regression model considering risk factors including lifestyle habits and an inverse probability weight to adjust for baseline characteristics: age, sex, Charlson comorbidity index, baseline care level, and risk score of coronary heart diseases. RESULTS: A total of 384, 9805, and 32,630 residents aged 40-74 years were included for the CHAP, Japan-specific health check-up, and no check-up groups, respectively. The Japan-specific health check-up group showed older and higher Charlson comorbidity index than the others. After inverse probability weight adjusting, the amount of all-cause medical costs was significantly lower only in the CHAP group. Faster walking speed and exercise habits were independently associated with lower all-cause medical and caregiving costs. CONCLUSIONS: We demonstrated a 5-year all-cause cost reduction in residents who participated in the CHAP and also suggested the effect of exercise habits in Hirosaki, which indicated the significance of individually-based data linkages to external third-party data for all local governments to improve the health condition of residents.

A Cohort Study of the Influence of the 12-Component Modified Japanese Diet Index on Oral and Gut Microbiota in the Japanese General Population.

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.

Correction: Kanda et al. Body Compression Corrective Garment and Eating Behavioural Change for Weight Reduction: The Mutsu City Randomised Controlled Trial. Healthcare 2023, 11, 942.

In the original publication [...].

Association between reactive oxygen species production in neutrophils and liver fibrosis in the general population.

Fibrosis, induced by reactive oxygen species (ROS) production in neutrophils, has harmful effects on the liver and various other organs. However, little is known about the association between liver fibrosis and ROS levels in neutrophils in the general population. This large-scale epidemiological study aimed to determine the association between liver fibrosis and neutrophil-generated ROS levels according to age and sex in the general population. This cross-sectional study included 1,000 participants from a district health promotion project. Participants were grouped based on sex (male; female) and age (young, <65 years; old, ≥65 years). The four groups were as follows: male, young (n = 289); male, old (n = 100); female, young (n = 425); and female, old (n = 186). Liver fibrosis was assessed using the fibrosis 4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Basal and stimulated ROS were considered in the analysis. Multiple linear analyses showed (1) significant positive correlations between all liver fibrosis scores and basal ROS in the young groups, and (2) significant negative correlations between NFS and stimulated ROS in females. Preventing liver fibrosis through neutrophil-related immune system enhancement may avert the development of lifestyle-related diseases and infections.

Does the Protective Effect of Zinc on Telomere Length Depend on the Presence of Hypertension or Type 2 Diabetes? Results from the Iwaki Health Promotion Project, Japan.

Telomeres, repeated TTAGGG sequences at chromosomal ends, shorten with age and indicate cellular lifespan. Zinc can protect against telomere damage through its anti-oxidative effect. Meanwhile, telomere shortening was correlated with metabolic diseases of hypertension and type 2 diabetes. The objective of this study was to investigate whether the association between zinc and telomere length differs by the presence or absence of hypertension/type 2 diabetes. This is a cross-sectional study with 1064 participants of the Iwaki area, Japan. Multiple linear regression models were performed to test the hypothesis. A higher serum zinc concentration was significantly associated with a longer G-tail length (ß = 48.11, 95% confidence intervals [CI]: 25.69, 70.54, p < 0.001). By multivariate linear regression analysis, there was a significant positive association between zinc and G-tail length in both hypertensive (ß = 46.84, 95%CI: 9.69, 84.0, p = 0.014) and non-hypertensive groups (ß = 49.47, 95%CI: 20.75, 78.18, p = 0.001), while the association was significant only in the non-diabetes group (ß = 50.82, 95%CI: 27.54, 74.11, p < 0.001). In conclusion, higher zinc concentration was significantly associated with longer G-tail length. The protective effect of zinc on G-tail did not differ by hypertension status; however, it disappeared in individuals with type 2 diabetes.

Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan-Aspartate Aminotransferase Score.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

The Association between Gut Microbiota and Depression in the Japanese Population.

Depression is a leading cause of disease worldwide. The association between gut microbiota and depression has barely been investigated in the Japanese population. We analyzed Iwaki health check-up data collected from 2017 to 2019 and constructed generalized linear mixed models. The independent variable was the relative abundance of each of the 37 gut microbiota genera that were reported to be associated with depression. The dependent variable was the presence of depression assessed by the Center for Epidemiologic Studies Depression Scale. Potential confounders, including grip strength, gender, height, weight, smoking, and drinking habits, were adjusted in the regression models. Nine genera's regression coefficients (Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, Holdemania, Lactobacillus, Mitsuokella, and Oscillibacter) showed statistical significance after multiple comparisons adjustment. Among these nine gut bacteria genera, Alistipes, Blautia, Coprococcus, Dorea, Faecalibacterium, and Oscillibacter were reported to be associated with butyrate production in the intestine. Our results indicate that gut microbiotas may influence the depression condition of the host via the butyrate-producing process.

Mouse Model of Anti-Obesity Effects of Blautia hansenii on Diet-Induced Obesity.

Reportedly, a relationship exists between intestinal microflora and obesity-related lifestyle diseases. Blautia spp. a major intestinal microbiota, accounts for 3-11% of human intestinal microflora. Epidemiological reports have described that people with more visceral fat have less Blautia hansenii in their intestinal tract irrespective of age or gender. However, the effect of oral administration of heat-sterilized Blautia hansenii on obesity has not been clarified. Therefore, the aim of this study was to evaluate the effects of dietary Blautia hansenii administration on obesity in high-fat-diet-induced obesity in a mouse model. Heat-sterilized cells of Blautia hansenii were used. C57BL/6J mice (normal mice, n = 7) were fed with each experimental diet for nine weeks. Diets for experimentation were: normal-fat (NF) diets, high-fat (HF) diets, and high-fat + Blautia hansenii (HF + Blautia) diets. The HF + Blautia group was administered about 1 × 109 (CFU/mouse/day) of Blautia hansenii. During the periods of experimentation, body weight, food intake, water consumption, and fecal weight were recorded, and glucose tolerance tests were performed. Subsequently, the white adipose tissue (WAT) weight and serum components were measured. Short-chain fatty acid contents in the feces and cecum were analyzed. Furthermore, changes in the intestinal microflora were analyzed using meta-genomics analysis. Results showed that the total weight of WAT in the HF + Blautia group was significantly lower (13.2%) than that of the HF group. Moreover, the HF + Blautia group exhibited better glucose tolerance than the HF group. Productivity of short-chain fatty acids in the intestinal tract was at a significantly (p < 0.05) low level in the HF group; on the other hand, it recovered in the HF + Blautia group. Furthermore, there was a higher ratio of Blautia (p < 0.05) in the intestinal tracts of the HF + Blautia group than in the HF group. These results suggest that Blautia hansenii administration suppresses obesity induced by a high-fat diet.

Gender and age influence the association between gait speed and mild cognitive impairment in community-dwelling Japanese older adults: from the Japan Prospective Studies Collaboration for Ageing and Dementia (JPSC-AD).

BACKGROUND: Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender. METHODS: Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross-sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender. RESULTS: Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable-adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47-2.76) for females and 1.75 (1.29-2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age-dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups. CONCLUSIONS: Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender- and age-dependent clinical implications.

Definition of a Dietary Pattern Expressing the Intake of Vegetables and Fruits and Its Association with Intestinal Microbiota.

Daily dietary habits directly or indirectly influence the intestinal microbiota, and the resulting changes in its composition and metabolic activity alter the health conditions of the host. Although many studies have analyzed the association between individual nutrients/food items and intestinal microbiota, the assessment of the diet and intestinal microbiota from a macroscopic perspective has not yet been performed in Japan. Therefore, we focused on vegetables and fruits and aimed to identify dietary patterns of high intake of these foods and to examine their relationship with the intestinal microbiota. This cross-sectional study included 1019 healthy individuals aged ≥20 years in a rural area in northern Japan. Six dietary patterns were detected by factor analysis using the brief-type self-administered diet history questionnaire (BDHQ) data to identify the "vege pattern", which was the dietary pattern rich in vegetables and fruits. Permutational multivariate analysis of variance revealed changes in ß-diversity according to dietary patterns. In multivariable-adjusted models, the adherence to the vege pattern was positively correlated with α-diversity. This is the first study to reveal a correlation between intestinal microbiota and dietary habits rich in vegetables and fruits in a rural area of Japan.

Association Between Frequency of Social Contact and Brain Atrophy in Community-Dwelling Older People Without Dementia: The JPSC-AD Study.

BACKGROUND AND OBJECTIVES: Epidemiologic evidence has shown that social isolation, a low frequency of social contact with others, is associated with the risk of dementia and late-life depressive symptoms. Therefore, we hypothesized that low frequency of social contact may be involved in brain atrophy, and depressive symptoms may play some role in this relationship. We aimed to evaluate the association between low frequency of social contact and the volumes of various brain regions and to assess the extent to which depressive symptoms mediate these relationships from a large population-based multisite cohort study. METHODS: Dementia-free community-dwelling Japanese aged 65 years or older underwent brain MRI scans and a comprehensive health examination. Frequency of contact with noncohabiting relatives and friends was determined by asking a single question with 4 categories: everyday, several times a week, several times a month, and seldom. Total and regional brain volumes, intracranial volume (ICV), and white matter lesion volume were estimated using FreeSurfer software. The associations between frequency of social contact and brain volumes per ICV were examined using analyses of covariance. Mediation analyses were conducted to calculate the proportion of the associations explained by depressive symptoms. RESULTS: We included 8,896 participants. The multivariable-adjusted mean of the total brain volume in the group with the lowest frequency of social contact was significantly lower compared with that in the group with the highest frequency of social contact (67.3% vs 67.8%), with a significant increasing trend across the groups (p value for trend <0.001). The white matter lesion volume increased significantly with lower frequency of social contact (0.30% in the lowest frequency group vs 0.26% in the highest frequency group, p value for trend <0.001). Lower frequency of social contact was associated with smaller volumes in the temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala (all q values of false discovery rate correction <0.05). The relationships seemed to be partly mediated by depressive symptoms, which accounted for 15%-29% of the observed associations. DISCUSSION: Lower frequency of social contact was associated with decreased total and cognitive function-related regional brain volumes. In addition, depressive symptoms partially explained the association in community-dwelling older people without dementia in Japan.

Body Compression Corrective Garment and Eating Behavioural Change for Weight Reduction: The Mutsu City Randomised Controlled Trial.

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period (p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss.

Annual stability of the plasma Aß40/42 ratio and associated factors.

OBJECTIVE: The plasma Aß40/42 ratio is a biomarker of brain amyloidosis. However, the threshold difference between amyloid positivity and negativity is only 10-20% and fluctuates with circadian rhythms, aging, and APOE-ε4 during the decades of evolution of Alzheimer's disease. METHODS: Plasma Aß40 and Aß42 levels in 1472 participants aged between 19 and 93 years in the Iwaki Health Promotion Project for 4 years were statistically analyzed. RESULTS: The means and standard deviations of annual inter-individual coefficients of variation were 5.3 ± 3.2% for Aß40, 7.8 ± 4.6% for Aß42, and 6.4 ± 4.1% for the Aß40/42 ratio. No significant age-dependent changes were observed in inter-individual coefficients of variation. Age-dependent increases in Aß42 levels were suppressed, whereas those in the Aß40/42 ratio were enhanced in APOE-ε4 carriers. The change points of Aß42, Aß40, and the Aß40/42 ratio were 36.4, 38.2, and 43.5 years, respectively. In the presence of APOE-ε4, the Aß40/42 ratio increased in middle-aged and elderly subjects while Aß42 levels decreased in elderly subjects. INTERPRETATION: Individual values for Aß40, Aß42, and the Aß40/42 ratio did not fluctuate annually or in an age-dependent manner. If the plasma Aß40/42 ratio changes by more than 14.7% (+2 standard deviations) relative to age- and APOE-ε4-adjusted normal annual fluctuations, other biomarkers also need to be examined.

Effects of body compositions on the associations between ferritin and diabetes parameters among Japanese community dwellers.

BACKGROUND: Ferritin is associated with an increased prevalence of diabetes mellitus. Moreover, the ferritin levels differ across the body compositions. Although there were studies reporting the association of ferritin and diabetes, the alteration in ferritin-diabetes association by body composition differences is rarely explained. Thus, the aim of this study is to identify the effects of body compositions on the association between ferritin and diabetes parameters among the Japanese population. METHODS: This study analyzed the data of a cross-sectional study with 1065 subjects aged over 19 years in the Iwaki area, Japan. Independent variables were ferritin and body compositions, while dependent variables were blood sugar, HbA1c, and diabetes mellitus. Correlations between serum ferritin and blood sugar and HbA1c were analyzed using Spearman's Rank Correlation. Multivariate linear or logistic regressions were used to investigate the effects of body compositions (body fat percentage, muscle mass, or visceral fat level) on the ferritin-diabetes associations by adjusting the confounders. RESULTS: There were significant positive correlations between ferritin and blood sugar in both sexes (p < 0.05), while a significant correlation between ferritin and HbA1c was found only in females (p < 0.001). Higher ferritin was significantly associated with an increase in blood sugar in individuals with normal body fat percentage (lowest vs. highest quartile group, coefficient=5.07, 95 % confidence intervals [CI]: 1.48-8.65), normal visceral fat level (lowest vs. highest quartile group, coefficient=4.84, 95 % CI: 1.74-7.94), and very high muscle mass (lowest vs. highest quartile group, coefficient=14.14, 95 % CI: 5.00-23.29). CONCLUSIONS: By our study findings, individuals' body composition notably influenced the associations of serum ferritin and diabetes parameters, and the association was attenuated in obese individuals.

Association of prediabetes with reduced brain volume in a general elderly Japanese population.

OBJECTIVES: Diabetes frequently results in cognitive impairment, but it is less clear if brain health is adversely affected during the prediabetic stage. Our aim is to identify possible changes in brain volume as measured by magnetic resonance imaging (MRI) in a large elderly population stratified according to level of "dysglycemia." METHODS: This is a cross-sectional study of 2144 participants (median age 69 years, 60.9% female) who underwent 3-T brain MRI. Participants were divided into 4 dysglycemia groups based on HbA1c levels (%): normal glucose metabolism (NGM) (< 5.7%), prediabetes (5.7 to < 6.5%), undiagnosed diabetes (6.5% or higher), and known diabetes (defined by self-report). RESULTS: Of the 2144 participants, 982 had NGM, 845 prediabetes, 61 undiagnosed diabetes, and 256 known diabetes. After adjustment for age, sex, education, body weight, cognitive status, smoking, drinking, and disease history, total gray matter volume was significantly lower among participants with prediabetes (0.41% lower, standardized ß = - 0.0021 [95% CI - 0.0039, - 0.00039], p = 0.016), undiagnosed diabetes (1.4% lower, standardized ß = - 0.0069 [95% CI - 0.012, - 0.002], p = 0.005), and known diabetes (1.1% lower, standardized ß = - 0.0055 [95% CI - 0.0081, - 0.0029], p < 0.001) compared to the NGM group. After adjustment, total white matter volume and hippocampal volume did not differ significantly between the NGM group and either the prediabetes group or the diabetes group. CONCLUSION: Sustained hyperglycemia may have deleterious effects on gray matter integrity even prior to the onset of clinical diabetes. KEY POINTS: • Sustained hyperglycemia has deleterious effects on gray matter integrity even prior to the onset of clinical diabetes.

Plasma ApoE4 Levels Are Lower than ApoE2 and ApoE3 Levels, and Not Associated with Plasma Aß40/42 Ratio as a Biomarker of Amyloid-ß Amyloidosis in Alzheimer's Disease.

BACKGROUND: APOE4 is the strongest risk factor for Alzheimer's disease (AD). However, limited information is currently available on APOE4 and the pathological role of plasma apolipoprotein E (ApoE) 4 remains unclear. OBJECTIVE: The aims of the present study were to measure plasma levels of total ApoE (tE), ApoE2, ApoE3, and ApoE4 using mass spectrometry and elucidate the relationships between plasma ApoE and blood test items. METHODS: We herein examined plasma levels of tE, ApoE2, ApoE3, and ApoE4 in 498 subjects using liquid chromatograph-mass spectrometry (LC-MS/MS). RESULTS: Among 498 subjects, mean age was 60 years and 309 were female. tE levels were distributed as ApoE2/E3 = ApoE2/E4 >ApoE3/E3 = ApoE3/E4 >ApoE4/E4. In the heterozygous group, ApoE isoform levels were distributed as ApoE2 >ApoE3 >ApoE4. ApoE levels were not associated with aging, the plasma amyloid-ß (Aß) 40/42 ratio, or the clinical diagnosis of AD. Total cholesterol levels correlated with the level of each ApoE isoform. ApoE2 levels were associated with renal function, ApoE3 levels with low-density lipoprotein cholesterol and liver function, and ApoE4 levels with triglycerides, high-density lipoprotein cholesterol, body weight, erythropoiesis, and insulin metabolism. CONCLUSION: The present results suggest the potential of LC-MS/MS for the phenotyping and quantitation of plasma ApoE. Plasma ApoE levels are regulated in the order of ApoE2 >ApoE3 >ApoE4 and are associated with lipids and multiple metabolic pathways, but not directly with aging or AD biomarkers. The present results provide insights into the multiple pathways by which peripheral ApoE4 influences the progression of AD and atherosclerosis.

Association between the Change in Blood Pressure during Normotensive Pregnancy and the Development of Hypertension in Later Life.

Introduction: Women who experience maternal complications, including pre-eclampsia, have a higher risk of cardiovascular disease development. Although the mechanism remains unclear, there is a hypothesis that pregnancy would be a stress test for cardiovascular disease. This study aimed to investigate whether changes in blood pressure during pregnancy would be associated with developing hypertension, which is a main risk of cardiovascular disease. Methods: We conducted a retrospective study by collecting Maternity Health Record Books from 735 middle-aged women. Of these, 520 women were selected based on our criteria. 138 were defined as the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of >140/90 mmHg at the survey. The rest 382 were defined as the normotensive group. We compared the blood pressures of the hypertensive group with those of the normotensive group during pregnancy and postpartum. Then, 520 women were divided into quartiles (Q1-Q4) according to their blood pressures during pregnancy. After the changes in blood pressure for each gestational month relative to nonpregnant measurements were calculated, the changes in blood pressure were compared among the four groups. Additionally, the rate of developing hypertension was evaluated among the four groups. Results: The average age of the participants was 54.8 years (range: 40-85 years) at the time of the study and 25.9 years (range: 18-44 years) at delivery. There were significant differences in blood pressure during pregnancy between the hypertensive group and the normotensive group. Meanwhile, these two groups did not indicate any differences in blood pressure in postpartum. Higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. The rate of development of hypertension in each group of systolic blood pressure was 15.9% (Q1), 24.6% (Q2), 29.7% (Q3), and 29.7% (Q4). The rate of development of hypertension in each group of diastolic blood pressure (DBP) was 18.8% (Q1), 24.6% (Q2), 22.5% (Q3), and 34.1% (Q4). Conclusions: Changes in blood pressure during pregnancy are small in women who have a higher risk of hypertension. Levels of blood pressure during pregnancy may be reflected in individual stiffness of blood vessels by the burden of pregnancy. If so, levels of blood pressure would be used to facilitate highly cost-effective screening and interventions for women with a high risk of cardiovascular diseases.