IntroductionThe unmitigated incidence of cardiometabolic diseases, such as type 2 diabetes and metabolic syndrome, has gained attention in Japan. ‘Big data’ can be useful to clarify conflicting observations obtained from studies with small samples and about rare conditions that are often neglected. We epidemiologically address these issues using data from health check-ups conducted in Kanagawa Prefecture, the prefecture with the second largest population in Japan, in the Kanagawa Investigation of the Total Check-up Data from the National Database (KITCHEN).Methods and analysisThis research consists of a series of population-based cross-sectional studies repeated from 2008–2014 and 6-year cohort studies. Since 2017, we have reviewed the data of people living in Kanagawa Prefecture who underwent a health check-up mainly for general health and the prevention of metabolic syndrome. The sample size ranges from 1.2 million to 1.8 million people in the cross-sectional studies and from 370 000 to 590 000 people in the cohort studies. These are people aged 40–74 years, whose clinical parameters were measured and who responded individually to a questionnaire. We investigate potential associations and causalities of various aetiologies, including diabetes and metabolic syndrome, using clinical data and lifestyle information. With multidisciplinary analysis, including data-driven analysis, we expect to obtain a wide range of novel findings, to confirm indeterminate previous findings, especially in terms of cardiometabolic disease, and to provide new perspectives for human health promotion and disease prevention.Ethics and disseminationEthical approval was received from the Ethics Committee of Kanagawa University of Human Services (10-43). The protocol was approved in December 2016 by the Japanese Ministry of Health, Labour and Welfare (No. 121). The study results will be disseminated through open platforms including journal articles, relevant conferences and seminar presentations.

Background: Many studies have shown that low copy number variation (CNV) of the salivary amylase gene (AMY1) and low serum amylase concentration are associated with impaired glucose metabolism and obesity. We aimed to clarify the conflicting results of previous studies by examining AMY1 expression and metabolic indices in a homogenous group of healthy participants.Methods: Sixty healthy non-obese young Japanese women aged 20 -39 years were examined for AMY1 CNV, salivary amylase, body mass index (BMI) and serum parameters including glycated hemoglobin (HbA1c), ketones, and total, salivary and pancreatic amylase. Respiratory quotient at rest and changes in blood glucose after starch loading were also examined.Results: AMY1 CNV (range, 4 -14) and the level of serum salivary amylase were correlated inversely with HbA1c (r = -0.36, P = 0.003 and r = -0.30, P = 0.02, respectively), whereas the percentage of serum salivary amylase in total serum amylase was positively correlated with blood glucose at 30 and 45 min after starch loading (r = 0.38, P = 0.004 and r = 0.27, P = 0.04, respectively). The level of serum total amylase, but not AMY1 CNV, was correlated inversely with BMI (r = -0.29, P = 0.02). Logistic regression analysis showed that low AMY1 CNV (4 -7) was significantly associated with an HbA1c of ≥ 5.4% (34 mmol/mol) even after adjustment for age, BMI and energy consumption, compared with high AMY1 CNV (8 -14).Conclusions: Although a higher percentage of serum salivary amylase was associated with higher levels of blood glucose at the early stage after starch loading, low AMY1 CNV was associated with chronic unfavorable glucose metabolism in healthy non-obese young women in Japan.

Recent reports have shown an association between obesity and periodontitis, but the precise relationship between these conditions has yet to be clarified. The purpose of this study was to compare the status of periodontitis, tooth loss, and obesity. Participants comprised 235 patients at the Center for Medical and Dental Collaboration in Kanagawa Dental University Hospital between 2018 and 2020. Clinical examinations such as blood testing, body composition analysis, periodontal measurement, assessment of chewing ability, salivary testing, and oral malodor analysis were performed. Periodontal inflamed surface area (PISA) was significantly associated with the number of teeth and body mass index (BMI). The number of teeth was negatively associated with age, but positively with chewing ability. Chewing ability was associated negatively with age, and positively with high-sensitivity C-reactive protein (hsCRP). The level of methyl-mercaptan in breath and protein and leukocyte scores from salivary testing were positively associated with PISA. The rate of insufficient chewing ability was increased in subjects with hemoglobin (Hb)A1c ≥ 7%. The high PISA group showed increased hsCRP. BMI as an obesity marker was positively associated with PISA, indicating periodontal inflammation. Chewing ability was related to serum markers such as HbA1c and hsCRP.

Background: Aspartate aminotransferase (AST) is pivotal in amino acid metabolism. However, the serum activity of AST, which leaks from multiple organs, including liver and skeletal muscle, is unknown in older underweight people, who are at high risk of skeletal muscle mass loss. Therefore, we measured the serum activities of AST and alanine aminotransferase (ALT), a liver-specific transaminase, in a large, community-based cross-sectional study. Methods: Clinical parameters and lifestyles were characterized in 892,692 Japanese people with a wide range of body mass indexes (BMIs; 13–39.9 kg/m2), aged 40–74 years old, who were undergoing a medical checkup. A general linear model was used to calculate the estimated mean of serum AST (EM-AST) in each BMI category after adjustment for confounding factors, including past history of cardiovascular disease and waist circumference. Results: Severe underweight (BMI 13–14.9 kg/m2) was present in 910 subjects (0.1%). Raw serum AST showed a J-shaped relationship with BMI, which was blunted in older subjects (60–74 years), and similar, but less curved relationships were identified for raw serum ALT and gamma-glutamyl transferase. These J-shaped relationships in serum AST were not altered when subjects were classified by sex, past history of cardiovascular and cerebrovascular diseases, and habitual exercise. EM-AST showed a U-shaped relationship, with a minimum at BMI 21–22.9 kg/m2, regardless of age and waist circumference. Conclusions: High serum AST but normal serum ALT is highly prevalent in older underweight people and might reflect skeletal muscle pathology.

Background: It is unknown whether extremely high high-density lipoprotein cholesterol (HDL-C) has a protective effect against diabetes, which plays a key role in cardiovascular disease. Methods: In a community-based cohort study of 387,642 subjects (40–68 years old) without diabetes, the incidence of diabetes 6 years later was determined according to baseline HDL-C (≤39, 40–49, 50–59, 60–69, 70–79, 80–89, 90–99, 100–109, or ≥110 mg/dL). Results: At baseline, HDL-C ≥100 mg/dL was present in 12,908 subjects (3.3%), who had a better lipid profile and a high prevalence of heavy alcohol consumption and habitual exercise. The incidences of diabetes according to baseline HDL-C were 14.7, 11.2, 7.7, 5.3, 3.8, 2.8, 2.7, 2.5, and 3.5 per 1000 person-years, respectively. The adjusted relative risks (ARRs) for diabetes showed concave relationships with HDL-C, with minima at 80–89 mg/dL. The ARR (95% CI) of the lowest HDL-C category was 1.56 (1.40–1.74) and of the highest HDL-C category was 1.46 (1.18–1.81) (both p < 0.001), regardless of alcohol consumption. The latter ARR was higher in men (n = 219,047) (2.45 (1.70–3.53), p < 0.0001) after adjustment for baseline glycemic index. Conclusion: Both extremely high and low HDL-C represent risks for diabetes, which deserves further study.