Hirofumi Ohnishi

Metabolic Syndrome and Cardiac Disease in Japanese Men: Applicability of the Concept of Metabolic Syndrome Defined by the National Cholesterol Education Program–Adult Treatment Panel III to Japanese Men—The Tanno and Sobetsu Study

Results of a 6-year follow-up study were used to determine whether the concept of and the criteria for metabolic syndrome as defined by the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP III) can be applied to Japanese men for prediction of the occurrence of cardiac disease. The subjects were 808 men who underwent mass health check-ups in 1993 and who were not on medication for hypertension, diabetes or hyperlipidemia. Individuals who had hypertriglyceridemia, hypo-high density lipoprotein (HDL) cholesterolemia, high blood pressure, and/or high fasting plasma glucose levels were identified on the basis of the NCEP-ATP III criteria. Not in conformity with the NCEP-ATP III, however, a cut-off value of 85 cm was used for waist girth as an indicator of abdominal obesity. The subjects who had 3 or more risk factors were judged as having metabolic syndrome. The proportion of subjects having metabolic syndrome was 25.3%. In the 6-year follow-up study, cardiac disease occurred in 11.7% of the subjects in the metabolic syndrome group and in 6.7% of the subjects in the non-metabolic syndrome group. Results of regression analysis using Coxs proportional hazards model showed that subjects in the metabolic syndrome group had a 2.2-times greater risk of developing cardiac disease than did subjects in the non-metabolic syndrome group. The concept of metabolic syndrome as defined in the NCEP-ATP III was therefore considered to be useful for predicting the occurrence of cardiac disease in Japanese men.

Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Objective Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. Methods From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1∼5 in their serum samples were assayed. Results Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMA-R after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. Conclusions Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting pre-clinical stage of metabolic syndrome, especially insulin resistance, in the general population.

Relationship between visceral fat and cardiovascular disease risk factors: the Tanno and Sobetsu study.

We assessed the amount of visceral fat using ultrasonography (US) and studied its relationship to cardiovascular disease risk factors, particularly blood pressure. The subjects in the first study were 45 male and 61 female outpatients. We measured the visceral fat area (VFA) of each subject using abdominal CT and waist circumference (WC), and visceral fat distance (VFD) using US. The subjects in the second study were 353 male and 457 female inhabitants of a rural community, for whom VFD and WC were measured. We divided subjects into tertiles based on VFD and WC, and studied the relationship between each group and individual risk factors. In an analysis of outpatient subjects, the correlation coefficient between VFA and VFD was satisfactory: r=0.660 for men and r=0.643 for women. In the analysis of the rural subjects, the high VFD group had a significantly higher odds ratio than the low VFD group in high blood pressure (HBP) and hypertriglyceridemia (HTG) for men and in HBP, HTG and low high-density lipoprotein cholesterolemia (LHDL) for women. Moreover, adjusting VFD for body mass index revealed that, in comparison to WC, VFD was significantly related to risk factors. VFD was used as an independent variable in multiple regression analysis with blood pressure level as a dependent variable; no significant association between WC and blood pressure was obtained. Visceral fat assessment by US may be useful for epidemiological study and for clinics with no abdominal CT equipment for identifying high-risk individuals, such as those with metabolic syndrome.

Incidence of Type 2 Diabetes in Individuals With Central Obesity in a Rural Japanese Population: The Tanno and Sobetsu Study

According to the new International Diabetes Federation (IDF) definition of metabolic syndrome, for a person to be defined as having metabolic syndrome they must have central obesity defined by waist circumference (1). In the definition, there are some ethnic or country-specific differences in the cutoff points of waist circumference, and Japanese cutoff points have been separately established in the IDF definition (≥85 cm for men and ≥90 cm for women). The Japanese Society of Internal Medicine and eight related scientific societies have also jointly announced new Japanese criteria of metabolic syndrome using the same cutoff points of waist circumference (2). However, the impact of central obesity using the cutoff points as a risk of type 2 diabetes is not known. In this study, we investigated the incidence of type 2 diabetes in citizens of two rural communities in Japan to determine the relationship between type 2 diabetes and central obesity, and we also investigated the independent effects of central obesity compared with those of overall obesity. The subjects were 348 men and 523 women selected from 938 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, both in 1994 and 2003 or 2004. The following participants in medical examinations in 1994 were excluded: those with missing data on blood …

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

BackgroundFatty 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.MethodsFrom 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.ResultsSerum 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’.ConclusionsElevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

Incidence of insulin resistance in obese subjects in a rural Japanese population: The Tanno and Sobetsu study

Objectives:  Although it is well known that obesity is closely related to insulin resistance, the incidence of the development of insulin resistance in people with obesity is not known. In this study, we investigated the incidence of insulin resistance in citizens of two rural communities in Japan.

Relationship between insulin resistance and accumulation of coronary risk factors

We examined correlations between the frequency of insulin resistance and the accumulation of coronary risk factors in residents of rural comities in Japanese, using simple criteria for determination of insulin resistance based on evaluation by the euglycaemic‐hyperinsulinaemic glucose clamp (GC) method. The subjects were 376 men and 589 women living in two rural communities in Japan. We measured body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), HDL cholesterol (HDL), and homeostasis model assessment (HOMA‐R). Correlations between HOMA‐R and those parameters were examined. To assess the existence of insulin resistance in these subjects, we used a practical index based on the GC method. The subjects with value of HOMA‐R ≥ 1.73 have insulin resistance. In addition, the HOMA‐R was divided into five quantiles based on the frequency distribution (0.60 or below, from 0.61 to 0.82, from 0.83 to 1.18, from 1.19 to 1.69, and 1.70 or higher), to examine the concentration of risk factors in each group. In total, 74 (19.6%) of the men and 119 (20.3%) of the women had insulin resistance (HOMA‐R ≥ 1.73). It was found that the higher the HOMA‐R, the higher was the number of coronary risk factors, such as hypertension, obesity, hypertriglyceridaemia and hypo HDL cholesterolaemia. The number of coronary risk factors was particular high in subjects with HOMA‐R ≥ 1.70. HOMA‐R in the case of no glucose loading is a useful and practical index for evaluation of insulin resistance and coronary risk factors in the epidemiological study.

FABP4 is secreted from adipocytes by adenyl cyclase‐PKA‐ and guanylyl cyclase‐PKG‐dependent lipolytic mechanisms

Fatty acid‐binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity‐mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated.

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day−1, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.

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.