Eiji Oda

Metabolic syndrome: its history, mechanisms, and limitations

In late twentieth century, Ruderman and Reaven showed that insulin resistance might be fundamental to metabolic syndrome (MetS) which means a constellation of obesity-related metabolic derangements predisposing to type 2 diabetes and cardiovascular disease. In 2001, user-friendly National Cholesterol Education Program (NCEP) criteria of MetS were proposed. In 2005, the International Diabetes Federation (IDF) and the Examination Committee for Criteria of Metabolic Syndrome in Japan issued different criteria of MetS where abdominal obesity is a necessary component. In 2009, IDF, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, and International Association for the Study of Obesity jointly adopted the revised NCEP criteria, where abdominal obesity is not a necessary component, as worldwide criteria of MetS. In 2010, WHO Expert Consultation warned that MetS is a concept that focuses attention on complex multifactorial health problems but has limited practical utility as a management tool. In animal studies, adipose tissue inflammation characterized by an increased number of crown-like structures in adipose tissue, rather than obesity per se, was shown to be a fundamental mechanism of metabolic derangements.

A possible cross-sectional association of serum total bilirubin with coronary heart disease and stroke in a Japanese health screening population

Bilirubin is a potent antioxidant, and serum total bilirubin (TB) is reported to be negatively associated with cardiovascular disease (CVD). There has been no report on the association between TB and CVD prevalence in Japanese. The aim of the study is to examine the association between TB and CVD prevalence in a Japanese health screening population. Prevalence of CVD was studied in 3,375 Japanese men and 2,069 Japanese women. Odds ratios (ORs) of each higher quintile of TB using the lowest quintile as the reference in men and of each higher tertile of TB using the lowest tertile as the reference in women were calculated for coronary heart disease (CHD) and stroke adjusting for age, liver function tests, smoking, physical activity, and alcohol consumption. The ORs [95% confidence intervals (CIs)] for CHD and stroke of the 2nd, 3rd, 4th, and 5th quintiles of TB were 0.63 (0.37–1.07) and 0.49 (0.24–1.00), 0.45 (0.22–0.90) and 0.65 (0.28–1.51), 0.69 (0.39–1.20) and 0.37 (0.15–0.87), and 0.61 (0.34–1.09) and 0.40 (0.18–0.92), respectively in men. The ORs (95% CIs) for CHD and stroke of the 2nd and 3rd tertiles of TB were 0.63 (0.37–1.07) and 0.49 (0.24–1.00), and 0.61 (0.34–1.09) and 0.40 (0.18–0.92), respectively in women. Low TB was associated with the higher prevalence of CHD and stroke in men and with the higher prevalence of stroke in women among a Japanese health screening population.

Tachycardia-dependent augmentation of “notched J waves” in a general patient population without ventricular fibrillation or cardiac arrest: Not a repolarization but a depolarization abnormality?

BACKGROUND J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood. OBJECTIVE The purpose of this study was to examine the J-wave dynamicity in a general patient population. METHODS The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals. RESULTS Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality. CONCLUSION J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this.

Gender differences in correlations among cardiovascular risk factors.

BACKGROUND Although the clustering of a few specific cardiovascular risk factors is known as the metabolic syndrome, sex-specific differences in correlations among risk factors have not been thoroughly examined. OBJECTIVE The analysis was undertaken to detect gender differences in correlations among cardio-vascular risk factors. METHODS Correlations among age, body mass index, systolic and diastolic blood pressures, and serum levels of fasting blood sugar (FBS), triglycerides (TG), high- and low-density lipoprotein cholesterol, high-sensitivity C-reactive protein (CRP), and uric acid were analyzed in apparently healthy Japanese men and women with TG<400 mg/dL and FBS<126 mg/dL. RESULTS Among the 136 men and 136 women examined, the frequency of significant correlations was marginally higher in women than in men: 28/45 correlations versus 17/45 correlations, respectively (P=0.017). Of a total of 45 possible correlations, 5 were marginally or significantly stronger in women, whereas no correlations among these risk factors were marginally or significantly stronger in men (P=0.021). These gender differences were considerably attenuated after adjustment for age. However, a significant sex-specific difference was observed in the correlation between TG and rank transformation of CRP, even after adjustment for age (P<0.01). CONCLUSIONS Correlations among cardiovascular risk factors were marginally stronger in women than in men. These results suggest that the existence of 1 additional risk factor may increase the risk of cardiovascular disease more steeply in women than in men.

Hypobilirubinemia Might be a Possible Risk Factor of End-Stage Kidney Disease Independently of Estimated Glomerular Filtration Rate

Background/Aims: The relationship between serum total bilirubin (TB) and estimated glomerular filtration rate (eGFR) is controversial and there is no report on the association between TB and end-stage kidney disease (ESKD). Methods: We examined the cross-sectional association between TB and eGFR and investigated whether TB can predict ESKD with multivariable logistic regression adjusted for age, sex, and baseline eGFR using hospital-based data. Results: The geometric mean TB of patients with eGFR ≥ 90 mL/min/1.73 m2 (S1), 8960 mL/min/1.73 m2 (S2), 59-30 mL/min/1.73 m2 (S3), 29-15 mL/min/1.73 m2 (S4), and < 15 mL/min/1.73 m2 (S5 = ESKD) was 0.55 mg/dL, 0.59 mg/dL, 0.56 mg/dL, 0.47 mg/dL, and 0.36 mg/dL (all p<0.0001 except for S1 vs. S3 where p=0.3726), respectively excluding patients with hyperbilirubinemia (TB > 1.24 mg/dL). The odds ratio (95% confidence interval) of incident ESKD for each 0.1 mg/dL increase in TB and hypobilirubinemia defined as TB ≤ 0.34 mg/dL were 0.92 (0.80-1.07) (p=0.2804) and 3.51 (1.56-7.88) (p=0.0023), respectively in patients with baseline eGFR ≥ 15 mL/min/1.73m2 and 0.59 (0.37-0.95) (p=0.0283) and 6.03 (1.63-22.30) (p=0.0071), respectively in patients with baseline eGFR 29-15 mL/min/1.73m2. Conclusions: Hypobilirubinemia might be a possible risk factor of ESKD.

A cross-sectional relationship between vital capacity and diabetes in Japanese men

AIMS The aim of the present study was to examine the cross-sectional relationship between vital capacity and diabetes, metabolic syndrome (MS), and high-sensitivity C-reactive protein (hs-CRP) among Japanese men. METHODS Medical check-up data of 1353 men were examined. Spearmans correlation coefficients between respiratory function and MS-related risk factors were calculated excluding subjects with hypoglycemic medication. The prevalence of diabetes and MS were compared between subjects with the lowest and the highest quartiles of % vital capacity (%VC). Area under receiver operating characteristic curve (AUC) were calculated for risk factors excluding fasting glucose. Logistic regression using diabetes as a dependent variable and %VC and MS-related risk factors excluding fasting glucose as independent variables was performed. RESULTS %VC was significantly correlated with some components of MS and hs-CRP. The prevalence of diabetes, MS, and MS components other than blood pressure were significantly lower in the highest quartile than in the lowest quartile of %VC. AUC of -%VC was highest among MS-related risk factors excluding fasting glucose though statistically not significant. %VC was an independent marker of diabetes in the multivariable logistic regression analysis. CONCLUSIONS Vital capacity was an independent marker of diabetes and associated with MS and hs-CRP in Japanese men.

Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of high-sensitivity C-reactive protein in apparently healthy Japanese

The aim of this study was to investigate the association between leukocyte subtype counts and hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia. Logistic regressions using hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia as a dependent variable and total leukocyte, basophil, eosinophil, neutrophil, lymphocyte, and monocyte counts as an independent variable were calculated adjusting for age, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), smoking, drinking, and physical activity in apparently healthy Japanese men (1,803) and women (1,150). The odds ratio (OR) of hyper-LDL cholesterolemia for total leukocyte, eosinophil, and lymphocyte counts, the OR of hypertriglyceridemia for total leukocyte, eosinophil, neutrophil, and lymphocyte counts, and the OR of hypo-HDL cholesterolemia for total leukocyte, neutrophil, and lymphocyte counts were significant in men, and the OR of hyper-LDL cholesterolemia, for lymphocyte count, and the OR of hypo-HDL cholesterolemia for eosinophil count were significant in women. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of hs-CRP in apparently healthy Japanese.

Metabolic Syndrome is a Poor Predictor of Incident Diabetes Compared with Hemoglobin A1c (Hba1c) in a General Japanese Population

Aims:To evaluated the usefulness of metabolic syndrome (MetS) as a predictor of incident diabetes comparing with other predictors of diabetes including hemoglobin A1c (HbA1c). Materials and Methods: It is a retrospective five-year follow-up study from annual health examination data in a community including 1,997 Japanese subjects without diabetes at baseline. Logistic regressions using incident diabetes as a dependent variable were calculated for each predictor adjusted for age, sex and drinking status. Area under receiver operating characteristic curves (AUCs) and population attributable risk fractions (PAFs) of incident diabetes were calculated for each predictor. Results:The odds ratios (95% confidence interval) of incident diabetes for MetS, fasting plasma glucose (FPG) ≥ 5.6 mmol/L and HbA1c ≥ 6.0% were 5.39 (2.72-10.7), 9.52 (5.08-17.9), and 33.5 (13.0-86.4), respectively. The AUCs (95% confidence interval) of diagnosing incident diabetes for FPG, HbA1c, and MetS were 0.82 (0.76-0.88), 0.89 (0.82-0.95) and 0.63 (0.53-0.72) respectively. The optimal cutoff points of FPG, HbA1c, and body mass index were 5.3 mmol/L, 6.0% and 23.5 kg/m2 respectively. The sensitivity and specificity of FPG, HbA1c and MetS for predicting diabetes were 0.67 and 0.80, 0.88 and 0.83, and 0.33 and 0.93, respectively. The PAFs of FPG ≥ 5.3 mmol/L, HbA1c ≥ 6.0%, and MetS were 59%, 86%, and 27%, respectively. Conclusions: MetS was a poor predictor of diabetes compared with FPG or HbA1c and A1C was the best predictor of diabetes in a general Japanese population.

Bilirubin Is Negatively Associated With A1C Independently of Fasting Plasma Glucose, Age, Obesity, Inflammation, Hemoglobin, and Iron in Apparently Healthy Japanese Men and Women

It has been reported that fasting plasma glucose (FPG) is not significantly associated with risks of cardiovascular disease (CVD) and death from any cause adjusting for A1C, but A1C was significantly associated with risks of CVD and death from any cause adjusting for FPG in nondiabetic adults (1). A1C levels appear to increase with age, and any condition that changes red cell turnover, such as hemolytic anemia, chronic malaria, major blood loss, or blood transfusions, will influence A1C levels (2). Other than age and iron deficiency, some cardiovascular risk factors related with inflammation and oxidant stress may have independent associations with …

LDL Cholesterol Is Associated With Blood Pressure in Japanese Women

HDL cholesterol is considered a component of insulin resistance syndrome or metabolic syndrome, but LDL cholesterol is not considered a component of metabolic syndrome (1–3). We have reviewed the literature and have found that there may be no report regarding the association between LDL cholesterol and blood pressure. We studied cross-sectional relationships between LDL cholesterol and other metabolic risk factors using medical checkup data from 2,449 Japanese men (age 51.9 ± 9.6 years) and 1,448 Japanese women (age 51.5 ± 9.8 years) who visited …