Resting heart rate predicts metabolic syndrome in apparently healthy non-obese Japanese men

Autonomic nervous dysfunction is considered to be one of the mechanisms of metabolic syndrome (MetS). The aim of this study is to investigate whether resting heart rate, a marker of autonomic nervous dysfunction, is a predictor of MetS in apparently healthy non-obese [body mass index (BMI) <25 kg/m²] Japanese men. This is an observational study through 3 years in apparently healthy Japanese 1,265 men and 793 women without MetS and with no history of cardiovascular disease and no use of antihypertensive, antidiabetic, or antihyperlipidemic medication at baseline. Hazard ratios (HRs) of incident MetS were calculated for each 1 SD increase in heart rate stratified by gender and obesity. Incidence of MetS for each tertile of heart rate and HRs of MetS for the highest tertile (T3) compared with the lowest tertile (T1) were calculated stratified by gender and obesity. The HRs [95 % confidence intervals (CIs)] of MetS for each 1 SD increase in heart rate were 1.319 (1.035–1.681) (p = 0.025) in non-obese men, 1.172 (0.825–1.665) (p = 0.377) in obese men, 1.115 (0.773–1.608) (p = 0.560) in non-obese women, and 1.401 (0.944–2.078) (p = 0.094) in obese women adjusted for BMI, age, smoking, alcohol drinking, and physical activity. The HRs (95 % CIs) of MetS for T3 were 2.138 (1.071–4.269) (p = 0.031) in non-obese men and 1.341 (0.565–3.180) (p = 0.506) in obese men adjusted for pre-existing five components of MetS, age, smoking, alcohol drinking, and physical activity. In conclusion, an increase in resting heart rate was a significant predictor of MetS in non-obese Japanese men.     

The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study

In men, hypoandrogenism is associated with features of the metabolic syndrome. It is not known whether men with the metabolic syndrome are at a higher risk of developing hypogonadism. We therefore assessed whether the metabolic syndrome predicts development of hypogonadism 11 yr later in 651 middle-aged Finnish men participating in a population-based cohort study. Men with the metabolic syndrome at baseline as defined by the World Health Organization (n = 114, 20%) had a 2.6-fold increased risk of developing hypogonadism as defined by total testosterone levels less than 11 nmol/liter at the 11-yr follow-up independent of age, smoking, and other potential confounders. Further adjustment for body mass index (OR, 2.0; 95% CI, 1.1-3.8) or baseline total testosterone levels (OR, 1.9; 95% CI, 1.0-3.4) attenuated the association. The association of the metabolic syndrome with hypogonadism as defined by calculated free testosterone levels less than 225 pmol/liter was similar, but weaker. The adjusted decrease in testosterone concentrations during the 11-yr follow-up was also greater in men with than without the metabolic syndrome. Smokers had a nonsignificantly lower risk of developing hypogonadism during follow-up, whereas a decrease in smoking increased the risk of hypogonadism. The metabolic syndrome predisposes to development of hypogonadism in middle-aged men. Prevention of abdominal obesity and the accompanying metabolic syndrome in middle age may decrease the risk of hypogonadism in men, especially in those who quit smoking.     

High-molecular-weight adiponectin is a predictor of progression to metabolic syndrome: a population-based 6-year follow-up study in Japanese men

Adiponectin is an adipocyte-specific secretory protein, which possesses antidiabetic and antiatherosclerotic properties. Adiponectin exists as multimers in serum, and high-molecular-weight (HMW) adiponectin is particularly considered to be the active form of the protein. The objective of the present study was to examine whether decreased HMW adiponectin is a predictor of progression to metabolic syndrome during a 6-year follow-up period in Japanese men. The study subjects were 416 Japanese men without metabolic syndrome, aged 30 to 59 years at baseline, who had participated in annual health checkups in both 2000 and 2006. Low concentration of HMW adiponectin (≤2.65 μg/mL) was associated with substantially higher hazard ratio of the progression to metabolic syndrome after adjustment for age and body mass index (hazard ratio, 1.561; 95% confidence interval, 1.051-2.292; P = .028). The number of subjects with the progression to metabolic syndrome in each tertile based on baseline HMW adiponectin concentration was significantly different among the 3 groups (HMW adiponectin: χ² = 7.473, P = .0238; total adiponectin: χ² = 4.477, P = .1066; HMW-total adiponectin ratio: χ² = 1.676, P = .4325). It was suggested that decreased HMW adiponectin is a predictor of the progression to metabolic syndrome in a 6-year follow-up study of Japanese men. Furthermore, it was suggested longitudinally that measuring HMW adiponectin is efficient to predict the progression to metabolic syndrome compared with measuring total adiponectin or HMW-total adiponectin ratio.     

Differences in the pathology of the metabolic syndrome with or without visceral fat accumulation: a study in pre-diabetic Japanese middle-aged men

To elucidate the role of visceral fat accumulation in the metabolic syndrome, differences in the pathology of the metabolic syndrome with or without visceral fat accumulation were investigated. A total of 472 prediabetic Japanese men (mean age, 47.5 +/- 7.2 yr) with impaired fasting glycemia (IFG) levels of 110-125 mg/dL were eligible for participation in the study. The study subjects were divided into the following four groups, and intergroup comparisons were made: group I without visceral fat area [VFA] > or = 100 cm2 but presenting with fewer than two other risk factors (i.e., TG > or =150 mg/dL, HDL-C < 40 mg/dL, BP > or = 130/ > or = 85 mmHg, or FPG > or = 110 mg/dL) (n = 231); group II without VFA of > or = 100 cm2 but presenting with three or more other risk factors (n = 57); group III with VFA of > or = 100 cm2 accompanied by FPG 110 mg/dL alone (n = 27); and group IV with VFA > or =100 cm2 and two or more other risk factors (n = 157). The prevalence of patients who had three or more risk factors with or without VFA > or = 100 cm2 was 45.3% (214 out of 472 patients), while that of those with VFA > or = 100 cm2 who had two or more other risk factors was 33% (157 out of 472 patients). Group II had significantly higher VFA values than group I (p < 0.05), and group IV had significantly higher VFA values than group II (p < 0.001). While no significant differences in HOMA-R values were seen between groups I and II, these values were significantly higher in group IV compared to groups I and II (p < 0.001 and p < 0.05, respectively). Furthermore, group IV showed significantly higher 2-h insulin levels after glucose loading compared to group I (p < 0.001). While no significant differences were seen between groups II and IV, insulin levels tended to be higher in group IV. Adiponectin levels showed an incremental fall in VFA from group I through groups II and III to group IV. Groups III and IV showed significantly lower adiponectin levels compared to group I (p < 0.05, p < 0.001, respectively); and group IV showed significantly lower adiponectin levels than group II (p < 0.05). A logistic regression analysis using VFA, TG and HDL-C, and BP as explanatory variables showed that the relative risk for high HOMAR values were 2.65 (p < 0.001) for patients with VFA > or =100 cm2; 1.64 (p < 0.05) for those with TG > or = 150 mg/dL and HDL < 40 mg/dL; and 1.79 (p < 0.01) for those with BP > or = 130/ > or = 85 mmHg. These findings demonstrate that the degree of insulin resistance and the risk of arteriosclerosis vary depending on whether or not the metabolic syndrome accompanied by a clustering of risk factors has visceral fat accumulation as an underlying pathology, strongly suggesting a crucial role for visceral fat accumulation in the metabolic syndrome.     

Brachial-ankle pulse wave velocity and metabolic syndrome in a Japanese population: the Minoh study.

To investigate the association between brachial-ankle pulse wave velocity (baPWV) and metabolic syndrome (MS), we examined 374 men and 622 women aged 40 to 69 years who did not have a past history of either coronary heart disease or stroke. We used a modified National Cholesterol Education Program definition of MS that utilizes body mass index instead of waist circumference. Age-adjusted mean values of baPWV were greater when obesity, high systolic and diastolic blood pressures, high triglyceride level, low high-density lipoprotein cholesterol, high fasting glucose level or MS itself were present. baPWV was also associated with fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) values. Mean values of baPWV (adjusted for age, smoking status, and drinking status) in men with 0, 1, 2, and > or =3 features of MS were 1,409, 1,517, 1,640, and 1,665 cm/s, respectively (p for trend <0.001). The respective adjusted mean baPWV values for women were 1,368, 1,531, 1,547, and 1,661 cm/s (p for trend <0.001). As for insulin resistance, the adjusted mean baPWV values across quartiles of HOMA-IR (lowest to highest) were 1,488, 1,514, 1,566, and 1,624 cm/s (p for trend <0.001) for men. The respective adjusted mean baPWV values for women were 1,395, 1,441, 1,464, and 1,539 cm/s (p for trend <0.001). Our findings indicate that clustered features of MS and insulin resistance are strongly associated with the risk for increased baPWV in Japanese men and women.     

Association of metabolic syndrome with depression and anxiety in Japanese men

AimThe evidence is conflicting as to whether or not metabolic syndrome (MetS) is associated with depression and anxiety. For this reason, we have investigated the association of MetS with depression and anxiety in Japanese men.MethodsMetS was defined as in the new (2006) criteria of the International Diabetes Federation (IDF), and depression and anxiety were assessed using the Profile of mood states (POMS), in 1215 male Japanese workers. The relationship between MetS and these mental conditions was assessed by logistic-regression analysis after controlling for age, gender, obesity, medical history (cardiovascular disease and diabetes), lifestyle habits (smoking, alcohol consumption, exercise and sleep) and work situation. Trend analyses for a positive association between MetS components and depression and anxiety were also performed.ResultsA total of 148 (12.2%), 92 (7.6%) and 170 (14.0%) patients were diagnosed with MetS, depression and anxiety, respectively. MetS was significantly related to depression, and waist circumference contributed significantly to the relationship. Trend analysis of the number of positive MetS components and depression showed a positive trend that was of borderline significance (P_trend = 0.06). No relationship was found between MetS and anxiety. Trend analysis of the number of positive MetS components and anxiety failed to show a clear trend (P_trend = 0.57).ConclusionA positive relationship was found between MetS and depression, but not between MetS and anxiety, in male Japanese workers. The specific factors comprising MetS, such as waist circumference, may be a reflection of the depression.     

Factors responsible for age-related elevation in fasting plasma glucose: a cross-sectional study in Japanese men

To evaluate the factors associated with age-related increase in fasting plasma glucose (FPG) in Japanese men with normal fasting glucose, we measured FPG, fasting immunoreactive insulin, glycated hemoglobin, total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels in health check examinees. Subjects with FPG less than 6.1 mmol/L together with glycated hemoglobin less than 5.6% were enrolled in the study. The homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA-beta were used as the indices of insulin sensitivity and insulin secretion, respectively. Fasting plasma glucose increased significantly with age (r = 0.30, P < .0001), and HOMA-beta decreased significantly with age (r = 0.24, P < .0001). The HOMA-IR had no significant relation with age (r = 0.06, not significant), whereas body mass index and serum triglyceride were associated with HOMA-IR (r = 0.49, P < .0001 and r = 0.33, P < .0001, respectively). Thus, in Japanese male subjects with normal fasting glucose, it is suggested that the FPG increment with age is associated with decreased beta-cell function rather than with insulin resistance. Further analyses were performed by comparing 3 groups: low FPG (FPG <5.0 mmol/L), high FPG (5.0 < or = FPG < 5.6 mmol/L), and mild impairment of fasting glycemia (mild IFG) (5.6 < or = FPG < 6.1 mmol/L). The insulin levels in mild IFG and high FPG were significantly higher than in low FPG (P < .001), but those in mild IFG were similar to those in high FPG. Analysis of the 3 subgroups revealed that, whereas insulin sensitivity was impaired more in high FPG, there was little compensatory increase in insulin in mild IFG, suggesting that beta-cell function is already deteriorated when the FPG level is greater than 5.6 mmol/L.     

HOMA-IR and the risk of hyperuricemia: A prospective study in non-diabetic Japanese men

Aims

To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia.

Methods

The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35–54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid >416.4 μmol/L (7.0 mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR.

Results

During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR ≤0.66, were 1.42 (95% confidence interval 1.02–1.98) for HOMA-IR 0.67–0.98, 1.20 (0.86–1.68) for HOMA-IR 0.99–1.49 and 1.44 (1.04–1.98) for HOMA-IR ≥1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03–1.28) (p for trend = 0.02).

Conclusions

Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia.     

The effects of changes in the metabolic syndrome detection status on arterial stiffening: a prospective study.

We conducted a prospective study to examine the effects of alterations of the metabolic syndrome detection status on the rate of progression of arterial stiffness, which is recognized as a marker of arterial damage and an indicator of cardiovascular risk. Brachial-ankle pulse wave velocity as an index of arterial stiffening was recorded twice over a 3-year period in 2080 Japanese men (age, 42 +/- 9 years). At the start of the prospective study, pulse wave velocity was higher in the subjects with metabolic syndrome (n=125) than in those without metabolic syndrome (n=1,955) even after adjusting for mean blood pressure. The annual rate of increase of the pulse wave velocity was higher in the group with persistent metabolic syndrome (27 +/- 51 cm/s/year, n=71) than in the group with regression of metabolic syndrome (6 +/- 39 cm/s/year, n=54) or the group in which metabolic syndrome was absent (13 +/- 37 cm/s/year, n=1843; p < 0.05) after adjustment for changes in blood pressure. In conclusion, the changes in the metabolic syndrome detection status of the subjects during the study period affected the annual rate of progression of arterial stiffening, and persistent metabolic syndrome during the study period was associated with acceleration of arterial stiffening in middle-aged Japanese men. On the other hand, resolution of metabolic syndrome may be associated with attenuation of the progression of arterial damage. Therefore, the increased cardiovascular risk associated with the presence of metabolic syndrome may be at least partly mediated by acceleration of the progression of arterial stiffening.     

Circulating leptin levels predict the development of metabolic syndrome in middle-aged men: an 8-year follow-up study

BACKGROUND: Because high circulating plasma leptin is associated with many features of the metabolic syndrome (MS), such as abdominal obesity, insulin resistance and high blood pressure (BP), we analysed the ability of plasma leptin concentration to predict the risk of developing MS in a prospective investigation of adult male participants of the Olivetti Heart Study (OHS). METHODS AND RESULTS: Three hundred and sixty out of 907 men participating in the 1994-95 and 2002-04 OHS examinations (mean age at baseline 50.4 years, range 25-73 years) were free of MS at first visit according to NCEP-ATP III criteria (modified for the lack of high-density lipoprotein cholesterol measurement at baseline). During an average follow-up period of 8 years, there were 52 incident cases of MS (14.5%) due, in particular, to a rise in the prevalence of high BP (+42.4%), abdominal obesity (+16.4%) and impaired fasting glucose (IFG, +6.1%). In multivariate analyses, a one standard deviation difference in baseline plasma leptin concentration was associated with a 1.58-fold greater risk of developing MS (95% confidence interval = 1.10-2.30, P = 0.016) accounting for age, waist circumference, homeostatic assessment model index, smoking, alcohol consumption and physical activity. In particular, plasma leptin was positively associated with the risk of developing high BP (0.006) and IFG (0.014), after adjustment for confounders. CONCLUSION: In this sample of an adult male population free of MS at baseline, circulating plasma leptin was a significant predictor of the risk of MS and, in particular, of its high BP and IFG components, independently of potential confounders.     

Plasma triglycerides, an independent predictor of cardiovascular disease in men: a prospective study based on a population with prevalent metabolic syndrome

BACKGROUND AND METHODS: We aimed to assess whether fasting plasma triglycerides independently predicted future fatal and nonfatal cardiovascular disease (CVD) in a population having a high prevalence of the metabolic syndrome. In the Turkish Adult Risk Factor Study, a population-based survey, 2682 men and women 20 years of age or over with fasting triglyceride values available and free of CVD at baseline examination in 1990, were prospectively followed up till 2003/04. Triglyceride concentrations were measured by the enzymatic dry chemistry method and stratified into sex-specific quintiles. Information on the mode of death was obtained from first-degree relatives and/or health personnel of local health office. Diagnosis of coronary heart disease and stroke among survivors was based on history, physical examination of the cardiovascular system and Minnesota coding of resting electrocardiograms. A total of 120 fatal and 221 new nonfatal CVD occurred among adults (mean age 43+/-14) during a mean 9.3 years of follow-up. RESULTS: CVD was significantly and independently predicted by the top versus the bottom fasting triglyceride quintile in logistic regression analyses when adjusted for age, sex, BMI, systolic blood pressure, total cholesterol, lipid-lowering medication, status of smoking and of glucose regulation (relative risk [RR] in men and all adults 2.38 and 1.79, respectively, p both <0.02). This corresponded to hazard ratios (HR) of 1.43 in men and 1.28 in men and women combined. Adjustment for HDL-cholesterol instead of total cholesterol in the same model gave also significant HRs corresponding to 1.42 in men and 1.32 in sexes combined. CONCLUSIONS: Fasting triglycerides are predictive of future CVD among men with an HR of 1.4, independent of age, diabetes, lipid-lowering medication, traditional risk factors including total cholesterol or HDL-C, in a population in which metabolic syndrome prevails. A modest independent risk increment in women did not reach significance.     

Total bilirubin is inversely associated with metabolic syndrome but not a risk factor for metabolic syndrome in Japanese men and women

Serum total bilirubin (TB) is a potent antioxidant and inversely associated with metabolic syndrome (MetS) in Asian populations. However, there has been no study which is aimed to investigate whether TB is a risk factor for MetS or not. We investigated cross-sectional and longitudinal associations between TB and MetS in 2,435 Japanese men and 1,436 Japanese women. The odds ratios [95 % confidence interval (CI)] of coexisting MetS for each 1 SD increase in log TB were 0.850 (0.754–0.958) (p = 0.008) in men and 0.809 (0.656–0.998) (p = 0.047) in women adjusted for sex, age, smoking, and other confounding covariates. Those for the third and fourth quartiles of TB compared with the lowest quartile were 0.720 (0.537–0.965) (p = 0.028) and 0.737 (0.530–1.052) (p = 0.095), respectively, in men and 0.822 (0.473–1.427) (p = 0.486) and 0.704 (0.362–1.369) (p = 0.301), respectively, in women. There was a tendency that TB and MetS changed inversely to each other. The similarly adjusted hazard ratios of developing MetS for each 1 SD increase in log TB and for the higher quartiles of TB compared with the lowest quartile were not significant either in men or in women. TB is inversely associated with MetS but not a risk factor for MetS in Japanese men and women.     

Uric acid and the development of metabolic syndrome in women and men

Associations between serum uric acid (UA) levels and metabolic syndrome (MetS) have been reported in cross-sectional studies. Limited information, however, is available concerning the prospective association of UA and the risk of developing MetS. The authors evaluated UA as a risk factor for incident MetS in a prospective study of 8429 men and 1260 women (aged 20-82 years) who were free of MetS and for whom measures of waist girth, resting blood pressure, fasting lipids, and glucose were taken during baseline and follow-up examinations between 1977 and 2003. Hyperuricemia was defined as >7.0 mg/dL in men and >6.0 mg/dL in women. Metabolic syndrome was defined with the National Cholesterol Education Program Adult Treatment Panel III criteria. The overall prevalence of hyperuricemia was 17%. During a mean follow-up of 5.7 years, 1120 men and 44 women developed MetS. Men with serum UA concentrations > or =6.5 mg/dL (upper third) had a 1.60-fold increase in risk of MetS (95% confidence interval, 1.34-1.91) as compared with those who had concentrations <5.5 mg/dL (lowest third). Among women, the risk of MetS was at least 2-fold higher for serum UA concentrations > or =4.6 mg/dL (P for trend = .02). Higher serum UA is a strong and independent predictor of incident MetS in men and women.     

Association of white blood cell count and clustered components of metabolic syndrome in Japanese men.

BACKGROUND: The role of inflammation in the genesis of cardiovascular disease has attracted attention and in the present study the association among metabolic syndrome (MS), white blood cell (WBC) count, and insulin concentration was investigated. METHODS AND RESULTS: A cross-sectional study of 3,594 Japanese men aged 34-69 years evaluated the MS components (high blood pressure, hypo-high density lipoprotein (HDL)-cholesterolemia, hypertriglyceridemia, hyperglycemia), as defined by the criteria given in the Third Report of the National Cholesterol Education Program Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults, except for obesity [body mass index (BMI) >/=25 kg/m(2)]. WBC count had a positive correlation with BMI, blood pressure, triglyceride, glucose and insulin, and a negative correlation with HDL-cholesterol. The multi-adjusted means of WBC count and insulin concentration were significantly higher in MS subjects defined as having 3 or more of the components than in non-MS subjects with no more than 2 components. Both means also increased with the number of MS components (p<0.001 for trend). In the multiple linear regression analysis, BMI, HDL-cholesterol, systolic blood pressure, glucose and triglyceride had a significant and independent association with WBC count, but the insulin concentration did not. CONCLUSIONS: The cluster of MS components based on insulin resistance may cause low-grade inflammation.     

A prospective study of determinants of the metabolic syndrome in adults

Background and aimFew studies have prospectively examined the development of the metabolic syndrome and comprehensive set of risk factors in a cohort. The objective of this study was to evaluate determinants of the metabolic syndrome in adults in a prospective study.Methods and resultsIn this population-based cohort study, a representative sample of 410 subjects (184 men and 226 women), aged 18–74 years, free of the metabolic syndrome at baseline, were studied. In the subsequent 3.5 years metabolic syndrome, defined according to ATP III guidelines, developed in 71 subjects (33men and 38 women) The best determinants of metabolic syndrome were hypertension [odds ratio (OR) by quartiles: 1, 1.2, 1.6, 4.2, p for trend <0.05], waist circumference (1, 1.1, 2, 5.3, p for trend <0.05), triglyceride (1, 1, 2, 3, p for trend <0.05) and HDL cholesterol (1, 0.4, 0.4, 0.3, p for trend <0.05). A prominent dose–response relationship across the carbohydrate and fat intake categories and the odds of metabolic syndrome was observed in univariate analysis. In multivariate analysis high waist circumference was the optimum predictor [OR 8 (4–12.2)].ConclusionThis report confirms importance of blood pressure, waist circumference and lipid measurements in risk stratification of metabolic syndrome in adulthood. Interventions that address obesity and reduce waist circumference and an appropriate diet may reduce the incidence of the metabolic syndrome in adults.