Nain-Feng Chu

Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men.

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk remain unclear. Hyperinsulinemia and insulin resistance are considered key components in the metabolic cardiovascular syndrome and as independent risk factors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-alpha), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of plasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possible mediators of the effect of obesity on atherogenic and thrombogenic CVD risk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47--83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting blood sample in 1994. We measured plasma insulin and leptin levels by radioimmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean=30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein A1 (Apo-A1). In a multivariate regression model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-A1 and positively associated with TG, Apo-B and t-PA antigen levels. The associations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the association between obesity and biological predictors of CVD may be mediated through changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on lipid metabolism.

Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men.

OBJECTIVE: Leptin, the product of the obesity (ob) gene, is a multi-functional polypeptide that is important in energy metabolism, which is strongly correlated with body fat mass and body mass index (BMI). In a recent prospective study, we found that leptin was positively associated with 4 y weight gain among overweight and obese men. This suggests that leptin resistance, marked by hyperleptinemia among obese subjects, may be an important marker for weight gain. The purpose of this study is to evaluate whether modifiable dietary and lifestyle factors are associated with plasma leptin concentrations among US men.METHODS: We included 268 men aged 47–83 y (who were free of cardiovascular disease, diabetes mellitus and cancer, except nonmelanoma skin cancer) from the ongoing Health Professionals Follow-up Study. These subjects completed a detailed dietary and lifestyle questionnaire (including cigarette smoking, alcohol drinking and physical activity) and provided a fasting venous blood sample in 1994. All blood samples were stored in a deep freeze (−70°C) for 4–5 y before being analyzed. Plasma leptin concentrations were measured by radioimmunoassay.RESULTS: Men in the highest quintile of plasma leptin (mean=14.4 ng/ml) weighed more, were less physically active, and had higher total and saturated fat and cholesterol intake than men in the lowest quintile (mean=3.0 ng/ml). Physical activity and current smoking were inversely associated with plasma leptin concentrations (P<0.001). A 20 MET difference in physical activity per week (equivalent to approximately 3 h of jogging) was associated with 0.38–0.58 ng/ml lower plasma leptin concentrations for normal weight and overweight men after adjusting for total energy and fat intake, BMI and other confounding variables. Total fat and monounsaturated fat intakes were positively associated with plasma leptin concentrations even after adjusting for BMI and other confounding variables; however, this association was limited to men of normal weight (BMI<25 kg/m2).CONCLUSION: These data suggest that physical activity may be a significant determinant of plasma leptin concentrations in men. Increasing physical activity is associated with lower plasma leptin concentrations even after adjusting for BMI. Physical activity may lower leptin concentrations not only due to decreased body fat mass, but potentially through an increase in leptin sensitivity.

Relationship between anthropometric variables and lipid levels among school children: The Taipei Children Heart Study

OBJECTIVES: To evaluate the association between anthropometric parameters and lipid levels among Taiwanese school children.DESIGN AND METHODS: Using a probability-proportional-to size sampling and multi-stages sampling procedure, we sampled 1500 school children from 10 schools in Taipei city. Anthropometric parameters including body weight, body height, waist circumference, hip circumference and skinfolds were measured. Serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) were measured by standard methods, low density lipoprotein-cholesterol (LDL-C) and CHOL/HDL-C ratio were calculated by formula.RESULTS: We included in our analyses 1366 children (681 boys and 685 girls) with a mean age of 13.3 y (from 12 to 16 y) and with valid anthropometric and biochemical parameters. The boys had higher body height (P<0.001) and larger body weight (P<0.05), waist circumference (P<0.01) and waist/hip ratio (WHR, P<0.001) than the girls. However, the girls had larger skinfolds than the boys. After adjusting for age, girls had higher total CHOL, TG, HDL-C, LDL-C, ApoA1 and ApoB concentrations than boys. In general, TG was positively associated with most anthropometric parameters (except body height); a similar negative association between HDL-C and anthropometric variables was noted. After controlling, for age, cigarette smoking, alcohol drinking and puberty development, shorter body height was the strongest predictor of total CHOL, LDL-C and ApoB concentrations among boys. Although body mass index (BMI) was a significant positive predictor (P<0.01) of the CHOL/HDL-C ratio; skinfold measurements were the strongest anthropometric predictors of most lipid concentrations among boys. Among girls, we found WHR and BMI to be the strongest positive predictors of TG and ApoB level respectively (both P<0.001), but skinfold measurements were best for predicting HDL-C, LDL-C, ApoA1 and the CHOL/HDL-C ratio.CONCLUSIONS: From this large study of school-age children from Taiwan, we found anthropometric parameters, such as body height, BMI or WHR, are adequate predictors of blood lipid levels; however, skinfold measurements are generally more strongly associated with lipid levels in both genders.

Glycemic status and soluble tumor necrosis factor receptor levels in relation to plasma leptin concentrations among normal weight and overweight US men.

OBJECTIVE: Leptin, an adipocyte-derived protein product of the obesity (ob) gene, is a multifunctional polypeptide associated with the development of obesity-related disorders in humans. There is considerable inter-individual variation in plasma leptin even among subjects with comparable obesity levels, which suggests that factors other than adipose mass may be involved in the regulation of leptin expression and/or production. The purpose of this study was to evaluate the potential role of glycemic status and adipose-derived cytokines in regulating plasma leptin levels among normal and overweight men.DESIGN: Cross-sectional study.SUBJECTS AND MEASUREMENTS: We measured plasma leptin, insulin, c-peptide and plasma soluble tumor necrosis factor receptor (sTNF-R) concentrations in 178 men. The subjects were selected from the Health Professionals Follow-up Study (HPFS), and aged 47–64 y in 1994, were free of cardiovascular disease, diabetes mellitus, malignant neoplasms, and had provided a fasting blood sample and a detailed lifestyle questionnaire.RESULTS: Men in the highest quintile of plasma leptin (mean=12.7 ng/ml) weighed more, were less physically active and had higher circulating insulin, c-peptide, sTNF-R1 and sTNF-R2 concentrations than men in the lowest quintile (mean=2.8 ng/ml). We found a significant correlation between plasma insulin, c-peptide, glycosylated hemoglobin (HbA1c), and sTNF-R1 on leptin concentrations (with Spearman correlation coefficients ranging from 0.17 to 0.48 and all P<0.05). Only HbA1c and sTNF-R1 were independently and positively associated with plasma leptin after further adjusting for body mass index and other metabolic parameters of interest. Interestingly, these observed associations were limited to men with a BMI ≥25 kg/m2.CONCLUSION: Our results suggest that glucose homeostasis and the activity of the TNF system may modulate leptin secretion and production among overweight men. Glucose homeostasis and TNF-α is important in metabolic disorders related to hyperleptinemia.

Relationship between hyperuricemia and other cardiovascular disease risk factors among adult males in Taiwan

Hyperuricemia is associated with cardiovascular disease risk factors such as obesity, impaired glucose tolerance, hypertension, and hyperlipidemia. However, this relationship between serum uric acid (SUA) concentrations and cardiovascular disease (CVD) is a controversial one, especially among males. The purpose of this study is to evaluate the association between SUA concentrations and other CVD risk factors among adult males in Taiwan. After multi-stage sampling procedures, we randomly selected 1743 Taiwanese males with a mean age of 35 years (from 22 to 54) in this study. Anthropometric, blood pressure and biochemical variables, including serum uric acid, glucose, total cholesterol and triglyceride concentrations, were measured. Among the study population, the mean SUA concentration was 6.5 ± 1.5 mg/dl. There were 290 (16.6%) subjects with SUA concentrations ≥ 8.0 mg/dl (defined as hyperuricemia). Compared to normouricemic subjects, hyperuricemic subjects had significantly greater age-adjusted body weight (75.3 vs. 69.2 kg, p < 0.001), body mass index (BMI, 25.5 vs. 23.6 kg/m2, p < 0.001), higher blood pressure (BP, 120.2 vs. 115.2 mmHg for systolic BP and 78.5 vs. 75.3 mmHg for diastolic BP, both p < 0.001) and blood lipid concentrations (193.8 vs. 182.1 mg/dl for total cholesterol and 123.7 vs. 94.4 mg/dl for triglycerides, both p < 0.001). SUA concentration was positively correlated with body weight, BMI, BP and serum lipid concentrations (all p < 0.001). In multivariate regression analyses, after adjusting for potential confounders, SUA concentration was significantly positively associated with diastolic BP, serum total cholesterol and triglyceride concentrations. An increase of 1 mg/dl of SUA was associated with a 2.1 mg/dl elevation in serum total cholesterol (p < 0.001) and a 5.4 mg/dl increase in triglyceride (p < 0.001). From this study, we found that hyperuricemia in subjects is associated with being overweight, and having high blood pressure and hyperlipidemia. There is a significantly positive association between SUA concentration and other CVD risk factors among adult males in Taiwan.

Plasma leptin concentrations and obesity in relation to insulin resistance syndrome components among school children in Taiwan—The Taipei Children Heart Study

OBJECTIVE: Leptin, an adipose tissue-derived product of the obesity (OB) gene, is an important regulator of energy metabolism and may be associated with the occurrence of insulin resistance and diabetes in humans. The purpose of this study was to evaluate the association of plasma leptin concentration with obesity and the components of insulin resistance syndrome (IRS) among school children in Taiwan.METHODS: After multistage sampling of 85 junior high schools in Taipei, we randomly selected 1264 children (617 boys and 647 girls) aged 12–16 y. Obesity measurements included body mass index (BMI) and waist-to-hip circumference ratio (WHR). We calculated an IRS summary score for each individual by adding the quartile ranks from the distribution of systolic blood pressure (BP), serum triglyceride (TG), HDL-cholesterol (inverse), and insulin levels.RESULTS: Boys had a higher BMI and WHR, BP and IRS score and lower leptin, insulin, TG and HDL-C levels than girls. BMI, WHR and plasma leptin levels were significantly associated with the IRS summary score and each of its components in both genders. Children with higher plasma leptin levels (>75th percentiles) have significantly higher BP, TG, insulin levels and IRS score than children with low leptin levels. The associations between plasma leptin level and the IRS components and score were still significant after adjusting for BMI in boys, but less so in girls. In both genders, after adjusting for WHR, plasma leptin levels were still significantly associated with the IRS components and summary score (P<0.001). The final model that included the standard covariates, BMI and leptin, but not WHR, was the most predictive of the IRS summary score among school children.CONCLUSIONS: Insulin resistance syndrome in childhood, characterized by high blood pressure, dyslipidemia, and hyperinsulinemia, may be an early marker of cardiovascular risk. From the present BMI and leptin in combination are the most predictive markers of insulin resistance syndrome among school children in Taiwan.

Plasma C-reactive protein levels and their relationship to anthropometric and lipid characteristics among children

C-reactive protein (CRP), a nonspecific marker of inflammatory status, is associated with cardiovascular disease (CVD) risk factors and the late occurrence of heart disease in adults. However, few studies assess the plasma CRP levels in healthy children. The purpose of this study is to evaluate the relationship between plasma CRP levels and anthropometric and lipid characteristics among children in Taiwan. After a multi-stage sampling of 85 junior high schools in Taipei, we randomly selected 835 children (410 boys and 425 girls) aged 12 to 16 years. Anthropometric and lipid profiles, including total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured. We also calculated low-density lipoprotein cholesterol levels and the total cholesterol-to-HDL-C ratio as shown on the atherosclerotic index. In both genders, plasma CRP levels were significantly positively correlated with anthropometrics measures and inversely correlated with HDL-C levels. After adjusting for age, cigarette smoking, alcohol consumption, heart rate, and puberty development, children in the fourth quartile CRP subgroups were heavier and had significantly higher body mass index (BMI) and lower HDL-C levels than children with nondetected CRP. In multivariate regression models, CRP was significantly negatively associated with HDL-C levels even after adjusting for BMI in both genders. In this study, anthropometrics measures, especially BMI, were positively associated with plasma CRP levels. Furthermore, elevated CRP levels were associated with adverse lipids profiles. These data suggest that elevated plasma CRP levels might be associated with CVD risk factors that may be related to the late development of CVD in some Taiwanese children.

Plasma leptin concentrations and four-year weight gain among US men

OBJECTIVE: Leptin, a primarily adipose tissue-derived protein product of the obesity (ob) gene, is an important regulator of energy metabolism. The strong association between body fat mass and elevated circulating leptin levels in humans suggests that leptin resistance, rather than leptin production, may contribute to the development of obesity and associated disorders. The purpose of this study is to evaluate the relationship between circulating plasma leptin levels and regulation of body weight over time among US men.DESIGN: Four-year prospective study.SUBJECTS: A total of 247 men from the Health Professionals Follow-up Study, who at baseline (1994), were 47–64 y of age, were free of cardiovascular diseases, diabetes mellitus and malignant neoplasmas, and completed a detailed lifestyle questionnaire. In addition, all participants completed a follow-up questionnaire in 1998.MEASUREMENTS: Baseline plasma leptin levels and 4-y weight change.RESULTS: At the start of follow-up, men in the highest quintile for plasma leptin (mean=12.1 ng/ml) weighed more, were less physically active, and had higher circulating insulin levels than men in the lowest quintile (mean=2.7 ng/ml). After adjustments for baseline age, weight, height, smoking status, alcohol intake, and physical activity, each 10 ng/ml increase in plasma leptin concentration was associated with a 1.68 kg (95% CI 0.14–3.18 kg) weight gain over the 4-y follow-up period. The observed association between leptin level and weight gain was limited to men with a baseline body mass index (BMI) of ≥25 kg/m2, in whom a 10ng/ml higher baseline leptin was associated with a 2.45 kg (95% CI 0.73–4.18-kg) weight gain. Further adjustments for baseline total energy intake, plasma insulin and soluble tumor necrosis factor receptors levels did not appreciably alter these results. Plasma insulin level was not independently associated with subsequent weight gain.CONCLUSION: These results suggest that elevated plasma leptin concentrations among overweight men may be a marker of leptin resistance and subsequent weight gain.

Alcohol Consumption Patterns and HbA1c, C-Peptide and Insulin Concentrations in Men

Objective: Observational studies support inverse associations between moderate alcohol consumption and fasting insulin concentrations, but the importance of drinking pattern on the effect of alcohol on insulin sensitivity has not been fully explored. We examined the relations of alcohol consumption patterns—including average daily consumption, frequency of consumption and drinking with meals—to fasting insulin, fasting c-peptide and hemoglobin A1c (HbA1c). Methods: A cross-sectional study of 462 disease-free men selected from the Health Professionals’ Follow-up Study to provide information on a range of drinking patterns. Study participants were 48 to 82 years of age who provided a blood sample and detailed information on diet, life-style and alcohol consumption patterns in 1994. Among the study participants, 267 men provided a fasting blood sample and contributed to the analyses of insulin and c-peptide. Results: Biologic markers were not strongly related to average alcohol consumption. Compared to abstainers, differences in insulin concentrations—all statistically non-significant—were 0.06, 1.25, 1.02, and 0.12 μU/mL for consumers of <1, 1–1.9, 2–2.9, 3+ drinks per day, respectively. The frequency of alcohol consumption was inversely related to fasting c-peptide and insulin concentrations after controlling for average alcohol consumption and other potential confounding variables. Compared to men who reported consuming alcohol one to three days per week, c-peptide concentrations were 0.08 ng/mL and 0.29 ng/mL lower (p-trend = 0.04) in men who reported consuming alcohol on four to five days per week and six to seven days per week, respectively. Men who consumed alcohol on most days also had lower fasting insulin levels than more irregular drinkers (p-trend = 0.05). Conclusions: Our results suggest that frequent alcohol consumption is inversely related to fasting c-peptide and insulin concentrations.

Prevalence and clustering of cardiovascular risk factors among healthy adults in a Chinese population: the MJ Health Screening Center Study in Taiwan

OBJECTIVE: To gain insight into the prevalence and clustering of multiple cardiovascular risk factors in a healthy Chinese adult population in Taiwan.DESIGN: A cross-sectional study was carried out in 1996.SUBJECTS: A total of 46 603 subjects (23 485 men and 23 118 women) who were aged 20–59 y and attended a private health screening center for health examination of their own volition.MEASUREMENTS: Multiple cardiovascular risk factors including cigarette smoking, overweight (23 kg/m2≤body mass index (BMI)<25 kg/m2) and obesity (BMI≥25 kg/m2), lipid disorder (a ratio of total cholesterol level to the level of high density lipoprotein cholesterol>5 or use of lipid-lowering drugs), hypertension (systolic blood pressure≥140 mmHg or diastolic blood pressure≥90 mmHg or use of anti-hypertensive medications), and diabetes mellitus (fasting serum plasma glucose level≥126 mg/dl or use of anti-diabetic medications) were determined.RESULTS: In comparison to women, men had a higher prevalence of current smoking (42.1 vs 5.6%), overweight (25.1 vs 17.1%) and obesity (33.1 vs 21.5%), lipid disorder (45.1 vs 19.6%), hypertension (17.4 vs 13.2%), as well as diabetes mellitus (4.1 vs 3.4%). The prevalence of men or women having two or more of the cardiovascular risk factors of interest was 54.3 and 21.7%, respectively. With advancing age, the prevalence of risk factors became greater for both genders. More importantly, the clustering of risk factors increased monotonically with increasing BMI levels for men and women.CONCLUSIONS: The prevalence and clustering of cardiovascular risk factors are commonplace in this healthy Chinese adult population. Considering the significant association between clustering of risk factors under study and BMI levels, this study gives an indication that population-based multifactorial interventions may work out favorably for specific groups.