Shyh-Ming Shieh

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.

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.

Increased oxidazability of plasma low density lipoprotein from patients with coronary artery disease

Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu2+ oxidation of lipoproteins monitored by changes in fluorescence, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While pooled VLDL and LDL of normal controls were oxidized at 5-10 microM Cu2+, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1-2.5 microM Cu2+, i.e., at relatively lower oxidative stress. At 5 microM Cu2+, VLDL and LDL of patients with coronary artery disease still showed a faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasma VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of healthy persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be an important factor influencing the development of coronary artery disease.

Angiotensin I Converting Enzyme Gene Polymorphism in Chinese Patients With Hypertension

Reports from different ethnic populations failed to show consistent findings on the association of hypertension with insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene. In this population association study in Chinese, we compared the distribution of the ACE genotypes and allele frequency in 150 healthy controls with normal blood pressure and 148 hypertensive patients categorized by age. Although the frequencies of homozygote deletion (DD) genotype and deletion allele were greater in Chinese with hypertension than in normotensive controls (0.23 vs 0.13 and 0.44 v 0.37, respectively), the differences were not significant by chi2 analysis (P = .07 and .09, respectively). Furthermore, we did not find the trend of decreasing number of DD genotype in older hypertensive Chinese patients. The results indicated a much lower prevalence of ACE/DD genotype in Chinese than in Caucasians and a modest association between I/D polymorphism of the ACE gene and hypertension in Chinese.

Effect of pravastatin treatment on glucose, insulin, and lipoprotein metabolism in patients with hypercholesterolemia

Treatment of patients with type IIA hyperlipoproteinemia (HLP) with pravastatin for 3 months led to significant decreases (p < 0.001) in total cholesterol (7.18 +/- 0.30 to 5.75 +/- 0.30 mmol/L), LDL cholesterol (5.56 +/- 0.33 to 4.02 +/- 0.32 mmol/L), and ratio of total cholesterol to HDL cholesterol (6.5 +/- 0.4 to 4.6 +/- 0.4). Decreases of a similar magnitude were also seen in patients with type IIB HLP. Plasma glucose and insulin concentrations after an oral glucose load and from 8 AM to 4PM in response to meals were higher in patients with Type IIB HLP, who also had higher steady-state plasma glucose concentrations after an infusion of somatostatin, insulin, and glucose (12.4 +/- 1 vs 5.5 +/- 0.8 mmol/L, p < 0.001). Because steady-state plasma insulin concentrations were similar in both groups, patients with type IIB HLP were relatively insulin resistant. Furthermore, day-long plasma glucose concentrations and insulin resistance were modestly, but significantly (p < 0.01), greater after treatment in both groups. In conclusion, LDL cholesterol metabolism improved in hypercholesterolemic subjects treated with pravastatin, but the hypertriglyceridemia, insulin resistance, relative glucose intolerance, and hyperinsulinemia present in patients with type IIB HLP either did not improve with treatment or was somewhat worse.

Angiotensin I converting enzyme gene polymorphism and insulin resistance in patients with hypertension.

Background The homozygote deletion (DD) genotype of the angiotensin I converting enzyme (ACE) gene has been shown to be associated with an increased risk of coronary heart disease independent of other risk factors. Objective To investigate the possible association of the insertion/deletion (I/D) polymorphism of the ACE gene with insulin resistance in a Chinese population with and without hypertension. Subjects and methods The I/D polymorphism of the ACE gene was determined for 361 Chinese including 148 women and 96 men with normal blood pressures and 64 male and 53 female patients with mild-to-moderate hypertension. Insulin resistance was estimated by the insulin suppression test and glucose intolerance evaluated with an oral glucose-tolerance test for all of the subjects. Results Three hypertensive subgroups with DD, DI and II genotypes having similar ages and body mass indexes presented insignificantly different degrees of glucose intolerance and insulin resistance both among men and among women. Similar results were found for normotensive subjects. In addition, ACE genotypes were not significant predictors of insulin resistance and glucose intolerance either among men or among women after adjustment for age, body mass index, and hypertension. Conclusion The present data indicated that the I/D polymorphism of the ACE gene was not related to insulin resistance for Chinese hypertensive and normotensive subjects. The increased risk of coronary heart disease associated with the DD genotype need not be mediated through the mechanism of insulin resistance and glucose intolerance for Chinese patients with hypertension.

Plasminogen activator inhibitor-1 and angiotensin I converting enzyme gene polymorphism in patients with hypertension.

Deletion polymorphism of angiotensin I-converting enzyme (ACE) gene has been reported to be an independent risk factor for myocardial infarction. Plasminogen activator inhibitor-1 (PAI-1) was proposed to be a link between the renin-angiotensin system and thrombotic risk. This study was undertaken to investigate the possible association between the insertion/deletion (I/D) polymorphism of the ACE gene and plasma PAI-1 levels in 160 patients with mild-to-moderate hypertension. The I/D genotypes were determined by polymerase chain reaction with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene. Baseline levels of PAI-1 antigen and activity and tissue plasminogen activator (t-PA) antigen were determined in fasting morning plasma samples. It was found that patients with homozygote deletion (DD, n = 37) ACE genotype did not have significantly higher plasma levels of PAI-1 antigen (31.2 +/- 15.6 ng/mL v 28.4 +/- 15.1 ng/mL or 27.2 +/- 13.2 ng/mL, P = .42), PAI-1 activity (16.2 +/- 10.6 IU/mL v 14.1 +/- 9.4 IU/ mL or 15.0 +/- 9.9 IU/mL, P = .60), or t-PA antigen (14.6 +/- 6.0 ng/mL v 13.4 +/- 4.9 ng/mL or 14.6 +/- 5.7 ng/mL, P = .40) as compared to those with heterozygote (DI, n = 67) or homozygote insertion (II, n = 56) genotypes. On multiple regression analysis, the ACE genotypes did not appear to be significant predictors for plasma PAI-1 levels and t-PA antigen after adjustment with age, sex, body mass index, plasma triglyceride, cholesterol, and glucose. In conclusion, the results indicated that the I/D polymorphism of the ACE gene was not related to plasma PAI-1 levels in a Chinese population with hypertension. The ACE genotypes may not have a role in influencing the fibrinolysis in hypertension.

Gemfibrozil treatment of hypertriglyceridemia: Improvement on fibrinolysis without change of insulin resistance

The fibrinolytic and metabolic changes associated with gemfibrozil treatment of hypertriglyceridemia were evaluated in 16 patients with type IV hyperlipidemia by criteria of triglyceride levels > 250 mg/dl and total cholesterol levels < 220 mg/dl. The plasma triglyceride level was significantly lower (323 +/- 71 vs 189 +/- 57 mg/dl; p = 0.000) and high-density lipoprotein cholesterol level significantly higher (33.5 +/- 4.6 vs 38.0 +/- 6.7 mg/dl; p = 0.005) after 3 to 4 months of gemfibrozil treatment. However, the glucose and insulin metabolism measured by oral glucose challenge and insulin suppression tests showed no significant changes after gemfibrozil therapy. In contrast, plasma plasminogen activator inhibitor-1 antigen (36.9 +/- 12.4 vs 27.3 +/- 11.4 ng/ml; p = 0.008) and activity (15.5 +/- 5.5 vs 11.8 +/- 3.0 IU/ml; p = 0.009) and tissue plasminogen activator antigen (13.2 +/- 4.0 vs 10.4 +/- 3.7 ng/ml; p = 0.007) were significantly depressed, and tissue plasimogen activator activity (0.57 +/- 0.31 vs 0.69 +/- 0.38 IU/ml; p = 0.015) was significantly elevated by gemfibrozil. The data indicate that lowering plasma triglyceride and raising high-density lipoprotein cholesterol levels by gemfibrozil treatment also improved the fibrinolytic system without changes of insulin resistance and glucose intolerance in patients with isolated hypertriglyceridemia.

Plasma TNF-R1 and insulin concentrations in relation to leptin levels among normal and overweight children

OBJECTIVES Leptin is a multifunctional polypeptide produced primarily by adipocytes and associated with the occurrence of obesity and insulin resistance. Tumor necrosis factor-alpha (TNF-alpha), a polypeptide cytokine produced primarily by mononuclear phagocytes, plays a key role in the initiation of the inflammatory response but has a multitude of effects in many tissues. The interactions between TNF-alpha and insulin on leptin expression are complicated and have not been completely described. The purpose of this study is to evaluate interactions between TNF-alpha and insulin on circulating leptin levels among normal and overweight children. DESIGN AND METHODS After multi-stage sampling, we randomly selected 1,500 school children in this survey. All children completed a questionnaire on their disease history and lifestyle characteristics. We measured body weight, height, waist and hip circumference of children and calculated BMI and Waist-to-hip ratio (WHR). We also measured plasma tumor necrosis factor-receptor 1 (TNF-R1) by ELISA, plasma insulin and circulating leptin levels by RIA using commercial kits. We divided the children into normal or overweight groups using BMI criteria (85th percentile) to evaluate the relationship of TNF-R1 and insulin on circulating leptin concentrations. RESULTS In general, boys were taller, heavier and had higher TNF-R1 and lower leptin levels than girls. Plasma leptin levels were positively correlated with anthropometric variables and insulin levels among children in both genders. In multivariate regression analyses, plasma insulin levels were significantly positive associated with leptin levels in normal weight children. Plasma TNF-R1 levels were positively associated with leptin levels even after adjusting for BMI in girls only. CONCLUSIONS From this study, we found that plasma insulin plays certain role in leptin expression among normal weight children. However, TNF-R1 plays a more significant role in leptin expression among girls only.