Kuo-Chin Huang

Optimal cut-off values for obesity: Using simple anthropometric indices to predict cardiovascular risk factors in Taiwan

BACKGROUND: The increased health risks associated with obesity have been found to occur in Asians at lower body mass indices (BMIs). To determine the optimal cut-off values for overweight or obesity in Taiwan, we examined the relationships between four anthropometric indices and cardiovascular risk factors.METHODS: The data were collected from four health-screening centers from 1998 to 2000 in Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean age=37.3±10.9 and 37.0±11.1 y, respectively). None had known major systemic diseases or were taking medication. Individual body weight, height, waist circumference (WC), and a series of tests related to cardiovascular risk (blood pressure, fasting plasma glucose, triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol) were assessed and their relationships were examined. Receiver operating characteristic (ROC) analysis was used to find out the optimal cut-off values of various anthropometric indices to predict hypertension, diabetes mellitus and dyslipidemia.RESULTS: Of the four anthropometric indices we studied, waist-to-height ratio (WHtR) in women was found to have the largest areas under the ROC curve (women=0.755, 95% CI 0.748–0.763) relative to at least one risk factor (ie hypertension or diabetes or dyslipidemia). The optimal cut-off values for overweight or obesity from our study in men and women showed that BMIs of 23.6 and 22.1 kg/m2, WCs of 80.5 and 71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45, respectively, may be more appropriate in Taiwan.CONCLUSIONS: WHtR may be a better indicator for screening overweight- or obesity-related CVD risk factors than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also supported the hypothesis that the cut-off values using BMI and WC to define obesity should be much lower in Taiwan than in Western countries.

High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection.

The influence of MSI on treatment outcome of colorectal cancers remains unclear and deserves further investigation. We recruited 244 patients with stage IV sporadic colorectal cancers for our study, based on appropriate eligibility criteria. Patients were nonrandomly allocated to 2 treatment groups of either with or without high‐dose 5‐FU plus leucovorin chemotherapy (HDFL, 5‐FU 2,600 mg/m2 leucovorin 300 mg/m2 maximum 500 mg). Each treatment group was further divided into 2 subgroups according to high‐frequency MSI (MSI‐H) status. MSI‐H was defined as the appearance of MSI in at least 2 of the 5 examined chromosomal loci (BAT‐25, BAT‐26, D5S346, D2S123, D17S250). We compared clinicopathologic parameters, p53 overexpression and overall survival between the groups. In addition, 4 subgroups were identified as follows: MSI‐H+HDFL+, n = 35; MSI‐H−HDFL+, n = 134; MSI‐H+HDFL−, n = 17; MSI‐H−HDFL−, n = 58. There was no significant difference of background clinicopathologic data between the HDFL+ and HDFL− treatment groups (p > 0.05). Survival analyses indicated that the patients of subgroup MSI‐H+HDFL+ survived significantly longer than those of subgroup MSI‐H−HDFL+, with median survival times of 24 (95% CI 20.2–27.9) and 13 (95% CI 11.6–14.4) months, respectively (p = 0.0001, log‐rank test). In contrast, in patients without chemotherapy, the prognosis was poor irrespective of MSI status, with median survival times of 7.0 (95% CI 4.6–9.4) and 7.0 (95% CI 6.1–7.9) months in the MSI‐H+HDFL− and MSI‐H−HDFL− subgroups, respectively (p = 0.8205, log‐rank test). MSI‐H cancers responded significantly better to HDFL (p = 0.001), with a mean response rate of 65.71% (95% CI 49.98–81.44%) in subgroup MSI‐H+HDFL+ compared to 35.07% (95% CI 26.99–43.15%) in subgroup MSI‐H−HDFL+. There appeared to be no preferential metastatic site where response to HDFL can be predicted based on the MSI status of the primary tumor. Toxicity to HDFL was similarly minimal between MSI‐H+ and MSI‐H− patients (p > 0.05). Multivariate analysis of all patients further indicated that MSI‐H and chemotherapy were independent favorable prognostic parameters (p < 0.05). Thus, the better prognosis of stage IV sporadic colorectal cancers with MSI‐H may be associated with better chemosensitivity, rather than lower aggressiveness in biologic behavior.

Impaired Lung Function Is Associated with Obesity and Metabolic Syndrome in Adults

Objective: Impaired lung function is associated with obesity and insulin resistance. In this study, we investigated the relationship between metabolic syndrome and impaired lung function in adults.

Clinicopathological and molecular biological features of colorectal cancer in patients less than 40 years of age

The aim of the present study was to identify the clinicopathological and molecular biological characteristics of early‐onset colorectal cancers.

Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents.

OBJECTIVE: The rising epidemic worldwide in overweight and obese children requires urgent attention. Leptin has been found to be associated with body weight control and possibly affects insulin sensitivity. Since insulin resistance is associated with obesity in adults and possibly in adolescents, we set out to investigate the association of plasma leptin level with various anthropometric indices, body fat mass (FM), lipids, and insulin resistance (IR) index in nondiabetic adolescents.DESIGN: A cross-sectional study from three high schools in Taipei City in Taiwan.SUBJECTS: A total of 402 nondiabetic subjects (162 boys and 240 girls; age range, 10–19 y; mean age, 15.8±1.9 y, and mean body mass index (BMI), 24.8±4.6 kg/m2) were recruited.MEASUREMENTS: The fasting plasma leptin, plasma glucose, insulin, lipids, and anthropometric indices including height, weight, waist (WC) and hip circumferences, and waist-to-hip ratio (WHR) were examined. Total body FM and percentage body fat (FM%) were obtained from dual-energy X-ray absorptiometry. The homeostasis model was applied to estimate the degree of IR.RESULTS: The plasma leptin levels were significantly higher in girls (17.45±10.13 ng/ml) than boys (8.81±6.71 ng/ml, P<0.001). The plasma leptin levels were positively correlated to BMI, WC, WHR, FM, FM%, and triglycerides (TG). The IR index was positively correlated to BMI, WC, WHR, FM, FM%, TG, and leptin. Using the multivariate linear regression models, we found that plasma leptin remains significantly associated with IR index even after adjusting for age, gender, BMI, FM, WC, Tanner stage, and TG.CONCLUSION: Plasma leptin was associated with IR index independent of age, gender, BMI, FM, WC, Tanner stage, and TG. Plasma leptin levels in adolescents could be a predictor for the development of the metabolic syndrome disorders and cardiovascular diseases.

Clinical implications of minimal residual disease monitoring by quantitative polymerase chain reaction in acute myeloid leukemia patients bearing nucleophosmin (NPM1) mutations

To explore the validity and prognostic significance of minimal residual disease detection by quantitative polymerase chain reaction (qPCR) in patients of acute myeloid leukemia (AML) bearing Nucleophosmin (NPM1) mutations, we quantified mutants in 194 bone marrow samples from 38 patients with a median follow-up time of 20.6 months. Following induction chemotherapy, a median of 2.78 log decline in mutant copy number was observed. Relapse was always accompanied by significant increase of mutant numbers (P<0.001). After achieving complete remission (CR), the mutant copy number was significantly higher in patients with subsequent relapse than in those remaining in continuous CR (P<0.001). Presence of detectable mutants after treatment predicted relapse if no further chemotherapy was administered. Furthermore, the patients with any rise of mutant signals during serial follow-up had 3.2-fold increase of relapse risk compared to those with persistently low or undetectable signals (P<0.001). Patients who could achieve mutant reduction to <0.1% of internal control had significantly longer overall survival (OS) (P=0.004) and relapse-free survival (RFS) (P<0.001). Failure to achieve 2 logs of reduction after consolidation predicted shorter OS (P=0.01) and RFS (P=0.001). In conclusion, qPCR monitoring may have prognostic impact in AML patients with NPM1 mutations.

Four anthropometric indices and cardiovascular risk factors in Taiwan.

OBJECTIVE: To examine the relationships between four anthropometric measurements and cardiovascular risk factors in Taiwan.DESIGN: The data was collected from four nationwide health screen centers in Taiwan from 1998 to 1999.SUBJECTS: A total of 38 556 subjects: 18 280 men and 20 276 women, mean age=37.0±11.1 y. None had any known major systemic diseases or were currently on medication.MEASUREMENTS: Individual body weight, height, waist circumference (WC), and cardiovascular risk factors (blood pressure, fasting plasma glucose, triglycerides, total cholesterol level, low-density and high-density-lipoprotein cholesterol level) were assessed and their relationships were examined.RESULTS: In both sexes, with increasing body mass index (BMI), WC, WHpR (waist-to-hip ratio) and WHtR (waist-to-height ratio), there were significantly higher risks of hypertension, impaired fasting glucose, diabetes and dyslipidemia (P<0.001) in almost all age groups. In the age groups older than 65, however, the relationships were statistically inconsistent.CONCLUSIONS: In Taiwan, the four anthropometric indexes (BMI, WC, WHpR, WHtR) are closely related to cardiovascular risk factors.

Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults

OBJECTIVES This study sought to evaluate the relationship between subclinical hypothyroidism (SCH) and all-cause and cardiovascular disease (CVD) mortality. BACKGROUND SCH may increase the risks of hypercholesterolemia and atherosclerosis. The associations between SCH and all-cause or CVD mortality are uncertain, on the basis of the results of previous studies. METHODS A baseline cohort of 115,746 participants without a history of thyroid disease, ≥20 years of age, was recruited in Taiwan. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0 to 19.96 mIU/l with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47 to 4.9 mIU/l. Cox proportional hazards regression analysis was used to estimate the relative risks (RRs) of death from all-cause and CVD for adults with SCH during a 10-year follow-up period. RESULTS There were 3,669 deaths during the follow-up period; 680 deaths were due to CVD. Compared with subjects with euthyroidism, after adjustment for age, sex, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol consumption, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of deaths from all-cause and CVD among subjects with SCH were 1.30 (1.02 to 1.66), and 1.68 (1.02 to 2.76), respectively. CONCLUSIONS Adult Taiwanese with SCH had an increased risk for all-cause mortality and CVD death.

HMG-CoA reductase inhibitors inhibit inducible nitric oxide synthase gene expression in macrophages.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, statins, are potent inhibitors of cholesterol synthesis and have wide therapeutic use in cardiovascular diseases. Recent evidence, however, suggests that the beneficial effects of statins may extend beyond their action on serum cholesterol levels. In this study, we investigated the effects of lovastatin, pravastatin, atorvastatin and fluvastatin on macrophage formation of nitric oxide (NO) in murine RAW 264.7 cells. Stimulation of macrophages with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) resulted in inducible NO synthase (iNOS) expression, which was accompanied by a large amount of NO formation. At concentrations of 0.1-30 microM, statins can inhibit stimuli-induced NO formation and iNOS induction to different extents. This inhibition occurs at the transcriptional level, and displays potency in the order of lovastatin > atorvastatin > fluvastatin >> pravastatin. We found that LPS-induced I kappa B kinase and nuclear factor-kappa B (NF-kappa B) activation, as well as IFN-gamma-induced signal transducer and activator of transcription 1 (STAT1) phosphorylation, were reduced by lovastatin. Moreover, inhibition by lovastatin of NO production and kappa B activation was reversed by mevalonate, geranylgeranyl pyrophosphate and farnesyl pyrophosphate. All these results suggest that inhibition of iNOS gene expression by statins can be attributed to interference with protein isoprenylation, which mediates both NF-kappa B and STAT1 activation in the upstream signaling pathways for iNOS gene transcription.

Adiponectin: a biomarker of obesity-induced insulin resistance in adipose tissue and beyond

Adiponectin is one of the most thoroughly studied adipocytokines. Low plasma levels of adiponectin are found to associate with obesity, metabolic syndrome, diabetes and many other human diseases. From animal experiments and human studies, adiponectin has been shown to be a key regulator of insulin sensitivity. In this article, we review the evidence and propose that hypo-adiponectinemia is not a major cause of obesity. Instead, it is the result of obesity-induced insulin resistance in the adipose tissue. Hypo-adiponectinemia then mediates the metabolic effects of obesity on the other peripheral tissues, such as liver and skeletal muscle and may also exert some direct effects on end-organ damage. We propose that deciphering the molecular details governing the adiponectin gene expression and protein secretion will lead us to more comprehensive understanding of the mechanisms of insulin resistance in the adipose tissue and provide us new avenues for the therapeutic intervention of obesity and insulin resistance-related human disorders.