Chun Hsien Hsu

Predictive Value of Serum Uric Acid Levels for the Diagnosis of Metabolic Syndrome in Adolescents

OBJECTIVE To evaluate the cause-effect relationships between serum levels of uric acid (UA) and metabolic syndrome (MetS) in an adolescent-male cohort that was followed for 2.7 years. STUDY DESIGN We enrolled male adolescents aged between 10 and 15 years at the baseline. A total of 613 subjects were divided into quartiles according to their UA levels, from UA-1 (the lowest) to UA-4 (the highest). RESULTS After the mean follow-up period of 2.7 ± 0.97 years, 19 (3.1%) subjects developed MetS. Waist circumference (WC), systolic blood pressure, high density lipoprotein cholesterol (HDL-C), and log triglyceride levels were significantly related to baseline UA levels. Compared with the UA-1 group, subjects in the UA-4 group had significantly higher OR for abnormal WC, blood pressure, and HDL-C at the end of follow-up and had a 6.39-fold higher OR (95% CI 1.41-29.08; P < .05) for having MetS. Subjects with UA >7.6 mg/dL had a 4.32 (95% CI 1.57-11.93) higher risk of developing MetS. CONCLUSIONS In this longitudinal study, we found that serum UA is correlated with future WC, systolic blood pressure, triglyceride, and HDL-C and is a risk factor for developing MetS. UA might be valuable in predicting adolescent MetS.

Beta-cell function and insulin sensitivity at various degrees of glucose tolerance in Chinese subjects

AIMS The aim of this study was to evaluate the relative importance of insulin sensitivity (SI), and the first (1st ISEC) and second phase insulin secretion (2nd ISEC) in the development of type 2 diabetes (T2D) in Chinese subjects. METHODS A total of 96 subjects, including 19 with normal fasting glucose, 21 with pre-diabetes, and 56 with T2D were enrolled. Subjects underwent a modified low dose graded glucose infusion (M-LDGGI; a simplified version of Polonskys method) and frequently sampled intravenous glucose tolerance test. The results were interpreted as the slope of the changes of plasma insulin against the glucose levels. By observing the respective percentage reduction, the deterioration rate of each parameter was compared. RESULTS As fasting plasma glucose (FPG) levels increased, SI decreased mildly and non-significantly, while the 1st and 2nd ISECs decreased more dramatically and significantly. More importantly, the decrease of the 1st ISEC from baseline was greater than that of the 2nd ISEC. CONCLUSIONS Since the 1st ISEC decreased the most with increasing FPG levels, it is concluded that the 1st ISEC is the key trigger of T2D development. On the contrary, the 2nd ISEC remained more stable across increasing FPG levels. This latter finding may explain the effectiveness of insulin secretagogues during the early stage of T2D. The results of this study can be helpful in the development of interventions aimed at stopping the progression and/or treating T2D in Chinese populations.

Associations between genetic variants and the severity of metabolic syndrome in subjects with type 2 diabetes

Metabolic syndrome (MetS) includes obesity, dyslipidemia, elevated blood pressure, and dysglycemia. Subjects with type 2 diabetes (T2D) exhibit features of MetS. The etiology of MetS is complex, involving both environmental and genetic factors. In this study, we examined the role of specific candidate genetic variants on the severity of MetS in T2D subjects. A total of 240 T2D subjects aged 35-64 years were recruited. Waist circumstance, plasma triglycerides, high-density lipoprotein cholesterol, fasting plasma glucose, and blood pressure were measured to define MetS. Subjects were divided into 4 groups according to MetS components. Target genes involved in fibrotic and inflammatory processes, insulin and diabetes, cell growth and proliferation, and hypertension were genotyped. A total of 13 genes and 103 single-nucleotide polymorphisms (SNPs) were analyzed to evaluate their genetic association with MetS severity in T2D subjects. Univariate ordinal logistic regression using a dominant model (homozygous for the major allele vs carriers of the minor allele) revealed 6 SNP markers within 4 genes with genotypes associated with MetS risk. For the SNP genotypes of rs362551 (SNAP25), rs3818569 (RXRG), rs1479355, rs1570070 (IGF2R), and rs916829 (ABCC8), heterozygotes showed a lower risk of MetS compared with the reference group. In addition, the CC genotype was comparable to the TT genotype for rs3777411. There was no gender-specific effect. In conclusion, our results suggest that among the Han Chinese population, several SNPs increase the risk of severe MetS in T2D subjects. Further study in a large population should be conducted.

Adiposity measurements in association with metabolic syndrome in older men have different clinical implications

Obesity is a major public health problem, and measuring adiposity accurately and predicting its future comorbidities are important issues. Therefore, we hypothesized that 4 adiposity measurements, body mass index (BMI), waist circumference (WC), waist-to-height ratio, and body fat percentage, have different physiological meanings and distinct associations with adverse health consequences. This study aimed to investigate the relationship of these 4 measurements with metabolic syndrome (MetS) components and identify the most associated factor for MetS occurrence in older, non-medicated men. Cross-sectional data from 3004 men, all 65 years of age and older, were analyzed. The correlation and association between adiposity measurements and MetS components were evaluated by Pearson correlation and multiple linear regression. Based on multivariate logistic regression, BMI and WC were significantly associated with MetS and were selected to build a combined model of receiver operating characteristic curves to increase the diagnosis accuracy for MetS. The results show that BMI is independently associated with systolic and diastolic blood pressure; WC and body fat percentage are associated with fasting plasma glucose and log transformation of triglyceride; BMI and WC are negatively associated with high-density lipoprotein cholesterol (HDL-C); and WC is a better discriminate for MetS than BMI, although the combined model (WC + BMI) is not significantly better than WC alone. Based on these results, we conclude that the 4 adiposity measurements have different clinical implications. Thus, in older men, BMI is an important determinant for blood pressure and HDL-C. Waist circumference is associated with the risk of fasting plasma glucose, HDL-C, triglyceride, and MetS occurrence. The combined model did not increase the diagnosis accuracy.

Relationship of blood pressure and cardiovascular disease risk factors in normotensive middle-aged men

We conducted this study to investigate whether subjects with high-normal systolic blood pressure (SBP) have an increased risk of cardiovascular disease (CVD) and/or diabetes compared to subjects with low-normal SBP, using metabolic syndrome (MetS) as a risk factor for future CVD/diabetes.The study included 6133 apparently healthy Taiwanese men aged 40-65 years. All subjects were normotensive, and none took medication for any abnormal MetS component. To avoid the effect of age on blood pressure, we stratified patients first by age then by SBP (that is, low, middle, and high SBP). We pooled all the low, middle, and high SBP groups from the different age strata to create 3 larger groups (Group 1, Group 2, and Group 3, respectively). The MetS components in subjects with the lowest SBP (Group 1) were compared with those in the other 2 groups. All of the MetS components, except for high-density lipoprotein cholesterol (HDL-C), were significantly lower in Group 1. Thus, it was not surprising that Group 2 and Group 3 had significantly higher odds ratios for abnormal body mass index, fasting plasma glucose, low-density lipoprotein-cholesterol (LDL-C), and triglycerides than Group 1 (but not for HDL-C). Specifically, Group 3 had a 1.7-fold higher odds ratio (p < 0.001) for having MetS than Group 1. Age, body mass index, fasting plasma glucose, LDL-C, and log triglycerides correlated significantly with SBP. In multivariate linear regression analysis, we found that only body mass index, fasting plasma glucose, and log triglycerides remained significantly related to SBP. Among them, body mass index had the highest &bgr; value.In conclusion, the level of SBP was highly correlated with body mass index, fasting plasma glucose, and triglycerides in subjects with normotension. Although there is not a cause-and-effect relationship, the risk of CVD and diabetes was significantly associated with an elevation of SBP, even when the SBP remained within the normal range. Further studies are needed to determine whether normotensive subjects would benefit from medical management.Abbreviations: ATP III = National Cholesterol Education Program Adult Treatment Panel III, BMI = body mass index, BP = blood pressure, CVD = cardiovascular disease, DBP = diastolic blood pressure, FPG = fasting plasma glucose, HDL-C = high-density lipoprotein cholesterol, LDL-C = low-density lipoprotein cholesterol, MetS = metabolic syndrome, OR = odds ratio, SBP = systolic blood pressure, WHO = World Health Organization.

Using white blood cell counts to predict metabolic syndrome in the elderly: A combined cross-sectional and longitudinal study

BACKGROUND Metabolic syndrome (MetS) has an important implication from a preventive medicine perspective as early recognition and intervention will reduce associated mortality and morbidity. To better identify patients at risk for developing MetS and cardiovascular disease, we conduct a combined cross-sectional and longitudinal study to shed light on the elevated white blood cell (WBC) level in elderly. METHODS A total of 10,463 subjects were eligible for analysis. In the first stage of study, subjects were enrolled in the cross-sectional study to find out not only the correlation between WBC and MetS but also the optimal cut-off value of WBC with higher chances to have MetS. In the second stage of current study, subjects with MetS at baseline were excluded from the same study group, and performed a median 6.8-year longitudinal study to validate the optimal cut-off value of WBC predicting MetS. RESULTS WBC is significantly higher in the group with than without MetS in both genders. All MetS components were associated with WBC in multivariate analysis except diastolic blood pressure and fasting plasma glucose. In the longitudinal study, WBC showed to be a good predictor of MetS in both genders. CONCLUSION WBC is a good marker to identify the high risk subjects having MetS in the current status or in the future. Elderly with a higher WBC and without any underlying chronic diseases should receive more attention on the potential to develop MetS.

ASSOCIATION BETWEEN THYROID FUNCTION AND METABOLIC SYNDROME IN ELDERLY SUBJECTS

To the Editor: Metabolic syndrome (MetS) consists of a cluster of cardiovascular risk factors including obesity, dyslipidemia, hypertension, and hyperglycemia. Thyroid disease has also been shown to be associated with cardiovascular risk factors. Thus, it is not surprising that a low to normal free thyroxin level is associated with hyperlipidemia and insulin resistance, although this relationship may vary according to age and sex. With the growth of the geriatric population, it is important to reevaluate the relationships between thyroid function and MetS in subjects aged 65 and older.

γ-Glutamyl transpeptidase in men and alanine aminotransferase in women are the most suitable parameters among liver function tests for the prediction of metabolic syndrome in nonviral hepatitis and nonfatty liver in the elderly

Background/Aims: Nonalchoholic fatty liver disease (NAFLD) has been reported as a hepatic manifestation of metabolic syndrome (MetS); it is common and accounts for 80% of the cases with abnormal liver function tests (LFTs). In addition, several studies have proved that there is a correlation between abnormal LFTs and MetS. Therefore, LFTs may represent the abnormal metabolic status of livers in the patients with MetS. To identify the early state of metabolic dysfunction, we investigate the value of LFTs for the future MetS development in the relatively healthy (non-NAFLD) elderly. Patients and Methods: A total of 16,912 subjects met the criteria for analysis. In the first stage of this study, subjects were enrolled in the cross-sectional study in order to find out the optimal cutoff value in different LFTs with higher chances to have MetS. In the second stage of the present study, subjects with MetS at baseline were excluded from the same study group, and a median 5.6-year longitudinal study was conducted on the rest of the group. Results: Among all LFTs, only aspartate aminotransferase in both genders and the α-fetal protein in women failed to show the significance in distinguishing subjects with MetS by the receiver operating characteristic curve. In the Kaplan–Meier plot, only γ-glutamyl transpeptidase (γ-GT) in men and the alanine aminotransferase (ALT) in women could be used to successfully separate subjects with higher risk of developing the MetS from those with lower risk. Finally, in the multivariant Cox regression model, similar results were identified. Still, the hazard ratio (HR) to have future MetS, γ-GT in men, and ALT in women showed significance (HR = 1.511 in men and 1.504 in women). Conclusion: Among all the different LFTs, γ-GT (>16 U/L) in male and ALT (>21 U/L) in female were the best predictors for the development of MetS in healthy elderly. These two liver markers could be an ancillary test in predicting future MetS development/diagnosis. Elevation of the LFTs without underlying liver diseases should be treated as a warning sign of the possible MetS development in the elderly.

Predicting metabolic syndrome by using hematogram models in elderly women

Abstract Background: Low-grade inflammatory status was thought to be a major underlying mechanism in MetS. White blood cell (WBC) count was one of the inflammatory markers identified to be associated with MetS. Moreover, not only WBC but also hemoglobin (Hb) and platelet (PLT) were all associated with MetS. Objective: In this study, we tried to build models by the hematogram components. In this way, we can not only predict the occurrence of MetS with a relatively low-cost and routine lab test, but also can understand more about the relationships between low grade inflammation and MetS. Methods: We randomly collected subjects over 65 years old from MJ Health Screening Center’s database between 1999 and 2008. After excluding subjects with medications for hypertension, hyperlipidemia and/or diabetes, 13 132 female were eligible for analysis. Results: All the MetS components, hematogram parameters and age were higher in group with MetS. In the correlation matrix, all these three hematogram parameters (WBC, Hb and PLT) were correlated with MetS components except for the correlation between Hb and HDL-C. The ROC curves showed that the model 3 (PLT + Hb + WBC) had greatest area under the curve of 0.631 with the sensitivity of 58.1% and specificity of 61.4%. Conclusions: Our findings have shown that all the three hematogram parameters are related to MetS. The results not only shed light on the complex relationships, but also demonstrate a common and easy model to aid clinicians to be more aware of the occurrence of MetS.

Elevated fasting glucose levels within normal range are associated with an increased risk of metabolic syndrome in older women

OBJECTIVE The prevalence of cardiovascular disease (CVD) and metabolic syndrome (MetS) increases with increasing fasting plasma glucose (FPG) levels in an elderly population with pre-diabetes or diabetes. However, it remains unknown whether the relationship between elevated FPG and increased risks of MetS exists in older women with normoglycemia (FPG<100mg/dL). Therefore, the present study was conducted to fill the lack of information in that area. MATERIALS AND METHODS We included 6505 apparently healthy women, aged 65years and older, with normoglycemia who participated in routine health checkups at health screening centers in Taiwan. Components of MetS (FPG, waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and systolic/diastolic blood pressure), body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and percentage body fat (PBF) were examined in all subjects. RESULTS Subjects were sub-grouped by FPG levels (<90mg/dL, 91-95mg/dL and >95mg/dL for group 1, group 2 and group 3, respectively). Subjects in group 2 and group 3 were 1.22-fold (P=0.017) and 1.25-fold (P=0.007) more likely to have MetS compared with those in group 1. Age, WC, BMI, PBF, systolic and diastolic blood pressure, total cholesterol, triglycerides, and HDL-C were significantly correlated with FPG, whereas HDL-C was negatively correlated with FPG. In a multivariate stepwise regression analysis, PBF, LDL-C, triglycerides, and age were significantly and independently associated with FPG. CONCLUSION Among older women, the risk of MetS was significantly associated with elevated FPG even for subjects with normal FPG. Lifestyle interventions for reducing PBF and controlling dyslipidemia could help reduce the risk of MetS in this population.