Jiunn Diann Lin

The Relationship between Thyroid Function and Bone Mineral Density in Euthyroid Healthy Subjects in Taiwan

Introduction. It has been reported that low normal circulating thyrotropin (TSH) levels correlate with lower bone mineral density (BMD) in the Korean postmenopausal female. The goal of this study is to evaluate this relationship in different sex and age groups in a Chinese population. Materials and methods. A total of 2,957 subjects in Taiwan, 1,343 males and 1,614 females, aged from 45 to 64 years, were enrolled in this study. They were divided into four groups: group 1 was males aged between 45 and 50 years (young male, YM); group 2 was females aged between 45 and 50 years (young female, YF); group 3 was males older than 50 years (old male, OM); and group 4 was females older than 50 years (old female, OF). Plasma total thyroxine (T4) and TSH were measured. BMD was quantified at the wrist using dual energy X-ray absorptiometry. Results. YM had the highest BMD whereas OF had the lowest BMD. Among the four groups, no significant correlation between TSH level and BMD was found in the four groups, but a significant negative correlation existed between T4 and BMD in OF (r = −0.089, p = 0.005) and YM (r = −0.109, p = 0.018). Conclusion. Our study did not find significant correlations between TSH and BMD in both men and women with normal thyroid function in Taiwan. Weak negative correlations existed between T4 and BMD in postmenopausal women and young men. Further studies with measurement of FT4 and TSH and with a longitudinal design may shed light on this population difference.

The first and second phase of insulin secretion in naive Chinese type 2 diabetes mellitus

Impaired insulin secretion (ISEC) has been recognized as one of the most important pathophysiologies of type 2 diabetes mellitus. There are 2 phases of ISEC: the first phase (first ISEC) and second phase (second ISEC). This study aimed to evaluate the 2 phases of ISEC in newly diagnosed type 2 diabetes mellitus patients. Fifty-two drug-naive type 2 diabetes mellitus patients were given 2 tests: a modified low-dose graded glucose infusion (M-LDGGI) and frequent sample intravenous glucose tolerance test. The M-LDGGI is a simplified version of the Polonsky method. Two stages of intravenous infusion of glucose with different rates were given, starting from 2 mg/(kg min) and then followed by 6 mg/(kg min). Each stage was maintained for 80 minutes. The results were interpreted as the slope of the changes of plasma insulin against the glucose levels. The slope of these curves was regarded as the second ISEC and used as the criterion for grouping-the responders and nonresponders. The responders are older and had higher body mass index and log (homeostasis model assessment of beta-cell function) (log HOMA-beta) but lower fasting plasma glucose and hemoglobin A(1c) (HbA(1c)) than the nonresponders. Significant correlations were only noted between the second ISEC and first ISEC (r = 0.278, P = .046) and between the second ISEC and log HOMA-beta (r = 0.533, P = .000). Correlation between different parameters and HbA(1c) was also evaluated. Only second ISEC and log HOMA-beta were correlated significantly with HbA(1c) (r = -0.388, P = .015 and r = -0.357, P = .026, respectively). In type 2 diabetes mellitus, subjects with higher second ISEC are older and have higher body mass index. At the same time, second ISEC is the most important factor for determining glucose levels in naive Chinese type 2 diabetes mellitus patients. The first and second ISECs were only modestly correlated, which indicated that the deterioration of these 2 phases was not synchronized. Finally, we also recommend using the M-LDGGI for quantifying second ISEC. This practical method could be done in many centers without difficulty.

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.

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.

The impact of metabolic syndrome on insulin sensitivity, glucose sensitivity, and acute insulin response after glucose load in early-onset type 2 diabetes mellitus: Taiwan Early-Onset Type 2 Diabetes Cohort Study

Diabetic patients with metabolic syndrome (MetS) have higher lifetime risks for cardiovascular disease, especially in early-onset type 2 diabetes mellitus (EODM). Increased insulin resistance (IR) and impaired insulin secretion are important pathophysiologies in diabetic patients. Therefore, the effects of MetS on IR and insulin secretion in EODM were investigated. Forty-eight EODM (mean age, 22.8 +/- 0.6 years) patients were enrolled in this study. Two grouping criteria were used: the first was whether the patient had MetS or not (MetS+ or Met-, with 31 and 17 patients, respectively); and the second was the number of MetS components each group had, that is, MetS (1,2) with 1 to 2, MetS (3) with 3, and MetS (4,5) with 4 to 5 components (17, 17, and 14 patients in each group, respectively). A frequently sampled intravenous glucose tolerance test was performed to measure insulin sensitivity, glucose sensitivity, acute insulin response after glucose load, and disposal index. Severe IR was noted with both homeostasis model assessment and frequently sampled intravenous glucose tolerance test both in MetS+ and MetS-. However, significantly higher acute insulin response after glucose load and disposal index were noted in MetS+ and MetS (4,5) than in Met-, MetS (1,2), and MetS (3), respectively. Early-onset type 2 diabetes mellitus patients with MetS had similar IR to those without MetS. This may be due to early deterioration of insulin action in these subjects. In addition, insulin secretion was higher in subjects with more MetS components, suggesting that EODM patients with MetS had better preserved ability of beta-cell compensation for IR than those without MetS.

Comparison of insulin sensitivity, glucose sensitivity, and first phase insulin secretion in patients treated with repaglinide or gliclazide.

The traditional sulfonylureas with long half-lives have sustained stimulatory effects on insulin secretion compared to the short-acting insulin secretagogue. In this study, we used the frequently sampled intravenous glucose tolerance test (FSIGT) to evaluate the insulin sensitivity (IS), glucose sensitivity (SG), and acute insulin response after glucose load (AIRg) after 4 months treatment with either gliclazide or repaglinide. The design of study was randomizedcrossover. We enrolled 20 patients with new-onset type 2 diabetes (mean age, 49.3 years). Totally three FSIGTs were performed, one before and one after each of the two treatment periods as aforementioned. No significant differences in fasting plasma glucose, insulin, body mass index, blood pressure, glycated hemoglobin, or lipids were noted between the two treatments. After the repaglinide treatment, higher AIRg, lower IS, and lower SG were noted, but they did not reach statistical significance. The disposal index (DI) was also not significantly different between the two treatments. In conclusion, since non-significantly higher DI, AIRg, lower IS and SG were noted after repaglinide treatment, it might be a better treatment for diabetes, relative to gliclazide.

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.

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.