Kun Wang’s research while affiliated with Fu Jen Catholic University and other places

Objectives: The metabolic syndrome (MetS) is proposed to predict future occurrence of cardiovascular diseases and diabetes. There are some other "non-traditional" risk factors such as hematogram components that are also related to the same endpoints as MetS. In this four-year longitudinal study, we used hematogram components to build models for predicting future occurrence of MetS in older men and women separately. Methods: Subjects above 65 years without MetS and related diseases were enrolled. All subjects were followed up until they developed MetS or until up to four years from the day of entry, whichever was earlier. Results: Among the 4539 study participants, 1327 developed MetS. Models were built for men and women separately and the areas under the receiver operation curves were significant. The Kaplan-Meier plot showed that the models could predict future MetS. Finally, Cox regression analysis showed that the hematogram model was correlated to future MetS with hazard ratios of 1.567 and 1.738 in men and women, respectively. Conclusion: Our hematogram models could significantly predict future MetS in elderly and might be more practical and convenient for daily clinical practice.

Background: The growing elderly population in Taiwan, as in many other countries, has resulted in increased importance of the metabolic syndrome (MetS). Although it has been reported in different age groups, the relationship between platelets and MetS remains unknown in geriatric patients. Patients and Methods: We enrolled 1460 women >65 years old. Women with a known history of diabetes, hyperlipidemia or hypertension or those taking medication for these conditions were all excluded. The women were further divided into quartiles arbitrarily according to platelet count (PC) (PC1–PC4, lowest to highest accordingly). Results: Among the MetS components, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol (LDL-C) and log transformation triglyceride (Log TG) were all significantly higher in the PC4 group (p

Insulin resistance is one of the important underlying abnormalities of type 2 diabetes. The effect of thiazolidinedione on liver functions has been controversial in different studies. In this study, we evaluated the effect of rosiglitazone on liver enzymes in subjects with type 2 diabetes with and without abnormal liver function. Seventy-three patients with type 2 diabetes taking rosiglitazone 4 mg daily were enrolled in this 3-month study. Forty-two of them had normal liver function (NLF), and 31 had abnormal liver function (ABLF). Blood biochemistries were collected monthly during the treatment period. At baseline, other than age and liver enzymes, there were no differences in body mass index, fasting plasma glucose, hemoglobin A1c (HbA1c), and lipid profiles between the NLF and ABLF groups. At the end of the treatment, HbA1c was lowered in both groups, but only significantly in the ABLF group (P = 0.027). More importantly, serum concentrations of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the ABLF group decreased significantly (AST: 57.8 ± 26.5 to 47.5 ± 20.2 U/L, P = 0.006; ALT 66.6 ± 35.0 to 51.9 ± 23.5 UL, P = 0.004), while in the NLF group, a similar change was not found. After 3-month rosiglitazone treatment in subjects with type 2 diabetes with mildly elevated liver enzymes, significant improvement in AST and ALT were observed. Our study provides some hints that rosiglitazone might not be contraindicated in subjects with diabetes with abnormal liver function as previously thought, but further well-designed studies are necessary to clarify this issue.

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 β 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.

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. 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. 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). 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 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.

There is no single method of measuring insulin resistance that is both accurate and can be easily performed by general researchers. We validate the accuracy of oral glucose insulin sensitivity (OGIS) in the Chinese by comparing the OGIS120 and OGIS180, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (OUICKI) with steady-state plasma glucose (SSPG) in different glucose tolerance subjects. We enrolled 515 subjects, aged between 20 and 75 years old, during routine health evaluations. All subjects were divided into normal, obese, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes (T2D) groups. Participants had a 3-hour oral glucose tolerance test (OGTT) and SSPG with an insulin suppression test. The relationships between SSPG and OGIS120, OGIS180, HOMA-IR, and QUICKI were evaluated. The normal group had the highest OGIS120, OGIS180 and lowest SSPG as compared with the other 4 groups. OGIS180, HOMA-IR and QUICKI in all 5 groups were significantly related to SSPG (r = 0.397-0.621, all P <0.05). OGIS120 in all 5 groups was not significantly related to SSPG (r = 0.003-0.226). Additionally, the r value of OGIS180 against SSPG was not higher than the other 2 insulin sensitivity surrogates from OGTT. Although OGIS180 was more accurate in estimating insulin sensitivity than OGIS120 in the Chinese, it was not superior to the traditional surrogates such as HOMA-IR or QUICKI.

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.

Components of metabolic syndrome (MetS) have been associated with several inflammatory factors, including white blood cell count (WBCC). In the present study, the relationships between WBCC and aspects of MetS in young adolescents were investigated. We enrolled 596 participants (328 males and 268 females) from 10 to 13 years of age and with normal WBCC in this study. They were divided into four quartiles according to WBCC (WBCC1-4, from lowest to highest WBCC). The mean values of MetS components for each group were compared in males and females separately. Multivariate linear regression analysis between the WBCC and the components of MetS after adjusted for age and body mass index (BMI) were also evaluated. In the male group, the BMI of WBCC1 and WBCC2 was significantly lower than WBCC4. The total cholesterol and low-density lipoprotein-cholesterol (LDL-C) of WBCC2 were significantly higher than WBCC1 and WBCC4. Triglyceride (TG) levels of WBCC1 were significantly lower than WBCC3 and WBCC4, and TG levels of WBCC2 were significantly lower than WBCC4. Alternatively, the BMI of WBCC1 and WBCC2 were significantly lower than WBCC3 in the female group. Finally, the TG and fasting plasma glucose (FPG) levels of WBCC1 were significantly lower than WBCC3 or WBCC4, respectively. After multivariate linear regression, WBCC was positively correlated to BMI and TG, but negatively correlated to FPG in males whereas in young adolescent females, WBCC was positively correlated to BMI and FPG. In conclusion BMI was positively correlated with WBCC in young adolescent females and males. Thus, BMI is the most important component of MetS in this age group. In addition, TG levels in males and FPG in females were significantly related to WBCC. These findings could be regarded an early indication for the future development of full-blown MetS or cardiovascular diseases.

This study was conducted to explore the association between nonalcoholic fatty liver disease and glucose metabolism as well as insulin resistance using the homeostasis model assessment method (HOMA). From July 2003 to June 2004, 23 patients with ultrasound-proved fatty liver and either normal (10 patients) or abnormal (13 patients) serum aminotransferase levels were enrolled. Blood tests included a routine biochemistry, a 75-g glucose oral glucose tolerance test (OGTT) with blood sampled at 30-minute intervals during a 120-minute period. Fasting and 120-minute serum leptin, insulin, and C-peptide concentrations were also measured. Using the Mann-Whitney U test, significant differences were found in gamma glutamyl transpeptidase (28.6+/-7.9 vs. 65.1+/-65.9 U/L, P=0.008), fasting insulin (FI) (13.11+/-7.53 vs. 31.76+/-42.95 muU/mL, P=0.02), fasting C-peptide (3.82+/-3.00 vs. 2.17+/-0.43 ng/mL, P=0.01), fasting leptin (10.34+/-4.05 vs. 24.27+/-24.97 ng/mL, P=0.01), HOMA-IR (3.34+/-1.06 vs. 8.81+/-13.18, P=0.02), and HOMA beta-cell function (120.32+/-52.50 vs. 242.20+/-247.29, P=0.02) between normal and abnormal ALT/AST function groups. From the 75-g OGTT, no significant difference of plasma glucose was noted at 0, 30, 60, and 90 minutes but significant change was noted in 120-minute plasma glucose (99.3+/-21.5 vs. 131.4+/-27.3 mg/dL, P=0.004) of 2 groups. In conclusion, patients with fatty liver proved by ultrasound sonography might be at high risk of developing type 2 diabetes, especially when they had elevated liver enzymes. OGTT is warranted for the early diagnosis of these high risk patients.