Chang Hsun Hsieh

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.

Correlation between white blood cell count and metabolic syndrome in adolescence.

Background: Metabolic syndrome (MetS) is associated with increased risk for diabetes and coronary heart disease. Data suggest that MetS starts even in children. Thus, it is important to understand the role of MetS and the risks related to it. Furthermore, white blood cell count (WBCC) is available in routine examination and it has been proved to be related to risks of 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.

Association between white blood cell count and components of metabolic syndrome

Background:  Components of metabolic syndrome (MetS) were found to be associated with several inflammatory factors including white blood cell count (WBCC), which is an easily available test in clinical practice. In the present study, the relationships between WBCC and MetS components were investigated in children.

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.

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.

Identifying Subjects with Insulin Resistance by Using the Modified Criteria of Metabolic Syndrome

The objectives of this cohort analysis were to explore the relationship between insulin resistance (IR) and the criteria for metabolic syndrome (MetS) and to evaluate the ability to detect IR in subjects fulfilling those criteria. We enrolled 511 healthy subjects (218 men and 283 women) and measured their blood pressure (BP), body mass index, high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and fasting plasma glucose levels. Insulin suppression testing was done to measure insulin sensitivity as the steady-state plasma glucose (SSPG) value. Subjects with an SSPG value within the top 25% were considered to have IR. The commonest abnormality was a low HDL-C level, followed by high BP. The sensitivity to detect IR in subjects with MetS was about 47%, with a positive predictive value of about 64.8%, which has higher in men than in women. In general, the addition of components to the criteria for MetS increased the predictive value for IR. The most common combination of components in subjects with MetS and IR were obesity, high BP, and low HDL-C levels. All of the components were positive except for HDL-C, which was negatively correlated with SSPG. The correlation was strongest for obesity, followed by high TG values. In subjects with MetS, sensitivity for IR was low. However, body mass index and TG values were associated with IR and may be important markers for IR in subjects with MetS.

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.

Using hematogram model to predict future metabolic syndrome in elderly: a 4-year longitudinal study.

Abstract 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.

The adipokines and inflammatory marker in young type 2 diabetics with metabolic syndrome: A pilot study

OBJECTIVE The purpose of the metabolic syndrome (MetS) concept was to early identify subjects having risk for developing cardiovascular diseases and diabetes, which of both are involved in low grade inflammation and obesity. We wish to explore the role of adipokines and inflammatory marker in young type 2 diabetics (YDM) with MetS. METHODS Forty-eight YDM patients were divided to 2 and 3 groups according to the presence of the MetS (MetS+ and MetS-), and the numbers of MetS component (MetS-2 to MetS-4 with 1-2, 3, and 4-5 components) respectively. Plasma adipokines (tumor necrosis factor-α; TNF-α and adiponectin) and C-reactive protein (CRP) were measured and compared among groups. RESULTS Blood pressure (BP), body mass index (BMI), and plasma triglyceride (TG) levels were higher in the group with MetS+ than that of MetS-. Except for diastolic BP, BMI, waist, and plasma TG levels, which were generally lower in the MetS-2 group, the rest demographic characteristics were not different among these three groups. Finally, the plasma adiponectin, CRP and TNF-αlevels were not different between both groups with or without MetS; and also among these three groups regardless the component numbers they had. CONCLUSION YDM with MetS might have non-significant lower adiponectin and higher CRP levels compared to subjects without MetS. It needs prospective study with larger scale to explicit the role of cytokines and inflammatory markers in YDM with MetS.