Ching-Jung Hsieh

Peripheral blood mitochondrial DNA content and dysregulation of glucose metabolism.

OBJECTIVE The aim of this study was to examine the potential influence of insulin resistance (IR), hyperglycemia and oxidative stress on leucocytes mitochondrial DNA (mtDNA) content. RESEARCH DESIGN AND METHOD One hundred twenty-five T2DM, 101 IFG and 70 normal subjects were enrolled in this study. The quantity of relative mtDNA content was measured by a real-time PCR and corrected by simultaneous measurement of the nuclear DNA. Parameters of lipid peroxidation, thiobarbituric acid reactive substance (TBARS), and total free thiols as antioxidative status were measured from serum samples. IR was assessed by homeostasis model assessment in the non-diabetic groups. Relationships among different variables were analyzed by general linear model correlation. RESULTS In all subjects, after correcting for age, sex and BMI, there were progressive increases of leucocyte mtDNA copy number, TBARS, and total reduced thiols with progressive dysregulation of glucose metabolism (normal vs. IFG vs. T2DM). Furthermore, correlation between mtDNA content and glucose dysregulation persisted after sequential correction for age, sex, BMI and TBARS. The independent predictor of mtDNA content by regression analysis was hyperglycemia. In non-diabetic group, influence of family history of diabetes on mtDNA content turned to non-significant after correcting for fasting plasma glucose (FPG). Correlation study revealed that mtDNA content was correlated with FPG (P<0.001), but not IR. CONCLUSION Our results indicate that hyperglycemia, not IR, is associated with an increase of leucocyte mtDNA copy number in cases of glucose dysregulation.

Long-term outcomes of distant metastasis from differentiated thyroid carcinoma

Background  The aim of this study was to identify the prognostic factors of long‐term survival and optimal therapeutic protocol for patients with distant metastasis secondary to differentiated thyroid carcinoma (DTC).

Tissue-specific differences in mitochondrial DNA content in type 2 diabetes

BACKGROUND To investigate whether the effect of hyperglycemia on mitochondrial DNA (mtDNA) content is tissue-specific. METHOD We compared the mtDNA contents in leg muscle, blood vessel, and peripheral leucocytes in seventeen patients with type 2 diabetes (T2DM) with those of seven controls. We measured 8-hydroxydeoxyguanosine (8-OHdG) expression in the muscles and thiobarbituric acid reactive substance (TBARS) in sera to evaluate oxidative stress. Immunohistochemical detection of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-α), mitochondrial transcription factor A (Tfam), and apoptosis were performed in the muscle tissue. RESULTS The mtDNA copy number was highest in muscle tissue, followed by blood vessel tissue, and lowest in leucocytes in both the diabetic and control subjects. The diabetic patients had less mtDNA content in the muscle than the controls (2.86±0.33 vs. 3.20±0.14, P=0.025), but more mtDNA content in the leucocytes (2.25±0.26 vs. 1.98±0.06, P=0.04). In both groups, there was a positive correlation between muscle tissue mtDNA content and the expression of 8-OHdG. Patients with T2DM had significantly increased 8-OHdG and TUNEL labeling index and non-significant increases in the expression of PGC1-α and Tfam. CONCLUSION Oxidative stress stimulates mitochondrial biogenesis but induces a greater degree of apoptosis in diabetic patients, resulting in a decrease in muscle tissue mtDNA content.

Evaluation of Periodontal Status and Effectiveness of Non-Surgical Treatment in Patients With Type 2 Diabetes Mellitus in Taiwan for a 1-Year Period

BACKGROUND The periodontal status and effects of non-surgical periodontal treatment in patients with type 2 diabetes mellitus and periodontal disease are assessed. METHODS One-hundred patients with type 2 diabetes (mean ± SD hemoglobin (Hb)A1c level: 7.3% ± 0.94%) and periodontal disease were recruited for this study. The group with moderate-to-severe periodontal disease included patients with >1 tooth with a probing depth (PD) ≥5 mm and >2 teeth with a clinical attachment loss (AL) ≥ 6mm, and the group with mild periodontal disease included patients with <1 affected tooth, and >2 affected with a clinical AL ≥ 6mm. Patients (28 patients in the mild group and 72 patients in the moderate-to-severe group) underwent non-surgical periodontal treatments. We analyzed differences in serum concentrations of metabolic parameters (glycated hemoglobin and low-density lipoprotein), inflammatory parameters (interleukin [IL]-1β and C-reactive protein [CRP]), and periodontal parameters between the two groups before treatment and at 3, 6, 9, and 12 months post-therapy. RESULTS Seventy-five patients with diabetes (21 patients in the mild group and 54 patients in the moderate-to-severe group) completed the study. Significant differences in the plaque index (PI), gingival index (GI), PD, and clinical AL at examination times were observed in the whole cohort (P <0.05). We observed significant differences in the PI, GI, and PD in the moderate-to-severe group (P <0.05), whereas there was only a significant difference in PD in the mild group (P <0.05) between baseline and 12 months post-treatment. Both groups experienced improved glycemic control, but the difference was insignificant. CRP and IL-1β levels were significantly different at examination times for the whole cohort (P <0.05). No significant positive association among metabolic and inflammatory parameters at 12 months post-therapy were found. CONCLUSION Non-surgical periodontal treatment improved and maintained the periodontal health of patients with well-controlled diabetes, but no significant reduction of metabolic parameters was observed over a 1-year period.

Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia : implication for impaired neovascularization in diabetes

Aims  This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia.

Genotype and Phenotype Predictors of Relapse of Graves' Disease after Antithyroid Drug Withdrawal

Background: For patients with Graves’ disease (GD), the primary goal of antithyroid drug therapy is to temporarily restore the patient to the euthyroid state and wait for a subsequent remission of the disease. This study sought to identify the predictive markers for the relapse of disease. Methods: To do this, we studied 262 GD patients with long enough follow-up after drug withdrawal to determine treatment outcome. The patients were divided into three groups by time of relapse: early relapse group (n = 91) had an early relapse within 9 months, late relapse group (n = 65) had a relapse between 10 and 36 months, and long-term remission group (n = 106) were either still in remission after at least 3 years or relapsed after 3 years of drug withdrawal. We assessed the treatment outcome of 23 SNPs of costimulatory genes, phenotype and smoking habits. We used permutation to obtain p values for each SNP as an adjustment for multiple testing. Cox proportional hazards models was performed to assess the strength of association between the treatment outcome and clinical and laboratory variables. Results: Four SNPs were significantly associated with disease relapse: rs231775 (OR 1.96, 95% CI 1.18–3.26) at CTLA-4 and rs745307 (OR 7.97, 95% CI 1.01–62.7), rs11569309 (OR 8.09, 95% CI 1.03–63.7), and rs3765457 (OR 2.60, 95% CI 1.08–6.28) at CD40. Combining risk alleles at CTLA-4 and CD40 improved the predictability of relapse. Using 3 years as the cutoff point for multivariate analysis, we found several independent predictors of disease relapse: number of risk alleles (HR 1.30, 95% CI 1.09–1.56), a large goiter size at the end of the treatment (HR 1.30, 95% CI 1.05–1.61), persistent TSH-binding inhibitory Ig (HR 1.64, 95% CI 1.15–2.35), and smoking habit (HR 1.60, 95% CI 1.05–2.42). Conclusion: Genetic polymorphism of costimulatory genes, smoking status, persistent goiter, and TSH-binding inhibitory Ig predict disease relapse.

Acute blood glucose fluctuations can decrease blood glutathione and adiponectin levels in patients with type 2 diabetes

INTRODUCTION Glutathione appears to have apparent antioxidant activity to counter regulate hyperglycemia induced oxidative stress. Adiponectin also plays a role in the suppression of the metabolic derangements in type 2 diabetes mellitus (DM). The aim of this study was to determine whether blood glucose fluctuations can alter blood levels of glutathione and adiponectin. METHODS We enrolled 34 patients with type 2 DM. As a measure of short-term glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from a continuous glucose monitor system (CGMS), and data were recorded over 72 h. For long-term glycemic variability, we calculated the standard deviation (SD) of HbA1c over a 2-year period. Glutathione and adiponectin levels were measured after completing the 72-h CGMS data collection. RESULTS The blood levels of glutathione were significantly and negatively correlated with MAGE (r = -0.543; P < 0.001), but not with HbA1c and SD of HbA1c. Adiponectin levels were also significantly and negatively correlated with MAGE and SD of HbA1c (r = -0.64 and r = -0.55, respectively; P < 0.001). Using generalized estimating equations, multivariate regression analysis revealed that MAGE is an independent predictor of serum levels of adiponectin (P = 0.002) and glutathione (P = 0.004). CONCLUSIONS We found strong associations between acute blood glucose variability, glutathione, and adiponectin in type 2 diabetic patients treated with oral hypoglycemic agent therapy.

The Influence of Self-monitoring Blood Glucose Frequency on the Oscillation of Hemoglobin A1c and Chronic Complications

BACKGROUND A fluctuating blood glucose level is one of the risks of chronic complications in diabetes. Previous studies indicated that hemoglobin A1c (HbA1c) values apparently improved after initiation of self-monitoring blood glucose (SMBG). The purpose of this study is to investigate the relationship between the frequency of SMBG, long-term fluctuatation of HbA1c, and risks of chronic complications in diabetes. METHODS We enrolled 1052 patients with type 2 diabetes. The mean follow-up was 4.7 years. The HbA1c level and frequency of SMBG were recorded every 3 months. Non-mydriatic retinal photography, semiquantitative neuropathy assessment, the lipid profile, serum creatinine level, and urine protein were measured at the beginning of the study and then every year. The fluctuation in HbA1c throughout the period was expressed as the standard deviations (SDs) of all measurements of the HbA1c. RESULTS The frequency of SMBG was significantly and negatively correlated with the SDs of the HbA1c (r = -0.553, p < 0.001) but not with the average HbA1c. After controlling for age, sex, body mass index, duration of diabetes and comorbidities (dyslipidemia and hypertension), the correlation was still apparent (r = -0.511, p = 0.008). Patients with progression of nephropathy, neuropathy, and retinopathy, exhibited greater fluctuation of HbA1cs (2.38 ± 0.99 vs. 0.93 ± 1.16, p-value 0.002; 0.97 ± 1.59 vs. 0.90 ± 0.56, p-value 0.04; 0.99 ± 1.33 vs. 0.90 ± 0.56, p-value 0.04, respectively) and less frequent SMBG (3.2 ± 2.6 vs. 4.3 ± 3.1, p-value 0.02; 3.2 ± 2.6 vs. 4.1 ± 3.9, p-value 0.05; 3.0 ± 3.1 vs. 4.2 ± 2.8, p-value 0.01, respectively) than patients without progression of these complications. CONCLUSION This study shows that frequent SMBG decreased the fluctuation of HbA1c and decreased microvascular complications. Decreasing fluctuation of HbA1c may play an important role in diabetes treatment.

Prevalence of haematuria positively associated with urine albumin excretion in Type 2 diabetes

Diabet. Med. 29, 1178‐1183 (2012)

Fatty liver and chronic inflammation in Chinese adults

OBJECTIVE To investigate the significance of fatty liver as predictor of insulin resistance (IR) and chronic inflammation. RESEARCH DESIGN AND METHODS This cross-sectional study included 450 adults of Han Chinese origin aged >or=35. Excluded were cases with hepatitis B or C, alcoholic liver disease, or currently using thiazolidinedione. The volunteers were screened for the presence of the components of metabolic syndrome (MtS). IR index was estimated by the homeostasis model assessment. The fatty liver index was evaluated by computed tomography, calculated as the liver/spleen (L/S) ratio arrived at by averaging Hounsfield values obtained for five 3-mm slices. Serum levels of adiponectin, C-reactive protein (CRP), leptin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were checked in 100 subjects with low-L/S ratio and 100 age- and sex-matched controls. RESULTS Fatty liver index correlated with all MtS traits and IR index. The values of L/S ratios in subjects with 0, 1, 2, 3 and >or=4 traits of MtS were 1.25+/-0.13, 1.18+/-0.16, 1.12+/-0.21, 1.05+/-0.25 and 0.92+/-0.25, respectively (p<0.001). In our stepwise regression analysis to compare the L/S ratios to the conventional traits of MtS for association with adipokine dysregulation, we found L/S ratio to be independently associated with most of them: adiponectin (p<0.001), CRP (p<0.001), IL-6 (p=0.005) and TNF-alpha (p=0.014). CONCLUSION In Chinese, fatty liver index correlated well with IR index and can be a better marker of chronic inflammation than the conventional components of MtS.