Consumption and market share of cholesterol-lowering drugs in high-risk patients before and after the release of the 2013 ACC/AHA cholesterol guidelines: a retrospective observational study.

OBJECTIVE: We examined the use of cholesterol-lowering drugs in Taiwan in high-risk patients before and after the release of the 2013 American College of Cardiology and the American Heart Association (ACC/AHA) cholesterol guidelines. DESIGN: Retrospective observational study. SETTING: Kaohsiung Chang Gung Memorial Hospital database, Kaohsiung City, Taiwan. PARTICIPANTS: Outpatients aged ≥20 years with atherosclerosis cardiovascular disease, familial hypercholesterolaemia and diabetes. PRIMARY AND SECONDARY OUTCOME MEASURES: Data on brand and generic names, use and dosage of cholesterol-lowering drugs in 2012 and 2015 were compiled and the total amount used was calculated. Differences in usage and market share were compared. Usage rates of single and fixed-dose combination (FDC) products were compared. RESULTS: The number of patients receiving ambulatory care increased from 36 367 in 2012 to 41 807 in 2015. Single (3 679 979-4 568 086 tablets) and FDC (540 522-572 954 tablets) product use increased from 2012 to 2015, respectively. Statins were the most commonly prescribed medications in 2012 (71.14%) and 2015 (72.91%). The average monthly consumption of statin among high-risk patients in 2012 was 269 948.8 tablets, and it increased significantly to 343 975.3 tablets in 2015. The average monthly consumption of pitavastatin was 34 113.4 tablets in 2015, which was significantly higher than 0 in 2012. Conversely, the highest decline was observed for fluvastatin use, with the average monthly consumption being 38 754.3 tablets in 2015, which was significantly lower than 45 929.8 tablets consumed in 2012. Regarding FDC therapy for cholesterol-lowering drugs, Vytorin (ezetimibe 10 mg + simvastatin 20 mg) use was the highest among all FDCs in 2015. CONCLUSIONS: The 2013 ACC/AHA cholesterol guidelines likely promoted the use of fixed-dose, high-intensity and moderate-intensity monotherapy and FDC therapy statins in high-risk groups, and this was consistent with the use of high-intensity or moderate-intensity statins in the present study. Furthermore, these changes were associated with increased effectiveness and reduced adverse effects.

Diabetic patients suffering dengue are at risk for development of dengue shock syndrome/severe dengue: Emphasizing the impacts of co-existing comorbidity(ies) and glycemic control on dengue severity.

BACKGROUND/PURPOSE: The impact of type 2 diabetes mellitus (DM2) on clinical severity of dengue has not been fully understood. We aimed to assess risk factors for dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) and severe dengue (SD) (defined based on the World Health Organization 1997 and 2009 dengue classifications), and additionally identify, among DM2 patients, who are at risk for developing DHF/DSS and severe dengue. METHODS: A retrospective analysis of dengue patients diagnosed between 2002 and 2010. Risk factors for development of DHF/DSS/SD were identified using multivariate analysis. To elucidate the impacts of coexisting comorbidity(ies) (i.e., hypertension, chronic kidney disease, old stroke, and/or ischemic heart disease) and glycemic control on clinical outcomes of dengue in DM2 patients, the overall DM2 patients and stratified DM2 patients (HbA1c < 7% vs. HbA1c â‰§ 7%), with or without comorbidity(ies), were separately compared to controls (patients without any morbidity). RESULTS: Of 767 (146 DM2 and 621 controls) included patients, 1.4% suffered DSS and 3.3% SD. While DM2 was an independent risk factor for DSS (adjusted odds ratio [AOR] = 7.473; 95% confidence interval [CI] = 2.221-25.146) and SD (AOR = 6.207; 95% CI = 2.464-15.636), only DM2 patients with additional comorbidity(ies) and suboptimal glycemic control (HbA1c â‰§ 7%) had significantly higher incidences of non-shock DHF (60.8% vs. 29%), DSS (8.7% vs. 0.8%) and SD (34.8% vs. 1.1%). CONCLUSIONS: These data could help narrow down the number of targets in the triage for risky DM2 dengue patients to those with suboptimal glycemic control and co-existing comorbidity(ies).

High Glucose Variability Increases 30-Day Readmission Rates in Patients with Type 2 Diabetes Hospitalized in Department of Surgery.

Glucose variability is common among hospitalized patients with type 2 diabetes mellitus (DM). I investigated to assess the variability of glucose in patients with type 2 DM accounts for in-hospital readmission rates in department of Surgery. I retrospectively analyzed 206 patients with type 2 DM, who was admitted to our hospital for surgical interventions and re-admitted within 30 days after discharge. I also enrolled 610 age, sex and diabetic duration matched patients with type 2 DM, as control. Outcomes measure included average and standard deviation (SD) of blood glucose during admission, glycated hemoglobin (HbA1c), lipid profile, renal function, length of stay (LOS). Patients who had re-admission within 30 days after discharge had higher SD of blood glucose levels than control (84.7 ± 53.5 mg/dL vs. 46.2 ± 42.8 mg/dL, p < 0.001) but not average of blood glucose levels. Comparing to control group, the study group also had higher HbA1c (8.4 ± 1.3% vs. 7.7 ± 1.1%, p = 0.015) and LOS (8.5 ± 2.5 days vs 7.0 ± 1.5 days, p = 0.020). The independent predictors of 30-day readmission rates were SD of blood glucose during admission and HbA1c (hazard ratio: 1.680, 1.493; p value < 0.001, 0.008, respectively). Decreasing glucose variability during admission for surgery is important for patients with type 2 DM to decreasing re-admission rates and LOS. HBA1c may also identify patients at higher risk of postoperative complications and possibility of re-admission.

Adjunctive Hyperbaric Oxygen Therapy for Healing of Chronic Diabetic Foot Ulcers: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare the effect of standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care alone on wound healing, markers of inflammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life in patients with diabetic foot ulcers (DFUs). DESIGN: Prospective, randomized, open-label, controlled study. SUBJECTS AND SETTING: The sample comprised 38 patients with nonhealing DFUs who were deemed poor candidates for vascular surgery. Subjects were randomly allocated to an experimental group (standard care plus HBOT, n = 20) or a control group (standard care alone, n = 18). The study setting was a medical center in Kaohsiung City, Taiwan. METHODS: Hyperbaric oxygen therapy was administered in a hyperbaric chamber under 2.5 absolute atmospheric pressure for 120 minutes; subjects were treated 5 days a week for 4 consecutive weeks. Both groups received standard wound care including debridement of necrotic tissue, topical therapy for Wagner grade 2 DFUs, dietary control and pharmacotherapy to maintain optimal blood glucose levels. Wound physiological indices were measured and blood tests (eg, markers of inflammation) were undertaken. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short Form. RESULTS: Complete DFU closure was achieved in 5 patients (25%) in the HBOT group (n = 20) versus 1 participant (5.5%) in the routine care group (n = 18) (P = .001). The amputation rate was 5% for the HBOT group and 11% for the routine care group (χ = 15.204, P = .010). The HBOT group showed statistically significant improvements in inflammation index, blood flow, and health-related quality of life from pretreatment to 2 weeks after the last therapy ended (P < .05). Hemoglobin A1c was significantly lower in the HBOT group following treatment (P < .05) but not in the routine care group. CONCLUSIONS: Adjunctive HBOT improved wound healing in persons with DFU. Therapy also reduced the risk of amputation of the affected limb. We assert that at least 20 HBOT sessions are required to be effective.

Early short-term intensive multidisciplinary diabetes care: A ten-year follow-up of outcomes.

OBJECTIVES: To evaluate the outcome of an early short-term intensive diabetic care program followed by a regular out-patient shared-care education program. METHODS: We retrospectively reviewed the medical charts of 196 patients newly diagnosed with type 2 diabetes mellitus (DM) who were admitted to the hospital for intensive multidisciplinary interventions. For comparison, we also enrolled 206 patients with type 2 DM newly diagnosed but not receiving short-term intensive program. Both groups all attended an out-patient shared-care education program for more than one year. Outcome measure included average and standard deviation (SD) of glycated hemoglobin (HbA1c) over ten years, serum creatinine (Cr), lipid profile, urine albumin/Cr (UACR), and chronic diabetic complications after 10years later. The Kaplan-Meier event happening rates were used to compare the event rate of two samples. Multivariate Cox proportional-hazards models were used to investigate the influence of different variables on chronic complications. RESULTS: Patients who received short-term intensive diabetic education had less SD of HbA1cs: (0.7±0.7% vs. 1.0±0.8% (5.3±5.3mmol/mol vs 9.2±6.4mmol/mol), p<0.001), less new-onset coronary heart disease (CHD) (8.2% vs. 13.7%, p=0.005), lower serum Cr (1.4±0.7mg/dL vs. 1.5±0.9mg/dL, p=0.005), less progression of nephropathy was also revealed (13.5% vs. 21.2%, p=0.009) and lower UACR (4.7±1.4mg/g vs. 5.3±1.0mg/g, p<0.001). There were no group differences in age, gender distribution, average HbA1c, lipid profile, and new-onset of neuropathy and retinopathy. The independent predictors of CHD and nephropathy were short-term intensive diabetic education and SD of HbA1cs. CONCLUSION: Initiation of earlier intensive short-term multidisciplinary interventions in patients with newly diagnosed DM may decrease coronary heart disease and nephropathy. These better outcomes may be related to less fluctuation in blood glucose levels.

Dynamic Risk Estimates of Outcome in Chinese Patients with Well-Differentiated Thyroid Cancer After Total Thyroidectomy and Radioactive Iodine Remnant Ablation.

BACKGROUND: This study was conducted to compare the staging systems for the prediction of long-term disease status in patients with well-differentiated thyroid carcinoma (WDTC), and to find out the earliest postoperative period predictor of long-term persistence/recurrence of disease. METHODS: Patients with WDTC (n = 356; Mage = 41.5 ± 12.7 years) followed for at least five years (12.3 ± 5.0 years) after thyroidectomy and 131I remnant ablation at a tertiary regional hospital in Taiwan were retrospectively studied. Each patient was risk stratified using the American Joint Cancer Committee (stage I-IV) and American Thyroid Association (low, intermediate, and high risk) staging systems after operation and first 131I remnant ablation and using response to initial therapy reclassification (RTR; excellent, indeterminate, biochemical incomplete, and structural incomplete response) system, which is determined 6-24 months after the first 131I ablation. The clinical outcome was defined as no evidence of disease (NED; suppressed thyroglobulin [Tg] <0.5 ng/mL, stimulated Tg <1 ng/mL, and no structural detectable disease), biochemical persistent disease (BPD; suppressed Tg ≥0.5 ng/mL or stimulated Tg ≥1 ng/mL in the absence of structural disease), structural persistent disease (SPD; locoregional or distant metastases with any Tg level), or recurrent disease (RD; biochemical or structural disease identified after a period of NED). RESULTS: At the time of final follow-up, 78.4% (n = 279) of the patients had NED, 9.3% (n = 33) had BPD, 10.1% (n = 36) had SPD, and 2.2% (n = 8) developed RD. All three systems could predict the increasing trend of SPD and the decreasing trend of NED with advancing stage of disease. However, the ATA risk estimates could be significantly refined by the RTR system, especially for the ATA high-risk group, in which 29.2% developed SPD/RD during follow-up. The RTR system reduced the likelihood of finding SPD/RD to 3.7% in those demonstrating an excellent response to therapy, and increased the likelihood to 78.6% in those demonstrating a structural incomplete response. Among the earliest postoperative factors, only the Tg level at the first 131I ablation could predict long-term persistence/recurrence. CONCLUSIONS: The results highly support incorporating the RTR system to modify the initial risk estimate during follow-up among Chinese patients with WDTC.

Rosuvastatin decreases testosterone levels but not sexual function in men with type 2 diabetes.

OBJECTIVE: Statins may decrease serum testosterone levels via decreasing cholesterol, a precursor to testosterone. This case series studied the effects of rosuvastatin on free testosterone levels and sexual function in men with type 2 diabetes. METHODS: We enrolled 151 men with type 2 diabetes and hypercholesterolemia. Biochemical assessments included serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, triglyceride, prolactin, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone, total testosterone and serum sex hormone binding globulin (SHBG). All parameters were measured before statin treatment, after 6months of statin treatment, and 6months after discontinuing statin treatment. The Sexual Health Inventory for Men (SHIM) was also administered at these times. RESULTS: Serum TC and LDL levels were high before statin therapy, decreased after six months of statin therapy, and increased significantly six months after discontinuing statin therapy (198.1±28.1mg/dl vs. 147.1±22.8mg/dl vs. 205.2±25.6mg/dl, p-value<0.001; 121.3±20.6mg/dl vs. 75.4±20.4mg/dl vs.124.9±20mg/dl, p-value<0.001). However, serum free testosterone levels calculated from total testosterone and SHBG calculated by formula were higher before statin therapy, obviously decreased after six months of statin therapy, and subsequently increased six months after discontinuing statin therapy (22.4±3.1ng/ml vs. 20.9±2.8ng/ml vs. 22.6±2.6ng/ml p value=0.006). SHIM scores did not obviously differ among the three stages (16.3±4.8 vs. 16.0±4.9 vs. 16.3±5.0 p=0.944). After adjustment for age, serum free testosterone levels correlated with SHIM scores and LDL (r=0.39, p=<0.001; r=0.26, p=0.02, respectively). SHIM scores did not correlate with TC or LDL. CONCLUSIONS: Rosuvastatin reduces free testosterone levels but does not influence sexual function in men with type 2 diabetes.

Association of adiponectin gene polymorphism with nonalcoholic fatty liver disease in Taiwanese patients with type 2 diabetes.

OBJECTIVE: Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease. METHODS: We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD. Body mass index (BMI), % body fat (% BF), glycated hemoglobin (HbA1c), high molecular weight (HMW) isoform of adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. Thirteen SNPs in 5 genes (adiponectin, leptin, peroxisome proliferator-activated receptor alpha, adiponutrin/patatin-like phospholipase domain-containing protein 3 and peroxisome proliferator-activated receptor γ co-activator 1α ) were measured. RESULTS: Only adiponectin rs266729 polymorphism was associated with susceptibility to NAFLD (p = 0.001). Subgroup analysis revealed that the proportion of subjects with homozygous genotype GG was higher in patients with NAFLD (31%) than in controls (11%) and that the proportions of heterozygous CG and homozygous CC were higher in controls (37% and 52%, respectively) than in patients with NAFLD (33% and 36%, respectively). Patients with NAFLD carrying the GG genotype of rs266729 showed significantly lower serum HMW adiponectin levels than patients carrying the GC or CC genotype (3.75±0.37 vs. 3.99±0.66 vs. 4.79±0.58 µg/ml, p< 0.001). Body fat and serum HMW adiponectin levels were the strongest predictors of developing NAFLD (p < 0.001 and 0.004, respectively). CONCLUSIONS: In patients with type 2 diabetes gene polymorphism of adiponectin rs266729 is associated with risk of NAFLD. G allele of rs266729 is associated with hypoadiponectinemia. Low serum adiponectin level may precipitate liver steatosis in patients with type 2 diabetes.

Genetic disposition and modifiable factors independently associated with anemia in patients with type 2 diabetes mellitus.

AIMS: Anemia is prevalent but under-recognized in patients with diabetes mellitus (DM). Genetic variants in angiotensin-converting enzyme (ACE), tumor necrosis factor-alpha (TNF-α) and erythropoietin (EPO) have been associated with diabetic nephropathy. In the present study, we investigated the associations between anemia and polymorphisms in EPO promoter (rs1617640), TNF-α G-308A and ACE Insertion/Deletion in Chinese patients with type 2 diabetes. METHODS: Polymorphisms in ACE, TNF-α and EPO were genotyped in 1142 patients. Anemia was defined as hemoglobin (Hb) levels below 12 g/dL for women and 13 g/dL for men. RESULTS: 286 (25%) patients had anemia. Patients with anemia were older, had longer duration of diabetes, worse renal function and more albuminuria. ACE Insertion/Deletion and TNF-a G-308A were not associated with anemia. The frequencies of EPO polymorphism (rs1617640) were significantly different between anemic and nonanemic patients. Patients with TT genotype had higher prevalence of anemia than those with TG and GG. Regression analysis identified EPO SNP, duration of DM, serum albumin, albuminuria and renal function independently associated with anemia. After adjusting for multiple variables, TT and TG genotypes were associated with 3-5-fold increased risk for anemia compared to GG. CONCLUSIONS: The EPO genotype in Chinese patients with type 2 diabetes is associated with anemia and may help to identify those at risk. Further evaluation of its effect on clinical outcomes in prospective studies may be useful to predict the outcomes of erythropoiesis stimulating therapy, and to individualize anemia management.

Severity of hearing impairment is positively associated with urine albumin excretion rate in patients with type 2 diabetes.

AIMS/INTRODUCTION: To identify risk factors for hearing impairment among patients with type 2 diabetes mellitus. METHODS AND MATERIALS: A total of 68 patients with type 2 diabetes were enrolled between March and September of 2011. Pure-tone auditory tests were carried out for each patient at the following speech frequencies: 250; 500; 1,000; 2,000; 4,000 and 8,000 Hz. Participants were classified as having hearing impairment if the average of the pure-tone thresholds measured at 500, 1000 and 2000 Hz in either ear exceeded 25 dBHL. Demographic, anthropometric, clinical, and laboratory parameters and diabetes-associated complications were analyzed. RESULTS: Patients were divided into those with (n = 32) and without (n = 36) hearing impairment. Hearing impaired participants had a higher urine albumin-to-creatinine ratio than those without (223.1 vs 56.5 mg/g, respectively). After adjustment for age, sex and other risk factors, the urine albumin-to-creatinine ratio remained significantly associated with hearing impairment (odds ratio 9.07, 95% confidence interval 1.73-47.43, P = 0.009). There were no significant differences in oxidative stress between the two groups. CONCLUSIONS: The present study showed increased albuminuria was positively associated with the severity of hearing impairment among patients with type 2 diabetes. Screening for hearing impairment in diabetic patients who develop albuminuria might provide early detection of hearing impairment.

The durability of sitagliptin in elderly patients with type 2 diabetes.

AIM: To evaluate the durability of sitagliptin and to assess changes in clinical chronic complications following sitagliptin monotherapy for 48 months in elderly patients with type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: We enrolled 76 drug-naïve patients (40 women and 36 men; mean age: 71.3±11.7 years) with T2DM who received 25-100 mg of sitagliptin therapy from an outpatient clinic. The observational period for each patient was >48 months, beginning at the time sitagliptin therapy was initiated. The following were measured or performed at the beginning of each year: body mass index; serum total cholesterol, low-density lipoprotein, high-density lipoprotein; triglyceride levels; creatinine (Cr) levels; urine albumin and urine Cr; nonmydriatic fundusgraphy; and semiquantified neuropathy. The fasting plasma glucose and glycated hemoglobin (HbA1c) was measured every 3-6 months. RESULTS: The change in HbA1c was significantly reduced after 6 months of therapy (7.1%±0.8% to 6.3%±0.2%). No changes in fasting plasma glucose, Cr, serum total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, body mass index, and microvascular complications were apparent. Using repeated measures to test the sequential changes in HbA1c from month 6 to month 48, the test of within-subjects effect was not significant (P=0.34). CONCLUSION: Sitagliptin has a durable effect and stabilizes microvascular complication progression in elderly patients. This study can provide useful data for clinicians and health care professionals using sitagliptin monotherapy in the treatment of elderly patients with T2DM.

Real-world effectiveness of sitagliptin as add-on therapy in patients with type 2 diabetes mellitus.

AIMS: To assess the effectiveness of sitagliptin in glycemic control in a clinical practice. METHODS: This was a retrospective medical chart review study conducted in a single hospital. A total of 3081 patients with diabetes mellitus who were prescribed sitagliptin were selected, including 2729 continuous sitagliptin users (defined as continuous usage ≥ 24 weeks) and 352 subjects who used sitagliptin for < 24 weeks. An additional 12-month observation period was monitored after initiating sitagliptin to extract clinical information at 3, 6, 9, and 12 months through patient medical chart review. RESULTS: In the 2729 continuous users, a baseline glycated hemoglobin (HbA1c) level of 9.0% was reduced to 8.1%, 8.1%, 8.1%, and 8.2% at 3, 6, 9, and 12 months, respectively, representing a 0.9% HbA1c level reduction at 3, 6, and 9 months and a 0.8% HbA1c level reduction at 12 months. With a goal of HbA1c value of < 7.0%, 9.1% of the patients were under control at baseline; after initiating sitagliptin, 22.7% of the patients achieved the HbA1c level goal at 3 months, 23.6% at 6 months, 20.8% at 9 months, and 20.4% at 12 months. The proportion of patients attaining the goal of HbA1c level < 7.0% at least doubled at different time points after treatment with sitagliptin. CONCLUSIONS: In this single-hospital retrospective chart analysis, a meaningful clinical improvement in glycemic control before and after sitagliptin treatment commenced, including HbA1c level reduction and the HbA1c goal attainment rate, was observed. The results reflect the actual clinical practice in a large hospital in Taiwan, and supplement data from randomized controlled trials.

The relationship between regional abdominal fat distribution and both insulin resistance and subclinical chronic inflammation in non-diabetic adults.

OBJECTIVE: Obesity is associated with a high risk of insulin resistance (IR) and its metabolic complications. It is still debated that distributions of adipose tissue relate to an excess risk of IR and chronic inflammation in different race. This study was designed to examine the relation between insulin sensitivity, chronic inflammation and central fat distribution in non-diabetic volunteers in Taiwanese. METHODS: There were 328 volunteers without family history of diabetes mellitus and with normal oral glucose tolerance test enrolled. Total body fat and abdominal fat were measured. Abdominal fat was categorized into intraperitoneal (IP), retroperitoneal (RP) and subcutaneous (SC) fat. The IR index was estimated by homeostatic model assessment. Five inflammatory markers: adiponectin, leptin, tumor necrosing factor-α (TNF-α), resistin and high sensitive CRP (hs-CRP) were measured. RESULTS: IR was related to IP fat (r = 0.23, p < 0.001), but not RP fat, SC fat or total body fat. After correcting for age and sex, IP fat was the only significant predictor of IR (r2 = 58%, p = 0.001). Leptin showed the strongest relationship with all fat compartments (IP fat: r = 0.44, p = 0.001; RP fat: r = 0.36, p = 0.005, SC fat: r = 0.54, p < 0.001; total body fat: r = 0.61, p < 0.001). The hs-CRP and adiponectin were closely related both to IP (r = 0.29, p = 0.004; r = -0.20, p = 0.046, respectively) and total body fat (r = 0.29, p = 0.004; r = -0.29, p = 0.005, respectively), but not RP, or SC fat. TNF-α and resistin were not correlated to any fat compartment. After correcting for age and sex, leptin variance was mostly explained by SC fat (41.3%), followed by IP fat (33.6%) and RP fat (25.3%). The hs-CRP and adiponectin variance were mostly explained by IP fat (40% and 49% respectively). CONCLUSIONS: IP fat is better predictors of IR and subclinical chronic inflammation in Taiwanese adults. A disproportionate accumulation of abdominal fat is associated with increased risk of cardiovascular diseases.

Sequential changes of serum antithyroglobulin antibody levels are a good predictor of disease activity in thyroglobulin-negative patients with papillary thyroid carcinoma.

OBJECTIVE: To investigate whether elevated and sequential changes in serum antithyroglobulin antibody (TgAb) levels are indicators of recurrence or persistence of papillary thyroid cancer (PTC) in patients with undetectable thyroglobulin. METHODS: In 56 patients followed for more than 7 years, we recorded all serum TgAb levels (except the ones determined within one year after (131)I therapy or diagnostic scans) and evaluated their disease status. All patients had undergone total thyroidectomy and remnant ablation by (131)I, and they were positive for TgAb and had undetectable thyroglobulin during follow-up. The sequential changes of TgAb were defined as persistently high, increasing, persistently medium, decreasing, and decreasing to negative. Recurrence or persistence of PTC was defined as active disease as assessed by (131)I scanning, (18)F-fluorodeoxyglucose positron emission tomography, ultrasonography, computed tomography, or surgical examination. RESULTS: Of the 56 patients enrolled, 10 patients had persistent PTC and 12 patients had recurrent PTC at more than 1 year after total thyroidectomy and (131)I therapy. TgAb was persistently high in 4 patients (3 with active PTC), increasing in 6 patients (4 with active PTC), persistently medium in 16 patients (12 with active PTC), decreasing in 5 patients (none with active PTC), and decreased to negative in 25 patients (3 with active PTC). According to the trend, the patients with persistently high TgAb, increasing TgAb, and persistently medium TgAb had active disease more often (p<0.001). In the multivariable regression analyses, the trend of TgAb change was a strong predictor of PTC activity (p<0.001, R(2)=-0.501). The most common diagnostic procedures performed for active disease were neck ultrasonography (21 patients) followed by (18)F-fluorodeoxyglucose positron emission tomography (11 patients). The patients with autoimmune thyroid disease had better prognoses than did the patients without autoimmune thyroid disease (18% active PTC vs. 53% active PTC, p=0.02). CONCLUSION: The presence of TgAb is indicative of an active tumor. Sequential TgAb change is a good predictor of disease prognosis and is helpful for clinical decision making.

Increased production of interleukin-4, interleukin-10, and granulocyte-macrophage colony-stimulating factor by type 2 diabetes' mononuclear cells infected with dengue virus, but not increased intracellular viral multiplication.

It has been reported that diabetes mellitus (DM) was an epidemiologically identified risk factor for development of dengue hemorrhagic fever (DHF)/severe dengue in dengue virus (DENV) affected patients, and T helper 2 (Th2) cytokines such as interleukin-4 (IL-4) and IL-10 each plays an important role in the immunopathogenesis of DHF in studies involving general population. To better understand the relationship between these epidemiological and immunological findings, we performed an in vitro study evaluating the sequential immunological reactions and viral load in the DENV infected mononuclear cells of adults with type 2 DM (T2DM group, n = 33) and normal adults (control group, n = 29). We found in the T2DM group significantly higher IL-4 level on the first (P = 0.049) and the third (P = 0.022) postinfection days, while higher IL-10 (P = 0.042) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (P = 0.009) were detected on the third postinfection day. No significant difference in DENV viral load between the cultured mononuclear cells from both groups was found on the first and third post-infection days. These data immunologically suggest that patients with T2DM are at higher risk for development of DHF/severe dengue and strengthen the previously epidemiologically identified role of DM being a predictive risk factor for progressing into DHF/severe dengue in DENV-affected patients.

Clinical Characteristics of Endogenous Cushing's Syndrome at a Medical Center in Southern Taiwan.

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing's syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing's disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 µ g, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days, P < 0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.

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.

Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus.

In order to investigate whether short- or long-term glycemic fluctuations could induce oxidative stress and chronic inflammation, we evaluated the relationships between glycemic variability, oxidative stress markers, and high-sensitivity C-reactive protein (hs-CRP). We enrolled 34 patients with type 2 diabetes. As a measure of short-term glycemic variability, mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring system data. For determining long-term glycemic variability, we calculated the standard deviation (SD) of hemoglobin A1c (HbA1c) levels measured over a 2-year period. Levels of oxidative stress markers: 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid-reactive substance (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), and hs-CRP were measured. MAGE was significantly correlated with the SD of HbA1c levels (r = 0.73, p < 0.001) but not with HbA1c level. The levels of hs-CRP, TBARS, 8-OHdG, and 8-iso-PGF2α were significantly correlated with MAGE (r = 0.54, p = 0.001; r = 0.82, p < 0.001; r = 0.70, p < 0.001; r = 0.60, p < 0.001) and the SD of HbA1c levels (r = 0.53, p = 0.001; r = 0.73, p < 0.001; r = 0.69, p < 0.001; r = 0.43, p = 0.01) but not with HbA1c level. Relationships between 8-iso-PGF2α and MAGE or the SD of HbA1c levels remained significant after adjusting for other markers of diabetic control (R(2) = 0.684, R(2) = 0.595, p < 0.001, respectively). Both acute and chronic blood glucose variability can induce oxidative stress and chronic inflammation.

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.