Mucosa-associated lymphoid tissue lymphoma of thyroid and adrenal glands with primary adrenal insufficiency.

Summary: A 69-year-old woman presented with weight loss, fever, dizziness, exertional dyspnea, and drenching night sweats. Imaging showed a thyroid goiter at the left lobe that measured 5.6 × 3.4 × 3.5 cm in size. On computed tomography, she was found to have large adrenal masses. Core needle biopsy of the left thyroid mass revealed the presence of a mucosa-associated lymphoid tissue extranodal marginal zone B cell lymphoma. Non-Hodgkin's lymphomas (NHL) typically develop in lymph nodes or other lymphatic tissues. There have been cases where the thyroid has been affected, and the secondary involvement of the adrenal gland is common. In reported cases, 7-59% of patients with NHL exhibited symptoms of thyroid dysfunction. Our patient presented no symptoms of thyroid dysfunction or Hashimoto's thyroiditis. The patient had bilateral adrenal lymphomas that led to adrenal insufficiency. Immunochemotherapy provided a good response in this case, as seen by the rapid improvement in thyroid and adrenal mass on follow-up PET/CT. Learning points: Thyroid lymphoma requires a high index of suspicion for diagnosis in patients with a rapidly growing thyroid tumor, even in the absence of chronic inflammatory thyroid disease. Depending on the extent of involvement, adrenal lymphoma may rapidly cause adrenal insufficiency. In the setting of acute illness, appropriate levels of plasma cortisol are often unclear, necessitating early initiation of glucocorticoid therapy based on clinical suspicion, especially when features like bilateral adrenal masses and elevated ACTH levels are present. Treatment modalities include chemotherapy and radiation therapy for localized lesions, together with hormone replacement for organ dysfunction. The origin of the tumor influences the clinical outcome of patients with lymphoma simultaneously involving the thyroid and adrenal glands.

Prevalence of hypertension and dyslipidemia and their associations with micro- and macrovascular diseases in patients with diabetes in Taiwan: an analysis of nationwide data for 2000-2009.

BACKGROUND/PURPOSE: Cardiovascular complication is the leading cause of mortality in patients with diabetes. Dyslipidemia and hypertension are the major risk factors contributing to cardiovascular disease (CVD). This study was carried out to investigate the prevalence of dyslipidemia and hypertension and their associations with microvascular and macrovascular complications in patients with type 2 diabetes in Taiwan. METHODS: Health-care data and diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files for the years 2000-2009. Based on these data the annual prevalences of dyslipidemia and hypertension were calculated and patients were stratified by age, gender, and diabetic complications. RESULTS: In patients with diabetes, the prevalence of dyslipidemia increased with age, with the highest rate recorded in adults (inclusive of both genders) between 40 and 65 years of age (p for trend <0.001). The prevalence of hypertension also increased with age with the highest rate seen in adults (inclusive of both genders) >65 years of age (p for trend <0.001). The prevalence of stroke and CVD decreased gradually (p for trend 0.025 and <0.001, respectively), while the prevalence of peripheral vascular disease (PVD) increased in patients with diabetes during the study period (p for trend <0.001). The prevalence of dyslipidemia increased in diabetic patients with eye diseases and in men with nephropathies, but decreased in women with nephropathies during the study period. In contrast, the prevalence of dyslipidemia decreased in patients with macrovascular complications, including CVD and cerebrovascular disease (cerebrovascular accident), but increased in those patients with PVD (p for all trends <0.05). In diabetic patients with various macrovascular complications, except PVD, there was a decrease in the prevalence of hypertension in the past 10 years. The prevalence of hypertension increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy. The prevalence of hypertension along with dyslipidemia increased in patients with microvascular complications including retinopathy, patients on dialysis (inclusive of both genders), and in men with nephropathy; however, the rate decreased in all macrovascular complications except in PVD. CONCLUSION: Although progressively increased prevalence of dyslipidemia and hypertension was observed in patients with diabetes in Taiwan, there was a decrease in the prevalence of stroke and CVD in the past 10 years. Among those with macrovascular diseases, except PVD, there was a trend of decreased prevalence of hypertension and dyslipidemia during the study period. In patients with microvascular diseases, prevalence of hypertension and dyslipidemia in patients with eye diseases increased in the past 10 years. More aggressive management of different risk factors is warranted in diabetic patients with various vascular diseases.

Aristolochic acid and the risk of cancers in patients with type 2 diabetes: Nationwide population-based cohort study.

BACKGROUND: Both aristolochic acid (AA) exposure and diabetic can increase risk of certain cancers,whetherAAexposureincreases cancer risk in diabetic patientsisunknown. The purpose of this study was to investigate the association between the use of Chinese herbal products containing AA and the risk of cancer in diabetic patients. METHODS: A cohort study was conducted using the National Health Insurance Research Database in Taiwan. Patients older than 18 years who were diagnosed with diabetes between 1997 and 2010 were enrolled in our cohort. The use of Chinese herbal products containing AA was recorded from the beginning of 1997 until the ban of herbs containing AA in November 2003. Patients were individually tracked to identify cancer incidence between 1997 and 2013. Only patients who visited traditional Chinese medicine clinics between 1997 and 1 year before the end of follow-up were included in the cohort to ensure comparability. Cox proportional hazards regression was used to calculate the hazard ratio for the association between the use of Chinese herbal products containing AA and the occurrence of cancer. RESULTS: Among the 430 377 male and 431 956 female patients with diabetes enrolled in our cohort, 37 554 and 31 535 cancer diagnoses were recorded during the study period, respectively. The use of AA-containing herbal products was associated with a significantly higher risk of liver, colorectum, kidney, bladder, prostate, pelvis, and ureter cancer in a dose-dependent manner. An increased risk of extrahepatic bile duct cancer in women was also associated with AA exposure at doses of more than 500 mg. CONCLUSIONS: Association between AA exposure and the risk of some cancers were found in this study. AA exposure might increase risk of kidney,bladder,pelvis, ureter,liver,colorectum,andprostatecancer in all patientsandextrahepatic bile duct cancerin women.

Dual-operation-mode liquid crystal lens.

We demonstrate a dual-operation-mode liquid crystal (LC) lens, which is fabricated with the silica nanoparticle-doped (SND) hybrid-aligned nematic (HAN) LC cell. With AC voltage, the cell behaves as a conventional LC lens. The response time of the SND HAN LC lens is faster than that of the conventional LC lens, which is fabricated using the pristine HAN LC cell. This is because that the doped silica nanoparticles may decrease the dielectric relaxation time constant of the cell. The addition of the silica nanoparticles also increases the viscosity of the LC host, suppresses the backflow motion of the LCs and then decreases the response time of the SND LC lens. With DC voltage, the electrophoretic motion of the doped silica nanoparticles and the agglomerate silica networks on the substrate surface cause the SND HAN LC cell to function as a bistable LC lens.

Glycemic excursions are positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy.

BACKGROUND: The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). METHODS: Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0-11.0 % (53-97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c - post-treatment HbA1c)/baseline HbA1c × 100. RESULTS: Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (ß = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P < 0.05 for all models). CONCLUSIONS: In patients with T2D on metformin monotherapy, baseline MAGE was positively correlated with relative HbA1c reduction from baseline after treatment with acarbose, but not glibenclamide. These findings highlight the importance of glycemic excursions in individualized treatment for patients with T2D.

Glycemic excursions are positively associated with changes in duration of asymptomatic hypoglycemia after treatment intensification in patients with type 2 diabetes.

AIM: The aim of this study was to examine the association between glycemic excursions and duration of hypoglycemia after treatment intensification in patients with type 2 diabetes (T2D). METHODS: Patients with T2D on oral anti-diabetes drug (OAD) with glycated hemoglobin (HbA1c) of 7.0-11.0% were switched to metformin monotherapy (500 mg thrice daily) for 8 weeks, followed by randomization to either glibenclamide or acarbose as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring (CGM) before randomization and at the end of study. Hypoglycemia was defined as sensor glucose level of less than 60 mg/dl in two or more consecutive readings from CGM. RESULTS: A total of 50 patients (mean age 53.5 ± 8.2 years, male 48%, mean baseline HbA1c 8.4 ± 1.2%) were analyzed. Duration of hypoglycemia significantly increased after treatment with glibenclamide (from 5.5 ± 13.8 to 18.8 ± 35.8 min/day, p=0.041), but not with acarbose (from 2.9 ± 10.9 to 14.7 ± 41.9 min/day, p=0.114). Post treatment MAGE was positively associated with change from baseline in duration of hypoglycemia after treatment with either glibenclamide (ß coefficient 0.345, p=0.036) or acarbose (ß coefficient 0.674, p=0.046). The association remained significant after multivariate adjustment (p<0.05 for all models). CONCLUSIONS: Post treatment glycemic excursions are associated with changes in duration of hypoglycemia after treatment intensification with OAD in patients with T2D. Glycemic excursions should be an important treatment target for T2D to reduce the risk of hypoglycemia.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study.

OBJECTIVE: Acarbose, an α-glucosidase inhibitor, has been shown to have antineoplastic effects on colorectal cancer in biomarker studies. We assessed the association between acarbose use in patients with diabetes and incident colorectal cancer. RESEARCH DESIGN AND METHODS: We conducted a nationwide, population-based study using a large cohort with diabetes in the Taiwan National Health Insurance Research Database. Patients with newly diagnosed diabetes (n = 1,343,484) were enrolled between 1998 and 2010. One control subject not using acarbose was randomly selected for each subject using acarbose after matching for age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression with a competing risks analysis was used to calculate the hazard ratios (HRs) and 95% CIs for the association between acarbose use and incident colorectal cancer for each eligible case-control pair (n = 199,296). RESULTS: There were 1,332 incident cases of colorectal cancer in the cohort with diabetes during the follow-up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases per 100,000 person-years. Patients treated with acarbose had a 27% reduction in the risk of colorectal cancer compared with control subjects. The adjusted HRs were 0.73 (95% CI 0.63-0.83), 0.69 (0.59-0.82), and 0.46 (0.37-0.58) for patients using >0 to <90, 90 to 364, and ≥365 cumulative defined daily doses of acarbose, respectively, compared with subjects who did not use acarbose (P for trend < 0.001). CONCLUSIONS: Acarbose use reduced the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner.

Post-meal ß-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose.

BACKGROUND: This study aimed to explore parameters which will predict good control of HbA1c after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. METHODS: Fifty-one patients (M/F: 25/26, mean age: 53.7 ± 8.2 years, mean glycated hemoglobin [HbA1c] 8.4 ± 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA-ß, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). RESULTS: At baseline, there was a significant inverse relationship between DI120 and HbA1c (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 ± 1.6% to 7.4 ± 1.2% (p < 0.001), and from 8.2 ± 0.8% to 7.5 ± 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 ± 24.2 to 74.9 ± 41.9 (p < 0.05), and in the acarbose group, from 62.5 ± 31.4 to 91.7 ± 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA1c and DI120 independently predicted reduction of HbA1c as well as final HbA1c after combination therapy. CONCLUSIONS: In patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA1c reduction and improvement of ß-cell function. Subjects with greater baseline ß-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose. TRIAL REGISTRATION: This study was registered in the ClinicalTrials.gov with registration number of NCT00417729.

Effects of acarbose versus glibenclamide on glycemic excursion and oxidative stress in type 2 diabetic patients inadequately controlled by metformin: a 24-week, randomized, open-label, parallel-group comparison.

BACKGROUND: Glycemic excursion is significantly associated with oxidative stress, which plays a role in the development of chronic complications in type 2 diabetes mellitus (T2DM). Acarbose has been reported to reduce cardiovascular risk in patients with impaired glucose tolerance and T2DM. We hypothesize that treatment with acarbose could attenuate glycemic excursions and reduce oxidative stress in patients with T2DM. OBJECTIVE: This study aimed to evaluate the effects of acarbose versus glibenclamide on mean amplitude of glycemic excursions (MAGE) and oxidative stress in patients with T2DM who are insufficiently controlled by metformin. METHODS: T2DM outpatients aged 30 to 70 years who were taking single or dual oral antidiabetic drugs for ≥3 months and had a glycosylated hemoglobin (HbA(1c)) value between 7.0% and 11.0% were eligible. Patients were treated with metformin monotherapy (1500 mg daily) for 8 weeks, followed by randomization to either acarbose or glibenclamide add-on for 16 weeks. The dosage of acarbose and glibenclamide was 50 mg TID and 2.5 mg TID, respectively, for the first 4 weeks. In the following 12 weeks, the dosage was doubled in both groups. Continuous glucose monitoring (CGM) for 72 hours and a meal tolerance test (MTT) after a 10-hour overnight fast were conducted before randomization and at the end of study. MAGE was calculated from CGM data. ß-cell response to postprandial glucose increments was assessed by the ratio between incremental AUC of insulin and glucose during MTT. Oxidative stress was estimated by plasma oxidized LDL (ox-LDL) and urinary excretion rates of 8-iso prostaglandin F(2α) (8-iso PGF(2α)). The primary outcomes included changes in MAGE, plasma ox-LDL, and urinary excretion of 8-iso PGF(2α). Adverse events, including hypoglycemia, were recorded. RESULTS: A total of 55 patients were randomized (mean age, 54 years; males, 47%; mean body mass index, 25.9 kg/m(2); mean duration of diabetes, 6.9 years; mean HbA(1c), 8.3%) and 51 patients completed this study (acarbose, n = 28; glibenclamide, n = 23). HbA(1c) decreased significantly in both treatment groups (acarbose: 8.2 [0.8]% to 7.5 [0.8]% [P < 0.001]; glibenclamide: 8.6 [1.6]% to 7.4 [1.2]% [P < 0.001]). MAGE did not change significantly in glibenclamide-treated patients (6.2 [2.8] mmol/L to 6.3 [2.3] mmol/L; P = 0.82), whereas ox-LDL (242.4 [180.9] ng/mL to 470.7 [247.3] ng/mL; P = 0.004) and urinary excretion of 8-iso PGF(2α) (121.6 [39.6] pmol/mmol creatinine to 152.5 [41.8] pmol/mmol creatinine; P = 0.03) increased significantly. Acarbose decreased MAGE (5.6 [1.5] mmol/L to 4.0 [1.4] mmol/L; P < 0.001) without significant change in ox-LDL levels (254.4 [269.1] ng/mL to 298.5 [249.8) ng/mL; P = 0.62) or 8-iso PGF(2α) excretion rates (117.9 [58.1] pmol/mmol creatinine to 137.8 [64.4] pmol/mmol creatinine; P = 0.12). Body weight and serum triglycerides (fasting and 2-hour postprandial) decreased (all, P < 0.01) and serum adiponectin increased (P < 0.05) after treatment with acarbose, whereas HDL-C decreased (P < 0.01) after treatment with glibenclamide. ß-cell response to postprandial glucose increments was negatively correlated with MAGE (r = 0.570, P < 0.001) and improved significantly with acarbose (35.6 [32.2] pmol/mmol to 56.4 [43.7] pmol/mmol; P = 0.001) but not with glibenclamide (27.9 [17.6] pmol/mmol to 36.5 [24.2] pmol/mmol; P = 0.12). CONCLUSIONS: In this select population of adult Taiwanese patients with T2DM who were inadequately controlled by metformin, add-on acarbose or glibenclamide significantly reduced HbA(1c). However, treatment with acarbose decreased MAGE, body weight, and serum triglyceride and increased serum adiponectin without significant effect on oxidative stress. Treatment with glibenclamide had no statistically significant effect on MAGE but increased oxidative stress and decreased HDL-C. ClinicalTrials.gov identifier: NCT00417729.

Association between metabolic syndrome (MS) and bone mineral loss: a cross-sectional study in Puli Township in Taiwan.

Results of studies regarding the association between the MS and osteoporosis have been largely controversial. The objectives of this study were to measure bone mineral density (BMD) with and without the MS and evaluate the associations between bone mineral loss and the components of the MS. In all, 352 men (mean age 70.6+/-11.9 years) and 468 women (mean age 67.8+/-12.0 years) in Puli township, Taiwan, were enrolled. Height (cm), weight (kg), waist circumference (cm), and blood pressure (mmHg) were measured. Fasting plasma glucose (FPG) and blood lipids were determined. Calcaneal BMD was measured using the ultrasound pulse transmission method. The prevalence of MS was 33.0% in men and 44.2% in women. In subjects with the MS, lower diastolic blood pressure (DBP) in both sexes (p < 0.001), lower triglycerides (p = 0.016) and more central obesity in men (p = 0.011) predicted bone mineral loss. The MS was not associated with bone mineral loss in either of sexes (p = 0.550 in men; p = 0.628 in women).