A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes.

Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (- 0.2% [95% CI - 0.4% to - 0.1%]) and from 8.1% to 7.8% in the placebo group (- 0.3% [95% CI - 0.5% to - 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

Diabetic ketoacidosis further increases risk of Alzheimer's disease in patients with type 2 diabetes.

AIM: Diabetes mellitus (DM) is a known risk factor for dementia. It is unclear whether diabetic ketoacidosis (DKA) further increases the risk of dementia in patients with type 2 DM. METHODS: This retrospective nationwide population-based cohort study was conducted using Taiwan's National Health Insurance database. We extracted claims data for 4451 patients with type 2 diabetes and DKA and 8902 diabetic controls matched for age, gender, diabetes complication severity index, frequency of clinic visits and baseline comorbidities between 2000 and 2002. Patients with type 1 diabetes or prior hypoglycemia before index date were excluded. All patients were tracked until new dementia diagnosis, death, or end of 2011. RESULTS: Of the 4451 DKA patients, 211 (4.7%) and 305 (3.4%) of the 8902 diabetic controls were diagnosed as having dementia during the follow-up period. The incidence rate ratio (IRR) for dementia was 1.62 (95% CI 1.35-1.93; P < 0.0001) for patients with DKA versus diabetic patients without DKA. After adjusting for age, baseline comorbidities, geographic area, and income, patients with DKA were found to have 1.86 times the risk of developing dementia, compared to controls (95% CI 1.56-2.22, P < 0.0001). They were found to have a higher risk of Alzheimer's dementia (HR:1.86; 95% CI 1.52-2.28, P < 0.0001) but not non-Alzheimer's dementia. CONCLUSION: Type 2 diabetes patients with DKA are at increased risk of Alzheimer's dementia but not non-Alzheimer dementia.

The impact of ambient temperature on HbA1c in Taiwanese type 2 diabetic patients: The most vulnerable subgroup.

BACKGROUND/PURPOSE: The relationship between temperature variability and HbA1c has been reported in Caucasians, but not for Asians of Taiwanese origin. This study investigated the impact of temperature on HbA1c in various groups of Taiwanese with type 2 diabetes in Taiwan. METHODS: For this longitudinal follow-up study which started in 2006, we recruited a total of 4399 patients with type 2 diabetes who had been regularly followed up at Chi Mei Medical Center and obtained local temperature data for 2006 to 2011 from Taiwan's Central Weather Bureau. We used a generalized estimated equation (GEE) to analyze the HbA1c level and its change over time with temperature and temperature changes, respectively. RESULTS: We found a negative correlation between HbA1c and temperature (R = -0.475, p = 0.001). For every 1°C decrement in temperature, there was an increase in the risk of having a HbA1c level >7% [p < 0.001, adjusted odds ratio (OR): 1.01]. There was a significantly higher risk of HbA1c > 7% among those in the lowest quartile of temperatures than the highest quartile (p = 0.0038, adjusted OR: 1.13). Patients with diabetic patients were at higher risk of HbA1C > 7% in the winter and spring than those in the summer (adjusted OR: 1.13, p = 0.0027; adjusted OR: 1.14, p = 0.0022). After adjusting for various confounders, we found people who were younger than 65 years old, people who had diabetes for longer than 6 years, and people who had a body mass index (BMI) < 24 to be more susceptible to temperature changes (p = 0.0022, ß: 0.0095; p < 0.0001, ß: 0.0125; p < 0.0001, ß: 0.016, respectively). CONCLUSION: Our study suggests cold weather may adversely affect HbA1c levels in Taiwanese people with type 2 diabetes, especially in people under 65 years old, people with diabetes for longer than 6 years, and those with a BMI < 24.

Increased Risk of Sudden Sensorineural Hearing Loss in Patients With Osteoporosis: A Population-based, Propensity Score-matched, Longitudinal Follow-Up Study.

CONTEXT: Previous studies have reported an increased prevalence of sudden sensorineural hearing loss (SSNHL) in osteoporotic patients. However, the risk of SSNHL in this population remains unclear. OBJECTIVE: This study investigated the risk of SSNHL in osteoporotic patients. SETTING: Taiwan launched a single-payer National Health Insurance (NHI) program on March 1, 1995. NHI covers nearly all of Taiwan's residents. DESIGN: Using randomized representative sample of one million individuals from Taiwan's National Health Insurance claims database, we compared the data of 10,660 patients with newly diagnosed osteoporosis from 1998-2008 and with 31,980 patients without osteoporosis. All patients were tracked until SSNHL was diagnosed, death, or the end of 2011. Osteoporosis was identified based on a primary diagnosis of osteoporosis (ICD-9-CM code 7330) by dual-energy x-ray absorptiometry. INTERVENTION: Identified the diagnosis of osteoporosis and SSNHL by ICD-9CM code. MAIN OUTCOME MEASURE: The identification of patients with newly diagnosed SSNHL by ICD-9CM code. RESULTS: The incidence rates of SSNHL in the osteoporosis cohort and comparison group were 10.43 and 5.93 per 10,000 person years. Patients with osteoporosis were at 1.76 times the risk of developing SSNHL than patients without osteoporosis. The incidence rate ratio (IRR) for SSNHL was significantly greater in older (50-64 y and ≥ 65 y), and female patients, and borderline greater in hypertensive patients with osteoporosis than the controls, IRRs being 1.50, 2.33, 1.87, and 1.59. CONCLUSIONS: Patients with osteoporosis are at significantly greater risk of developing SSNHL.

Obstructive sleep apnea and risk of osteoporosis: a population-based cohort study in Taiwan.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with metabolic, endocrine, and cardiovascular diseases. It is characterized by repetitive episodes of apnea/hypopnea and hypoxia in tissues, which might also impact bone metabolism. This study investigates the possible association between OSA and osteoporosis. METHODS: Random samples of 1 million individuals were collected from Taiwan's National Health Insurance database. A total of 1377 patients with newly diagnosed OSA from 2000 to 2008 were recruited and compared with a matched cohort of 20 655 patients without OSA. All patients were tracked until an osteoporosis diagnosis, death, or the end of 2011. RESULTS: During the 6-year follow-up period, the incidence rates of osteoporosis in the OSA cohort and comparison group were 2.52 and 1.00 per 1000 person-years, respectively. Patients with OSA were found to be at 2.74 times the risk of osteoporosis than patients without OSA (95% confidence interval 1.69-4.44, P < .05), after adjustment for age, gender, diabetes, hypertension, coronary artery disease, obesity, stroke, hyperlipidemia, chronic kidney disease, gout, monthly income, and geographical location. Subgroup analysis showed that older patients and female patients had a higher risk for osteoporosis than their younger and male counterparts. Log-rank analysis revealed that patients with OSA patients had significantly higher cumulative incidence rates of osteoporosis than the comparison group (P < .0001). CONCLUSION: People diagnosed with OSA are at increased risk for subsequent osteoporosis.

Obstructive sleep apnea and the risk of atopic dermatitis: a population-based case control study.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with systemic inflammation and induces various comorbid medical diseases. To date, no study has explored the relationship between OSA and atopic dermatitis (AD), an inflammatory and autoimmune skin disorder. This study investigated the longitudinal risk for AD in patients with OSA. METHODS: A random sample of 1,000,000 individuals from Taiwan's National Health Insurance database was collected. From this sample, 1222 patients with newly-diagnosed OSA between 2000 and 2005 were identified and compared with a matched cohort of 18330 patients without OSA. All patients were tracked for 5.5 years from the index date in order to identify which patients subsequently developed AD. RESULTS: During the 5.5-year follow-up period, the incidence rates of AD in the OSA cohort and comparison groups were 9.81 and 6.21 per 1000 person-years, respectively. After adjustment for age, gender, diabetes, hypertension, coronary heart disease, obesity, allergy, allergic rhinitis, asthma, monthly income, and geographic location, patients with OSA were 1.5-times more likely to develop AD than patients without OSA (95% CI = 1.15-1.95, p = 0.0025). The hazard risk for AD was greater in male OSA patients and young OSA patients (0-18 and 19-34 years), adjusted HRs being 1.53 (95% CI = 1.14-2.06, p = 0.005), 4.01(95% CI = 1.57-10.26, p = 0.0038) and 1.75(95% CI = 1.00-3.04, p = 0.0483), respectively. The log-rank test indicated that OSA patients <35-years-old had significantly higher cumulative incidence rates of AD than those patient of the same age in the comparison group (p = 0.0001). CONCLUSION: Patients with OSA, especially male patients and younger patients, are at an increased risk for AD later in life.

Acarbose plus metformin fixed-dose combination outperforms acarbose monotherapy for type 2 diabetes.

AIM: To compare the efficacy and safety of acarbose plus metformin fixed-dose combination (FDC) versus acarbose monotherapy for type 2 diabetes (T2D). METHODS: Eligible T2D patients undergoing treatment with diet control only or oral antidiabetic medications were run-in on acarbose 50mg thrice-daily for 4 weeks, then randomised either to continue this monotherapy, or to acarbose 50mg plus metformin hydrochloride 500mg FDC (acarbose/metformin FDC), each thrice-daily for 16 weeks. RESULTS: Acarbose/metformin FDC therapy significantly reduced HbA1c, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) from baseline (all p<0.0001) with superior efficacy compared with acarbose monotherapy (between-group differences; HbA1c -1.35%; FPG -29.5mg/dl; PPG -41.6mg/dl; all p<0.0001). Proportionally more patients treated with acarbose/metformin FDC achieved HbA1c <7.0% (47.8% vs. 10.7%, p<0.0001). Both treatments reduced bodyweight (p<0.0001), with a significant between-group difference (-0.6kg, p<0.01) favouring acarbose/metformin FDC. Hypoglycaemia was not reported with either treatment, and the incidence of other adverse events did not differ significantly between the groups. CONCLUSIONS: Compared with acarbose monotherapy, acarbose/metformin FDC has superior antihyperglycaemic efficacy, brings proportionally more T2D patients to HbA1c goal, and further reduces bodyweight. Acarbose/metformin FDC is well-tolerated without significant risk of hypoglycaemia and is a potentially advantageous therapy for T2D.

Apolipoprotein E polymorphism and the progression of diabetic nephropathy in type 2 diabetes.

BACKGROUND/AIMS: Three different apo E alleles (E2, E3 and E4) produce apo E isoproteins, which regulate the metabolism of lipoproteins. This study investigated the apo E polymorphisms as a prognostic factor for the development of diabetic nephropathy (DN). METHODS: A total of 525 type 2 diabetic patients were enrolled to participate in this prospective observational study. Apo E gene polymorphisms were analyzed by polymerase chain reaction. The progression of DN was defined as a shift to a higher stage of DN or a doubling of the baseline serum creatinine level by the end of the study. RESULTS: The mean follow-up period was 42.4 months. The patients whose DN progressed had significantly higher urine albumin/creatinine ratios and fewer used diuretics than those in whom DN did not progress. In the Cox regression analysis, the apo E4 carriers were found to be at greater risk of progression of DN than non-apo E4 carriers (p = 0.007, hazard ratio 2.252). After adjusting for confounding factors, apo E4 carriers remained at increased risk of progression to more severe DN (p = 0.002, hazard ratio 2.820). CONCLUSION: Our study suggests the apo E4 carrier might serve as a predictor of DN progression in Taiwan.

Schwannomas of the left adrenal gland and posterior mediastinum.

Schwannoma is a rare tumor of neural crest cell origin. Most schwannomas occur in the head, neck, stomach or limbs, with a few cases occurring in the retroperitoneal space. A 30-year-old Taiwanese woman presented with a 1-week history of left anterior chest discomfort and left flank pain. The laboratory findings and endocrine studies were all within normal limits. Chest X-ray revealed masses in the posterior mediastinum. Chest computed tomography and magnetic resonance imaging showed several masses in the left paraspinal region and in the left adrenal region. The patient underwent total excision of the left paraspinal tumors and laparoscopic left adrenalectomy. Pathologic studies showed a picture of benign schwannoma. In conclusion, preoperative differentiation of benign schwannoma from malignant peripheral nerve sheath tumor or other tumors is important for good prognosis. Total excision of benign schwannoma is associated with favourable outcome in patients.

Primary aldosteronism caused by unilateral adrenal hyperplasia: rethinking the accuracy of imaging studies.

A rare type of aldosteronism, known as unilateral adrenal hyperplasia (UAH), is difficult to diagnose, not only because it fails to conform to the typical common subtypes, but also because imaging results are unreliable. We report 2 Taiwanese patients with UAH. Case 1 was a 44-year-old man with 2 episodes of hypokalemic paralysis. Hypertension and suppressed plasma renin activity (PRA) with elevated plasma aldosterone concentration (PAC) were observed. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) showed a right adrenal mass, but adrenal scintigraphy revealed no definite laterality. The patient underwent a laparoscopic right adrenalectomy. Adrenal cortical hyperplasia was discovered from results of the histologic analysis. Case 2 was a 33-year-old woman referred for hypokalemia, hypertension, and a left adrenal mass found on a CT scan. However, MRI revealed normal adrenal glands. The adrenal vein sampling for PAC showed overproduction of PAC from the left adrenal gland. A laparoscopic left adrenalectomy was done. Pathology results revealed micronodular cortical hyperplasia with central hemorrhage. Blood pressure, plasma potassium, aldosterone, and renin activity levels returned to normal after operation in both cases. Both patients have been well for 3 years and 16 months, respectively, after surgery. We review the literature and discuss the limitations of imaging studies.

Klinefelter's syndrome with seizure, pseudohypoparathyroidism type Ib and multiple endocrine dysfunctions.

Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP) type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47,XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

Recurrent pulmonary embolism in an elderly patient with Cushing's syndrome, adrenocortical adenoma, pheochromocytoma and prostate adenocarcinoma.

Pulmonary embolism (PE) is a major health problem. Mortality in untreated PE is high, but with adequate (anticoagulant) treatment, can be reduced. Multiple primary and secondary risk factors are responsible for PE. But there is rare association of mixed adrenal tumor with PE. Here, we report a case of adrenocortical adenoma with Cushing's syndrome coexistent with pheochromocytoma with recurrent PE in an elderly patient with prostate adenocarcinoma. A 78-year-old Taiwanese retired veteran was admitted in July, 2002 with the presentation of syncope. Three years before, he was diagnosed with prostate adenocarcinoma and had received Androcur therapy since then. Five months later, he was admitted with Cushingoid appearance and hypertension. Abdominal imaging studies revealed a left adrenal tumor. Laparoscopic adrenalectomy revealed an adrenocortical adenoma. Two years later, a recurrent left adrenal tumor was found. Repeated laparoscopic adrenalectomy revealed pheochromocytoma. One month after the repeat laparoscopic surgery, the patient was admitted due to syncope. Chest X-ray revealed cardiomegaly with pulmonary venous congestion. Echocardiogram showed impaired right ventricle global systolic function. Perfusion lung scan showed a high probability of PE. Heparin and coumadin were given but stopped 5 weeks later due to the development of severe skin ecchymosis. In December 2002, the patient was admitted again with consciousness disturbance. Chest computed tomography (CT) revealed bilateral PE, and he died 5 hours later due to cardiogenic shock. In conclusion, in elderly patients with Cushing's syndrome with pheochromocytoma and prostate carcinoma, there is probability of pulmonary embolism.