Poster Presentation

PE-01

THYROID TUBERCULOSIS

1,2Tsung-Ju CHuang, 1JHIH-SYUAN LIOU, 1YI-JEN HUNG, 1CHANG-HSUN HSIEH

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan

We presented a patient underlying thyroid cyst got pulmonary tuberculosis (TB) and then received treatment of anti-TB agents. Moreover, the thyroid cyst increased in size gradually despite repeated aspirations and progressed to acute thyroid abscess. Thyroid TB was diagnosed by acid fast stain of pus. However, resudial thyroid cyst remained but diminished in size after drainage of abscess and a 6-month duration of anti-TB agents therapy. Thyroid cysts are often benign with high recurrence rate and usually didn’t need aggressive treatment unless compressive symptoms. Nevertheless, they may be sensitive to TB infection and need aggressive treatment such as surgery as early as possible in patients with pulmonary TB with thyroid involvement to avoid progression to a thyroid abscess.

PE-02

PRIMARY ADRENAL INSUFFICIENCY DUE TO ISOLATED ADRENAL CRYPTOCOCCOSIS IN A IMMUNOCOMPETENT MAN SUCCESSFULLY TREATED WITH ORAL FLUCONAZOLE

1YI-CHIH Hung, 1CHING-CHU CHEN, 1TZU-YUAN WANG, 2MAO-WANG HO

1Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C;2Division of Infection Disease, Department of Internal Medicine, China Medical University Hospital Taichung, Taiwan, R.O.C

background: Cryptococcosis was commonly developed in immune compromised patients presenting with pulmonary cryptococcosis and meningitis. There are only a few reports describing isolated adrenal cryptococcosis in immunocompetent subjects. Furthermore, adrenal cryptococcosis is usually refractory to antifungal therapy alone and unilateral or bilateral adrenalectomy was often required in such cases.

Case presentation: We present an individual who is a hepatitis c virus carrier with hyperpigmentation and reducing 20kg in weight within two years. He had non-bilious vomiting for three days before visiting emergency department. In addition to hyponatremia(Na:120 mmol/L) and hyperkalemia(K: 5.1 mmol/L), high serum adrenocorticotropic hormone (ACTH) (347 pg/mL) with low random serum cortisol (Cortisol:3.13 ug/dL) was observed. Contrast enhanced abdominal CT showed bilateral adrenal masses without enhancement. The serum cryptococcal antigen titer was elevated to 1:256 and adrenal cryptococcosis was confirmed by biopsy of the adrenal masses. He was diagnosed as having primary adrenal insufficiency due to adrenal cryptococcosis without central nervous system or lung involvement. After 10 months of oral fluconazole and cortisone acetate treatment, the serum cryptococcal antigen titer was 1:16 and high serum ACTH also subsided (ACTH: 25.1 pg/mL).

Conclusion: To our knowledge, this is the first case report describing isolated adrenal cryptococcosis in an immunocompetent patient successfully treated with oral fluconazole. It is difficult to make the diagnosis of this rare disease prior to resection or autopsy. Therefore, adrenal cryptococcosis should be considered in patients with bilateral adrenal masses with primary adrenal insufficiency.

PE-03

PROLACTINOMA PRESENTING AS DELAYED PUBERTY: A CASE REPORT

1YI-Lun CHIang, 1SZU-HUI LEE, 1PEI-CHI CHEN, 1YEN-LING CHEN, 1CHUNG-YEN HUANG, 1,2HONG-DA LIN, 1SHIH-MING LAI 1Division of Endocrinology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Taipei-Veterans General Hospital , Taipei

Prolactinomas are benign pituitary tumors that are frequently seen in females aged 20 to 50. In children and adolescents, pituitary adenomas are rare, and prolactinomas are the most common secretory tumors in these. As in adults, prolactinomas are also predominant in girls.

The symptoms are heterogeneous and differ according to the prolactin level, tumor volume, age of onset and gender. We reported a case of prolactinoma presenting as delayed puberty and reviewed the literature of prolactinomas in young population.

Case presentation: An 18-year-old boy was referred to our hospital with the chief problem of delayed puberty. His body weight was 68 kg, height 170 cm, arm span 169, upper segment 82 cm, and lower segment 88 cm. Physical examination revealed no axillary hair. Pubic hair and genital were underdeveloped (Tanner stage 3). Laboratory data showed high prolactin level (598.7 ng/mL) and low testosterone (1 ng/mL). The bone age survey revealed 14 years old. The magnetic resonance imaging (MRI) of sella revealed a pituitary tumor about 1.8 cm in diameter, with stalk deviation to right side. After undergoing cabergoline treatment, the prolactin level decreased in the first month and the testosterone level became normal after treatment for 3 months. His secondary sexual development improved gradually. discussion: Clinical presentation with prolactinomas in childhood and adolescents varies by their age and gender. The symptoms include headache, visual field defects, galactorrhea, pubertal arrest and short stature. In girls, most of the symptoms are manifestation of reproductive axis abnormalities, such as amenorrhea and galactorrhea; while in boys, the mass effect symptoms are more common. In our case, medical treatment with cabergoline showed a good efficacy in controlling clinical symptoms and signs, and is safe for young population.

PE-04

THE THYROID HORMONE RESISTANCE SYNDROME: A CASE REPORT

1sHIH-HuI Huang, 1CHUNG-YEN HUANG, 1SHIH-MING LAI, 1YEN-LING CHEN,

1PEI-CHI CHEN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Shin Kong Wu Ho-Su Memory Hospital, Taiwan, R.O.C.

Impaired sensitivity to thyroid hormone is a rare inherited disease. Resistance of thyroid hormone (RTH) is the most common form of impaired sensitivity to thyroid hormone. It is an autosomal dominant disease. Most RTH is caused by mutation of THRβ gene, leading to the defect of thyroid hormone action. The hallmark of RTH is the paucity of symptoms and signs despite the presence of high serum T4 and T3 concentrations. The most common symptoms, if present, are goiter, tachycardia, and hyperactivity. Here, we present a case of suspect resistance of thyroid hormone.

A 19-year-old man with symptoms of hand tremor and tachycardia was presented in June, 2014. Lab data showed elevated free T4 with nonsuppressed TSH. However, there were no pituitary tumor on MRI and no any other pituitary axis dysfunction. Thyroid echogram showed bilateral lobes were enlarged and thyroid scan showed diffusely increased tracer uptake. TRH stimulation test was also done and revealed exacerbated response. As a result, RTH was highly suspected. We had tried levothyroxin 0.1 mg/day but the TSH level had not been suppressed. Currently, only propranolol was prescribed for controlling his symptoms of hyperactivity and tachycardia.

This case highlights that we should, in addition to pituitary TSH-secreting tumor, take RTH into consideration when we met a case of thyrotoxicosis with nonsuppressed TSH.

PE-05

SUBACUTE THYROIDITIS PRESENTING AS DIFFUSE UPTAKE OF THYROID GLAND ON 18F-FDG PET/CT: A CASE REPORT

1CHen-TI wang,

1, 2YUNG-CHUAN LU, 1YU-HSI KAO, 1SHU-JU KU, 1JU-CHUN HUANG, 1KUO-BIN TSENG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 2School of Medicine, I-Shou University, Kaohsiung, Taiwan

Subacute thyroiditis is an inflammatory disease of the thyroid gland and is usually preceded by an upper respiratory tract infection and is thought to be caused by a viral infection or a postviral inflammatory process. The postviral inflammatory response leads to giant cell infiltration into the thyroid follicles resulting in disruption and collapse of thyroid follicles, and necrosis of follicular cells. This in turn causes pain and tenderness on palpation of thyroid. Radioiodine or technetium imaging study will show low uptake or a faint heterogeneous pattern of radionuclide uptake during the hyperthyroid phase. Ultrasonography of the thyroid appears to be normal or enlarged but is diffusely or focally hypoechogenic. Imaging studies of subacute thyroiditis shown on 18F-FDG PET/CT is scarce.

We report a case of subacute thyroiditis presenting as diffuse uptake of thyroid gland on 18F-FDG PET/CT. The patient was a 49-year-old man who went for health examination due to symptoms of poor appetite, body weight loss 9kg in recent 3 months and poor concentration. 18F-FDG PET/CT revealed diffuse hypermetabolic process in both lobes of thyroid. Patient was then referred to Endocrinology and Metabolism outpatient department for further evaluation. Physical examination revealed tenderness of bilateral lobes of thyroid. Laboratory tests revealed elevated erythrocyte sedimentation rate (ESR: 54mm/hr; normal range: 0-20mm/hr), low thyroid-stimulating hormone (TSH: 0.06 uIU/ mL; normal range 0.35-4.94 uIU/ml), mild elevation of free-T4 (FT4: 1.54 ng/dL; normal range 0.7-1.48 ng/dL), elevation of thyroglobulin (Thyroglobulin: 157.14 ng/dL; normal range <50 ng/ dL), negative antimicrosomal antibody, negative thyroglobulin antibody and negative thyrotropin receptor antibody. Thyroid ultrasonography showed enlargement of bilateral thyroid lobes with illdefined irregular margin and hypoechoic hypovascular areas, compatible with subacute thyroiditis of both lobes. Thyroid fine needle aspiration was performed and the results of cytologic examination were consistent with subacute thyroiditis. Patient subsequently had a Tc99m thyroid scan and hardly shows visualization of the thyroid gland, which is also compatible with subacute thyroiditis. Oral prednisolone was prescribed and patient’s thyroid tenderness improved rapidly.

Decreased uptake shown on Tc99m thyroid scan indicates disruption of the follicles of the thyroid. Diffuse uptake shown on 18F-FDG PET/CT was probable due to inflammatory changes of thyroid. Tc99m thyroid scan and 18F-FDG PET/CT can show different findings for subacute thyroiditis. Subacute thyroiditis in clinical practice is not rare. While 18F-FDG PET/CT is known to be helpful for making clinical decisions for thyroid lesions, there are still indeterminate clinical cases for diagnosing subcute thyroiditis. Therefore, clinical symptoms and other accompanying studies should be considered for diagnosis.

PE-06

A CASE OF CUSHING’S SYNDROME WITH BILATERAL ADRENAL TUMOR

1sHIH-Tang Yan, 1,2PIN-FAN CHEN

1Divison of Endocrinology and Metabolism, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

Purpose: A 52-year-old man with Cushing’s syndrome was noted to have bilateral adrenal tumors. Initial ACTH data was still detectable (12.3 pg/dl, normal range 5-77, by RIA). Finally, unilateral functional adrenal tumor was proved. abstract: A 52-year-old man came for leg weakness, rounding of face, and protruding of abdomen since 2 years ago, with weight gain 9 kg. Leg edema was noted from 3 months ago. He ever visited Ortho. Dr. for suspecting spondylosis. Abdominal CT revealed right adrenal nodule (12 mm) and left adrenal mass (around 3 cm in size) incidentally. So he was referred to our OPD. He was 79 kg weight and 175 cm height, BP 164/116 mmHg, with rounding of face, globular abdomen without striae, central obesity, without leg edema. Na: 145 and K: 3.6 mmol/L. Overnight dexamethasone suppression test (DST), 1 mg, showed cortisol level still 19.15μg/dl. The results of low-dose and highdose DST were 24.3 and 26.8μg/dl of morning cortisol, respectively. Baseline ACTH by RIA method was 12.3pg/ml by our lab. (repeat and the same) and caused diagnosis confusion. MRI of sella reported a small (4.9×4.4 mm) left pituitary tumor. We referred the case to Tai-Chung Veteran General Hospital, where the data of ACTH was undetectable. So the diagnosis of adrenal Cushing’s syndrome was more definite. NP-59 adrenal scan with SPECT showed uptake over left adrenal mass and no significant uptake over right adrenal tumor. Left adrenal mass was removed by laparoscopy uneventfully. After operation, significant reduction of weight, rounding face and protruding abdomen were noted. Blood pressure also became normal spontaneously. But he had symptoms of adrenal insufficiency and needed steroid supply for several months.

Conclusion: A 52-year-old man with Cushing’s syndrome was noted to have bilateral adrenal tumors. Series of tests and image finding favored adrenal cause. However, initial inaccuracy of ACTH test leaded to diagnosis confusion. NP-59 adrenal scan helped to localize the side of functional tumor. After removal the tumor, symptoms much improved.

PE-07

HYPerProLaCTIneMIa assoCIaTed wITH unruPTured aneurYsM: Case rePorT

weI-Tsen LIao, MING-JE TSAI, CHUN-CHUAN LEE

Division of Endocrinology & Metabolism, Department of Internal Medicine, Mackay Memorial hospital, Taiwan, R.O.C.

Prolactin level is regulated by hypothalamic-pituitary-prolactin axis. The dopamine produced in hypothalamus transports to the pituitary via hypothalamic hypophysial system and inhibits pituitary prolactin secretion. Stalk compression usually interrupts this pathway and leads to hyperprolactinemia. An 48-years-old woman was referred by OB/GYN clinic because of hyperprolactinemia (91.8 µg/L) which was treated with Cabergoline. Our investigation showed hyperprolactinemia (52.8 µg/L) but other pituitary hormones were within normal range. The MRI of the pituitary fossa showed a 1.8x2x2.1cm nodular lesion in suprasellar region with compression of pituitary gland and optic chaism. The differential diagnosis of the mass includes prolactinoma, or non-functional pituitary tumor with stalk compression that induces hyperprolactinemia. We also noted the tumor flow-void on T1WI & T2WI connecting to right ICA. Under the aneurysm arising from right ICA, the patient received angiography. Carotid artery aneurysm was confirmed by angiography and aneurysm surgery was performed. The symptoms of hyperprolactinemia was improved after surgery. The causes of hyperprolactinemia include physiologic cause, pathologic cause and pharmacologic cause. Among the pathological causes, the two most common etiologies are prolactinomas and decreased dopaminergic inhibition of prolactin secretion. Clinically, serum prolactin levels greater than 200 µg/L suggests the presence of a macroprolactinoma, and ranging from 25 to 100 μg/L usually indicates microadenoma or medication-induced hyperprolactinemia. However, a minimal to moderate elevation can also indicate secondary stalk interruption. Stalk compression caused by unruptured aneurysm is rare but very risky because it indicates large aneurysm which need aggressive treatment including surgery and adequate blood pressure control.

PE-08

SEVERE HYPERTENSION IN A PATIENT WITH PRIMARY ALDOSTERONISM WITHOUT SUPPRESSED RENIN

TZu-Yuan wang, CHING-CHU CHEN, CHWEN-TZUEI CHANG, RONG-HSING CHEN, WEN-LIANG HUANG, KUO-CHIN HUANG, YI-CHIH HUNG

Division of Endocrinology and Metabolism, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.

Introduciton: Primary aldosteronism (PA), first described by Conn in 1955, is characterized by hypertension, increased aldosterone secretion and suppressed plasma renin activity (PRA). Previous reports indicate that primary aldosteronism is rarely to cause malignant or accelerated hypertension. Here we report a case of PA presented with severe hypertension without suppressed PRA.

Case report: A 27-year-old woman with a history of hypertension was refered to our hospital because of severe hypertension noted prior to tooth extraction. He had hypertension for 2 years without regular medications . Her blood pressure was 223/153 mmHg in supine position. His pulse rate 101/ min, respiratory rate 14/min and body temperature 36 ℃ .Physical examination revealed an acutely ill woman weighting 49 kg and measuring 159 cm tall. His heart beat was rapid without murmur and his breath sounds was clear. Neurologic examination was normal. Laboratory data consisted of the following: BUN 17 mg/dl, Cr 0.9 mg/dl, Na 137 mEq/L and K 2.8 mEq/L. PRA (plasma renin activity 1.73 ng/ml/hr , aldosterone 73.3 ng/ml. She received triple antihypertensive drug therapy. But her blood pressure still around 159/113mmHg. Two repeat assays of PRA and aldosterone were PRA 1.6 ng/ml/hr, aldosterone 76.8 ng/ml; PRA 2.6 ng/ml/hr, aldosterone 76.4 ng/ml separately. Persistent hypokalemia 3.2 mEq/L was found. Renal artery stenosis was highly suspected. A computed tomography (CT) scan showed a hypodense nodule of 1.2 cm of diameter in the left adrenal gland and patent both renal arteries. Unilateral left adrenalectomy was then performed due to considered PA . One yellowish adrenal gland tumor 1.0 x 1.0 cm of left adrenal gland was removed. The pathology showed cortical adenoma, which is compatible with Conn’s syndrome. Her blood pressure gradually returned to normal range with only one antihypertensive drug.

Conclusion: PA can complicated with severe hypertension. A normal or even a high normal PRA does not necessarily exclude the diagnosis of PA. PA should be considered as a possible underlying cause of normal renin malignant hypertension.

PE-09

CAN ROBOTIC THYROIDECTOMY APPLIED TO THYROID CARCINOMA WITH LUNG METASTASES?

1HsIao-wen CHang, 2YI-FENG CHEN, 1CHANG-HSUN HSIEH, 2DANIEL HUENG-

YUAN SHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan; 2Department of Nuclear medicine, Tri-Service General Hospital, National Defense Medical Center, Taiwan

background: Robot-assisted trans-axillary endoscopic thyroidectomy (RTET) is an emerging surgical technique. Compared to the conventional thyroidectomy, it leaves no cervical scar and less neck discomforts. While Korean experience in RTET is impressive, the reproducibility and validity of its surgical completeness and oncological outcomes remains questionable elsewhere and the patient’s selection is still in debates. Herein we present a case of cytological suspected thyroid malignancy undergoing RTET while, post-operatively, without histological evidence of primary thyroid cancer but noted multiple lung metastases.

Case presentation: A 49-year-old woman presented bilateral thyroid nodules, which was suspected to be papillary thyroid cancer (PTC) within right lobe via fine needle aspiration cytology. RTET was done in a local teaching hospital and the pathology indicated nodular goiter without malignancy. Due to post-operative hoarseness, she was referred to the ENT specialist, who recognized her pulmonary nodules via chest films incidentally. Lung metastases from follicular thyroid carcinoma were proved and then she was referred to our hospital for 131I therapy. 99mTc thyroid scan demonstrated left-sided thyroid remnant with appreciable uptake. 131I therapy (150 mCi) via rhTSH stimulation was utilized and post-therapeutic scan demonstrated those pulmonary lesions with iodine avidity. Four months after treatment, the lesional uptake disappeared and serum thyroglobulin (Tg) level subsided from 119.9 to <0.2 ng/ml and anti-Tg antibody also fell from 11.16 IU/ml to negative. discussion: It is unusual to note cytological diagnosis of PTC not confirmed by subsequent histopathology and also uncommon to see evident lung metastases without primary thyroid cancer. It might be explained by the cytological features of PTC sometimes shared with other benign tumors (false positive finding) and/or primary lesion misdiagnosed (occult follicular thyroid cancer). Surgical incompleteness of RTET can also be one other concern. Contrast to Korea’s expert opinions, European study include BMI <22, unilateral small-sized nodules and low risk of malignancy as selection criteria of RT. Apart from controversy of RTET, we also face problems like limited case numbers and unfulfilled established surgeon training in Taiwan. From this case, we call for attention that RTET should only be opted when the risk of advanced thyroid cancer can be excluded.

PE-10

HYPERTRIGLYCERIDEMIA INCREASES THE SEVERITY OF THROMBOCYTOPENIA IN DENGUE INFECTED PATIENTS

1,3MeI-YueH Lee,

2CHUNG-YUAN CHEN, 3KUN-DER LIN, 3YU-LI LEE, 1,3WEI -HAO HSU, 3PI-JUNG HSIAO, 3SHYI-JANG SHIN

1Department of Internal Medicine,Kaohsiung Municipal Hsiao-Kang Hospital; 2Chin-Pin Clinic, Kaohsiung; 3Division of Endocrinology and Metabolism , Kaohsiung Medical University Hospital

background: The severity of thrombocytopenia is an indicator of the severity of dengue virus infection.We investigated whether hyperlipidemia especially hypertriglyceridemia is associated with thrombocytopenia in dengue-infected patients.

Methods: We studied clinical characteristics of 644 patients with dengue infection at a Kaohsiung Medical University Hospital during the epidemic June 1, 2002 to December 31, 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. results: Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression β of -2.947 (p= 0.004 ), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively.

Conclusion:Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

PE-11

INITIAL FALSE NEGATIVE ALDOSTERONE-TO-RENIN RATIO IN PRIMARY ALDOSTERONISM WITH SEVERE HYPOKALEMIC RHABDOMYOLYSIS- A CASE REPORT

1YI-weI wu, 1YA-HUI HU, 2YAO-CHOU TSAI, 1SHI-WEN KUO

1Division of Endocrine and Metabolism, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taiwan; 2Division of Urology, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taiwan

A 50-year-old female came to our neurology outpatient clinic for a sudden onset of right arm weakness which had occurred twice in 3 months. She had a history of hypertension under irregular medication for 7~8 years. Brain MRA was performed and revealed a right MCA aneurysm at M1-2 junction. She was referred to neurosurgery outpatient department. Surgery was suggested but the patient hesitated. However, the patient had severe neck pain with general weakenss and muscle pain 2 weeks later. Severe hypokalemia (1.7 mmol/L) with elevated creatine kinase level (6086 IU/L) was noted. After admission under the impression of hypokalemic rhabdomyolysis and hypertension, the patient was given potassium supplement and blood pressure control with carvedilol 6.25mg twice daily, amlodipne 5mg twice daily and telmisartan 80mg once daily. Because of her hypertension and hypokalemia, primary aldosteronism was highly suspected. Functional test was performed and the patient’s aldosterone-to-renin ratio (ARR) was 15 initially. Hypokalemia induced lab error was suspected. The patient’s creatine kinase level peaked at 27930 IU/L 3 days later. We gave the patient spironolactone and her hypokalemia and rhabdomyolysis improved. We repeated ARR after hypokalemia had been corrected and it was 324. Contrast adrenal computed tomography revealed a 1.9 cm left adrenal tumor. NP-59 SPECT/CT was performed and it showed a left adrenal gland tumor with increased NP-59 uptake, compatible with a functional adenoma. The patient was then referred to urology for left unilateral adrenalectomy . Pathology reported left corticol adenoma. At follow-up, her hypertension had been gradually improving and she was free of hypokalemic rhabdomyolysis. A 50-year-old female came to our neurology outpatient clinic for a sudden onset of right arm weakness which had occurred twice in 3 months. She had a history of hypertension under irregular medication for 7~8 years. Brain MRA was performed and revealed a right MCA aneurysm at M1-2 junction. She was referred to neurosurgery outpatient department. Surgery was suggested but the patient hesitated. However, the patient had severe neck pain with general weakenss and muscle pain 2 weeks later. Severe hypokalemia (1.7 mmol/L) with elevated creatine kinase level (6086 IU/L) was noted. After admission under the impression of hypokalemic rhabdomyolysis and hypertension, the patient was given potassium supplement and blood pressure control with carvedilol 6.25mg twice daily, amlodipne 5mg twice daily and telmisartan 80mg once daily. Because of her hypertension and hypokalemia, primary aldosteronism was highly suspected. Functional test was performed and the patient’s aldosterone-to-renin ratio (ARR) was 15 initially. Hypokalemia induced lab error was suspected. The patient’s creatine kinase level peaked at 27930 IU/L 3 days later. We gave the patient spironolactone and her hypokalemia and rhabdomyolysis improved. We repeated ARR after hypokalemia had been corrected and it was 324. Contrast adrenal computed tomography revealed a 1.9 cm left adrenal tumor. NP59 SPECT/CT was performed and it showed a left adrenal gland tumor with increased NP-59 uptake, compatible with a functional adenoma. The patient was then referred to urology for left unilateral adrenalectomy . Pathology reported left corticol adenoma. At follow-up, her hypertension had been gradually improving and she was free of hypokalemic rhabdomyolysis.

PE-12

ADRENAL LYMPHOMA: A CASE REPORT

1LI-weI HsIao, 1CHIA-LIN LEE, 2CHIEH-LIN TENG, 1SHI-YI LIN, 1WAYNE HUEY-

HERNG SHEU

1Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taiwan; 2Division of Hematology and oncology, Department of Medicine, Taichung Veterans General Hospital, Taiwan

A 60-year-old old woman suffered from spiking fever for 3 days and initially visited the local hospital, where scrub typhus was impressed. After taking Doxycycline for one week, high fever still persisted, and the serology test result was negative. Finally, she came to emergency department of our hospital for further management. Incidentally, the abdomen computed tomography (CT) showed bilateral enlarged adrenal glands, both about 4.4cm. Therefore, she was admitted to our ward for adrenal incidentaloma and fever survey.

At admission, the endocrine function tests showed that blood cortisol, ACTH, renin and aldosterone concentrations were all within normal limit, and therefore, the non-functional incidentaloma was impressed. The tumor survey of the other sites also showed negative findings. However, after a detailed review of her serial blood routine data, a progressively increased monocyte fraction was noted within 10 days after fever onset, and the peripheral blood smear demonstrated that monocyte was 9%, lymphocyte 21% and atypical lymphocyte 1%. Her LDH and ferritin level were increased to 946 U/L, and 1842 ng/ml, respectively, and an inverted albumin to total protein ratio was noted, A/G ratio=0.75. Then, we consulted the oncologist because of suspicion of hematological malignancy. The bone marrow biopsy proved to be diffuse large B cell lymphoma. A further adrenal mass biopsy was ever suggested, but the patient refused. Under the impression of adrenal lymphoma with bone marrow involvement, she received chemotherapy with R-CHOP+IT regimen for one cycle, and then shifted to R-hyper CVAD regimen for 3 cycles till now because of aggressive lymphoma pattern. After 4 months chemotherapy, her follow–up abdominal CT showed that bilateral adrenal glands size were both reduced to 1.2 cm, and the repeated bone marrow biopsy showed remission status.

PE-13

THYROIDITIS AND HYPERCALCEMIA AFTER UNILATERAL ADRENALECTOMY FOR CUSHING’S SYNDROME : A CASE REPORT

1Yu-weI CHen, 1CHIA-PO FU, 2WEN-MING CHEN, 1SHI-YI LIN, 3WAYNE H-H SHEU

1Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan;2Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan; 3Professor and Chairman, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

We reported a 46-year-old man with adrenal Cushing’s syndrom who developed thyroiditis complicated with symptomatic hypercalcemia after adrenalectomy. Initially, he was admitted to hour hospital for right adrenalectomy due to a cortisol-secreting adrenocortical adenoma in Jun, 2014. After adrenal surgery he was given glucocorticoid substitution, but later the patient discontinued steroid treatment and lost follow-up. In Jul, 2014, he began to suffer from fatigue, nausea, anorexia, vomiting and diffuse joint pain for weeks, and then was sent to ER due to drowsy consciousness and tremor of extremities on Jul 24, 2014. On admission, the patient’s GCS score was E3V4 M5, blood pressure was 138/85 mmHg, pulse rate 134/min, repiratory rate 19/min body temperature was 37.0 ° C. His height was 171 cm, weight 54 kg, and body mass index 18.4 kg/m2 .Laboratory tests showed that serum cortisol was les than 1μg/dl and ACTH was 34.4 pg/ml, correct serum calcium 13.9 mg/dl, PTH less than 3 pg/ml, free thyroxine (FT4) 42.10 pg/ml, and suppressed thyroid stimulating hormone (TSH) 0.006 uIU/ml. Serum thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were undetectable. The technetium thyroid scintigraphy found a complete absence of thyroid uptake, and thyroid ultrasound that revealed a diffusely hypoechogenic gland with low blood flow. According to these findings and the patient’s past history, he was diagnosis to have acute adrenal insufficiency and thyroiditis with hypercalcemia. Following steroid treatment his symptoms resolved gradually with improved consciousness. In addition, serum calcium level returned to 8.7 mg/dl on day 5 after steroid treatment, and FT4 level was 9.98 pg/ml and TSH level was 10.5 uIU/ml on day 87 after steroid treatment.

PE-14

THYROGEN, RECOMBINANT HUMAN TSH (RHTSH) - INDUCED HYPERCALCEMIC CRISIS IN A PATIENT WITH FOLLICULAR THYROID CARCINOMA : A CASE REPORT AND REVIEW OF THE LITERATURE

CHIen-an CHou, SZU-TAH CHEN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C

background: Follicular thyroid cancer (FTC) associated hypercalcemia is a rare condition coupling to increase mortality. The possible mechanisms of hypercalcemia in FTC are direct bone destruction and/or paraneoplastic effect. Through a different mechanism, rhTSH has been reported to induce hypercalcemia in far advanced thyroid cancer with massive residual cancer secondary to it’s thyrotropic effect on inducing hyperthyroidism. Here we present a case of hypercalemic crisis after administration of rhTSH for cancer treatment.

Patient: A 50-year-old woman noted of inoperable recurrent FTC with pulmonary metastasis since 2011. Soft tissue mass and bone metastasis developed since 2014. rhTSH was prescribed for high dose radioactive iodine (RAI) therapy because patient could not tolerate her symptomatic hypothyroidism. results: The patient was admitted to our hospital with severe nausea and vomiting the day after rhTSH administration. Laboratory data showed severe hypercalcemia >15mg/dL with low i-PTH(< 2.5pg/mL) and mild thyrotoxicosis [triiodothyronine (T3) 161.6 ng/dL, free thyroxine (FT4) 0.79 ng/ dL, TSH 0.009 µU/mL]. Plain X-ray revealed bony destruction of right scapula and right humerus. Patient was discharged with her total serum calcium level returned to normal range after massive fluid replacement, loop diuretics and intravenous bisphosphonate. discussion: In the literature, rhTSH was reported to induce hypercalcemia in well differentiated thyroid carcinoma due to TSH induced hyperthyroidism or increased bone resorption by TSHenhanced tumor activity. In this case, we suspect that the hypercalcemic crisis may be associated with dehydration secondary to thyrogen induced nausea and vomiting. We report this case to remind doctors to be aware of possible sever complication of thyrogen to prepare patients for RAI treatment in far advanced well-differentiated thyroid carcinoma.

PE-15

A CASE OF RETROPERITONEAL MASS LESIONS: PARAGANGLIOMA

1CHIn CHou Yang, 3CHING WEI CHANG, 2CHUN LU LIN, 1YA CHUN HSIAO, 2CHUN CHUAN LI, 1YA CHUN HSIAO, 2CHUN CHUAN LI

1Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Hsinchu, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan; 3Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taiwan

Pheochromocytoma and paraganglioma are rarely seen cathecolamine-secreting neuroendocrine tumors. In our case, a retroperitoneal paraganglioma with a diameter of 5 cm was detected in a 71 years old man. After admission, he was found loss of consciousness suddenly. Myocarditis related to pheochromocytoma was the most possible reason of sudden collapse. The diagnosis of paraganglioma was made later in ICU, which would be subsequently removed. Pheochromocytoma or paraganglioma may cause hypertensive emergency which can lead to end organ damage. It should never been neglected in the differential diagnosis of retroperitoneal mass lesions, even though initial manifestations are not suggestive for the diagnosis.

Case report: A 71 years old man presented with acute palpitation, abdominal pain, headache and dizziness in ER. He has history of hypertension for 4 years, and his condition remained stable while taking daily combination therapy with CCB, ARB, and B-blocker. Abdominal CT revealed a 5cm heterogeneous soft tissue mass occupied at right para-aortic region with anterior displacement of duodenum and pancreas head. He was admitted on Aug 20, 2014 under the tentative diagnosis of pancreatic tumor. On Aug 22 early morning, he was found loss of consciousness suddenly. After CPR and intubation with mechanical ventilator support, vital sign recovered. He was then transferred to ICU. Elevation of cardiac enzyme was noted. (Troponin-I: 12.67ng/mL, CK: 966IU/L, CKMB: 74.5ng/ mL). EKG revealed QS pattern and disappearance of R wave over anterior wall. Diagnostic cardiac catheterization was performed on Sep 10 and it revealed non-significant CAD. (RCA patent; LAD-D 50% stenosis；LCX hypoplasia) Fluctuating blood pressure was noted in ICU. We checked 24hr-Urine VMA and catecholamine for 2 days. The data revealed elevation of both VMA and catecholamine (VMA: 11.8, 13 mg/day, norepinephrine: 205.6, 168.7 ug/day). Correlated the clinical condition with laboratory data and CT findings, functional paraganglioma was highly suspected. Surgery is indicated. After discussion with the family, the patient was dischanged on Sep 27 and operation will be arranged later. discussion: The terms of “pheochromocytomas” and “catecholamine-secreting paragangliomas” are referred to as catecholamine-secreting tumors that arise from the adrenal medulla and the sympathetic ganglia, respectively. Because of similar clinical presentations and treatments, some clinicians might use “pheochromocytoma” to refer to both of them. The classic triad of pheochromocytoma includes symptoms of episodic headache, sweating, and tachycardia. The pathogenesis of secondary hypertension and the role of catecholamines in the pathophysiology of pheochromocytoma have been well documented. Indeed, sustained or paroxysmal hypertension

is common, but about 5 to 15 percent of patients present with normal blood pressure. With high sensitivity, plasma metanephrines reamins the first-line test as diagnosis of pheochromocytomas. However, it is not available in some hospital. Another reliable method for diagnosis is measuring metanephrines and catecholamines in a 24-hour urine collection, both of them have high sensitivity and specificity. Adrenalectomy by an experienced surgeon is suggested as treatment of adrenal pheochromocytomas. However, surgical intervention does not always lead to long-term cure. Longterm monitoring is indicated in all patients, even those apparently cured.

In our case, a 5cm heterogeneous retroperitoneal mass occupied at right para-aortic region was found in CT scan. In the differential diagnosis of retroperitoneal mass lesions, pheochromocytoma should never been neglected. The diagnosis was made later because of fluctuating blood pressure. The laboratory data revealed high levels of catecholamines and VMA in 24hr-urine studies. Correlated with the finding of CT scan, a paraganglioma is the most likely diagnosis, which would be subsequently removed. The diagnostic cardiac catheterization revealed no significant CAD. LVG demonstrated preserved LV systolic function. Myocarditis related to pheochromocytoma was suspected, although it has not been proven by tissue biopsy. Paraganglioma was the most possible reason of sudden collapse. In fact, unusual presentation of pheochromocytoma as acute myocarditis or cardiogenic shock has ever been reported. Also, the pathophysiology of cardiomyopathy due to pheochromocytoma has been tried to be explained. Furthermore, pheochromocytoma may also cause hypertensive emergency which can lead to end organ damage, including myocardial infarction. Although most clinicians could recognize the classic symptoms, the clinical presentation of pheochromocytoma may mimic severe diseases. If fewer symptoms were presented, early diagnosis may be more difficult. Patients with unrecognized pheochromocytoma presenting with critical illness such as sepsis, shock, or acute myocardial infarction may have poor prognosis. For clinicians, pheochromocytoma or paraganglioma should always be kept in mind even though initial manifestations are not suggestive for the diagnosis.

references:

1. Shlomo Melmed, Kenneth S. Polonsky, Reed Larsen and Henry M. Kronenberg. Williams Textbook of Endocrinology, 12th Edition 2. Gaurav Agarwal, Dhalapathy Sadacharan, Aditya Kapoor, Aditya Batra, Preeti Dabadghao, Gyan Chand, Anjali Mishra, Amit Agarwal, Ashok K. Verma, and Saroj K. Mishra. Cardiovascular dysfunction and catecholamine cardiomyopathy in pheochromocytoma patients and their reversal following surgical cure: Results of a prospective case-control study. Surgery, Volume 150, Number 6, 2011 3. Xue-Ming Wu, Jien-Jiun Chen, Cho-Kai Wu, Lian-Yu Lin and Chuen-Den Tseng. Pheochromocytoma Presenting as Acute Myocarditis with Cardiogenic Shock in Two CasesInter. Med 47: 2151-2155, 2008 4. P.Kounatiadis, V.Kolettas, A.Megarisiotou, I.Stiliadis. Cardiomyopathy due to pheochromocytoma. Herz 2013, DOI 10.1007/s00059-013-3951-7 5. Soo Kyung Cho, Kye Hun Kim, Jae Yeong Cho, Hyun Ju Yoon, Hyung Wook Park, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Myung Ho Jeong, Jeong Gwan Cho, and Jong Chun Park. Pheochromocytoma as a Rare Hidden Cause of Inverted Stress Cardiomyopathy. J Cardiovasc Ultrasound 2014;22(2):80-83 6. Graham J. Fent*, Hazlyna Kamaruddin, Pankaj Garg, Ahmed Iqbal, Nicholas F. Kelland and Ian R. Hall. Hypertensive Emergency and Type 2 Myocardial Infarction Resulting From Pheochromocytoma and Concurrent Capnocytophaga Canimorsus Infection. The Open Cardiovascular Medicine Journal, 2014, 8, 43-47

PE-16

A CASE REPORT – PAPILLARY THYROID CANCER POST THYROIDECTOMY FOLLOWED BY LYMPHADENOPATHY CAUSED BY CASTLEMAN’S DISEASE

1YI-Hong Zeng, 2SHIH-PING JHENG, 3DAO-YUAN WANG, 1CHUN-CHUAN LEE

1Division of Endocrinology and Metabolism, department of internal medicine, Mackay Memorial Hospital, Taiwan, ROC.; 2Department of General Surgery, Mackay Memorial Hospital, Taiwan, ROC.; 3Department of Pathology, Mackay Memorial Hospital, Taiwan, ROC.

Introduction: Neck nodular lesion may origin from several structures. The raise of concern of malignancy would be noticed, particularly in the patient with history of head and neck cancer. We reported a case who had papillary thyroid cancer (PTC) and she had accepted total thyroidectomy. During follow up, neck nodular lesion was noted, and we performed a series of examination and considered it as PTC recurrence. However, pathology revealed Castleman’s disease (CD).

Case Presentation: The 55 year-old woman had papillary thyroid cancer and she accepted radical thyroidectomy with unilateral neck lymph node dissection on 8th Aug, 2011 (pT3N0M0, stage 3). She also received radioiodine therapy (120mCi). Then she visited out-patient department of general surgery regularly and took Thyroxine. There was no thyroid remnant in sonography and Thyglobulin level was undectable. However, abnormal lymphnode was noted at left level IV (1.16cm*1.46cm) in April, 2013 (Figure 1). The result of fine needle aspiration revealed negative for malignant cells. Although I-131 whole body scan (Figure 2) reported no definite evidence of abnormal uptake in the thyroid bed, we arranged positron emission tomography (PET, Figure 3) because stimulated Tg is 3.93ng/ml (Table 1). However, it revealed the possibility of lymph nodes metastases in the bilateral submandibular, bilateral upper jugular, bilateral lower cervical, left lower posterior cervical, left supraclavicular regions. Thus, radical neck dissection was done on 21th Oct, 2013 and the operation finding is multiple enlarged lymph node along left level III to V. Several lymph nodes are dissected and the largest one measures 2.7*1.5*0.5cm in size. Sections show enlarged lymph nodes expanded by lymphoid follicles, showing germinal centers progressive transformation and hyalined vessels within follicles. Thin mantles surrounding the follicles are seen. CD21, Bcl-2 & Ki-67 stains support the diagnosis of Castlenan’s disease (Figure 4).

PE-17

FALSE-NEGATIVE 99MTC SESTAMIBI PARATHYROID SCAN IN PATIENT WITH PARATHYROID ADENOMA: A CASE REPORT

CHIH-Hung LIn

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan, R.O.C.

Purpose: 99mTc sestamibi parathyroid scan is currently the radionuclide study of choice for preoperative parathyroid localization. But several factors could contribute to a false-negative result. We reported a case of primary hyperparathyroidism with false-negative 99mTc sestamibi parathyroid scan result.

Method: A 66 y/o gentleman visited the out-patient clinic due to persisted malaise and back pain for months. Blood test revealed deteriorated renal function (BUN 44.2 mg/dL, creatinine 2.3 mg/dL) and hypercalcemia (corrected calcium 14.0 mg/dL). Urine protein electrophoresis was negative for light-chain proteins. Test for parathyroid function showed elevated i-PTH level (761 pg/mL). result: Thyroid ultrasonography revealed a hypo-echoic lesion at left thyroid bed, which favored parathyroid adenoma. Spine X-ray showed no dislocation or fracture. The result of bone mineral density (BMD) study indicated osteoporosis (hip T-score -2.57). There was no evidence of co-existent pituitary or pancreatic lesion. However, the result of 99mTc sestamibi parathyroid scan was negative. Hydration, calcitonin and pamidronate were used to control persisted hypercalcemia, with limited response.

Conclusion: After general surgeon consultation, left parathyroidectomy was performed. The pathology diagnosis was consistent with parathyroid adenoma. His symptoms relieved after the operation. Follow-up data showed decrement in i-PTH level (181 pg/mL), improvement of renal function (BUN 36.0 mg/dL, creatinine 1.8 mg/dL) and hypercalcemia (corrected calcium 8.8 mg/dL).

PE-18

SYNCHRONOUS PAPILLARY THYROID CARCINOMA AND SECONDARY HYPERPARATHYROIDISM: CASE REPORT

1HsIao-LIen CHen, 2MING-YU LAI

1Division of Endocrinology and Metabolism, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal medicine, Lo Tung Poh Ai Hospital ,Taiwan, R.O.C.

objective: Papillary thyroid carcinoma (PTC) is known to occur in association with primary hyperparathyroidism (HPT). Although, in secondary hyperparathyroidism (HPT), isolated cases have been reported and are often detected by surgery. We report two cases of thyroid cancer diagnosed at the time of parathyroidectomy for secondary HPT in patients with end-stage renal disease (ESRD).

Case reports:

Patient I - A 64 years old woman, with no personal or family history of neck irradiation, thyroid cancer,was admitted for a surgical parathroidectomy because of medically uncontrolled HPT. The patient had developed ESRD secondary to diabetes , and had been established on hemodialysis for 146 months at the time of admission. Investigation showed elevated alkaline phosphatase 355 U/l (35–129), elevated PTH 2255 pg/ml(14–72), serum calcium 12.2 mg/dl (8.6–10.2), and phosphorus 7.8 mg/dl (2.7-4.5).Technetium 99m (Tc 99m) MIBI revealed persistent uptake in the upper and lower pole of right thyroid and lower pole of left thyroid.Thyroid ultrasonography revealed multiple nodule bilaterally.Right side nodule >1cm in diameter.The left lobe revealed 1.5cm nodule with calcification. Surgical total parathyroidectomy and left subtotal thyroidectomy. The final histologic analysis of the resected four parathyroid gland confirmed adenoma. The left thyroid gland had a focal follicular variant of PTC.

Patient II - A 57 years old man with a history of ESRD secondary to polycystic kidney disease and on long-term hemodialysis for 120 months. Three months prior to his admission,he had biochemical evidence of HPT.Laboratory investigation demonstrated serum calcium 10.3mg/ dl (8.6–10.2), hyperphosphatemia 5.6 mg/dl (2.7-4.5), with a peak PTH level of 1440 pg/ml(14–72). Technetium 99m (Tc 99m) MIBI revealed persistent uptake in the upper pole of right thyroid. Thyroid ultrasonography revealed multiple nodule bilaterally.Right side nodule > 1cm in diameter.The left lobe two nodule > 2 cm in diameter. FNAB was performed from left side larger nodule and the cytology was benign. Surgical parathyroidectomy and left total thyroidectomy.The histological report diagnosed hyperplasia of the parathyroid glands of right and left upper parathyroid gland.The left thyroid had a focal follicular variant of papillary carcinoma (diameter 0.3 X 0.3X0.2cm) and nodule (2.5X 2.3X 2.0cm) revealed follicular adenoma with suspect capsule invasion.Regional lymph nodes were not affected.

Conclusions: We suggest that the association of simultaneous pathology of the thyroid and parathyroid glands should be considered in uremic patients with secondary HPT.

PE-19

EXOME SEQUENCING OF A CASE WITH MIXED ADRENAL CORTICOMEDULLARY ADENOMA

1LI Lun CHuang, 2DAU YANG HWANG, 3SHAN-YIN TSAI, 1WEI-WEN HUNG, 1KUN-DER LIN, 1,4SHYI-JANG SHIN, 1,4PI-JUNG HSIAO

1Division of Endocrinology and Metabolism, 2Department of Nephrology, 3Department of Pathology, Kaohsiung Medical University Hospital; 4School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Mixed corticomedullary tumor is a single adrenal tumor containing both cortical and medullary cells intermixed throughout the entire neoplasm. It is extremely rare to be regarded as a new disease entity. Genetic mutation for the tumor formation is still unclear.

We ever reported a 32-year-old female patient who has diagnosed with a huge mixed corticomedullary adenoma. She was clinically manifested with typical Cushing’s syndrome and pheochromocytoma diagnosed by biochemical and immunohistochemical evidences. For further evaluation of the possible gene mutation, the genomic DNA was extracted from blood and tumor together. High throughput next generation sequencing was performed by Illumina HiSeq system. Exome sequencings were performed on patient’s blood and adrenal tumor. Blood DNA was sequenced of more than 96 million reads with depth of 10-fold coverage of 96.8% and 30-fold coverage of 92.4%. Formalin fixed paraffin embedded tumor DNA was sequenced of >58 million reads with 10fold coverage of 92% and 30-fold coverage of 73.1%. The variants filtering criteria included minor allele frequency less than 1% from the database of dbSNP 141 and nonsynonymous variants. More than 1400 rare or unreported variants in both blood and tumor samples. After comparing these 2 variants set, more than 100 variants were found in the tumor but not in the blood, and more than 200 variants were found in the blood but not in the tumor. None of these variants was found to be the same with the reported mutations for pheochromocytoma (RET, VHL, NF1, SDHB, SDHC, SDHD, SDHA, TMEM127, KIF1B, PHD2 and MAX) or adrenal Cushing syndrome (PRKAR1A, ARMC5, hGR, GNAS, ENDRA, KCNJ5, and PDE11A).

From our result, mixed corticomedullary adenoma of this case is really a diverse disease dissimilar to pheochromocytoma or adrenal Cushing syndrome. The true etiology may be secondary to an undiscovered mutation or existence of other mutations in the upper stream to stimulate growth of cortex or medulla cell origins of adrenal gland.

PE-20

ELECTRONEGATIVE LDL IMPAIRS KIDNEY THROUGH DAMAGE OF STRA6 SIGNALING

1ZHao-Hong CHen, 2LIANG-YIN KE, 2HUA-CHEN CHAN, 2CHU-HUANG CHEN, 2,3,4SHYI-JANG SHIN

1Graduate Institute of Medicine, 2Center of Lipid and Glycomedicine Research, 3School of Medicine, College of Medicine, Kaohsiung Medical University; 4Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan, R.O.C.

background: Cardiovascular, cerebrovascular and kidney diseases have been remaining as the leading cause of death in Taiwan. Diabetes and dyslipidemia is the most important risks of these diseases. Increased serum retinol-binding protein 4 (RBP4) levels have been shown in subjects with diabetes, dyslipidemia, obesity, cardiovascular, cerebrovascular and chronic kidney disease (CKD). A multi-transmembrane receptor, called as “stimulated by retinoic acid 6 (STRA6)”, was identified as a specific membrane receptor for RBP4. We also found that free RBP4 can cause apoptosis through the reduction of RBP4 binding activity with STRA6 (stimulated by retinoic acid 6) and in turn through JAK2/STAT5/JNK/p38MAPK pathway in renal cells. Therefore, we reasonably hypothesized electronegative LDL (L5) might cause kidney injury via damages of STRA6 signaling.

Method: The expression of STRA6, CRBP1, RAR, caspase 3, and collagen 1 were measured by western blot analysis in kidney of L5-injectied mice and human renal tubular epithelial cells. Immunofluorescent and immunochemical stain method were also done to detect STRA6 expression in kidney of L5-injectied mice and L5-stimulated human renal tubular epithelial cells. LOX1 knockout mice and LOX1 siRNA transfection were performed to investigate whether the reversal of CRBP 1 and RAR can reverse apoptosis and fibrosis in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. result: The expression of caspase 3 and collagen 1 are remarkably increased, whileas STRA6, CRBP1 and RAR expression are reduced in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. Immunofluorescent and immunochemical stain method experiments also showed an decreased expression of STRA6 in L5-injectied mice and L5-stimulated human renal tubular epithelial cells. However, LOX1 siRNA or LOX1 gene knockout reverse above changes induced by L5.

Conclusion: L5 can cause kidney damage via damage of STRA6/CRBP1/RAR signaling and finally enhancing apoptosis and fibrosis in vivo and vitro. These results indicate that L5-impaired STRA6/CRBP1/RAR signaling is one novel molecular mechanism of diabetic nephropathy with dyslipidemia.

PE-21

CHYLOTHORAX AS A RARE PRESENTATION IN GRAVES’ DISEASE

1Lee I-sHuan, 1,2LEE TING-WEI, 1CHANG CHUN-JEN, 1LEE TING-I, 1FAN CHI, 1CHIEN YU-MEI, 1CHOU CHUAN-LIANG, 1LIU HAN-WEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Medical University- Wan Fang Hospital; 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University

Cardiovascular diseases, such as arrhythmia and heart failure are common complications in patients with poorly controlled hyperthyroidism. Here, we reported a patient presented with chylothorax, which is a rare manifestation of Graves’ disease. A 37-year-old woman was admitted because of abdominal fullness, legs swelling, and shortness of breath. The patient was diagnosed to have Graves’ disease about 9 years prior to this admission. However, she took 9 months of antithyroid drugs and lost follow-up afterward. Laboratory studies revealed severe thyrotoxicosis (TSH 0.007 uIU/ml, free-T4 > 7.77 ng/dl) associated with decompensated heart failure. After proper treatment, the patient got much improvement. However, on the fifth hospital day, the patient had fever and dyspnea. Chest X-ray showed acute onset of left pleural effusion. Pleural effusion analysis revealed transudative pleural effusion with high triglyceride levels in contents, the findings were consistent with chylothorax. Lymphoscintigraphy showed no evidence of thoracic duct leakage. But chest and abdomen CT scan demonstrated enlarged bilateral supraclavicular, axillary, mediastinal, and paraaortic lymph nodes. The patient underwent excisional biopsy for axillary lymphadenopathy and the pathological examination reported lymphoid hyperplasia. Survey for other common causes of chylothorax showed negative findings. Treatments for heart failure and hyperthyroidism led to a remarkable improvement in the clinical condition including a recovery of heart function and disappearance of chylothorax. From the literature review, there were only three patients with congestive heart failure and chylothorax that resulted from hyperthyroidism. Therefore, thyrotoxicosis should be included in the differential diagnosis in patients with unclear etiology of chylothorax.

PE-22

ACUTE DECOMPENSATION OF METHYLMALONIC ACIDEMIA IN AN ADULT PATIENT-A CASE REPORT

1.2PIn-Fan CHen,

1BING-RU GAO, 1.2WEI-CHENG LIAN, 1SHIH-TANG YAN, 1TING-CHANG CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

objective: Methylmalonic academia (MMA) is a rare chromosome recessive inborn error with prevalence of 1 in 100,000 in Taiwan. Patients with MMA rarely grew up to be adults except having residual enzyme activity or cobalamin-responsive type. Toxic metabolites could cause neurological disorders, progressive renal and liver failure. Restricted high-protein diet with sufficient energy intake is the main treatment concept of MMA.

Case report: we reported an adult case of MMA, presented with foods refusal, vomiting and confused consciousness after she had unrestricted high protein diet for days in Dec. 2012. At ER, metabolic acidosis, acute kidney injury and hyperammonemia were found. Intravenous 10% Dextrose fluid at 150% maintenance, intralipid 2gm/kg/day, and high dose of Vitamin B12 were adopted. The general condition and associated aberrant metabolic markers improved gradually. After suffering this episode, oral carnitine and high dose Vit. B12 keep using. There is not any acute metabolic decompensation till now. However, chronic renal disease and hyperuricemia persist.

Conclusion: In patients with acute decompensation of methylmalonic academia, treatment of high dose of Vit. B12, carnitine, glucose and fat supplement with zero tolerance on protein consumption are essential. Key factors to determine acute decompensation are vomiting, high ammonia level and changes of acid-base homeostasis.

PD-01

PATIENT-REPORTED OUTCOMES FROM A 104-WEEK, PHASE 3, RANDOMISED, PLACEBO-CONTROLLED STUDY COMPARING ONCE-WEEKLY DULAGLUTIDE TO SITAGLIPTIN AND PLACEBO IN METFORMIN-TREATED PATIENTS WITH TYPE 2 DIABETES; THE ASSESSMENT OF WEEKLY ADMINISTRATION OF DULAGLUTIDE IN DIABETES (AWARD-5) TRIAL

1THoMas Lew, 2M REANEY, 3M YU, 4O ADETUNJI, 5Z MILICEVIC

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, UK; 3Eli Lilly and Company, Toronto, Canada; 4Eli Lilly and Company, Basingstoke, UK; 5Eli Lilly and Company, Vienna, Austria

objective: To evaluate patient-reported outcome (PRO) data from the AWARD-5 trial.

Materials and Methods: 1098 patients (mean age 54.1 years; HbA1c 8.1%; weight 86.4 kg; diabetes duration 7.1 years) were randomised to once-weekly dulaglutide 1.5 mg or 0.75 mg, sitagliptin 100 mg once daily, or placebo only (switched to sitagliptin after 26 weeks) in a 2:2:2:1 ratio. 831 (75.7%) completed the 12-month visit. PRO measures for Impact of Weight QoL-Lite (IWQoL-Lite) and EQ-5D were administered at baseline, 26, 52, 78 (only IWQoL-Lite), and 104 weeks (analysis LOCF ANCOVA). results: Both dulaglutide doses showed a greater decrease (p<.001) vs sitagliptin in HbA1c at 52 and 104 weeks; dulaglutide 1.5 mg showed a greater decrease (p<.001) vs sitagliptin in body weight. Significant (p<.05) improvements from baseline were observed in EQ-5D visual analog scale (VAS) scores at 26 weeks (dulaglutide 1.5 mg, sitagliptin), 52 weeks (dulaglutide 1.5 mg), and 104 weeks (dulaglutide 1.5 mg, 0.75 mg, sitagliptin). EQ-5D UK population index scores did not significantly change from baseline (all groups). Significant improvements from baseline were observed in all groups in IWQoL-Lite total score as well as physical functioning and self-esteem domain scores (52, 78, 104 weeks). The improvement in total score was significantly larger with dulaglutide vs sitagliptin at 78 (dulaglutide 1.5 mg, dulaglutide 0.75 mg) and 104 (dulaglutide 1.5 mg) weeks. Some other domain scores also significantly improved with dulaglutide and sitagliptin postbaseline.

Conclusion: Dulaglutide and sitagliptin showed improvements from baseline in EQ-5D VAS scores and IWQoL-Lite total scores. Improvement in IWQoL-Lite total scores (as well as work and physical functioning domain scores) was greater with dulaglutide vs sitagliptin.

PD-02

PATIENT-REPORTED OUTCOMES WITH ONCE-WEEKLY DULAGLUTIDE VERSUS INSULIN GLARGINE (AWARD-2)

1THoMas Lew, 2M REANEY, 3M YU, 2BRUNT K VAN BRUNT, 4V PETCHNER, 5CP HAYES

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Eli Lilly and Company, Windlesham, UK; 3Eli Lilly and Company, Toronto, Canada; 4Eli Lilly and Company, Paris, France; 5Eli Lilly and Company, Indianapolis, IN, USA

objective / Materials and Methods: This 78-week, Phase 3, open-label, randomized study compared the once-weekly GLP-1 receptor agonist dulaglutide 1.5 mg and dulaglutide 0.75 mg to glargine titrated-to-target in patients with type 2 diabetes on stable and maximal doses of metformin and glimepiride. results: Dulaglutide 1.5 mg was superior in HbA1C (p<.001) and dulaglutide 0.75 mg was noninferior vs glargine at 52 weeks and 78 weeks. Dulaglutide was associated with weight loss, whereas glargine was associated with weight gain (p<.001); there was less hypoglycemia but more nausea with dulaglutide vs glargine (p<.05). Patient-reported outcome (PRO) instruments were administered at baseline and at 52 and 78 weeks; analysis of covariance models with country, baseline score, and treatment factors were used. At 52 and 78 weeks, significant (p<.05) improvements from baseline were demonstrated in both dulaglutide doses for EQ-5D visual analog scale (VAS) and low blood sugar survey (LBSS) behavior and worry measures and in dulaglutide 1.5 mg for ability to perform physical activities (APPADL) and impact of weight on self-perception (IW-SP). EQ-5D UK index scores decreased from baseline with glargine at 52 weeks (p<.05). Significant differences were observed between dulaglutide 1.5 mg and glargine for LBSS behavior and worry measures and APPADL at 52 and 78 weeks.

Conclusion: Patients with type 2 diabetes, who added once-weekly dulaglutide injectable therapy to 2 oral antihyperglycemic medications, achieved glycemic benefit and, in comparison to glargine, greater improvement in some PROs.

PD-03

INSULIN LISPRO LOW MIXTURE TWICE DAILY VERSUS BASAL INSULIN GLARGINE AND PRANDIAL INSULIN LISPRO ONCE DAILY IN EAST ASIAN AND CAUCASIAN TYPE 2 DIABETES MELLITUS PATIENTS

1THoMas Lew, 2JH HAN, 3D EDRALIN, 4R DUAN, 5A RODRIGUEZ

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Lilly Korea Ltd, Seoul, Korea; 3Eli Lilly, Pasig City, Philippines; 4Eli Lilly and Company, Indianapolis, IN, USA; 5Lilly Spain, Alcobendas, Spain

objective: This post-hoc analysis described efficacy and safety of insulin lispro low mixture (LM) twice daily versus bedtime insulin glargine plus prandial insulin lispro administered once daily before the largest meal (IGL) in East Asian (EA) and Caucasian type 2 diabetes mellitus patients who previously failed to reach glycemic targets on basal insulin glargine with metformin and/or pioglitazone.

Materials and Methods: This Phase 4, randomized, open-label, multinational, multicenter trial included patients with glycosylated hemoglobin (HbA1c) between ≥7.5% and ≤10.5%, and fasting plasma glucose ≤6.7 mmol/L. results: Baseline mean (standard deviation [SD]) HbA1c values were numerically similar between groups in EA (N=79) and Caucasian (N=278) patients (EA: LM=8.78% [0.71] vs IGL=8.72% [0.90]; Caucasian: LM=8.56% [0.78] vs IGL=8.51% [0.70]). Mean (SD) HbA1csignificantly (p<.001) decreased from baseline to 24 weeks for both treatments in both subpopulations (EA: LM=1.32% [0.96] and IGL=-0.89% [0.98]; Caucasian: LM=-1.24% [0.98] and IGL=-1.05% [0.97]). The proportion reaching HbA1c≤7% at Week 24 was LM=33.3% and IGL=22.9% for EA patients, and LM=37.2% and IGL=34.1% for Caucasian patients. Mean (SD) rate of hypoglycemia per 30 days was LM=0.74 (1.16) and IGL=1.22 (1.36) in EA patients, and LM=1.38 (2.04) and IGL=1.65 (2.43) in Caucasian patients. Mean (SD) change in weight gain was LM=0.62 kg (2.78) and IGL=0.51 kg (2.63) in EA patients, and LM=1.77 kg (2.91) and IGL=0.67 kg (3.09) in Caucasian patients.

Conclusion: Improved glycemic control was observed in EA and Caucasian patients treated with either LM or IGL.

PD-04

SIMILAR EFFICACY AND SAFETY WITH LY2963016 INSULIN GLARGINE COMPARED WITH LANTUSR INSULIN GLARGINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS (T2DM): THE ELEMENT 2 STUDY

1JoYCe YeH, 2JULIO ROSENSTOCK, 3PRISCILLA HOLLANDER, 4ANJU BHARGAVA, 5LIZA ILAG, 5ROBIN K. POLLOM, 5WILLIAM J HUSTER, 5MELVIN PRINCE

1Presenting on behalf of Eli Lilly and Company, Indianapolis, IN, USA; 2Dallas Diabetes and Endocrine Center, Dallas, TX, USA; 3Baylor Endocrine Center, Dallas, TX, USA; 4Iowa Diabetes and Endocrinology Center, Des Moines, IA, USA; 5Eli Lilly and Company, Indianapolis, IN, USA

objective: Even though LY2963016 (LY IGlar) and Lantus® (IGlar) are both insulin glargine products, with identical amino acid sequences, they are manufactured by distinct processes and must be shown to be clinically similar.

Materials and Methods: A 24-week, Phase 3, randomized, double-blind, parallel study was performed to compare the efficacy and safety of LY IGlar and IGlar in 756 patients with T2DM on ≥2 oral antihyperglycemic medications (OAMs) who were insulin naïve (n=455, HbA1c ≥7.0% to ≤11.0%) or previously on IGlar (HbA1c ≤11.0%). The primary objective was to test the noninferiority (0.3% margin) of LY IGlar to IGlar as measured by change in HbA1c from baseline to 24 weeks. results: Both treatment groups had within-group similarly significant (p<.001) decreases in mean HbA1c values (approx. -1.3%; endpoint HbA1c LY IGlar 7.04%, IGlar 6.99%; least-squares mean difference [95% confidence interval] 0.052 [-0.070, 0.175]). The change in HbA1c from baseline with LY IGlar was noninferior to IGlar. Noninferiority of IGlar to LY IGlar was also demonstrated; thus, the criteria for equivalence in clinical efficacy between LY IGlar and IGlar were met. There were no treatment differences in secondary efficacy or safety outcomes including hypoglycemia (21.3 versus 22.3 events/patient/year for LY IGlar and IGlar, respectively). Adverse event frequencies (LY IGlar 52%, IGlar 48%) were similar. The mean insulin dose at endpoint was 0.50 and 0.48 U/kg/day for LY IGlar and IGlar, respectively.

Conclusion: LY IGlar compared with IGlar, used in combination with OAMs, provided equivalent efficacy and a similar safety profile in patients with T2DM.

PD-05

PredICTIon oF gLuCose eFFeCTIveness wITH rouTIne MeasureMenTs In CHInese

1dee PeI, 2CHUN-TIEN LIN, 3YEN-LIN CHEN

1Department of Internal Medicine, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan, ROC; 2Division of Endocrinology, Department of Internal Medicine,Shuang Ho Hospital, School of Medicine, Taipei Medical University, Taipei, Taiwan, ROC; 3Division of Pathology, Cardinal Tien Hospital, Medical School, Fu Jen Catholic University, New Taipei City, Taiwan, ROC

aims: Glucose effectiveness (GE) is the capacity of glucose itself to increase glucose uptake and to inhibit endogenous hepatic glucose output under basal insulin level. Other than decreased insulin sensitivity (IS) and impaired insulin secretion, it also plays an important role on glucose balance in type 2 diabetes. In the study, we aimed to develop an equation for predicting GE.

Methods: We enrolled 227 participants, from normal glucose tolerance to diabetes, in our study. Seventy five percent (171 subjects) were randomly assigned to the study group, whose data would be used to build the equation for estimating the GE. The remaining 56 participants comprised the validation group. A frequently sampled intravenous glucose-tolerance test was performed for all participants, and the IS, GE, and the acute insulin response after the glucose load were determined. results: Age, triglyceride (TG) and fasting plasma glucose (FPG) were independently related to GE and thus were selected from multiple linear regression analysis. The following equation was made and we constructed the equation GE=(29.196-0.103×age-2.722×TG-0.592×FPG)×10-3. Using this same equation, GE was also calculated in the validation group. This calculated GE was significantly correlated with the measured GE (r=0.430, P=0.001).

Conclusions: By using the equation based on the routine measurements, the GE could be predicted with acceptable accuracy(r=0.430).This method of predicting GE may help further clinicians’ understanding of the underlying pathological mechanisms in T2DM.

PD-06

NOT ALL COMBINATION THERAPY OF METFORMIN AND STATINS CAN DECREASE HEPATOCELLULAR CARCINOMA IN DIABETIC PATIENTS IN TAIWAN

HsIn-Hung CHen

Institute of Public health and Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Metabolism & Endocrinology, Changhua Christian Hospital, Changhua, Taiwan;Nantou Christian Hospital

objective: Based on previous studies, metformin or statins can decrease hepatocellular carcinoma (HCC) in diabetic patients. Our aim is to evaluate whether combination therapy can further reduce HCC in diabetic patients in Taiwan. research design and Methods: For this nested-case control study, we collected the Longitudinal Health Insurance Database 2000 (LHID2000), established by the Taiwan Bureau of National Health Insurance .Patients with newly diagnosed type 2 diabetes mellitus (DM), excluding those with histories of HCC prior to the date of DM diagnosis, were recruited to form a DM cohort. Diabetic patients developed HCC as case group and the date for HCC diagnosis as index date. results: In general ,patients treated with statins showed a significantly decreased risk of HCC (OR=0.37; 95% CI=0.27–0.49) instead of patients treated with metformin(OR=0.84; 95%CI=0.651.08). Based on metformin use, patients treated with simvastatin, atorvastatin, and rosuvastatin showed significantly decreased risks of HCC (OR=0.35, 0.41, and 0.24; 95% CI=0.18–0.68, 0.24–0.71, and 0.08–0.74) instead of pravastatin ,fluvastatin and lovastatin. Interestingly, the comorbidities for patients with HCC were decreased in metformin combined with the two statins simvastatin and atorvastatin (OR=0.29 and 0.37; 95% CI= 0.11-0.76, and 0.16-0.85).

Conclusion: Not all combination therapy of metformin and Statins can decrease the incidence of HCC in diabetic patients in Taiwan.

Keywords: metformin; statins; hepatocellular carcinoma (HCC).

PD-07

THE ASSOCIATION OF HEMATOGRAM WITH METABOLIC SYNDROME IN THE YOUNG-OLD, OLD-OLD AND OLDEST-OLD POPULATIONS

1,2Tsung-Ju CHuang, 1YI-JEN HUNG, 3DEE PEI, 4YEN-LIN CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2Department of Internal Medicine, Armed Forces Taichung General Hospital, Taichung, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Cardinal Tien Hospital, Taipei, Taiwan; 4 Department of Pathology, Cardinal Tien Hospital, Taipei, Taiwan

objectives: The prevalence of metabolic syndrome (MetS) increases with age and is associated with future occurrence of cardiovascular diseases (CVD) and diabetes. Previous studies found that abnormal hematogram components could predict future MetS. However, there was no study focused on different ages groups in the elderly, i.e. the young-old (YO), old-old (OO) and oldest-old (ODO) subjects. In this ten-year longitudinal study, we investigated the association between hematogram components and future MetS and diabetes in the aforementioned three aged groups.

Methods: Subjects above 65 years were enrolled and divided into three groups by age ( youngold, 65-74; old-old, 75-84; oldest-old ≥85 years-old) of both sexes. All subjects were followed up until they developed MetS or until up to 10 years from the day of entry, whichever was earlier. By using multiple logestic regression, the hazard ratio (HR) of higher hemoglobin (Hb), white blood cell count (WBCC) and platelet (Plt) to have future MetS, diabetes and CVD were evaluated. results: There were 7648 males and 7521 females in the YO group, 1963, 1573 in the OO group and 121, 81 in the ODO groups respectively. The prevalence of having MetS were 33.9%, 35.1%, 31.4%for males and 46.7%, 54.3%, and 62.9%for females at baseline. After 10 years follow-up,only higher WBCC and Hb levels (>5.0×103, 15 g/dL, respectively) was correlated to future MetS in YO males (HR: 1.612, 1.443, respectively). In female, only higher Hb (>13.7 g/dL) was associated with future MetS in YO and OO groups (HR:1.335 and 3.690, respectively). Finally, higher chances of diabetes could be noted with higher WBC in both males and females (HR: 1.589, 1.582, respectively) and higher Hb in females (HR: 2.273).

Conclusion: In this large longitudinal study, focusing on the elderly, we have shown that predicting future MetS and diabetes in elderly by hematogram components is valuable only in youngold groups of both genders and old-old female.

PD-08

SODIUM GLUCOSE COTRANSPORTER 2 (SGLT2) INHIBITION WITH EMPAGLIFLOZIN REDUCES MICROALBUMINURIA IN PATIENTS WITH TYPE 2 DIABETES

1davId CHerneY,

2MAXIMILIAN EYNATTEN, 3SØREN LUND, 3STEFAN KASPERS, 3SUSANNE CROWE, 3HANS WOERLE, 3THOMAS HACH

1Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; 2Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 3Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

objective: We examined the effect of 24 weeks’ treatment with empagliflozin on urine albumin to creatinine ratio (UACR) by pooling data from patients with T2DM and microalbuminuria (UACR 30–300 mg/g) who participated in four Phase III randomized placebocontrolled trials.

Methods:

Study population and design • Data were pooled from four Phase III trials in which 2477 patients with T2DM were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks as monotherapy, add-on to metformin, add-on to metformin plus sulfonylurea, or add-on to pioglitazone ± metformin.3-6 Patients who completed 24 weeks’ doubleblind treatment in the initial study could elect to continue their treatmentin a 52-week extension study. • 458 (18%) of the patients treated in these four trials (157 on placebo, 146 on empagliflozin 10 mg, and 155 on empagliflozin 25 mg) had microalbuminuria (UACR 30–300 mg/g) at baseline. • UACR was calculated from spot urine samples at study visits.

Endpoints • Changes from baseline in HbA1c and systolic blood pressure (SBP) at week 24. • Percentage change in geometric mean (gMean) UACR from baseline to week 24. • The ratio of relative change from baseline in UACR over time. • Safety was assessed via reporting of adverse events (AEs) in the initial and extension studies (≥76 weeks).

Analyses • Changes in HbA1c, SBP and UACR at week 24 were analyzed using analysis of covariance (ANCOVA). For HbA1c analyses, data following initiation of anti-diabetes rescue therapy were set to missing. For SBP and UACR analyses, data following a change in type or dose of antihypertensive medication were also set to missing (changes in dose were only captured in one trial). Missing data were imputed using the last observation carried forward (LOCF) approach.

results:

At week 24, empagliflozin 10 mg and 25 mg reduced UACR by 30% and 25%, respectively, compared with placebo (p<0.01) in patients with microalbuminuria at baseline.

Change in UACR in all patients

In the overall pooled population (n=2349; gMean [gCV] baseline UACR of 12.9 [217.1], 12.7 [215.2] and 13.6 [231.2] mg/g for the empagliflozin 10 mg, 25 mg and placebo groups, respectively), including patients with microalbuminuria, macroalbuminuria (UACR >300 mg/g) and normoalbuminuria (UACR <30 mg/g), the percentage change in gMean UACR compared with placebo was -10% (95% CI -3, -16%; p=0.009) with empagliflozin 10 mg and -10% (95% CI -3, -17%; p=0.005) with empagliflozin 25 mg at week 24.

Safety

Adverse events over ≥76 weeks in patients with microalbuminuria at baseline

Conclusions:

• Empagliflozin 10 mg and 25 mg reduced microalbuminuria when added to standard therapy in patients with T2DM. • Empagliflozin 10 mg and 25 mg significantly reduced HbA1c and SBP in patients with T2DM and microalbuminuria. • Empagliflozin was well tolerated in patients with T2DM and microalbuminuria. • Reduced albuminuria may be related to reduced intraglomerular pressure, as indicated by a reduction in renal hyperfiltration with empagliflozin in patients with T1DM. • Prospective studies are needed to examine the potential renal protective effects of empagliflozin in patients with T1DM and T2DM. • An ongoing cardiovascular outcome trial (EMPA-REG OUTCOME™; NCT01131676) is investigating the effect of empagliflozin in patients with T2DM and high cardiovascular risk.

PD-09

EFFECT OF EMPAGLIFLOZIN COMPARED WITH GLIMEPIRIDE AS ADD-ON TO METFORMIN FOR 2 YEARS ON THE AMOUNT AND DISTRIBUTION OF BODY FAT IN PATIENTS WITH TYPE 2 DIABETES

1gabrIeL KIM, 2MARTIN RIDDERSTRÅLE, 3KNUT ANDERSEN, 4CORDULA ZELLER, 1HANS WOERLE, 1ULI BROEDL

1Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 2Steno Diabetes Center, Gentofte, Denmark; 3Boehringer Ingelheim Norway KS, Asker, Norway; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany

background and aims: In a randomized, double-blind, Phase III trial in patients with type 2 diabetes (T2DM), the SGLT2 inhibitor empagliflozin (EMPA) 25 mg qd as add-on to metformin for 104 weeks led to significant and sustained reductions in body weight compared with an increase in body weight with glimepiride (GLIM). Patients had the option to participate in a dedicated body composition sub-study in which we aimed to determine the effects of EMPA vs GLIM on the amount and distribution of body fat.

Materials and methods: Body composition was evaluated in 91 randomised patients in the sub-study. Using whole body dual energy X-ray absorptiometry (DXA), changes from baseline to week 52 and week 104 in trunk fat, limb fat, total fat mass and fat-free mass were assessed in 62 patients (36 receiving EMPA and 26 receiving GLIM). Using magnetic resonance imaging (MRI), changes from baseline to week 52 and week 104 in abdominal visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) were assessed in 51 patients (29 receiving EMPA and 22 receiving GLIM). Changes from baseline were evaluated using mixed model repeated measures (MMRM) analyses. results: In the 91 patients evaluated in the sub-study, baseline mean [SD] age was 55.7 [10.4] years, weight was 85.1 [14.7] kg, BMI was 31.9 [4.9] kg/m2 and 60% had BMI ≥30 kg/m2. EMPA significantly reduced trunk fat, limb fat and total fat mass vs GLIM at week 52 and week 104. EMPA also significantly reduced fat-free mass vs GLIM at week 52 but not at week 104 (table). Adjusted mean (SE) changes from baseline in abdominal VAT at week 52 were -15.5 (5.2) cm2 with EMPA compared with +10.0 (6.1) cm2 with GLIM (p<0.01) and at week 104 were 16.0 (8.4) cm2 with EMPA compared with +17.7 (10.0) cm2 with GLIM (p<0.05). Adjusted mean (SE) changes from baseline in abdominal SAT at week 52 were 29.9 (7.3) cm2 with EMPA compared with +25.8 (8.6) cm2 with GLIM (p<0.001) and at week 104 were 32.5 (9.2) cm2 with EMPA compared with +34.4 (10.7) cm2 with GLIM (p<0.001).

Conclusion: When used as add-on to metformin, treatment with EMPA led to reductions in trunk fat, limb fat, abdominal VAT and SAT at week 52 and further reductions at week 104 compared with GLIM. Reductions in fat-free mass with EMPA vs GLIM were observed at week 52 but not at week 104.

PD-10

EFFECTS OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONIST LIRAGLUTIDE ON MONOCROTALINE-INDUCED PULMONARY ARTERIAL HYPERTENSION IN RATS

1, 3MeI-YueH Lee,

2KUN- PAO TSAI, 4JONG-HAU HSU, 4JIUNN-REN WU, 3KUN-DER LIN, 3PI-JUNG HSIAO, 3SHYI-JANG SHIN, 5JWU-LAI YEH

1Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, 2Department of Pathology; 3Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital; 4Department of Pediatrics; 5Department of Pharmacology, School of Medicine, Kaohsiung Medical University

objectives: Glucagon-like peptide-1 receptor (GLP-1R) agonists are used to treat type 2 diabetes, however, the effect of GLP-1R agonists on pulmonary arterial hypertension (PAH) is unknown. In this study, we investigated the pulmonary vasodilatory effects of liraglutide, a GLP-1 receptor agonist, on chronic monocrotaline (MCT) administration-induced PAH and pulmonary artery smooth muscle cells (PASMC) in rats.

Materials and Methods: Two doses of liraglutide (75 and 200 μg/kg) i.p. twice daily for 21 days were tested in two rat models of MCT-induced PAH: prevention and treatment groups. The hemodynamic and body weight changes, right heart hypertrophy, lung morphology, immunoreactivity of endothelial nitric oxide synthase (eNOS) in the pulmonary artery, endothelin-1 and cyclic guanosine monophosphate levels, eNOS, sGCα, PKG and ROCK2 protein expressions were measured in both lung tissue and PASMC. Cell migration and cell cycle by flow cytometry were also determined. results: Pulmonary arterial pressure induced by MCT was reduced in both liraglutide prevention and treatment groups, with a reduction in mean arterial blood pressure and body weight, but no significant effect on mean heart rate and glucose level. Right ventricle and pulmonary vascular wall hypertrophy caused by MCT was also shown to be effectively reduced by liraglutide. The protein expression of Rho kinase was over expressed in the MCT-induced saline treated group and PASMC treated alone with platelet derived growth factor (PDGF), but decreased in eNOS, sGC and PKG, and liraglutide could reverse these expressions. The immunoreactivity of eNOS was decreased in the MCTtreated saline group, and this was improved by liraglutide.

Conclusion: Liraglutide may have both preventive and treatment effects on MCT-induced PAH. The proposed mechanism of the inhibition of PAH by liraglutide may be due to activation of eNOS, sGCα and PKG in pulmonary arterial endothelium and inhibition of ROCK2 in PASMC.

PD-11

C-REACTIVE PROTEIN IS ASSOCIATED WITH INTRAOCULAR PRESSURE INDEPENDENTLY OF METABOLIC SYNDROME

I-Te Lee, WAYNE H-H SHEU, JUN -SING WANG, SHIH-YI LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Intraocular pressure (IOP) is associated with metabolic syndrome, a cluster of cardiovascular risk factors. Circulating levels of C-reactive protein (CRP) was reported, independent of metabolic syndrome, to be associated with cardiovascular disease. In the present study, we examined the effect of CRP on IOP in subjects with or without metabolic syndrome. A total of 1041 subjects underwent physical check-up in one of medical center in central Taiwan were enrolled. The levels of IOP was significantly higher in the subjects with metabolic syndrome than those without (14.1±3.0 vs. 13.4± 3.0 mmHg, P=0.002). The IOP were also significantly different among the subjects with different CRP tertiles. There was highest mean IOP in the subjects with metabolic syndrome and highest CRP tertile, while the lowest mean IOP in the subjects with lowest CRP tilter and without metabolic syndrome (P value for trend <0.001). In mulitivariate liner regression analysis, levels of CRP were independently associated with levels of IOP (95%CI between 0.080 and 1.297, P=0.027) even after adjustment for metabolic syndrome. In conclusion, systemic inflammation, reflected by serum CRP, might be associated with high IOP.

PD-12

EFFECT OF METFORMIN ON BONE LOSS IN OVARIECTOMIZED RATS FED WITH HIGH-FRUCTOSE DIET

1JIANN-LIANG LIN, 1YI-JIng sHeen, 2SHIH-YI LIN, 3TSUNG-HAN TENG, 4ZIHCYUN LIN, 4SHU-CHI CHIANG, 5SHIH-MING HUANG, 2WAYNE HUEY-HERNG SHEU, 4HUI-TING YANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Hospital, Ministry of Health and Welfare; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital; 3Department of Pathology, St. Martin De Porres Hospital; 4Department of Nutrition, China Medical University; 5Department of Pathology, Taichung Hospital, Ministry of Health and Welfare

aims: Osteoporosis is a silently progressive disease that confer a high burden of disease-related morbidity and mortality. Recent studies have reported bone loss in diabetic patients and the osteogenic potency of the anti-diabetic drug metformin in vitro. We aimed to investigate the role of metformin on bone mass in an ovariectomized (OVX) rats fed with high-fructose diet.

Methods: Female Wistar rats at 6 weeks of age were randomly assigned to six groups: (1) the sham, (2) OVX, (3) high-fructose diet, (4) OVX + high-fructose diet,(5) OVX + metformin (300 mg/ kg/day), and (6) OVX + high-fructose diet + metformin (300 mg/kg/day) groups. Thirteen weeks after either sham surgery or bilateral ovariectomy, the rats were sacrificed. We collected serum biochemical data, including the levels of bone metabolism markers, receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin, and pathologically examined resected cardiac and aortic specimens. Then, the femurs were harvested for micro-computed tomography. results: The rats in the high-fructose diet groups presented with higher body weight, fasting blood glucose, insulin homeostasis model assessment of insulin resistance, and triglyceride levels but lower estrogen levels. Bilateral ovariectomy increased the body weight, serum low-density lipoprotein level, and fasting blood glucose level. Obvious aortic atherosclerotic changes were observed in the high-fructose diet groups, with or without ovariectomy. We found that the use of metformin improved the metabolic abnormalities in the fructose-fed OVX group, including body weight, fasting blood glucose level, serum low-density lipoprotein level, and triglyceride level; furthermore, metformin decreased the RANKL level (from 138.9±74.0 to 116.2±42.2 pg/mL) and significantly improved the bone volume percentages (from 17.8%±2.5% to 31.2%±3.5%, p<0.001) and the trabecular bone number (from 1.7±0.3 to 2.5±0.6 1/mm). In addition, metformin had no obvious benefit for the bone markers or morphology of the OVX rats without feeding with high-fructose diet.

Conclusion: Our findings provide evidence that metformin has an inhibitory effect on bone loss in OVX rats fed with a high-fructose diet.

Keywords: Fructose, Metformin, Osteoporosis, Receptor activator of nuclear factor kappa-B ligand (RANKL)

PD-13

A SUCCESSFULLY TREATED CASE OF EXTREMELY HYPERGLYCEMIC CRISIS ACCOMPANIED WITH RHABDOMYOLYSIS, STAGHORN STONE AND ACUTE KIDNEY INJURY

CHIa-Luen Huang, I-REN HUNG, CHIENG-HSING LEE

Division of Metabolism and Endocrinology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

background: We reported a 37-year-old man who demonstrated extremely high level of serum glucose (3355 mg/dL) complicated with diabetic ketoacidosis and hyperosmolar hyperglycemic state after excessive consumption of sweetened beverage within one day. His blood sugar levels were gradually decreased by aggressive fluid resuscitation and insulin infusion. However, the laboratory evaluation revealed elevated levels of creatinine, creatinine kinase and myoglobin on day 2. Simultaneously, a huge renal stone was found on abdominal plain film. The diagnosis of rhabdomyolysis, staghorn stone and acute kidney injury were made based on these laboratory tests. Interesting, his creatinine kinase concentration continued to rise and persisted with high levels for one week even blood glucose, ketoacidosis and renal function were recovered. Finally, this case was successfully survived after aggressive treatments.

Conclusion: Rhabdomyolysis is an uncommon but underestimated complication of hyperglycemic crisis. Hence, physicians should be alerted to this under detected complication of hyperglycemic crisis which may lead to acute renal failure yet can be easily diagnosed by a readily available test—the creatinine kinase level.

PD-14

CORRELATION BETWEEN PERIODONTAL DISEASE AND CLINICAL FEATURES IN TYPE 2 DIABETIC PATIENTS

1JHIH-sYuan LIu, 1CHIEN-HSING LEE, 1KAI-YUEN HSU, 2YI-SHING SHIEH, 1CHANG-HSUN HSIEH, 1YI-JEN HUNG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.; 2Dental Department of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Introduction: Diabetes mellitus is currently considered as an established risk factor for periodontitis. In previous reports, the risk factors of periodontitis severity include poor glucose control, age and duration of disease in diabetic patients. In this study, we try to determine whether severity of periodontitis is associated with glycemic control, clinical features, biochemical variables or proinflammatory markers in our type 2 diabetic patients.

Methods: A total of sixty-six type 2 diabetic adults were recruited from outpatient department at the Tri-Service General Hospital. All of them were collected general plus biochemical data, markers of the blood glucose level and oral X-ray. results: Our data demonstrated no significant associations between glycemic control (fasting blood glucose and glycated hemoglobin) and marginal alveolar bone loss (crown to all tooth length ratio value). However, marginal alveolar bone loss revealed significantly positive correlation with age, high-sensitivity C-reactive protein (hsCRP) and missing teethes. The multiple logistic regression analysis also showed age, hsCRP and missing teethes were associated with marginal alveolar bone loss. Finally, the stepwise regression analysis indicated age and hsCRP were the major risk factors of the severity of marginal alveolar bone loss in our type 2 diabetic patients.

Conclusions: Our study revealed that age and systemic inflammatory condition might have more significant roles than glycemic control in variations of periodontitis in our type 2 diabetic patients.

Keywords: diabetes, periodontal disease, periodontitis,

PD-15

THE LEVELS OF GROWTH ARREST-SPECIFIC PROTEIN 6 (GAS6) ARE REDUCED IN PATIENTS WITH TYPE 2 DIABETIC UREMIA

1sHeng-CHIang su, 2YU-JUEI HSU, 1YI-JEN HUNG, 1CHIEN-HSING LEE

1Division of Endocrinology and Metabolism, 2 Division of Nephrology, Department of Internal Medicine, TriService General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.

objectives: We aimed to not only investigate levels of growth arrest-specific protein 6 (Gas6), but also verify its unique role in patients with type 2 diabetic uremia.

Methods: One hundred and nine adults were recruited including 23 subjects were type 2 diabetes with uremia and 56 patients were newly diagnosed type 2 diabetes without remarkable nephropathy as well as 30 adults with normal glucose tolerance without significant clinical co-morbidity served as control. Plasma Gas6 concentration and common anthropometric and biochemical variables were measured. results: Plasma Gas6 levels were significantly lower in patients with type 2 diabetes than control, regardless of status of nephropathy. A trend of declined levels of Gas6 among three groups were also observed. Moreover, the Gas6 levels significantly inversely correlated with plasma creatinine, BUN and uric acid in all subjects. In multivariate logistic regression analyses, higher plasma Gas6 concentrations were significantly associated with a decreased risk of type 2 diabetic uremia even after adjusting for age, sex and fasting glucose.

Conclusions: Our results suggest that plasma Gas6 levels are associated with type 2 diabetes and may play a potential role for developing diabetic nephropathy.

PD-16

THE LINK OF IN VIRTUAL SCREENING TO HEALTH INSURANCE DATABASE IN THE CHEMICAL GENETIC STUDY OF OBESITY

1CHIeH-Hua Lu, 2WU-CHIEN CHIEN, 3LI-JEN TSAI, 4PO-SHIUAN HSIEH

1Division of Endocrinology and Metabolism, Tri-service general hospital; 2School of Public Health, National Defense Medical Center; 3Ching Kuo Institute of Management and Health; 4Graduate Institute of Physiology, National Defense Medical Center

background: We are attempting to reduce obesity and the burden of obesity-associated comorbidities through drug discovery and to study the target mechanisms of drugs by virtual screening. We used forward chemical genetics by screening a chemical library to characterize abnormal fat accumulation by targeting specific proteins. We studied the library using a similar molecular approach to find possible targets of bioactive molecules. A connectivity map was created to link the signaling pathway and network using Pathway Studio and MetaCoreTM software to find potential targets for treatment. We selected Caenorhabditis elegans (C. elegans) and 3T3-L1 cells to screen in silico for active compounds and to find their targets. For detail regarding obesity-related comorbidities, we searched Taiwan’s national health insurance database to count its comorbidity types and their prevalence. Results: We found many active compounds which were similar with 15-lipoxygenase inhibitor, phospholipase A2 inhibitor, etc and compared the crosstalk of each target using Pathway Studio and MetaCore to find one important pathway, beta-transducin repeat containing (BTRC), which links with ubiquitin and glycogen synthase kinase-3beta (GSK3ß), and one unexplainable pathway, ephrin tyPE-A receptor 4 (EPHA4), which can involve fat accumulation. We found from the database that Taiwan has seen an increase in obesity and obesity-related comorbidities distributed across almost all fields of disease. Conclusions: This study represents a promising approach to study the target mechanisms of drugs by virtual screening and can link these mechanisms with obesity and its related comorbidities.

PD-17

PROLONG HYPOGLYCEMIA ASSOCIATED WITH LONG ACTING INSULIN ANALOGUE INJECTION— A CASE REPORT

weI-HsIn Hsu, I-MIN PAN

Department of Internal Medicine, Division of Endocrinology, Tainan Sin-Lau Hospital, Tainan, Taiwan, R.O.C.

The action duration of long acting insulin analogues can last their hypoglycemic effect as long as 24 hours after subcutaneous injection. We report a case of prolong hypoglycemia up to 80 hours associated with insulin detemir injection.

Case report: An 89-year-old woman with Type 2 DM, dementia, and bed sore was admitted under the impression of hypoglycemia, upper gastrointestinal bleeding, asthma, and hypothyroidism. She was just discharged with metformin and galvus, because she previously had experienced hypoglycemia with levemir subcutaneous injection. She has been taken augmentin, nexium, cortisone acetate, and eltroxin. As fingertip sugar showed 453 mg/dl at 9:30pm, 10 unit levemir was injected subcutaneously. One hour later (10:30 pm), an additional dose of levemir 30 units was injected at right thigh for another finger sugar result of 480 mg/dl. Follow-up blood glucose tests revealed 390 mg/dl at 11:30PM and 350mg/dl at 0:30AM on the next day. Unfortunately, an episode of hypoglycemia with blood glucose 60mg/dl and cold sweating was found at 6:00AM. After taking some milk and cubic sugar, blood glucose increased to100mg/dl. As the patient was still in confusion status at noon and blood sugar showed 50mg/dl, she was sent to emergency room where blood glucose revealed 41 mg/dl, insulin level 2820 mU/L and C-peptide level 1.3ng/ml. She was treated with a bolus dose of 50% glucose 40cc and continuous intravenous infusion of 10 % dextrose at a rate of 60cc per hour. In addition to close monitoring finger sugar and electrolytes, food intake of 1250 kcal/day through nasogastric tube was given. However, there are at least five episodes of hypoglycemia during 72-hour admission period. The long hypoglycemia duration with such a dose was rarely reported.

PD-18

ASSOCIATION BETWEEN PLASMA GROWTH ARREST-SPECIFIC PROTEIN 6 AND COMPONENTS OF METABOLIC SYNDROME

1Peng-FeI LI, 2FU-HUANG LIN, 1CHANG-HSUN HSIEH, 1YI-JEN HUANG, 1CHIENHSING LEE

1Division of Endocrinoy and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 2School of Public Health, National Defense Medical Center, Taipei, Taiwan

background: Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and its receptors of the TAM (Tyro-3, Axl, Mer) family may be involved in the pathogenesis of obesity, systemic inflammation and insulin resistance. Our aim was to investigate the link between Gas6 protein and metabolic syndrome (MetS) components.

Methods: In total, 205 adults (88 men and 117 women) were recruited in this study. Plasma Gas6 concentration, general and biochemical data were measured. They were divided into three groups according to plasma Gas6 concentration (lowest, Gas6(1); highest, Gas6(3)). The mean values of each MetS component for every group were compared in men and women separately. results: Plasma Gas6 levels were not different between gender groups. Gas6 concentrations were declined parallel with various MetS components in all group.(P=0.017 for trend). In group comparison, only the high-density lipoprotein-cholesterol (HDL-C) was found to be significantly higher in Gas6(3) in all and female groups. Other components were not different. Plasma Gas6 values were significantly positively correlated with HDL-C and negatively correlated with fasting glucose levels.

Conclusion: Our result first demonstrate positive correlation between Gas6 proteins values and HDL-C and reinforce the association with fasting glucose. The potential role of the Gas6/TAM system in the involvement of MetS deserves further attention.

Keywords: Growth arrest-specific protein 6, Metabolic syndrome, Gender

PD-19

COMPARSION OF BRACHIAL-ANKLE PULSE WAVE VELOCITY (BAPWV) IN POOR-GLYCEMIC CONTROL TYPE 2 DIABETES PATIENTS IN EASTERN-SOUTHERN TAIWAN

1KaT-YIen ngu, 1SHIH-MING CHUANG, 1YUE QIU HUANG, 2CHUN-QUAN LI

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taitung branch; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei

objective: Brachial-ankle pulse wave velocity (baPWV), as an indicator of atherosclerosis in diabetes patients, was studied in 522 subjects randomly selected from outpatient department in Taitung Mackay Memorial Hospital. research design and Methods: Fasting blood glucose (FBS), lipid parameters (including total cholesterol, triglyceride, LDL and HDL), ankle brachial pressure index (ABI), and baPWV were measured in each subject between July-2014 and September-2014. ABI and baPWV were measured using the recently developed device, form ABI/PWV. All selected subjects were divided into two groups according HbA1c level: a conventional group consisting of subjects with HbA1c < 9.0 mg/ dl and a poor-controlled group consisting of subjects with HbA1c >9.0 mg/dl, and all subjects taking hypoglycemic agents. The parameters in the two groups were compared. results: It was found that the baPWV value increased with increasing plasma glucose level. Significant differences were found between the baPWV values in the conventional and poor-controlled groups (1402 vs. 1570 cm/s, P=0.033).

The results of multiple regression analysis showed that HbA1c was closely related to baPWV as well as to HDL level.

Conclusions: The relationship between diabetes control and atherosclerosis remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in diabetes patients will result in the prevention of atherosclerosis progression.

PD-20

DIABETIC KETOACIDOSIS DEVELOPMENT IN A YOUNG WOMAN WITH THE STIFF PERSON SYNDROME

1Hung-Yu Huang, 2RONG-HSING CHEN, 1,3MING-KUEI LU, 1,3CHON-HAW TSAI

1Department of Neurology, China Medical University Hospital; 2Department of Endocrine and Metabolism, China Medical University Hospital; 3School of Medicine, Medical College, China Medical University

Introduction: Stiff person syndrome is a rare and intriguing disease entity that was characterized with stiffness of the low back and lower limbs. Progressive encephalomyelitis with rigidity and myoclonus (PERM) is one of the unique variants of stiff person syndrome. The accurate diagnosis of the disorder is of important not only for academic interest but also for the appropriate immunomodulation therapy of the disease. Case report: This 35-year-old woman, elementary English teacher, with 48 kg of body weight and 19.2 kg/m2 of BMI, was admitted in November 2013 due to exacerbated difficulty in walking for 17 years. During the symptomatic period, which may usually last for about 2 months and remitted spontaneously, the ambulatory difficulty commenced intermittently, continuing for one to five minutes in duration, with preceding uncomfortable low trunk spasm with legs stiffness, which made her walk like a robot. The low back spasm following by legs stiffness is drawn out by psychological stress, unexpected noise or touch on the head, or crowded environment; it may present as triple flexion of legs at lying position, during walking, and while she is just arising from sitting. Excessive startles response to sound and touch on the upper trunk and head is fatigable and reappeared after a period of time. Double vision and left ptosis appeared since 2 years with spontaneous recovery of ptosis 6 months later. She was found to have hyper-reflexia of the lower limbs with clonus and flexor plantar responses. Limitation of the left eye downward and right eye upward gazing were detected. MRI for brainstem, and whole spinal cord was unremarkable. The serum levels of anti-glutamic acid decarboxylase (anti-GAD) antibodies were over 300 u/mL. During the follow up, she had improved ability of daily chores under daily diazepam and regular methylprednisolone pulse therapy with a four-month interval. However, nine months after the diagnosis of stiff person syndrome, she was diagnosed as diabetes melliatus and diabetic ketoacidosis with the presentation of progressive thirsty and body weight loss (from 48 kg to 40 kg of body weight) for three months. The HbA1c (13 %) level, flunctuated C-peptide level (<0.1 ng/ml, 1.04 ng/ml, in separated time), and marked response of C-peptide level to glucagon stimulation test suggested that she has possible type 1 diabetes, but the status of insulin dependence should be further elucidated. Conclusion: The patient has diagnosed as PERM by the appearance of intermittent lower trunk and legs stiffness in association with stimulus sensitive reticular reflex myoclonus, eye movement limitation and excessive startle response, and positive anti-GAD antibodies. Among the autoantibodies, the antiGAD antibody is the prototype of autoimmune-related SPS. It was found in about 80 % of newly diagnosed type 1 diabetes melliatus (T1DM), and almost half of SPS might be diagnosed as T1DM before or after the diagnosis of SPS in about five years. The possible associated comorbidities, such as diabetes mellitus, thyroid disorder, and autoimmune and paraneoplastic disorder, should be checked conditionally during follow-up. Since the immune modulation therapy may benefit the patients with stiff person syndrome, the correct diagnosis is important for the long term impact.

PD-21

E-SELECTIN AS A MARKER OF ENDOTHELIAL DYSFUNCTION IN METABOLIC SYNDROME AND GENDER DIFFERENCES IN THE EXPRESSION OF E-SELECTIN AND OTHER MARKERS OF INFLAMMATION

wen-Hao Tang, FENG-CHIH KUO, FU-HUANG LIN, CHANG-HSUN HSIEH, YI-JEN HUNG, CHIEN-HSING LEE

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chen-Kung Rd.,Nei-Hu, Taipei, Taiwan

objectives: Associations are established between metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction. We investigated associations between E-selectin and MetS and gender differences in biomarker expression.

Patients: A convenience sample of 205 patients aged 20-75 years with/without MetS was recruited from outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Included patients had BMI < 35 kg/m2, no recent infection, no anticoagulant or diabetes medications. Pregnant or breastfeeding women, patients with liver disease, pancreatitis, previous malignancy, stroke or myocardial infarct, psychiatric disorders, alcoholism, or taking beta blockers, diuretics, cholestyramine or steroids were excluded.

Measurements: Demographic, anthropometric and MetS index data were compared by gender. Markers of inflammation (TNF-α, IL-6, hsCRP) and endothelial dysfunction (E-selectin, ICAM1, VCAM-1) were measured and compared by gender. Associations were determined by correlation analysis and multivariate logistic regression. results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. Elevated E-selectin levels were significantly associated with number of MetS components in females (P<0.001) but not in males (P=0.125). In females, E-selectin levels in highest quartile (≥61.074 ng/ml) were significantly associated with increased MetS risk (OR=6.80, 95% CI=1.46 to 31.75; P=0.015) compared to lowest quartile levels (<30.24 ng/ml).

Conclusion: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males.

PD-22

DIABETIC PATIENT OUTCOMES BY DIFFERENT SPECIALTIES CARE: A 5-YEAR OBSERVATIONAL STUDY IN A MEDICAL CENTER

TZu-Yun Yu, CHIA-LIN LEE, JUN-SING WANG, CHIA-PO FU, I-TE LEE, YEN-MIN SONG, SHIH-YI LIN, WAYNE HUEY-HERNG SHEU

Division of Endocrinology and Metabolism, Taichung Veterans General Hospital

background: In previous studies, endocrinologists have been reported to execute better glycemic control in diabetic patients than non-endocrinologists. This study was aimed to compare the outcome differences between endocrinologists and other subspecialists.

Methods: Diabetic patients were enrolled from July 2006 to December 2006 in a medical center in central Taiwan. The patients were divided into two groups according to their main healthcare provider - either an endocrinologist (EN) or non-endocrinologist (non-EN). They were prospectively followed up for 5 years (till Dec 2011). Baseline characteristics, laboratory data, medications, and outcomes of the 1930 patients who were still alive one year after enrollment were analyzed. results: A total of 1992 diabetic outpatients were recruited from Jul 2006 to December 2006. In comparison with non-EN group (n=813), the EN group (n=1117) is younger in age and has a lower mortality during the follow up period (EN group mortality=12.7%, non-EN group mortality = 18.9%, p<0.001). Comparing with non-EN subgroups, mortality was significantly lower in four of the EN subgroups: (1) diagnosis of hypertension (HR=0.612, 95% CI: 0.41-0.916, p=0.017), (2) using antihypertensive medications (HR=0.655, 95% CI: 0.444-0.967, p=0.033), (3) no coronary artery disease (non-CAD) (HR=0.658, 95% CI: 0.446-0.970, p=0.035), and (4) younger than 65 years-old (HR=0.406, 95% CI: 0.172-0.961, p=0.04). In addition, in the above four subgroups, more annual glycated hemoglobin(HbA1C) decrease was observed in (1) hypertensive patients (annual difference=0.1%, p=0.007), (2) using antihypertensive medications (annual difference=0.096%, p=0.011), (3) no coronary artery disease (non-CAD) (annual difference=0.068%, p=0.048), but annual HbA1C decrement did not significantly differ in patients aged less than 65 years old (annual difference=0.052%, p=0.319).

Conclusion: Compared with diabetic patients cared by non-endocrinologists, greater annual HbA1C decrement and survival benefit were shown in three subgroups of patients cared by endocrinologists: (1) hypertensive patients (2) patients who receive antihypertensive medications (3) patients without CAD. However, in the subgroup aged less than 65 years old, survival difference was noted without significant difference in HbA1C decrement rates between these two groups. This may suggest factors other than HbA1C decrement rate as the cause of the survival benefit.

PD-23

ORAL GLUCOSE LOWERING WITH LINAGLIPTIN PLUS METFORMIN IS A VIABLE INITIAL TREATMENT STRATEGY IN PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES AND MARKED HYPERGLYCAEMIA

1baPTIsT gaLLwITZ,

2STUART A. ROSS, 3A. ENRIQUE CABALLERO, 4STEFANO DEL PRATO, 5DIANE LEWIS-D’ AGOSTINO, 6ZELIE BAILES, 7SANDRA THIEMANN, 6SANJAY PATEL, 7HANS-JUERGEN WOERLE, 5MAXIMILIAN VON EYNATTEN

1Dept. Medicine IV, Universitätsklinikum Tübingen, Tübingen, Germany; 2LMC Endocrinology Centres, University of Calgary, Calgary, AB, Canada; 3Joslin Diabetes Center and Harvard Medical School, Boston, MA, USA; 4Department of Endocrinology and Metabolism, Section of Diabetes, University of Pisa, Pisa, Italy; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 5 6Boehringer Ingelheim Ltd, Bracknell, UK; 7Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

background and aims: Newly diagnosed type 2 diabetes (T2D) patients commonly present with marked hyperglycaemia. This condition has rarely been studied for novel oral diabetes drugs and insulin is often proposed as the preferred starting therapy.

Materials and methods: We explored oral glucose-lowering combination therapy in newly diagnosed (≤12 months) T2D patients with marked hyperglycaemia (n=316) utilising prespecified exploratory subgroup analyses from a randomised double-blind study of initial combination of linagliptin+metformin versus linagliptin. Baseline mean±SD age and HbA1c was 48.8±11.0 years and 9.8±1.1%, respectively. The primary endpoint was HbA1c change from baseline to week 24. results: Mean±SE HbA1c reduction was -3.4±0.2% versus -2.5±0.2% with linagliptin +metformin and linagliptin, respectively, in patients with baseline HbA1c ≥9.5%, and -2.1±0.2% versus -1.4±0.2% in patients with baseline HbA1c <9.5%. Similar HbA1c reductions occurred in all subgroups of age, body-mass index (BMI), renal function, race, and ethnicity. Hypoglycaemia was rare (1.9% and 3.2% of patients, respectively) with no severe episodes. Conclusion: In our analysis of newly diagnosed T2D patients presenting with marked hyperglycaemia, initial linagliptin+metformin elicited consistent HbA1c reductions across different subgroups. Oral glucose-lowering combination therapy may be a viable initial alternative to insulin for effective treatment of these patients.

PD-24

RISK OF HYPOGLYCEMIA IN PEOPLE RECEIVING LINAGLIPTIN: POOLED DATA FROM 1489 ADULTS AGED ≥65 YEARS WITH TYPE 2 DIABETES MELLITUS

1KaMLesH KHunTI, 2MICHAEL NAUCK, 3ATSUSHI ARAKI, 4SUSANNE CROWE, 4YAN GONG, 4DOUGLAS CLARK, 5MAXIMILIAN VON EYNATTEN, 4HANS-JUERGEN WOERLE

1University of Leicester, Leicester, UK; 2Diabetes Center Bad Lauterberg, Bad Lauterberg im Harz, Germany; 3Tokyo Metropolitan Geriatric Hospital, Tokyo, Japan; 4Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA

objectives: Risk of hypoglycemia (HYPO) in elderly patients with T2DM is a major concern, especially when drug regimens include either insulin (INS) or secretagogues (SECR). We pooled data from a global clinical trials program to further assess the safety, focusing on HYPO, of the DPP-4 inhibitor linagliptin (LINA).

Methosd: Adults with T2DM aged ≥65 years who participated in 11 randomized, placebo (PBO)controlled, Phase III trials were included. Efficacy was assessed by change in HbA1c from baseline to Week 24 using the full analysis set (FAS). Incidence of confirmed HYPO (plasma glucose ≤70 mg/dL) or severe HYPO (requiring third-party assistance) was assessed in the treated set (TS) with consideration for background therapy: regimens including INS but no SECR, SECR but no INS, or neither therapy. results: Overall, 1489 patients were treated (TS: LINA, n=948; PBO, n=541). Mean ± SD age was 70.9 ± 4.6 y (range, 65-91). In both treatment groups (FAS: LINA, n=936; PBO, n=530), mean baseline HbA1c was 8.1 ± 0.8%. Linagliptin significantly decreased HbA1c at Week 24 by a PBOadjusted mean (95% CI) of −0.60% (−0.69, −0.51; p <0.0001). Incidence of confirmed HYPO was 26.3% in the LINA group and 34.0% in the PBO group (RR: 0.77 [95% CI: 0.66, 0.91; p <0.05]). In the subgroup of patients receiving INS but no SECR (LINA, n=247; PBO, n=256), incidence was 53.4% vs. 55.9%, respectively (RR: 0.96 [CI: 0.82, 1.12; p ≥0.05]). In the subgroup receiving a SECR but no INS (LINA, n=309; PBO, n=126), incidence was 32.0% vs. 25.4% (RR: 1.26 [CI: 0.90, 1.77; p ≥0.05]). Finally, in those whose regimens included neither SECR nor INS (LINA, n=371; PBO, n=152), incidence was 1.3% vs 3.3% (RR: 0.41 [CI: 0.12, 1.39; p ≥0.05]). Overall, incidence of severe HYPO was low in both groups (LINA, 0.8%; PBO, 1.3%).

Conclusions: In an elderly population, overall risk of HYPO was not increased when LINA was added to improve hyperglycemia, with lower incidence rates compared to PBO when LINA was given with background INS but higher rates with background SECR.

PD-25

IGG4 RELATED DISEASE IN A PATIENT WITH DIABETES MELLITUS

wu Lung CHuang, DONG-HWA TSAI, SHU-YI WANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

We report a rare case of IgG4 related disease in a patient with diabetes mellitus.A 48-year-old man with an seven-year history of diabetes mellitus presented skin rash after linagliptin use.He had been treated for diabetes mellitus with metformin for many years. Due to poor glycemic control, linagliptin was added at one year ago.Then he developed skin rash.Because it’s suspected adverse effects of DPP4-inhibitor drug, linagliptin was then withdrawed and metformin dose was titrated up. Then he presented gastrointestinal upset so that metformin dose was titrated down and repaglinide was added. Because he developed chronic diarrhea and weight loss, upper GI scope and liver sonography were arranged.Liver sonography revealed pancreas swelling with heterogenous parenchyma, common bile duct and intrahepatic duct dilatation, gall bladder wall thickness and one gall bladder polyp.Pancreatic cancer was suspected so that abdominal CT scan was arranged. Abdominal CT scan revealed relatively prominent pancreatic parenchyma with encapsulated appearance around the pancreatic body ; prominent and symmetric mural thickening of the common hepatic duct to the common bile duct, with dilated intrahepatic ducts.Due to suspect Ig G4 related disease, IgG and subgroups blood levels were checked.IgG and IgG4 levels were elevated and IgG1,IgG2,IgG2 were all within normal range.Then Ig G4 related disease was diagnosed. Prednisone was then administered. The patient’sGI upset and diarrhea gradually improved and IgG and IgG4 levels decreased after prednisone use which was suggestive of good response to steroid.

PD-26

EMPHYSEMATOUS PYELITIS WITH PNEUMONEPHROSIS IN TYPE 2 DIABETES PATIENT

1CHIu CHIH-Huang, 2WANG SHU-Y, 3TSAI DONG-HWA

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

This 54-year-old Taiwanese woman, with a history of diabetes mellitus for 7 years with oral anti-diabetic agents control and proliferative diabetic retinopathy under ophthalmology OPD following up.

General weakness and fever were noted since 4 days before admission. She hold oral antidiabetic agents by herself. She ever came to LMD 7 days ago and urinary tract infection was suspected. Empiric antibiotics was used. Due to fever off and on, she was admitted to further survey. NO travel occupation contact cluster history was noted.

PE: Pulmonary: symmetric expansion, no wheezes, rales, rhonchi.

Abdominal: Normoactive bowel sounds. Soft, no tender, knocking pain: both kidney

Lab:

WBC HB Plet neutrophil lymphocyte Monocyte 17100/սL 11g/dl 266000/ սL 89.5% 3.5% 6.9% Bun Cre Na K GPT sugar 34mg/dl 1.7 mg/dl 124 5.0 11 675 Urine sugar Urine protein Urine WBC Epithelial cell >0.5g/dl 100 mg/dl 38.2/HPF 2/HPF

Image:

Renal echo: renal stone and hydronephrosis

KUB: free air over bladder, urethral tube and pelvis

Abdomen CT: extensive gas collection in the parenchyma and perinephric space of the left kidney; bilateral hydroureteronephrosis and pneumonephrosis

According to laboratory exam, image studies, emphysematous pyelitis was diagnosed. Antibiotics with ertapenem for blood culture and urine culture revealed multiple drug resistant Escherichia coli. Due to hyperglycemia, initial insulin pump and then basal bolus insulin regimen were prescribed for blood sugar control. After completion of antibiotic treatment, with good glycemic control, symptoms of hydroureteronephrosis got improved gradually. She was discharged and received outpatient department follow up. discussion: Emphysematous pyelitis is defined as isolated gas production inside the excretory system, secondary to acute bacterial infection. It is relatively benign entity, and needs accurate differentiation from emphysematous pyelonephritis, which is much morbid condition. It has excellent prognosis with good response to medical management. The incidence of emphysematous pyelitis in DM is unknown. Disease is more common in female2, associated with diabetes and urinary tract obstruction. The common pathogenic bacterium were Escherichia coli, Klebsiella pneumoniae, Aerobacter aerogenes and Proteus mirabilis. When diabetic patient with urinary tract infection, early survey such as renal echo or abdomen CT should be done. Empiric antibiotics should consider (1) clinic status ( severe sepsis or not) (2)previous antibiotics sensitivity and pathogenic bacterium (3)recurrent hospital admission or Foley’s tube using(4) common pathogenic bacterium in the area or this hospital (5) survey effection of emperic antibiotics per 3 days (6) Drugs resistance of pathogenic bacterium or not (7) antibiotics side effect and cast effection. Emphysematous pyelitis was a kind of special disease in DM poor control patient.

PD-27

EFFECT OF PITAVASTATIN ON GLUCOSE CONTROL AND LIPID PROFILE IN TYPE 2 DIABETIC PATIENTS

CHung-HueI Huang, YU-YAO HUANG, BREND RAY-SEA HSU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

background: Hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors are important for prevention of cardiovascular diseases in type 2 diabetic patient with dyslipidemia. Clinical data concerning the effect of statins on glucose metabolism in diabetics are limited. We investigated the effect of pitavastatin treatment on glycemic and dyslipidemic control in diabetic patients.

Patients and Methods: Within the period of 1 August 2013 to 31 May 2014, 196 type 2 diabetic patients with dyslipidemia who started pitavastatin treatment were studied. They were either statinnaïve (statin-naïve group) or were treated with atorvastatin in the past (atorvastatin-switched group). Among them, the change of A1c levels were analyzed in 139 patients who had no adjustment of antidiabetic agents during study period. Clinical data were collected every 3 months. results: Significant decrease of total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) was observed in the statin-naïve group (p<0.001). An increment of high-density-lipoprotein cholesterol (HDL-C) was observed in patients with baseline hypo HDL-C in both groups at 3 months. A correlation between the improvement of A1c and baseline A1c were noted in both groups (r= 0.23 and r=0.53 in statin-naïve group and atorvastatin-switched group, respectively). Further analysis by tertile baseline A1c levels revealed that the glycemic benefit of pitavastin treatment is significantly noted in relatively poorly-controlled diabetes group at 6 months of pitavastatin treatment in both groups (p=0.017 in the statin-naïve group, p=0.034 in the atorvastatin-switched group).

Conclusions: Dislipidemic patients with type 2 diabetes can achieve not only improvement of lipid profile, but also better glycemic control when treated with pitavastatin. The latter effect is more prominent in the poorly-controlled patients.

Further studies are needed to lucid the mechanism of glucose lowering effect of pitavastatin treatment.

PD-28

A 31-YEAR-OLD TAIWAN WOMAN HAD FULMINANT TYPE 1 DIABETES MELLITUS

Fang-CHuan Huang, HON-KE SIA, SHI-DOU LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Fulminant type 1 diabetes is a new clinical entity in which the process of beta-cell destruction, and the subsequent progression of hyperglycemia and ketoacidosis, are extremely rapid with near normal HbA1C. Until now, this subtype of type 1 diabetes has only been reported in the Asian population, especially Japanese and Koreans.

We report one case of fulminant type 1 diabetes mellitus in Taiwan.

A 31-year-old Taiwan woman complained of nausea, vomiting and abdominal discomfort for 2 days and she had short of breath, polyuria and thirst just on the day of her admission to hospital. Flulike symptoms (cough, chills, fever) had developed five days. There was no weight loss (BMI: 26.7 kg/ m2,71 kg,163cm).

Upon admission, her blood glucose levels were highly elevated (1029 mg/dL) and associated with severe ketoacidosis (urine ketone 2+; arterial blood pH: 7.035; arterial blood HCO3: 5.2 mEq/L, serum β-hydroxybutyrate:5.3 , normal<0.6 mmol/L). Hyperkalemia was also noted: K:7.7 mmol/L with EKG show sinus tachycardia with Peaked T waves and prolonged QRS, develop of nearing a sine wave appearance.

HbA1c was normal at 5.6%. Her fasting serum C-peptide levels were below the detection limit (<0.1 ng/mL) at the time of admission and after metabolic decompensation. As for autoantibodies, anti-GAD antibody, and antithyroperoxidase antibodies were all negative, and serum pancreatic enzyme levels were elevated at the time of admission day 7 (lipase: 145 UI/L, normal range:19–47;amylase:109 IU/L, normal range: 28–100). Abdominal CT revealed no significant abnormality. She was initially treated in the intensive care unit (ICU) with intravenous insulin and a large volume of intravenous normal saline for diabetic ketoacidosis. Her dyspnea, thirsty, polyuria nausea, vomiting and abdominal pain got improved after two days. She was subsequently treated with a daily injection of a long-acting insulin analogue along with three daily injections (at each meal) of a rapid-acting insulin analogue. She had no ‘honeymoon period’, and her HbA1c levels were up to 6.8 % 2 months later with 54 IU/day of insulin.

PD-29

INDICATOR ANALYSIS FOR RESPONSIVENESS TO GLUCAGONLIKE PEPTIDE RECEPTOR AGONIST, LIRAGLUTIDE IN TAIWANESE TYPE 2 DIABETIC PATIENTS

I-wen CHen, YU-YAO HUANG, SZU-TAH CHEN, SHIN-YUAN HUNG, CHIA-HUNG LIN, BREND RAY-SEA HSU

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

background: Liraglutide, a glucagon-like peptide receptor agonist (GLP-1 RA) is approved to use for a second-line glucose-lowering agent to maintain and improve glucose control in type 2 diabetic patients. Here, we compared the characteristics and parameters among Liraglutide responders and non-responders to identify possible indications for GLP-1 RA treatment. design and Methods: This observational study included 94 patients with type 2 diabetes mellitus being treated with Liraglutide. Clinical characteristics and parameters were documented every 3 months at initiating Liraglutide treatment. All patients have used Liraglutide and followed up for 3 to 12 months. The adjustment of Liraglutide dosing or other antidiabetic agents was depended on clinical judgment. Those patients had benefit from liraglutide treatment for more than 1% of serum glycohemoglobin decrement was defined as responder group. The other patients without such effect were defined non-responders. Binary logistic regression analysis was used to compare between these 2 groups results: Liraglutide treatment significantly decreases serum HbA1c (9.66±0.17% to 8.73±0.17%, P<0.001) and body mass index (30.43±4.75 to 29.89±4.54, P< 0.001) in the study patients. Forty-one of the 94 patients (43.6%) were reported as responders. Demographically, known diabetic duration was 9.90±5.16 years for responders and 13.52±5.97 years for non-responders (p=0.002); pre-treatment body mass index (BMI) was 33.27 ± 5.07 kg/m2for responders and 28.53 ± 3.60 kg/m2 for nonresponders (p<0.001); pretreatment HbA1c level was 10.15±1.62% for responders and 9.29±1.51% for non-responders (p=0.016); fasting C-peptide level was 4.15±2.21 ng/ml among responders and 2.39±1.22ng/ml among non-responders (p=0.011); triglyceride was 237.09±138.08 mg/dL among responders and 173.95±86.94 mg/dL among non-responders (p=0.024). Stepwise regression analysis demonstrated that baseline BMI (adjusted OR and 95% CI: 1.313, 1.136-1.517, p<0.001) and HbA1c

(adjusted OR and 95% CI: 1.437, 1.017-2.029, p=0.040) may predict for Liraglutide response.

Conclusion: We conclude that Liraglutide effectively maintained better glycemic control by reducing BMI and increasing C-peptide in type 2 diabetic patients. The response of Liraglutide was significantly associated with baseline body mass index and HbA1c, that is, patients with higher BMI and HbA1c may be a better Liraglutide responder.

PD-30

RELATION OF BODY MASS INDEX, C-REACTIVE PROTEIN AND MORTALITY IN INPATIENTS OF CARDIOVASCULAR WARD

1YI-TIng Kuo,

2I-TE LEE, 2JUN-SING WANG, 2CHIA-LIN LEE, 2SHIH-YI LIN, 2WAYNE HUEY-HERNG SHEU

1Department of Internal Medicine, Taichung Veteran General Hospital, Wancian Branch, Chiayi, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veteran General Hospital, Taichung, Taiwan, R.O.C.

background: Obesity causes many serious medical complications that impair quality of life and lead to increase morbidity and mortality. Besides, several studies have linked obesity with elevated levels of C-reactive protein, which is associated with cardiovascular disease and mortality. Most of these studies enrolled subjects without cardiovascular disease. Recently, being overweight or obese is associated with lower mortality rates than for similar patients with normal BMI values in some chronic disease, such as cardiovascular disease, which is called “obesity paradox”. The study aim to evaluate the correlation of body mass index and C-reactive protein in patients with cardiovascular disease.

Methods: This study enrolled 1456 subjects admitted to cardiovascular ward during March, 1999 to July, 2004. Relationships between body mass index and C-reactive protein with all-cause mortality were examined. results: Be overweight or obese (BMI≥23) was found to associate with lower mortality compared to normal. Death subjects had higher level of mean C-reactive protein compared to survivor (1.09±1.58 v.s. 0.57±1.22, p<0.0001). However, mean C-reactive protein was found to be decreased with elevated body mass index level. (BMI<18.5:1.41±1.92, 18.5≤BMI<23:1.12±1.67, 23≤BMI<25:0.70±1.31, 25≤BMI<30:0.71±1.31, BMI≥30:0.65±1.17, p=0.0025).

Conclusion: Obesity and inflammation may lead to cardiovascular disease. But in patients with developed cardiovascular disease, overweight, obese and chronic inflammation, such as the relationship of body mass index and C-reactive protein, may be different from normal subjects. C-reactive protein seemed to be a better predictor in mortality compared with body mass index in studies. The correlation of obesity and inflammatory marker in these patients still need further evaluation.

PD-31

MEASURABLE GLUCOSE IMPACT MITOCHONDRIAL QUALITIES VARIATION WITH CONFOCAL MICROSCOPY

1Hong-weI sHen, 1YUNG-SHENG CHANG, 1PEI-YU CHENG, 1SHIH-TE TU, 1,2SHIHLI SU, 2CHIN-SAN LIU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.; 2Vascular Medical Research Laboratory, Changhua Christian Hospital, Changhua, Taiwan, R.O.C.

aim: Assess the effect of treatments with high glucose concentration on mitochondrial morphological changes in human renal mesangial cell

Methods: Human renal mesangial cells are cultured in normal glucose (5mM) and high glucose (30 mM) medium. We had been using the XF24 seahorse to examine sequential electron flow through mitochondrial electron transport chain complexes which can be identified the status of mitochondrial dysfunction and modulation. The previous study applied the quality changes, including metabolic dysfunction and extracellular acidification. The morphological changes of mitochondrial had been done with same MES cell line by confocal microscopy.

MitoTracker Green FM can detect the mitochondrial real activities without an affect mitochondrial membrane potential. Tetramethylrhodamine ethyl ester can disclose the apoptosis of cells with decade red color. Combine both stain made us recognizing the mitochondrial quality variations.

Conclusion: Our experiments suggest that mitochondria quality variation of mesangial cell of kidney displays significant increase mitochondrial amounts. The apoptosis and membrane potential also enhanced. Glucose is the source of energy to provide mitochondrial essential functions which demonstrate as an increment of total mitochondrial amounts. For the purpose to keep balance, apoptosis also amplify.

PD-32

THE ANALYSIS OF OUTCOME AND MORTALITY IN DIABETIC PATIENTS WITH NECROTIZING FASCITIS IN SOUTHEAST TAIWAN

sHIH-MIng CHuang, KAT-YIEN NGU, YUEN-CHIU HUANG

Division of Endocrinology and Metabolism, Department of Internal Medicine,Mackay Memorial Hospital, Taitung

objective: Necrotizing fasciitis (NF) is a life threatening insidiously advancing or sometimes fulminant soft tissue infection characterized by widespread fascial necrosis. Necrotizing fasciitis on thewhole is higher in patients with immunosuppressive conditions(such as diabetes mellitus and liver cirrhosis). research design and Methods: We invesigated 104 case of necrotizing fascitis(NF) with or without diabetes within recent 10 years(2004-2013) in Taitung Mackay Memorial Hospital. 48 case of NF(46.2%) with diabetes and most involvement over lower extremities(66.67%). All NF patients were divided into two groups according to diabetes history, all biochemical parameter, sequent complinactions and outcome in the two groups were compared. results: It was found that the NF patients with diabetes have higher CRP(P=0.01), lower sodium(P=0.043), lower eGFR(P=0.019) as compared without diabetes. Elderly NF patient with T2DM has high mortality rate(35%) as compared younger patients (13%). Old-aged diabetes was increasing risk of moltality(Odds ratio: 2.54, 1.18-5.46, P=0.022) in NF patients.

Conclusions: The relationship between diabetes control and NF remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in diabetes patients will change outcome of Necrotizing fascitias.

PD-33

SUCCESSFUL MANAGEMENT OF TYPE 2 DIABETES MELLITUS WITH MORBID OBESITY AND INSULIN ANTIBODIES-A CASE REPORT

1.2PIn-Fan CHen, 1BING-RU GAO, 1.2WEI-CHENG LIAN, 1SHIH-TANG YAN, 1TING-

CHANG CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Buddhist Da Lin Tzu Chi General Hospital; 2School of Medicine, Tzu Chi University, Hualien, Taiwan

objective: Patients with type 2 diabetes mellitus have an option to receive bariatric surgery if BMI are over 32 kg/m2 and glycemic control are not quite well in Asia. The result, focusing on diabetes remission, is tremendously well if C-peptide level before operation is above 3.0 ng/ml, compared with medical control.

Case report: We reported a case of severe obesity (height 180 cm, weight 118kg and BMI 36.4 kg/m2), who was diagnosed with type 2 diabetes since Nov. 2011 in Tai-Chung. At that time, high daily insulin requirement (over 1U/kg) was found and having insulin antibodies was told. The need of unusual high daily insulin requirement was confirmed by continuous subcutaneous insulin infusion (CSII). As a resulting increase in daily insulin doses by using insulin analogues over 300IU/day, He received RI 70U, 60U, 50U, 30U four times a day along with IVII 5U/hr to control finally before he received laparoscopic Sleeve Gastrectomy on 31 Oct. 2013. Six days after operation, diabetes remission has been found till now.

Conclusion: In patients with type 2 diabetes with morbid obesity, who has insulin antibodies, bariatric surgery is the more favored choice than other medical methods and should be performed as soon as possible.

PD-34

M&ouML;nCKeberg’s arTerIosCLerosIs In a dIabeTIC PaTIenT wITHouT HYPerLIPIdeMIa

YI-HsIn LIn, CHIH-HSUNG HUANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taiwan Adventist Hospital, Taiwan, R.O.C

Mönckeberg’s arteriosclerosis, also called medial calcific sclerosis, is a form of arteriosclerosis or vessel hardening, where calcium deposits are found in the muscular middle layer of the walls of arteries (the tunica media). Its clinical significance and etiology are not well understood but may be associated with poorer prognosis. Probably it causes increased arterial stiffness, increased pulse pressure and resulting in exaggerated damage to the heart and kidneys. We described a 70-year-old female diabetic patient, without hyperlipidemia and calcium/phosphate imbalance, had gradually aggregative Mönckeberg’s arteriosclerosis from thoracic to abdominal aorta, which looked like “a pipestem” in X-ray radiograph, in 7 years follow-up.

Key words: Mönckeberg’s arteriosclerosis, medial calcific sclerosis, diabetic

PD-35

PAY-FOR-PERFORMANCE PROGRAM REDUCE THE INCIDENCE OF DKA AND HHS IN DIABETIC PATIENTS

1HuI-MIn HsIeH,

2,3,5SHYI-JANG SHIN, 4HERNG-CHIA CHIU 1Department of Public Health; 2School of Medicine, College of Medicine; 3Center of Lipid and Glycomedicine Research; 4Department of Healthcare Administration and Medical Informatics, Kaohsiung Medical University; 5Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Taiwan

Introduction: The effectiveness of diabetes pay-for-performance program (P4P) in Taiwan and even in the world has not been elucidated. In this study, we compared the probability of incidence for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS) between P4P and non-P4P patients during the 5-year period to assess the effectiveness of diabetes P4P.

Methods: We conducted a longitudinal cohort study using a nationwide diabetes P4P database and the National Health Insurance (NHI) administrative claims database in Taiwan from 2007 to 2012. We included diabetic patients who had primarily diabetes diagnosis (ICD-9-CM codes with 250.xx or A-code 181) in at least two outpatient visits or at least one inpatient hospitalization during 2007 and 2008. Using the P4P database, we identified newly enrolled P4P patients as study P4P cohorts and the date when they were first enrolled as index date. We then identified non-P4P diabetic patients if they were not found in the P4P program in study period. To avoid potential confounding by selection bias and confounding factors, we used propensity score matching approach (PSM) to determine comparison group. Incidence rates per 1,000 person-years for DKA and HHS were calculated until the end of study date on December 31, 2012. Multivariate logistic regression and cox proportional hazard model were used to calculate HR for DKA and HHS in comparison between P4P and non-P4P patients. results: Before matching, we included 34,710 P4P patients and 341,312 non-P4P diabetes patients. After PSM for 1 to 1 matching, the two groups were found to be similar in demographic characteristics, comorbidities (CCI index, categories) and institution of health care. Incidence rates per 1,000 person-years of DKA (2.69 vs 3.00) and HHS (2.09 vs 2.53) were lower in P4P patients than non-P4P patients. Using multivariate logistic regression, the HR for DKA was 0.900 (95% CI=0.813, 0.997) (p<0.044) and for HHS was 0.884(95% CI=0.787, 0.992) (p<0.036) between P4P and nonP4P groups. Using cox proportional hazard model, the HR for DKA was 0.796 (95% CI=0.717, 0.883) (p<0.001) and for HHS was 0.726(95% CI=0.643, 0.819) (p<0.001) between P4P and non-P4P groups.

Conclusion: Our findings provided evidences for the potential long-term benefit of pay-forperformance programs for diabetic care on the incidence of DKA and HHS.

PD-36

10-YEAR FOLLOW-UP OF GLYCEMIC CONTROL DURING HOLIDAY TIME IN PATIENTS WITH TYPE 2 DIABETES

1,3Tseng-HuI Kao, 2,4TZU-EN WU, 1,2HARN-SHEN CHEN, 1CHUN-JUI HUANG

1Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital ,Taiwan,R.O.C.; 2Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan,R. O.C.; 3Division of Endocrinology and Metabolism, Department of Medicine, Taipei City Hospital Yangming Branch,Taiwan,R.O.C.; 4Department of Ophthalmology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan,R.O.C.

objective: We carried out this follow-up study to investigate whether HbA1c gain during the Chinese New Year’s holiday exist every year and contribute to the substantial increase in HbA1c among patients with type 2 diabetes in the 10-years follow-up. researche design and Methods: We measured HbA1c in 108 patients with type 2 diabetes to determine the glycemic change during Chinese New Year's holiday from November 2000 to April 2001. In this 10-year follow-up, we collected the data from November 1st to the beginning of Chinese New Year’s holiday as the pre-holiday period, and from the end of the holiday to April 30th as the post-holiday period. results: The significantly increment of HbA1c values after holiday period were seen in 2001, 2002, 2006 and 2008. Compared with the pre-holiday HbA1c in the first year, the pre-holiday HbA1c in the 10th year was increased significantly (0.57±1.52%, [95% CI, 0.17-0.96]). The time-weighted HbA1c levels were significantly higher in subjects with HbA1c increased in the upper half of the first year (8.02±0.30% vs. 7.69±0.28%, p=0.0003).

Conclusions: The level of HbA1c increased significantly after Chinese New Year’s holidays for four times during the 10-years follow-up in which three times occurred during the 9-day vacation and another one occurred during a lower temperature in Taipei City. Longer holiday period and lower temperature are risk factors for poor glycemic control during Chinese New Year’s holidays.

PD-37

THE IMPACT ON RENAL FUNCTION FOR PARTICIPATING DIABETES SHARED-CARE NETWORK IN TYPE 2 DIABETES PATIENTS

1TZu-HsIng Hung,

2JIUN-YIAN LIN, 2PI-YUAN WONG, 2I-CHUAN LIN, 2I-JU LIEN, 2CHUNG-HSUEH CHUNG, 2TONG-YUAN TAI

1Department of Family Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Jen-Chi Hospital, Taiwan, R.O.C.

aims: To evaluate the impact of participation of diabetes shared-care network to renal function of type 2 diabetes patients.

Methods: One hundred nine cases of type 2 DM patients, well controlled by entering DM sharedcare network (participants) for a certain period of time and thirty eight cases without entering (nonparticipants) were observed for 3.53± 0.57 years and 3.45±0.65 years, respectively. The mean ages were 64.7±10.4 years and 66.4±10.7 years, DM durations 9.72±7.33 years and 9.49±8.71years, gender distributions of male participants 44.0% and 42.1%, respectively. The differences of corresponding parameters between two groups were not significant. Their renal functions were expressed by eGFR, which was derived from yearly determination of serum creatinine levels. resuts: The initial and final HbA1c values of the participants were 7.59±1.07 % and 7.17±1.12%, and respective values for the non-participants were 8.24±1.59 % and 7.38±1.35%. AT the beginning, the participants showed better glycemic control (p value=0.02, by Mann-Whitney U test), however, at the end of observation, HbA1c of both groups showed no significant difference. The initial and final eGFR of the participants were 74.70±17.97 mL/min/1.73 m2and 74.01±21.89 mL/min/1.73m2 and those of the non-participants were 71.65±20.78 mL/min/1.73 m2 and 68.03±20.64 mL/min/1.73m2 , respectively. The change of eGFR of the participants was -0.87% (eGFR, final-initial/initial x100%) and that of the non-participants was -7.9%(p value=0.023, by Mann-Whitney U test).

Conclusions: The earlier correction of glycemic control through entering the DM shared-care network may do a better job in preserving the renal function of diabetic patients.

PD-38

ASSOCIATION BETWEEN FRAMINGHAM STROKE RISK SCORE AND SUBCLINICAL ATHEROSCLEROSIS IN ELDER TYPE 2 DIABETIC PATIENTS WITHOUT CARDIOVASCULAR DISEASE

1YI-MeI wang, 2WEN-JANE LEE, 3WAYNE H-H SHEU

1Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, R.O.C. 2Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, R.O.C. 3Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, R.O.C.

objective: Stroke is the third leading cause of death in Taiwan. Diabetes greatly increases the risk of stroke. Framingham stroke risk score (FSRS) is a widely used tool to identify asymptomatic individuals who are at risk to stroke. Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of subclinical atherosclerosis. We aim to investigate the association between subclinical atherosclerosis and FSRS in elder Type 2 Diabetes Mellitus (T2DM).

Methods: This cross-sectional study enrolled 68 T2DM participants (33 men and 35 women, with age of 67.5±4.8 years (mean±SD)) and 34 non-DM participants (16 men and 18 women, with age of 66.8±4.8 years (mean±SD)) without history of CVD and cerebrovascular disease, aged ≥60 years, was analyzed. The baPWV, FSRS, clinical variables, basic laboratory data, plasma lipid profile, coagulation, fibrinolytic, and inflammation parameters were measured for each participant. A modified version of the Framingham stroke Risk Profile (incorporating age, sex, systolic blood pressure (SBP), smoking status, hypertensive medication, DM, atrial fibrillation, left ventricular hypertrophy, and prior CVD) was used to assess 10-years risk of stroke. Multiple regression assessed the independent correlates of baPWV. results: A significant increase of FSRS (15.8±8.6% vs. 6.7±4.9%; p<0.05), baPWV (16.4±2.3 m/sec vs. 14.9±1.9 m/sec; p<0.05), body mass index (BMI), heart rate (HR), SBP, pulse pressure (PP), haemoglobin A1c (HbA1c), fasting plasma glucose (FPG), creatinine (cre), estimated glomerular filtration rate (eGFR), uric acid (UA), and homocysteine (Hcy) was present in the T2DM group, with a significant decrease of total cholesterol (TCHO), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and vitamin B12 (Vit B12) levels compared to non-DM group. Compared with the non-DM group, the T2DM group had significantly higher rate of hypertension (HTN) (77.9% vs. 35.3%; p<0.05), use of anti-hypertensive drugs (76.5% vs. 32.4%; p<0.05), dyslipidemia (DLP) (64.5% vs. 34.3%; p<0.05), use of lipid-lowering drugs (55.9% vs. 11.8%; p<0.05), and Smoking (27.9% vs. 11.8%; p=0.07). Among the T2DM group baPWV had significant positive correlations with the duration of diabetes (r=0.265, p<0.05), age (r=0.395, p<0.001), BMI (r= -0.321, p<0.01), SBP (r=0.639, p<0.001), DBP (r=0.451, p<0.001), PP (r=0.489, p<0.001), MAP (r=0.654, p<0.001), HbA1c (r=0.339, p<0.05), cre (r=0.308, p<0.05), eGFR (r= -0.329, p<0.01), Hcy (r=0.209, p=0.088), D-dimer (r=0.201, p=0.099), and FSRS (r=0.582, p<0.001). In a multiple linear regression analysis, FSRS (95% CI: 0.015-0.233; p=0.027), HR (95% CI: 0.001-0.929; p=0.045), and PP (95% CI: 0.009-0.100; p=0.02) were independently associated with baPWV in T2DM after adjustment for other risk factors.

Conclusions: These results suggest that higher FSRS, HR, and PP are associated with baPWV in Elder T2DM patients without CVD.