PD：Poster presentation- Diabetes (1-27

PD-1 MATERNAL AND FETAL OUTCOMES OF PREGNANT WOMEN WITH TYPE 1 DIABETES, A NATIONAL POPULATION STUDY

1SHU-FU LIN, 2CHANG-FU KUO, 3MENG-JIUN CHIOU, 4SHANG-HUNG CHANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Office for Big Data Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan;4 Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Purpose: Pregnancy in women with type 1 diabetes is associated with poor maternal and neonatal outcomes. However, the risk of these outcomes has never been evaluated in an Asian national population. In this work, we report the maternal and fetal outcomes of pregnant women with type 1 diabetes in Taiwan.

Experimental Design and Results: A total of 2,350,339 pregnancy records created between 2001 and 2012 were obtained from the National Health Insurance database and analyzed. Here, 630 pregnancy records were identified in women having type 1 diabetes. Compared with pregnant women without type 1 diabetes, pregnant women with the disease showed increased risk of multiple adverse outcomes, including preeclampsia, eclampsia, cesarean delivery, adult respiratory distress syndrome, pulmonary edema, sepsis, chorioamnionitis, pregnancy-related hypertension, puerperal cerebrovascular disorders, acute renal failure, and shock. Fetuses of type 1 diabetic mothers were at increased risk of stillbirth, premature birth, large for gestational age, low birth weight, and low Apgar score. Of the studied endpoints, only preeclampsia showed an improvement in the late period (2011–2012) when compared with the early period (2001–2010).

Conclusion: These findings reveal that pregnant women with type 1 diabetes are at significantly increased risk of developing many adverse maternal and fetal outcomes. Therefore, pregnancy outcomes in women with type 1 diabetes should be improved.

PD-2 TPL2 (THERAPEUTIC TARGETING TUMOR PROGRESSION LOCUS-2) / ATF4 (ACTIVATING TRANSCRIPTION FACTOR-4) / SDF1Α (CHEMOKINE STROMAL CELL-DERIVED FACTOR-Α) AXIS SUPPRESSES DIABETIC RETINOPATHY

1DE-WEI LAI, 2KENG-HUNG LIN, 3WAYNE HUEY-HERNG SHEU, 1,4MEEI-LING SHEU

1Institute of Biomedical Sciences, National Chung Hsing University, Taiwan; 2 Department of Ophthalmology, Taichung Veterans General Hospital, Taiwan; 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 4 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan

Rationale: Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood–retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. Objective: TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of Nε(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. Methods and Results: Serum Nε-(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between Nε-(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell–derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). Conclusions: This study demonstrates that inhibiting the Nε-(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus–mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema. (Circ Res. 2017;121:e37-e52. DOI: 10.1161/ CIRCRESAHA.117.311066.)

PD-3 HIGH GLUCOSE VARIABILITY INCREASES RE-ADMISSION RATES WITHIN 30 DAYS OF DISCHARGE IN DEPARTMENT OF SURGERY

CHING JUNG HSIEH

Department of Internal Medicine, Paochien Hospital, Ping Tung, Taiwan, R.O.C.

Objectives: Glucose variability is common among hospitalized patients with type 2 diabetes mellitus (DM). We investigated to assess the variability of glucosein patient with type 2 DMaccounts for in-hospital readmission rates in department of surgery.

Methods: We retrospectively analyzed 196 patients with type 2 DM, who was admitted to our hospital for surgical interventions and re-admitted for the same disease (including wound infection) within 30days since January 2007 to December 2016. We also enrolled 610age and sex matched patients with type 2 DM, who received the same types of surgery at the same year as control. Outcome measure from electronic medical record included average and standard deviation (SD) of blood glucose during admission,glycated hemoglobin (HbA1c) within 1 month before and after admission, length of stay (LOS), medication for DM and co-morbidity

Results: Patients who had re-admission within 30 days of admission had higher SD of blood glucose levels than control ( 84.7 ± 53.5 mg/dL vs. 46.2 ± 42.8 mg/dL, p < 0.001) but not average of blood glucose levels (165.7 ± 27.5 mg/dL vs. 158.3 ± 27.2 mg/dL, p < 0.088). Comparing to control group, the study group also had higher HbA1c ( 8.4 ± 1.3% vs. 7.7 ± 1.1%, p < 0.015). There were no group differences in body weight, blood pressure, lipid profile, LOS, medication and co-morbidity. SD of blood glucose was highly correlated with average blood glucose levels and HbA1cs (r = 0.350; 3.48 respectively, all p < 0.001).The independent predictors ofSD of blood glucose levels during admission and recent HbA1c levels.

Conclusion: Decreasing glucose variability during admission and well blood glucose control before surgery are important for patients with type 2 DM to decreasing re-admission rates.

PD-4 EFFECT OF GLP-1 RECEPTOR AGONIST ON PATIENTS WITH TYPE 2 DIABETES IN REAL PRACTICE: EXPERIENCE FROM A REGIONAL HOSPITAL

WEI KYANT WANG, CHING-CHIEH SU

1 Internal medicine, Cardinal Tien hospital; 2 Division of endocrinology and metabolism, internal medicine, Cardinal hospital. School of medicine and Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University and

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) is a new injectable antidiabetic medicine. It can lower blood glucose and also result in a neutral or lowered body weight. However, the interaction of changes in blood glucose and body weight is not clear. Method: This study is a retrospective chart review study. Patients with type 2 diabetes who initiated liraglutide therapy from 1, Sep. 2016 to 30 Nov. 2016 were enrolled. We assessed the change in blood glucose and body weight after liraglutide treatment. Result: The study found that most patients had lower A1C and body weight simultaneously but no relationship between body weight and blood glucose change was found. Univariate correlations revealed baseline A1C was negatively correlated to the change of A1C. Age, gender, duration of diabetes, numbers of oral antidiabetic drugs, baseline body weight and BMI are not correlated to change of A1C. In terms of the change of body weight, younger patients lost more body weight. Numbers of antidiabetic drugs was borderline correlated to body weight change. In multivariable linear regression models,varibles such as male, diabetes duration, and baseline A1C are all positively correlated and numbers of antidiabetic drugs is negatively correlated to the change of A1C. Age is positively correlated and the number of antidiabetic drugs is negatively correlated to body weight change. As a conclusion, we found that liraglutide could decrease body weight and blood glucose. However, there is no relationship between the glucose reduction and body weight lowering effects. In respect of glucose reduction, male patients with longer diabetes durations, using less oral antidiabetic drugs or higher baseline A1C are good candidates for liraglutide treatment. In respect of body weight reduction, younger patients with less antidiabetic drugs are less likely to lose their body weight.

PD-5 EMPAGLIFLOZIN REPLACEMENT FOR DIPEPTIDYL PEPTIDASE-4 INHIBITORS IMPROVES GLYCATED HEMOGLOBIN IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES

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, Taoyuan, Taiwan

Aims/Introduction: To evaluate the efficacy of empagliflozin replacement for dipeptidyl peptidase-4 inhibitors (DPP4is) in patients with poorly controlled type 2 diabetes.

Methods: This study retrospectively reviewed the data of 197 patients with type 2 diabetes. Their DPP4is were switched to Empagliflozin. Twenty-four patients with upper-titrated other anti-diabetic agents were excluded. Data of the remaining 173 patients with no change of other anti-diabetic agents for 6 months were collected. The body weight (BW) and glycated hemoglobin (HbA1c) values at baseline, and 3 and 6 months after the switch were analyzed.

Results: Sixty-six percent of patients had benefit of glucose-lowering following the switch (9.2% to 8.1% at 3 months and to 7.9% at 6 months, both p < 0.001). The baseline HbA1c level is the only factor that predicts the responsiveness. Negative correlations were found between baseline HbA1c and delta HbA1c after the switch (3 months: ρ = -0.512, p < 0.001; 6 months: ρ = -0.637, p < 0.001). When baseline HbA1c values were equally sub-grouped into tertiles, glucose-lowering at both 3 and 6 months were found in patients of the second and third tertiles, but not in the first tertile (the lowest HbA1c tertile). A cutoff value of baseline HbA1c 8.4% showed benefit of the switch therapy (74.6% sensitivity and 67.8% specificity). The BW of the patients in all tertiles decreased significantly after the switch.

Conclusions: Empagliflozin replacement for DPP4is showed additional glucose-lowering effects for patients with higher baseline HbA1c and weight reduction effects regardless of baseline HbA1c.

PD-6 ASSOCIATION BETWEEN SERUM BILIRUBIN LEVELS AND PROGRESSION OF ALBUMINURIA IN TAIWANESE WITH TYPE 2 DIABETES MELLITUS

1WAI KIN CHAN, 1SUNG-SHENG TSAI, 1YAN-RONG LI, 1WEI-YU CHOU, 2HSIAOLIEN CHEN, 1SZU-TAH CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan City, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of internal medicine, Lo-Hsu Medical Foundation, Lotung Poh-Ai Hospital, Ilan county, Taiwan

Background To investigate the association between serum bilirubin levels and the progression of albuminuria in type 2 diabetic Taiwanese. Methods Longitudinal data from January 2001 to June 2015 were retrospectively reviewed from Chang Gung Memorial Hospital (CGMH). A total of 2788 type 2 diabetic patients with normal total serum bilirubin (BIL) levels were divided into four groups according to BIL quartiles, with the highest BIL in the fourth quartile. The trend and progression of urinary albumin/creatinine ratio (UACR), as well as other laboratory measurements, were compared among the four groups. The cumulative incidence and Cox proportional hazard model analysis were used to examine the relationship between BIL and the risk of albuminuria progression (AUPr), i.e., progression of the stage and/or persistent macroalbuminuria. Results The mean duration of followup was 1.5 years (± 1.37 years). The mean patient age, glycosylated hemoglobin level, and duration of diabetes were 62.52 years, 7.89%, and 3.98 years, respectively. A significant correlation was observed between BIL and both the UACR at baseline (P < 0.001) and the cumulative incidence of AUPr (log–rank test, P = 0.022). In hazard ratio (HR) analysis, patients in the fourth BIL quartile were shown to have the lowest HR among the four groups (adjusted HR = 0.69; 95% CI = 0.53–0.88, P < 0.05). Conclusions Higher serum BIL levels are associated with a lower risk of albuminuria progression in type 2 diabetes patients in Taiwan.

PD-7 A CASE REPORT OF ACUTE PANCREATITIS RELATED TO GLP-1 RECEPTOR AGONIST

LI JUI-HSIANG, LO SU-HUEY

Division of Endocrinology and Metabolism, Department of Internal Medicine Tao-Yuan General Hospital,

Introduction

In animal experiment studies, pancreas related to acute or chronic disease was described as sideeffect of GLP-1 receptor agonist. Clinical studies failed to demonstrated a correlation in humans. But we reported a case with pancreatitis history related to hypertriglyceridemia recurred after liraglutide therapy for 3 months.

Case report

A 33 year-old male had diabetes for 2 years and acute pancreatitis history due to hyperlipidemia. Chronic treatment was conducted with novomix 52u bid for diabetes, Sevikar 1# PO BID for hypertension and vytorin 1#qd+fenofibrate 1# qd for hypertriglycemia. The GLP-1 receptor agonist, liraglutide 1.8mg was started 3 months prior to presentation. This time, he suffered from severe left abdomen and flank pain for one day with vomiting and nausea. He visited our ER for help. Biological exams showed high lipase level 459 U/L-normal range<60u/L), high amylasemia (220U/L, normal range < 100u/), Lactic acid 2.8 mmol/L, elevation creatinine ratio 1.4 mg/dl, CRP 0.124mg/dl , normal hemoglobin level(13.0mg/dl), leukocytosis WBC=12990/ul without left shift and a total Ca level of 8.4mg/dl. Also glycemia was high 200mg/ dl. Ultrasonography scan showed heterogenous echotexture of pancreas, no gallbladder stone or intra/ extrahepatic biliary ducts dilatation and fatty liver. The case was interpreted as acute pancreatitis. The other laboratory finding was total cholesterol 121 mg/dl, triglyceride=356 mg/dl, LDL=74mg/dl, LDL=136/mg/dl. HbA1c=10.2%. After the exclusion of all other possible causes for acute pancreatitis, the pathology was related to liraglutide treatment. The treatment was interrupted.

Discussion

The exact mechanism for this potential adverse effect is not clear; it may be related to the development of antibodies. Liraglutide treatment was studied by pharmaceuticals companies and only 8 cases of acute pancreatitis (all as mild forms) in over 6000 patients treated were reported. A clear causal relationship is difficult to establish. Clinicians should use liraglutide cautiously in patients with history of pancreatitis particularly with disease of hypertriglycemia, alcohol use or cholelithiasis. If pancreatitis is confirmed, liraglutide should be discontinued.

PD-8 A CASE OF KLEBSIELLA PNEUMONIA LIVER ABSCESS WITH MULTIPLE SEPTIC METASTATIC INFECTIONS

LI JUI-HSIANG, LO SU-HUEY

Division of Endocrinology and Metabolism, Department of Internal Medicine Tao-Yuan General Hospital

Introduction Liver abscess is highly prevalent among diabetic patients. In this report, we described a rare case of klebsiella pneumonia liver abscess with multiple metastatic infections to perinephric abscess, perirectal abscess, prostate abscess, posterior pelvic cavity and presacral space. Case report A 52-year-old male admitted to the emergency room for acute conscious change with irritable behavior. On examination, no significant weakness or numbness was found on neurologic examination. Finger sugar showed Hi. Laboratory analyses produced the following results: sugar = 1675 mg/dl, BUN = 38 mg/dl, Cr = 1.9 mg/dl, AST/ALT = 54/60 IU/L, Na = 109 mg/dl, K = 3.6mg/ dl, Osmolarity = 343 mosm/L,PCT = 11.74 ng/ml, WBC = 28550 /mm3, seg = 92.3%, band = 3.9%, Hb = 10.7g/dl. Therefore, Under the impression of 1.HHS, 2.AKI, 3.Sepsis. He was admitted to our ICU for further evaluation and treatment. The patient was treated with third-generation antibiotics (ceftriaxone) and IV insulin. Abdominal echo revealed cirrhosis of the liver, hepatic tumor suspected abscess. Abdominal CT showed a 2.6 cm lobulated cystic lesion at S7 of liver, favor liver abscess, left perirectal abscess and prostate abscess formation, bilateral acute pyelonephritis, suspected perinephric abscess. The cultured blood and urine were positive for klebsiella pneumonia sensitive to cefazolin and ampicillin. Repeated abdominal CT still showed bilateral sides abscess formation of posterior pelvic cavity and presacral space, hepatic abscess Due to his condition not improving, the patient left the hospital seeking second opinion to Linkou Chang Gung Memory Hospital. Discussion: In patients with diabetes, liver abscess caused by Klebsiella pnuemonia is a known risk factor for embolic complications such as endophamitis, renal abscess, septic pulmonary emboli, chest wall abscess and meningitis. The pathogenic mechanism of primary Klebsiella pneumoniae liver abscess complicated with metastatic infection remains unclear. Fang et al. reported that mag A is an important virulence gene in invasive Klebsiella pneumoniae strains causing primary liver abscess and septic metastatic complications. Physicians should be aware of Klebsiella pneumonia liver abscess and should identify early signs of septic embolic because on the time management remains critical for a good outcome.

PD-9 ELEVATED SERUM CYTOKERATIN-18 LEVELS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE

1YU-HUNG CHANG, 2HSIEN-CHANG LIN, 1DER-WEI HWU, 1DAO-MING CHANG, 1KUN-CHEN LIN, 1YAU-JIUNN LEE

1Lee’s Endocrinology Clinic, 2LiTzung Biotechnology, Inc

Background: Cytokeratin-18 (CK-18) is a caspase-cleaved fragment released by injured hepatocytes, and serum levels of CK-18 were believed to be a marker of hepatic cell damage such as inflammation. Patients with type 2 diabetes (T2DM) were well known to have a high prevalence of the fatty liver condition. However, rare studies had been reported the serum CK-18 level in patients with T2DM and investigated the association between the levels with metabolic biomarkers.

Material and Methods: Healthy participants and T2DM patients who followed in the specialized diabetes polyclinic were enrolled. Physical and metabolic factors were collected, and NAFLD was screened by abdominal ultrasound and fatty liver index. Cytokeratin 18 level was detected by commercially available immunoassay (M30 and M65 ELISA kit, Previa AB, Sweden).

Results: There were 22.8% (29/127) and 35.9% (42/117) participants were diagnosed with NAFLD in the non-DM group and T2DM group, respectively. Both serum levels of CK-18 M30 and CK-18 M65 were significantly higher in patients with T2DM as compared with those of the non-DM group. Patients with non-alcoholic fatty liver disease (NAFLD) had higher serum CK-18 M30 level whatever with T2DM (205.8 ± 135.1 vs. 108.4 ± 66.19 U/L; P < 0.001) or without (177.69 ± 70.53 vs. 87.07 ± 34.57 U/L; P < 0.001). Similarly, serum CK-18 M65 was also higher in patients with NAFLD in the T2DM group (513.9 ± 271.2 vs. 285.4 ± 115.3 U/L; P < 0.001) and in the non-DM group (353.5 ± 162.4 vs. 248.51 ± 111.3 U/L; P < 0.001). Multi-variate regression analyses demonstrated that fasting plasma glucose was independently and significantly associated with CK-18 M30 (β coefficient: 0.002; P = 0.011)) and CK-18 M65 (β coefficient: 0.003; P < 0.001). These results suggested that CK-18 level was closely connected with diabetes mellitus.

Conclusions: Independent of NAFLD, our result suggests that CK-18 level was closely associated with the hyperglycemic milieu. The association between serum CK-18 and T2DM may worth for further investigation.

PD-10 THE EARLY CHANGES IN AXONAL NEUROPHYSIOLOGY OF AXON IN PRE-DIABETES

1NGUYEN THI THU TRANG, 4,5TING-I LEE, 2TSUI-SAN CHANG, 2,3JIA-YING SUNG

1International Master Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 2Department of Neurology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, R.O.C.; 3Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 4Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 5Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C

Introduction The sensory neuropathy in diabetes patients has been reported in previous studies. Sometimes the sensory symptoms have complained at the beginning of diagnosis of diabetes. The possible pathogenesis of neuropathy might start since hyperglycemia stage. Therefore it is supposed that the nerve axonal dysfunction in the pre-diabetes stages. Methodology 95 subjects were enrolled in this study; 72 subjects are pre-diabetic patients with/without neurological symptom and 23 are healthy subjects. All subjects received blood test, standard neurological examination and neuropathy scorereduced (TNSr), nerve conduction study (NCS) and sensory nerve excitability testing (NET). All subjects have their blood test checked one year later to make sure that the blood sugar is persistently higher than normal or not. We excluded the blood sugar is lower Results In compared to healthy control (HCs) cohort, pre-diabetes group had higher fasting glucose (P0.05). Conclusion These results revealed that the electrophysiological changes in peripheral sensory nerves might occur prior to diagnosis of diabetes. According to NET, the changes of superexcitability indices indicated the dysfunction of fast potassium channels which contribute to the stable of membrane potential in the paranodal region of sensory nerve axons. Our results also suggest that the possible pathogenesis in prediabetes might start from the paranodal, which might due to the pumping dysfunction.

PD-11 PROTECTIVE EFFECT OF ANGIOTENSIN RECEPTOR BLOCKERS ON DIABETIC NEPHROPATHY

1WU MING-HSIEN, 1CHEN SZU-TAH, 2,3LIN CHIA-NI, 3,4,5CHIU DANIEL TSUN-YEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Chang Gung Memorial Hospital Linkou Branch, Chang Gung University, Taoyuan, Taiwan; 3Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan; 4Healthy Aging Research Center, Chang Gung University, Taoyuan City, Taiwan; 5Department of Pediatric Hematology/ Oncology, Chang Gung Memorial Hospital, Lin-Kou, Taiwan

Objectives: Diabetic nephropathy (DN) is diagnosed on the presence of micro- or macroalbuminuria (mau or MAU) with or without deteriorated eGFR. Through direct or indirect mechanisms, the renin-angiotensin-aldosterone system plays critical roles in renal disease progression. Aside from their anti-hypertensive effect, a group of angiotensin receptor blockers (ARB) has been proposed to have reno-protective effect, we thus attempted to determine the effect of ARB on the progression of MAU and eGFR in DN.

Patients and Methods: We performed a prospective analysis in 46 type 2 diabetic patients (aged 41-75 y/o) with at least stage 3 CKD (eGFR< 60 ml/min/1.73 m2). In patients with newly diagnosed or pre-existed DN, ARB was prescribed or re-prescribed after a drug holiday for 2-4 weeks with careful adjustment for their blood pressure control. Blood and urinary biomarkers including Cr, eGFR, UACR, HbA1c and lipid profile were recorded before and 1-3 months after ARB treatment.

Results: ARB treatment significantly decreased UACR from 1157.4 ± 1565.0 mg/g (471.0, [159.0, 1864.0], median, [Q1, Q3]) to 1105.1 ± 1518.5 mg/g (328.0, [89.5, 1762.5]) (p = 0.001), especially in patients with MAU (MAU 1844.9 vs 1099.6 mg/L, p = 0.004; mau 184.9 vs 139.7 mg/ L, p = 0.123). Meanwhile, patients with better blood sugar control (HbA1c < 8.0) showed lower MAU; ARB treatment significantly improved UACR in this group but not in the poor controlled group (UACR 1801.3 vs 1683.6, p = 0.128 in HbA1c ≥ 8.0, UACR 795.9 vs 756.3, p = 0.016 in HbA1c < 8.0). LDL level also showed significant improvement (118.2 ± 31.1 vs 104.4±26.4 mg/dl, p = 0.020) after ARB treatment, especially in better sugar controlled group but was not associated with poor controlled group or status of UACR (HbA1c ≥ 8, LDL 131 vs 112, p = 0.293, HbA1c < 8, LDL 114.7 vs 99.7, p = 0.037; mau 94.2 vs 115, p = 0.432, MAU 114.2 vs 98.3, p = 0.056). None of the serum Cr, eGFR, HbA1c, HDL, triglyceride and blood pressure showed significant difference before and after ARB treatment.

Conclusion: ARB remarkably reduces macroalbuminuria and LDL cholesterol, which may reflect a proportional reno-protective effect. Although Cr and eGFR was not changed in this short-term study, the long-term effect of ARB on renal perfusion requires further study.

PD-12 FACTITIOUS HYPOGLYCEMIA IN TYPE 2 DIABETES PATIENT-A CASE REPORT

1,2YU-YI LIN, 1YI-CHUN LIN

1Section of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan; 2Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

Hypoglycemia is one of the major and dangerous complication of diabetes mellitus (DM) which may lead to permanent brain damage. There are numerous causes of hypoglycemia in DM patients including poor drugs and dietary compliance, organic causes (autonomic neuropathy, malabsorption, primary adrenal failure, hypopituitarism, gluten-sensitive enteropathy, Addison’s disease) and psychological issues (depression, malingering, factitious disorders). Levels of plasma insulin and c-peptide in the occurrence of hypoglycemia are essential for differential diagnosis. Factitious hypoglycemia, although difficult to document and only few case series were reported in the literature, is more common in patients with DM than normal population, which occurs secondary to the surreptitious use of insulin or insulin secretagogues (sulfonylureas, meglitinides). It is most common among young women or medical auxiliary and typically associated with a higher incidence of suicide, depression, and personality disorders. Clinical and biochemical findings are similar to those of insulinoma. High plasma insulin with suppressed plasma c-peptide and proinsulin concentrations indicates factitious hypoglycemia due to exogenous insulin injection. Prompt and accurate diagnosis is important to avoid severe hypoglycemic complications, unnecessary multiple extensive and expensive investigations, and surgical intervention for insulinoma. Psychotherapy is the cornerstone once confirmed diagnosis. Here we reported a case of insulin-induced factitious hypoglycemia in a chronic type 2 diabetes mellitus female patient who was initially misdiagnosed as dumping syndrome after subtotal gastrectomy.

PD-13 A CASE REPORT OF IMMUNE CHECK-POINT INHIBITOR INDUCED AUTOIMMUNE DIABETES MELLITUS

1YU-PING HUANG, 2SHANG-YIN WU, 1HORNG-YIH OU

1Division of Endocrinology and Metabolism, 2Division of Oncology and Hematology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Immunotherapy is effective in multiple malignancies refractory to standard chemotherapies. With the increasing use of immunotherapy, more and more autoimmune side effects are noted. Here, we describe a case with metastatic lung cancer who developed autoimmune diabetes after an immune checkpoint inhibitor, nivolumab, treatment. This patient is a 67-year-old woman with metastatic non-small cell lung cancer treated with nivolumab as the third line setting after disease progression despite a standard chemotherapy. She had no personal or family history of diabetes. Three weeks after receiving two doses of nivolumab, she developed diabetic ketoacidosis with hyperosmolality, complicated with altered mental status. Autoimmune diabetes was diagnosed on the basis of undetected C-peptide levels (C-peptide New onset autoimmune diabetes mellitus associated with immune checkpoint inhibitor treatment is extremely rare, occurring in less than 1% of patients. Time from drug administration to diabetes onset spanned 1 week to 12 months. The autoimmune diabetes mellitus is caused by destruction of pancreatic beta cells by autoreactive T-cells. Most patients exhibited inappropriately low or undetectable C-peptide. Current management includes traditional treatment strategies for diabetes ketoacidosis. Almost all of the patients remained insulin-dependent for glucose control. With the increasing use of immune checkpoint inhibitors, the incidence of autoimmune side effects associated with these agents is expected to rise. New onset autoimmune diabetes mellitus associated with nivolumab is rare but critical. Early recognition is important to prevent serious morbidity and mortality.

PD-14 HISTONE DEACETYLASE INHIBITION OF CARDIAC AUTOPHAGY IN RATS ON A HIGH-FAT DIET WITH LOW DOSE STREPTOZOTOCININDUCED TYPE 2 DIABETES MELLITUS

1,2TING-I LEE,

3YAO-CHANG CHEN, 2,4TING-WEI LEE, 4,5CHENG-CHIH CHUNG, 6SHIN-YI TSAO, 4,7YU-HSUN KAO

1Department of General Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C.; 3Department of Biomedical Engineering, National Defense Medical Center, Taiwan, R.O.C.; 4Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taiwan, R.O.C.; 5Division of Cardiovascular Medicine, Department of Internal Medicine, Wan Fang Hospital, Taiwan, R.O.C.; 6Division of Endocrinology and Metabolism, Department of Internal Medicine, Sijhih Cathay General Hospital, Taiwan, R.O.C.; 7Department of Medical Education and Research, Wan Fang Hospital, Taiwan, R.O.C.

Objective: Autophagy serves a role in preserving cellular homeostasis. Diabetes mellitus (DM) impairs cardiac autophagy and is associated with an accumulation of cytotoxic proteins that may provoke apoptosis and damage cardiomyocytes. Histone deacetylase (HDAC) inhibitors attenuate cardiac fibrosis and inflammation, and improve cardiomyopathy resulting from DM. However, the effect of HDAC inhibition on autophagy in DM cardiomyopathy has not been investigated. The purpose of the present study was to evaluate whether histone deacetylase (HDAC) inhibition modulates cardiac autophagy and to investigate the potential mechanisms in type 2 DM (T2DM) hearts. Methods: Electrocardiography was used to evaluate cardiac function and western blotting was used to evaluate protein expression in autophagy, the serine/threonine protein kinase mTOR (mTOR) signaling pathway, poly adenosine diphosphate ribose polymerase 1 (PARP1), insulin signaling, advanced glycosylation end product-specific receptor (RAGE), and proinflammatory cytokines in control rats and in rats treated with a high-fat diet (60% fat) and low-dose streptozotocin (35 mg/ kg) in order to induce T2DM, with or without an HDAC inhibitor (MPT0E014; 50 mg/kg/rat daily for 7 days). Results: Compared with the control rats, T2DM and T2DM rats treated with MPT0E014 exhibited elevated blood glucose levels and similar body weights. However, T2DM rats treated with MPT0E014 and control rats had a smaller left ventricular end-diastolic diameter compared with the T2DM rats. The control and T2DM rats treated with MPT0E014 had greater protein expression of cardiac phosphorylated (p)-5’adenosine monophosphate - activated protein kinase α 2, light chain 3-II, Beclin-1, glucose transporter 4, p-protein kinase B, and insulin receptor substrate-1 (Ser 307) compared with T2DM rats. In addition, control and T2DM rats treated with MPT0E014 had decreased cardiac protein expression of cleaved PARP1, p-mTOR-S2448, p-P70S6K-Thr-389, RAGE, tumor necrosis factor-α, and interleukin-6 compared with T2DM rats. Conclusion: The present study demonstrated that MPT0E014 may improve cardiac function in T2DM rats by modulating myocardial autophagy, inflammation and insulin signaling.

PD-15 DECREASED RISK OF GINGIVITIS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS USING CALCIUM CHANNEL BLOCKERS

HSIN-HUNG CHEN

Nantou Christian Hospital

Abstract Objective: To evaluate the association between gingivitis and the use of calcium channel blockers (CCBs) in patients with type 2 diabetes mellitus (DM). Methods: We used a nationwide health insurance claims database to select patients with type 2 DM and aged 20 years or older as the study population who received CCBs or without received CCBs between 2000 and 2008. Cox proportional hazards regression analysis was used to calculate the hazard ratio of gingivitis in these 2 groups. Results: The incidence density rates of gingivitis were 16.7 and 10.7 per 1000 personyears for the non-CCB and CCB groups, respectively. After adjustments for sex, age, comorbidity, and medications, the risk of gingivitis in patients with type 2 DM using CCBs decreased by approximately 25% compared with that of those without using CCBs. The male patients with type 2 DM using CCBs had a 0.72-fold lower risk of gingivitis than did those not using CCBs. Diabetic patients with CCBs was significantly associated with a declined risk of gingivitis than those without CCBs in both study group without any comorbidity. Conclusions: Data analyses revealed that CCBs can reduce the risk of gingivitis in patients with type 2 DM. Further survey is required for validating the association between CCB usage and risk of gingivitis among patients with type 2 DM.

PD-16 FIRST LINE THERAPY WITH METFORMIN AND PEMETREXED IN TYPE 2 DIABETES WITH ADVANCED LUNG ADENOCARCINOMA

1YI-TING TSAI, 2JIUN-LONG WANG, 3SHIH-NI CHANG, 3CHING-HENG LIN, 4,5CHUAN-MU CHEN

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital 2Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital 3Department of Medical Research, Taichung Veterans General Hospital 4Department of Life Sciences, National Chung Hsing University, Taichung 5Rong-Hsing Translational Medicine Center, iEGG Center5, National Chung Hsing University, Taichung.

Introduction and Objective: In Taiwan, first line therapy for advanced lung adenocarcinoma (wild type) consider chemotherapy with platin based chemotherapy with Pemetrexed. Among Type 2 Diabetes patients, the Metformim bears the anti-tumor effect. When combination of Metformin and Pemetrexed in first ling therapy in advanced lung adenocarcinoma, the efficacy is unclear. The aim of our study is to try to illustrate the synergistic effect of Metfomrin with Pemetrexed.

Methods: We retrospectively analyzed the National Health Insurance Registered Database (NHIRD) since 2004 to 2013 and figure out the effect of Metformin on overall survival for those type 2 Diabetes with advanced lung adenocarcinoma.

Result: Initially 88,467 patients were enrolled into the study and finally total 495 patients met the criteria. The mean age was about 67.4 ± 9.5 years old and Male predominant. We analyzed the antiDM medication respectively and found Metformin provided the survival benefit for those patients, the hazard ratio (HR) was around 0.61 (P value < 0.001).

Conclusion: In our study, we found preliminary result of Metformin on survival benefit for type 2 Diabetes with advanced lung adenocarcinoma received first line chemotherapy with Pemetrexed. Further Validation needs prospective randomized control studies.

PD-17 AUTOIMMUNE POLYENDOCRINE SYNDROMES TYPE 3 PRESENTING WITH SLOWLY PROGRESSIVE TYPE 1 DIABETES MELLITUS, PERNICIOUS ANEMIA AND AUTOIMMUNE THYROID DISEASE : TWO CASE REPORT

2KAO-MING HSU, 1SZU-HAN LIN, 1DONG-HWA TSAI, 1PEI-YUNG LIAO

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

Background: Autoimmune polyendocrine syndrome (APS) is a rare form of autoimmune disorder involving at least two glandular autoimmune-mediated diseases. APS type 3 is defined as the association between autoimmune thyroid disease and an additional autoimmune disease other than Addison’s disease. Only 3% to 5% of patients with isolated autoimmune thyroid disease have pancreatic islet autoimmunity and/or clinical type 1 diabetes. Autoimmune gastritis clusters with the autoimmune endocrinopathies that include autoimmune thyroiditis and type 1 diabetes mellitus.

Methods: We reports two cases with coexistence of slowly progressive type 1 diabetes mellitus, pernicious anemia and autoimmune thyroid disease.

Results: The first patient is a 78-year-old male diabetic patient presented with recurrent diabetic ketoacidosis, macrocytic anemia, vitiligo vulgaris and autoimmune thyroid disease. The second case is a 64-year-old female diabetic patient present with frequent hypoglycemia, macrocytic anemia with jaudice and thrombocytopenia, Alopecia and autoimmune thyroid disease. Both of them have an initial non-insulin-dependent stages and delay in the diagnosis of latent autoimmune diabetes of adult, pernicious anemia related to autoimmune gastritis and occult autoimmune thyroid disease. They were treated with intensive insulin therapy as well as intramuscular vitamin B12 injection; therefore, glycemic control became stable and anemia was alleviated.

Conclusions: In cases of concomitant diabetes and macrocytic anemia, the potential existence of latent autoimmune diabetes of adult and other associated autoimmune disease should be taken into account in daily practice. As both pernicious anemia and autoimmune thyroiditis tend to appear long after the onset of diabetes, particular attention must be paid to them.

PD-18 HYPERDENSE BASAL GANGLIA IN NONKETOTIC HYPERGLYCEMIA WITH STROKE-LIKE PRESENTATION

1SHIH-CHE HUA, 2PO-YEN YEH

1Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.; 2Division of Neurology, Department of Internal Medicine, St. Martin De Porres Hospital, Taiwan.

The imaging finding of lateralizing/asymmetric basal ganglia lesions (hyperdense on computed tomography) with clinical finding of hemichorea-hemiballism is highly suggestive of nonketotic hyperglycemia. We presented an unusual case of a patient with vague stroke-like complaints, not typical chorea, and imaging findings notable for lateralizing basal ganglia lesions. A 64 year-old gentleman with past medical histories of hypertension and dyslipidemia presented to the emergency department with a one week history of progressively worsening general weakness, especially left side. The patient’s neurologic exam revealed mild left upper and lower limb muscle power deficits (4+). The remainder of the neurological exam was unremarkable. Due to concern for acute ischemia, a non-contrast head computed tomography exam was performed which demonstrated hyperdensity in right basal ganglia (Fig. 1). Laboratory evaluation was notable for serum glucose of 1128 mg/dL and osmolarity of 339 mOsm/kg (normal 275-295). The patient was admitted later with impression of newly diagnosed diabetes mellitus with nonketotic hyperosmolar hyperglycemia. His symptoms improved and his neurologic exam returned to baseline with insulin administration and the normalization of his serum glucose level. Therefore, the presumed etiology for his initial neurologic symptoms was a global neurologic dysfunction secondary to hyperglycemia. After a four day hospitalization, the patient was discharged in his usual state of health and instructed to follow-up as an outpatient. There have been not a few case reports of chorea or another movement disorder in association with this pathognomonic imaging appearance of the basal ganglia. Here we presented a rare case of subjective sensation of generalized weakness and mild left hemiparesis on neurologic exam, initially concerning for a new ischemic insult. Hyperdense basal ganglia in nonketotic hyperglycemia may present as mimicking storke-like signs, instead as hemichorea-hemiballism.

PD-19 RISK OF MORTALITY INCREASES IN DIABETIC NEPHROPATHY IN UREMIA WITHOUT TREATMENT OF ANTI-DIABETIC AGENTS OR INSULIN

1CHUNG-ZE WU, 2JIN-SHUEN CHEN, 3LI-CHIEN CHANG, 4YUH-FENG LIN, 1JIUNNDIANN LIN, 5DEE PEI

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital;

4Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.; 2Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital; 3 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, R.O.C.; 5 School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, R.O.C.

Background: The suggestion “diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs” from our group has been published. However, the retrospective cohort study was between 2002 and 2007. In the period, in Taiwan, oral anti-diabetic agents (OADs) was sulfonylurea, alpha-glucosidase inhibitors, meglitinide, and thiazolidinedione. New OADs were market in Taiwan after that period. A new longitudinal 5-year (2011 – 2015) observational study was conducted to investigate whether the use of anti-diabetic medications, including new OADs, affected survival rates of diabetic dialysis patients or not.

Methods: A retrospective cohort study by data sample of 2 million patients from Taiwan’s National Health Insurance Database surveyed patients with diabetes who began dialysis between 2011 and 2015. The population were divided using and non-using anti-diabetes medicine. Furthermore, the populations in non-using anti-diabetes medicine were sub-divided to only insulin, only oral antidiabetes agent (OAD), and combination of insulin and OADs. Survival prognosis, causes of death, and effects on survival prognosis of different classes of anti-diabetic medicine (sulfonylurea, a-glucosidase inhibitors, meglitinide, thiazolidinedione, DPPIV inhibitor, GLP-1 receptor agonist) were analyzed.

Results: There were 1,887 patients with diabetic nephropathy in uremia enrolled and followed up for 5 years or to date of death. Of 882 patients died in the period, those non-using anti-diabetic medicine (62.36 %) had a higher mortality rate than those using anti-diabetic medicine (41.98%). After the multivariate analysis, group of combination of insulin and OADs had the lowest risk of death (HR 0.59, 95 % CI 0.57–0.61), followed by OADs alone (HR 0.68, 95 % CI 0.52–0.70) and then insulin alone (HR 0.781, 95 % CI 0.72–0.83). Furthermore, there were no significant differences in survival prognosis for the six classes of anti-diabetes medicine.

Conclusion: This 5-year observational study results suggested that diabetic dialysis patients with anti-diabetic drugs had a lower risk of death compared with those without anti-diabetic drugs. Despite insulin therapy, appropriate OADs should play an important role in treating these patients.

PD-20 BASELINE HBA1C LEVEL AND BODY MASS INDEX PREDICT EFFICACY OF DIPEPTIDYL PEPTIDASE-4 INHIBITORS IN TAIWANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS

1YI-HSIN LIN

1Division of endocrinology and Metabolism, department of internal Medicine, Taiwan Adventist Hospital

Background/Purpose: Dipeptidyl peptidase-4(DPP-4) inhibitors are the most popular oralantidiabetic drugs (OADs) in recent 20 years because of low hypoglycemic risk, intermediate efficacy (HbA1c): 0.5-0.9%, neutral effect on body weight change, convenience for usage (mostly once daily) and rare major side effects. The purpose of the study was to find out the important predictors for efficacy of naïve use of DPP-4 inhibitors in Taiwanese patients with type 2 diabetes mellitus (T2D).

Methods: It was a retrospective observational study. 193 T2D patients (122 males) were naïve DPP-4 inhibitor users at the age 58.0 ± 12.6 years with disease duration 5.4 ± 4.7 years, body mass index (BMI) 26.1 ± 4.3 kg/m2 and eGFR 95.9 ± 27.0 (mL/min/1.73 m2) were assessed for HbA1c in 6 months.

Results: 193 T2D patients used DPP-4 inhibitors as 2nd or 3rd line of OADs (2.8 ± 0.7 kind of OADs). The efficacy was HbA1c: 1.1 ± 1.2% in average. 138(71.5%) patients were effective (HbA1c ≥ 0.5%) with mean HbA1c(1.5 ± 1.1%, compared with non-effective (HbA1c < 0.5%) group, 0.0 ± 0.4%, p < 0.001). The efficacy was significantly better in statistic in the BMI < 25 group than the BMI ≥ 25 group (HbA1c(%) (1.4 ± 1.4 vs. 0.9 ± 0.9, p = 0.012). The higher baseline HbA1c (%) level group (< 7.5 vs. 7.5-9.0 vs. > 9.0) had significantly better efficacy (HbA1c (%) (0.4 ± 0.5 vs. 0.9 ± 0.8 vs. 2.3 ± 1.5, p < 0.001), compatible with positive association in single regression analysis. Finally, gender, age, duration of T2D, number of kinds of OADs and eGFR level played no role in efficacy.

Conclusion: Using DPP-4 inhibitors as 2nd or 3rd line of OADs, the study predicted higher baseline HbA1c level and lower BMI as important factors for efficacy of DPP-4 Inhibitors in Taiwanese diabetic patients.

Keywords: dipeptidyl peptidase-4 inhibitor, type 2 diabetes, HbA1c, predictor of efficacy

PD-21 REVIEW OF SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS INDUCED EU-GLYCEMIC DIABETIC KETOACIDOSIS : POSSIBLE PATHOPHYSIOLOGY AND CONTRIBUTING FACTORS

1YI-HSIN LIN

1Division of endocrinology and Metabolism, department of internal Medicine, Taiwan Adventist Hospital

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the newest class of oral antidiabetic drugs (OADs), approved to be a second-line OAD for type 2 diabetes in Taiwan since 2016. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) had both released statements associating the use of SGLT-2 inhibitors may increase the risk of eu-glycemic diabetic ketoacidosis(euDKA). This review reveals the possible pathophysiology with a chain of metabolic adaptions to decrease plasma glucose and increase plasma ketone bodies through pancreas, kidney, liver and adipose tissue. Moreover, euDKA is a potential and rare complication of treatment with SGLT-2 inhibitors when coexisting with triggering factors. It is an emerging challenge for clinical physicians and patients treated with SGLT-2 inhibitors. Therefore, literature review of possible pathophysiology and contributing factors is presented in order to make more attentions in public.

PD-22 CASE REPORT: THE SAFETY AND EFFICACY OF LIRAGLUTIDE IN PATIENT WITH MITOCHONDRIA DIABETES AND PSORIASIS IN SHORT-TERM USE

JIN-WEI HUANG

Lohas Clinics

A 31-year-old female with normal body weight, mitochondrial diabetes, asthma, and psoriasis was under basal-bolus insulin therapy for more than 10 years. Her mother was diagnosed of mitochondrial diabetes with 3,243 nucleotide pair (NP) mutation about 30 years ago. Due to the progress of insulin control in past 3 to 6 months even under intensive diet control and self-monitor blood glucose, the glucagon-like peptide-1 receptor (GLP1) agonist liraglutide was added for better sugar controlled. The patient experienced marked improved in her psoriasis after 2 to 3 months of treatment course. The severity of Itching and the area of psoriasis was improving. The Hba1c and rates of hypoglycemia was also improving. However, the body weight did not been changed. The treatment of liraglutide was shifted to empagliflozin. Psoriasis progress again with large area of psoriasis and itching progress. The empagliflozin was shifted back to liraglutide. After 2 months of re-add liraglutide, the severity of itching and the area of psoriasis was improving again. The HbA1C and rates of hypoglycemia was improving again. However, the body weight was kept stationary. Except of mild nausea sensation, no adverse effect was observed during this treatment course. There are few study focus on obesity patient with diabetes and psoriasis received the treatment of liraglutide. There reports disclosed the benefit of liraglutide treatment for both diabetes and psoriasis. However, this is the first case of patient with mitochondrial diabetes and psoriasis received the liraglutide therapy. This case report disclosed the safety and efficacy of liraglutide for patient with mitochondria diabetes and psoriasis in short-term use.

PD-23 CASE REPORT: THE SAFETY AND EFFICACY OF SGLT2 INHIBITOR EMPAGLIFLOZIN IN PATIENT WITH MITOCHONDRIAL DIABETES.

1JIN-WEI HUANG, 2HUI-CHUN HSU

1 Lohas Clinics; 2 Po Sin Clinc

A 34-year-old male with overweight and mitochondrial diabetes received basal-bolus insulin therapy for more than 10 years. His mother was diagnosed of mitochondrial diabetes with 3,243 nucleotide pair (NP) mutation about 30 years ago. Due to progress of diabetes control, he agreed of SGLT2 inhibitor empagliflozin therapy. After 3 months of therapy, the hba1c(6.0% → 5.6%) and the body weight (69.6kg → 61kg) was improving. The total daily dose of insulin was also decreased during the treatment (92U → 81U). No diabetes ketoacidosis nor lactate acidosis was noted during this treatment course. There are few case report disclosed the efficacy and safety of SGLT2 inhibitor in patient with mitochondrial diabetes. This is the first case report in Taiwan disclosed the safety and efficacy of SGLT inhibitor in patient with mitochondrial diabetes. Most patient with mitochondrial diabetes failure of oral anti-diabetes medication and need insulin for long-term treatment. In this case report, it disclosed that SGLT2 inhibitor for patient with mitochondrial diabetes had similar effect on HbA1C, total daily insulin dose and body weight compared with the effect on patient with type 2 diabetes. There is also no adverse effect observed during this short-term treatment However, there is no muscle power test nor ejection fraction test was done during the treatment course. In conclusion, SGLT2 inhibitor empagliflozin is safe and effect for patient with mitochondria diabetes during shortterm used.

PD-24 A CASE REPORT: ADVANCED PANCREATIC NEUROENDOCRINE TUMOR WITH PRESENTATION OF EPISODIC HYPOGLYCEMIA

1I-CHEN CHEN, 1YI-HONG ZENG, 1,2CHUN-CHUAN LEE

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Medicine, Mackay Medical College, New Taipei City, Taiwan

Background: Hypoglycemia is an uncommon clinical problem in patients not being treated for diabetes mellitus. The causes are variable, encompassing drugs, critical illnesses, hormone deficiency, nonislet cell tumor and endogenous hyperinsulinism. Here, we present a young female of episodic hypoglycemia, which was subsequently diagnosed as advanced pancreatic neuroendocrine tumor (PanNET).

Case report: A 35 year-old G1P1 female presented to Mackay Memorial Hospital with episodic consciousness change caused by hypoglycemia since Oct-2015. There was no significant medical disease and contributory family history. Her high was 158 cm and weighted 45 kg with the BMI of 18 kg/m2. She also complained of poor appetite and loss of weight 10kg within 1years. The family stated she can’t be awakened in the morning for several times and serum glucose showed 37mg/dL in emergent department. Her consciousness improved after glucose supplement. Laboratory tests revealed ALT 67 IU/L, Creatinine 0.6 mg/dL, CEA 1.45 ng/ml, AFP 8.63 ng/ml, CA-125 21.65 U/ml, CA-153 10.03 U/ml, CA-199 0.01 U/ml, Chromogranin A (CgA) 997.2 ng/ml, Gastrin 289.00 pg/ml, Prolactin 13.16 ng/ml, Calcium 8.6 mg/dL, intact-PTH 21.34 pg/ml. Prolonged fasting test revealed insulin 14.1 uIU/mL, C-peptide 3.82 ng/mL, serum glucose 47 mg/dL, ACTH 29.95 pg/mL, Cortisol 6.48 ug/dL, IGF-1 220 ng/mL. MRI in July-2016 demonstrated a space occupying lesion abutting the pancreatic tail and metastatic lesions in both lobes of liver. Endoscopic ultrasound guided fine needle aspiration of pancreas tumor and echo-guided biopsy of liver reported neuroendocrine tumor grade 2. Somatostatin analogue (SSA) had been instituted for hypoglycemia and then she received Everolimus treatment.

Discussion: The incidence of neuroendocrine tumor is rising because of the improvement of image investigation. It is categorized as functioning and non-functioning subtype. An insulinproducing Pan-NET causing episodic hypoglycemia is considered to be an insulinoma. Unique features of insulinoma are 90% benign, 90% solitary, 90% intrapancreatic and 90% small (< 2 cm). The laboratory workup of insulinoma is directed to hyperinsulinism, comprising tests of insulin, C-peptide and proinsulin. In addition to primary imaging as US, CT and MRI, nuclear medicine imaging and invasive study such as EUS (endoscopic ultrasonography) and ASVS (arterial stimulation venous sampling) are often warranted for diagnosis of insulinoma. Once diagnosed, insulinoma is classified into locoregional and metastatic disease. For locoregional insulinoma, there is great chance to cure with surgery. For metastatic disease, the first step of treatment is to manage hypoglycemia

with medications, of which diazoxide and somatostatin analogs (SSA) are most commonly used. The next step is surgery for resectable liver metastasis and systemic antitumor therapy, including SSA, chemotherapy, targeted therapy and peptide receptor radionuclide therapy (PRRT). SSA and targeted therapy have been shown to improve progression-free survival. Although neuroendocrine tumor is not rapid progression, metastatic tumor would cause mortality and morbidity. Early detection and intervention will improve patient’s life quality and survival.

PD-25 ASSOCIATION OF DIABETIC KETOACIDOSIS AND GLYCEMIC CONTROL AMONG TYPE 1 DIABETES WITH PREMIX VS BASAL BOLUS INSULIN THERAPY

1WEI-YU CHOU, 1SZU-TAH CHEN

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taiwan, R.O.C.

OBJECT: To determine the rate difference of diabetic ketoacidosis (DKA) among children, adolescents and young adults with type 1 diabetes receiving basal bolus or premixed insulin therapy.

RESEARCH DESIGN AND METHODS: 9597 type 1 diabetic patients were retrospectively studied from Chang Gung Research Database (CGRD) between 2001 and 2016, the incidence of DKA requiring hospitalization was analyzed. Exclusion criteria include use of different regimen during the follow-up period, missing data, DKA episode before confirmed diagnosis and insulin exposure and Age > 20. Propensity score with inverse probability of treatment weighting analyses with age, sex and glycated hemoglobin(A1C) as covariates were used to account for relevant confounders.

MAIN OUTCOMES AND MEASURES: Primary outcome was event rate of DKA during the follow-up treatment year. Secondary outcome aims on metabolic indicators control such as glycated hemoglobin levels, triglyceride, LDL and HDL.

RESULTS: Of 825 patients (mean age, 12.2 ± 4.31 years; 55%male), 273 used premixed regimen (mean duration, 9.02 years) and 552 used basal bolus regimen (mean duration, 7.82 years). Among those patients, 226 patient using premixed regimen were matched to identical number of patients using basal bolus regimen. In the entire cohort, premixed regimen comparing with basal bolus regimen was associated with higher rates of DKA (4.53 vs 10.62 per 100 patients; P < 0.001). The trend was also found in matched cohort. (HR 2.0, P = 0.0371). In the cox regression hazard model, the glycated hemoglobin level showed significant influences on the incidence of DKA. (HR 1.354, P < 0.001) The influences were not significant if the A1C level lower than 7.5%. In the secondary outcome, A1C levels were lower with basal bolus regimen than with premixed regimen (8.87 ± 1.62% vs 10.02 ± 2.03%; P < 0.001). Triglyceride level were lower for basal bolus regimen compared with premixed regimen (88.32 vs 109.1; P = 0.015). There was no significant difference in HDL and LDL level between both treatment regimens.

CONCLUSIONS: Patients used premixed insulin regimen may increase DKA event rate comparing to basal bolus regimen in T1D children, adolescents and young adults.

PD-26 REGUATION OF THE GUT–LIVER AXIS BY GLP-1 RECEPTOR AGONIST TO ATTENUATE THE FATTY LIVER

1HSIN-YING CHIOU, 1HE-JIUN JIANG, 2KUN-BOW TSAI, 1WEI-WEN HUNG, 1PI-JUNG HSIAO

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University,Taiwan, R.O.C.; 2Department of Pathology, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, R.O.C.

Background: Prevalence of the non-alcoholic fatty liver disease (NAFLD) is estimated 20-30% in Western countries and up to 18% in Asia with an increasing trend in the whole world. Diabetes and aging could deteriorate and fasten the progression from NAFLD to steatohepatitis and end-stage liver diseases. Until now, it is still lack of effective medicine to treat NAFLD. The gut-liver axis is balanced by the homeostasis of gut microbiome, intestinal and liver immunity to response the dietary nutrition. The “Leaky Gut” theory evidenced the potential mechanism for the development and progression of the NAFLD and type 2 diabetes. Derangement of gut barrier may lead to translocation of bacteria/ bacteria product into portal circulation, and activate inflammation and NAFLD progression. GLP1 is a gut hormone to amplify the insulin secretion by -cell in a glucose independent pathway. GLP1 receptor agonist (GLP-1 RA) has been proved to have hepato-protective effect in animal and human studies. But the molecular mechanism remains unclear. This study aims to investigate whether GLP1 RA ameliorate hepatic steatosis through gut-liver axis. Methods: Based on a high fat diet (HFD) induced NAFLD model, C57BL/6 mice were divided into 3 groups and fed with chow diet, HFD, HFD combined with weekly s.c. injected GLP-1 RA for 16 weeks. Parameters of body weight, insulin resistance (HOMA-IR), hepatic steatosis and proinflammatory surrogate markers were measured and compared among groups. Protein expressions of the gut barriers integrity, including (1) physical barrier: tight junction (occludin and zona occluden (ZO-1)) and mucus thickness, (2) biological barrier: compositions of fecal microbiota, (3) immunological barrier: macrophage infiltration, were all examined to determine the effect of GLP-1 RA in the regulation of gut-liver axis. Results: The HFD related body weight increment, insulin resistance, and hepatic steatosis were significantly ameliorated by GLP-1 RA administration. Hepatic expressions of lipogenesis (FASN, ACC, and SREBP-1) and proinflammatory proteins (NLRP3, pNFkB, and IL-1) were also reduced by GLP-1 RA by western blot. The metagenomic analysis of fecal microbiota with16S rRNA sequencing revealed a structural and diversity changes of the intestinal microbiota with the use of GLP-1 RA. Integrity of the gut barriers was apparently impaired by HFD, evidenced by the decreased expression of occludin, ZO-1, mucus thickness, and more macrophage infiltration. However, the above protein expressions all were reversed and attenuated by using GLP-1 RA even in HFD. Discussion and Conclusion: From our

biochemical and histological evidences, GLP-1 RA could regulate the gut-liver axis through improving leaky gut, diminishing the gut inflammation, and modulating the gut microbiota, which may contribute to the attenuation of hepatic steatosis and inflammation. It may also provide the molecular evidence to support the clinical indication of treating NAFLD by GLP-1 RA.

PD-27 THE GLUCOSE PATTERN CHANGES BETWEEN PREMIXED AND BASAL-BASED INSULIN THERAPIES IN PATIENTS WITH POORLY CONTROLLED TYPE 2 DIABETES MELLITUS

HSUEH-HUA CHIU, SZU-TAH CHEN, BREND RAY-SEA HSU, WEN-CHUN LU,

CHIA-HUNG LIN

Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkuo, Taiwan

Aims/Introduction: The premixed insulin is widely used in patients with type 2 diabetes mellitus (T2DM) in Taiwan even with fluctuated glucose control. The shifting to basal-based regimen is suggested but the comprehensive comparison of glucose patterns between different insulin therapies in patients with poorly controlled T2DM is controversial. The use of recently launched U-300 glargine insulin is supposed to have prolonged action and moderate glucose excursion. The objective of this study is to access glucose pattern changes among patients with shifting insulin therapies by continuous glucose monitoring (CGM).

Material and methods: Outpatient subjects received professional non-real time CGM before and after the insulin change while maintaining their usual diet and daily activities. The relationship of the mean amplitude of glucose excursion (MAGE), different glucose distribution, hyperglycemia, hypoglycemia risk, and estimated A1C among the changes of anti-diabetic therapy were then analyzed.

Results: There were 13 outpatient subjects (age = 61.3 ± 13.9 years; HbA1c = 8.2 ± 1.5%) with poorly controlled T2D enrolled. The pre-change CGM showed frequent lack of awareness of hypoglycemic events as recorded by CGM (3.6 % duration at a day time and 12.9% at night period with hypoglycemia). By comparison between pre- and post-insulin change glucose sensor data, the pre-mixed insulin revealed a higher nocturnal hypoglycemia rate than basal insulin-based therapy (4% vs. 2% duration of a day and 12% vs. 4.3% duration at night, P <0.05).

Conclusions: Hypoglycemia unawareness is not rare in poorly controlled diabetes patients in premixed therapy. The decreased risk of hypoglycemia unawareness may be achieved in these patients after shifting to basal insulin based therapy.