SD：Symposium-Diabetes (1-9

SD1-1 OVERVIEW OF TYPE 1 DIABETES IN TAIWAN: THE INCIDENCE, PREVALENCE AND MORTALITY RATE

YI-CHING TUNG

Division of Pediatric Endocrinology, Department of Pediatrics, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan, ROC

Type 1 diabetes (T1D) only consists 0.7% of diabetes population in Taiwan. However, these patients have onset at the young age and require lifelong insulin therapy.

Material: The Database of Taiwan National Health Insurance from 2000 to 2016.

Incidence: The number of new-onset T1D cases in Taiwan is about four to five hundred per year. Current incidence data reveals a trend towards younger age onset, increase by 30% in children. The standardized incidence of T1D in the general population is 2.23/105 person-year, and 6.70/105 personyear in the early adolescents. However, we still found forty percent of T1D having their onset in the adulthood.

Prevalence: The prevalence of T1D in all age groups is increasing. There are more females than males having T1D. The standardized prevalence of T1D in the general population is 49.3/105 persons, and 81.54/105 persons in the late adolescents. Ninety percent of adults with T1D have been diagnosed for more than 5 years. Therefore, the transitional care from pediatrics to adults should include patient education on potential chronic complications.

Mortality Rate: The standardized mortality ratio in T1D patients is three times higher than those of the general populations. In T1D patients, the most common cause of death is diabetes mellitus. Other causes include cancer, cardiovascular disease and cerebral vascular disease. Men with T1D had the higher mortality rate, and this may be associated with higher cardiovascular risks in these male patients.

SD1-2 INSULIN TREATMENT OF TYPE 1 DIABETES AND DIABETIC COMPLICATIONS IN TAIWAN

CHIA-HUNG LIN1,2

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan City33302, Taiwan

2Department of Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan City33302, Taiwan

The treatment guidelines suggest multiple daily injections (MDI) in type 1 diabetes (T1D). However, there are still patients, especially children at school, only choosing twice daily regimen because of the difficulty in multiple injections. Insulin analogs have accounted for 93.2% of the total insulin use. The proportion of insulin prescriptions is gradually shifting from human insulin to insulin analogue, and there is a consistent trend regardless of the T1D duration.

Pre-mixed insulin prescriptions are mainly used for a small number of adult T1D patients over the age of 20, and the proportion has shown a downward trend year by year, which is gradually consistent with Western countries, and shifts to the direction of MDI. From the perspective of all age groups, only 64.5% of patients with type 1 diabetes use MDI. Compared with advanced western countries, the proportion of patients with T1D who use intensive insulin therapy (including MDI and insulin pump) is still insufficient and must be promoted.

The acute hyperglycemic and hypoglycemic complications are decreased slowly in recent years. The prevalence of chronic micro- and macro-vascular complications is also going down although the risk is increased after 10 years of diagnosis. The reimbursement of SMBG test strips and insulin analogue is account for the improvement of diabetic control. In conclusion, the quality of T1D control is improving but more advanced help in new treatment paradigm shift in the near future is needed.

SD1-3 UTILIZATION OF MEDICAL RESOURCE AND QUALITY OF CARE IN PATIENTS WITH TYPE 1 DIABETES IN TAIWAN

1JUN-SING WANG

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

The incidence of type 1 diabetes is continuously increasing worldwide in recent decades. Patients with diabetes are at risks of chronic micro- and macro-vascular complications. Treatments for these complications lead to huge burden for medical cost, especially for inpatient care. The medical cost for patients with diabetes was more than double the amount for patients without diabetes in the United States, among which 25% was for inpatients care. The prevalence of patients with type 1 diabetes in Taiwan was lower than that in the United States. Moreover, we did not have data on medical resource utilization for patients with type 1 diabetes in Taiwan. Here, we reported findings regarding the utilization of medical resource using data from National Health Insurance Research Database.

SD2-2 UPDATE OF DKD IN TAIWAN FOCUS ON DKD TREATMENT GUIDELINE.

SHU-HENG HUANG

Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

It has been near 6 years since the National Institutes of Health published the guideline for " Clinical diagnosis and treatment of chronic kidney disease in Taiwan " in 2015. In these chronic kidney disease patients, diabetic kidney disease(DKD) accounts for a major part of this population. Prevention and treatment of diabetic kidney disease is an indispensable part of Taiwan. In the past few years, many studies have published grant advances in the medical treatment of DKD, including sodiumglucose cotransporter-2 inhibitors(SGLT2i) and glucagon-like peptide 1 agonists (GLP-1 agonist). Successive reports are showing that the use of these drugs has a clear effect on the control of diabetes, cardiovascular disease, and DKD.

Diabetes Association of the R.O.C. had published " 2019 Taiwan Clinical Practice Guideline for Diabetic Kidney Disease", based on the epidemiology, prevalence, definition, and risk factors of diabetic kidney disease. Diabetes Association has made an integrated overview, according to the evidence of clinical trials in the last few years. The guideline also integrated nutrition and daily activity. Besides, recent studies have also shown that DKD can also be affected by other specific diseases. Thus, the guideline also explored specific groups like individuals with hepatitis C, renal urinary tract disease, obesity, end-stage of renal disease, and older adult.

At present, there are more and more researches on DKD like DAPA-CKD (Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease) and FIDELIO-DKD (Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes). Diabetic Association expected to revise the latest DKD guidelines this year based on the latest level of evidence and immediate rolling updates. This section will share the main content of the upcoming changes.

SD2-3 DIABETIC KIDNEY DISEASE AND ESRD IN TAIWAN

SHANG-JYH HWANG, M.D.

Nephrology Division, Department of Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan. Taiwan Society of Nephrology.

The persistent high incidence and prevalence of dialysis ESRD is still a big issue in Taiwan. However, the trends of incidence and prevalence become flatten after age standardization, which indicates a significant contribution of elderly dialysis population to the growth of ESRD. Similar trend is also noted in both the incidence and prevalence in DM. Diabetes still has a 45-47% contribution to incident ESRD population in these years. Aged, diabetes, acute kidney injury, and/or AKI on CKD are the most common encountered situations in CKD care before entering dialysis, Diabetes with multisystemic comorbidities is the most difficult clinical situation to be cared, especially combined with cardiovascular comorbidity and complication.

Diabetes is known to be associated with CKD and CVD independently. It not only causes the morbidity and mortality of the affected persons, but also develops lots of complications in diabetic patients. Subsequently, the major target organ damages result in organ failure, especially in kidney and heart, and thus ESRD and EFrHF become major issue in clinical care. Dialysis diabetic patients even further develop multiple complications in various system, which constitute the major part of medical expenditures and burdens.

Taiwan has launched series of projects for prevention of DM, kidney diseases and care of DM/ CKD patients in the past 20 years, including Diabetes Integrated Care in 2000, Program, Pre-ESRD care project for stage 3b-5 patients in 2007 and Early CKD project for stage 1-3a in 2011. All projects provided patient education and multi-disciplinary care management, which were reimbursed by NHI. Recently, there is a project to include the CVD patients under planning. Definitely, a well collaboration of care among different specialists and professionals is the essential factor for successful care. With the discovery of ACEI/ARB and recent new DM treatment drugs of SGLT2 inhibitors. Effectiveness has been proved in many prestigious clinical trials. Their roles in control of sugar, prevention of early DKD, reduce incidence of HF, and improvement of long hard outcomes are confirmed.

We expect a new era of treatment not only in diabetes but also in kidney and heart field.

SD3-1 NOVEL INSIGHTS INTO THE THERAPEUTIC POTENTIAL OF THERMOGENIC FAT

YU-HUA TSENG, PH.D.

Joslin Diabetes Center, Harvard Medical School, MA, USA

We are amid a global epidemic of obesity and metabolic syndrome. Crucial to these pathologies is adipose tissue. However, not all adipose tissue is linked to storing energy. Instead, there are functionally distinct types of adipose tissue. White adipose tissue is the primary site of triglyceride storehouse, whereas thermogenic fat, which consists of classical brown and inducible beige/brite adipocytes, concentrates on thermogenic energy expenditure. The identification of active brown adipose tissue (BAT) in adult human subjects over a decade ago has ignited interest in this thermogenic tissue as a potential target for developing anti-diabetic and anti-obesogenic therapies. The primary physiologic function of BAT is to convert nutrients into physical heat. A key pathway for generating heat in BAT is by uncoupling oxidative phosphorylation through uncoupling protein 1 (UCP1). Numerous recent studies have shown that, in addition to its role as a thermogenic organ, BAT secretes several factors (i.e., the ‘batokines’) that regulate whole-body metabolism. In this talk, I will discuss our recent efforts in exploring new therapeutic pathways by harnessing the power of thermogenic fat and the impacts on energy metabolism.

SD3-2 METAINFLAMMATION OF ADIPOCYTES AND BEYOND

1,2W-S YANG, 1Y-T CHEN, 2F-R YANG, 3C-I HSIEH, 4H-C NIEN, 5T-W KAO, 1P-C CHOU,

2Y-C CHI, 6P-J YANG

1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taiwan. Departments of 2Internal Medicine, 4Family Medicine, and 6Surgery, National Taiwan University Hospital, Taiwan.

3

Departments of Internal Medicine, Chang Gung Memorial Hospital, Taiwan. 5Departments of Family Medicine, Tri-Service General Hospital, Taiwan.

OBJECTIVE To investigate the genetic factors related to metainflammation in adipocytes and their biological and clinical implications

METHODS Reduction of adiponectin gene expression was adopted as a biomarker of insulin resistance in adipocytes. Metainflammation has been considered as an important factor for insulin resistance. We treated mouse 3T3-L1 adipocytes with IL-1β to mimic metainflammation in adipocytes. The mRNA from 3T3-L1 cells treated with or without IL-1βwas sent for cDNA microarray study. Genes with significant up or down-regulation were further investigated in human studies. We also studied relevant issues of MFLD and myosteatosis in humans or cells.

RESULTS We found that indeed adiponectin gene expression was reduced by IL-1β treatment. Several genes from the microarray assays were chosen for human studies. We found that RNase-L, S14, and LBP were related to metabolic syndrome, MFLD or inflammation. LRG1 was demonstrated to inflammation and cardiovascular disorders. We also showed that increased adiposity may reduce muscle function at human and cellular level.

CONCLUSION This genomic approach is a sensible way to relate metainflammation of adipocytes to many aspects of human metabolic disorders and their compliations.

SD3-3 THE ROLE OF METFORMIN AND ORGANIC CATION TRANSPORTER 2 IN MANAGEMENT OF RENAL CELL CARCINOMA

1Y-F DU, 2C-Y HU, 3H-T WU, 1H-Y OU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 2Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei, Taiwan.

OBJECTIVE This study explores the association the pathophysiological role of metformin and organic cation transporter 2 (OCT2) expression in management of renal cell carcinoma.

METHOD We used lentiviral vectors to overexpress OCT2 in 786-O RCC cells (786-O-OCT2). The percentage of surviving cells were calculated after treatment with metformin, compared with control and cells lack of OCT2 expression (786-O). We also implanted 786-O cells or 786-O-OCT2 cells subcutaneously into the right flanks of two groups of mice. When tumors grow up to 50 mm3, we treated both groups of mice with metformin 50 mg/kg/day for 20 days. The volume of the tumors was calculated, and the weight of the excised tumor was measured after sacrificing the mice.

RESULT The cell viability of OCT2-overexpressed 786-O RCC cells treated with metformin was significantly decreased compared with cells without OCT2 expression. Under metformin treatment, the tumor size in OCT2-overexpressed 786-O xenograft is smaller than GFP-control.

CONCLUSION Metformin exerted better anti-cancer activity in OCT2-overexpressed RCC cells.

SD4-1 UPDATE OF GENETIC, BASIC, AND TRANSLATIONAL RESEARCHES OF TYPE 2 DIABETES AND OBESITY

YI-CHENG CHANG1,2,3

1Division of Endocrinology and Metabolism, National Taiwan University Hospital 2Graduate Institute of Medical Genomics and Proteomics, National Taiwan University 3Institute of Biomedical Sciences, Academia Sinica

Recent advance of genomics have shaped the genetic architecture of type 2 diabetes and obesity. Most of the genes associated with type 2 diabetes are related to pancreatic beta-cell function and most genes associated with obesity is related to neuronal control and immune function. Recent advance in appetite control, thermogenesis control, gut microbiota, metabolomic signature, and the role of immune cells in metabolism will be presented. In addition, some promising preclinical anti-diabesity therapy will be introduced.

SD4-2 LIFESTYLE AND MEDICAL INTERVENTION OF DIABESITY

1K-C HUANG

1Department of Family Medicine, National Taiwan University Hospital, Taiwan, R.O.C.

Obesity is highly associated with type 2 diabetes mellitus (T2DM), therefore diabesity indicates the coexistence of diabetes and obesity. Adequate weight reduction can prevent T2DM incidence in high risk subjects and improve the blood glucose control among those with diabetsity. Lifestyle modification, restricted balanced diet and increased physical activity, remains as the mainstream in the management of diabesity. Anti-obesity medications may be considered if lifestyle modification does not work. In Taiwan, only Xenical and Saxenda are two available anti-obesity drugs. Furthermore, weight neutral or reducing anti-diabetic medications should be considered as the first line of blood glucose lowering drugs for patients with diabesity. Bariatric surgery is indicated if the patient fail after lifestyle modification and pharmacotherapy. In the future, long acting or oral form GLP-1 agonists or other gut hormones will be on the market to assist patients with diabesity to control their body weight as well as blood glucose.

SD4-3 SURGICAL INTERVENTION FOR DIABESITY: A STORY OF 5%

WEI-JEI LEE, MD&PHD

Professor of Surg, Min-Sheng General Hospital, National Taiwan University, Taiwan

Diabesity, obesity and associated type 2 diabetes mellitus (T2DM), is becoming a serious medical issue worldwide. Bariatric surgery has been shown to be the most effective and durable therapy for the treatment of morbid obese patients. Today, bariatric surgery is played as metabolic surgery for the treatment of diabesity. Because Asian people are more sensitive to diabesity and tend to have an earlier onset T2D than Caucasian, Asian surgeons had more experience in using metabolic surgery to treat diabesity. The status and future of metabolic surgery for Asia diabesity depends on the 5% of medical statistics. 1) 5% of Taiwan National Health Budget: According to the report of Taiwan National Health Insurance Department, they spend 10% (55 billion Taiwan dollars) of their annual budget for hemodialysis of patients with end stage renal disease (ESRD). Half of the cause of ESRD in Taiwan is due to T2DM. Among them, most of them had their T2DM develop before age 40, so called young onset disease. Metabolic surgery plays a very important role in this group of patients and might prevent them from going into ESRD, and markedly reduce the dollars in treating them. 2) 5% of the whole T2D population in Taiwan: According to the data of Taiwan Diabesity Study (TDS), 5% of the whole T2DM population in Taiwan are possible candidate for metabolic surgery. However, metabolic surgery provided a better glycemic control, improving peripheral neuropathy and increasing renal function than patients received only medical treatment. Therefore, patients with high risk of T2DM complication and high response rate to metabolic surgery, such as young onset diabesity, should be the patients of priority to receive metabolic surgery.

SD5-1 THE PARADIGM OF CGM AND CSII BASED ON ADVANCED A.I. TECHNOLOGY FOR THE ARTIFICIAL PANCREAS

ROBERT A. VIGERSKY, M.D.

Chief Medical Officer, Medtronic Diabetes and Professor of Medicine of the Uniformed Services University of the Health Sciences

There have been major advances in automated insulin deliver systems over the past 10 years. The most recent iterations are the Medtronic MiniMedTM 780G and the Tandem Control-IQ which provide automated basal insulin delivery and automated correction boluses for persons with type 1 diabetes. However, these systems remain “hybrid” closed loop (HCL) systems because of the need for persons with diabetes (PWD) to interact with the system for the multiple insulin-dosing decisions surrounding their meals, exercise and other predictable activities. Thus, HCL’s fall short of being true artificial pancreas systems (APS). To become a true APS, artificial intelligence (AI) and machine learning (ML) must be incorporated into current algorithms to reduce or eliminate the need to rely on accurate carbohydrate counting and appropriately timed insulin administration. Using geolocation data from a smartphone, ML can assist an APS by predicting the content of an upcoming meal based on past behavior and help safely initiate the appropriate amount of insulin in advance of the meal. The amount of the insulin dose can be confirmed by a smart watch that contains an AI-derived hand gesture algorithm thereby informing the APS algorithm about when a meal is initiated, how long the meal lasts, and the likely quantity of the food being eaten. Accelerometers and heart rate monitors can identify the amount and intensity of exercise to further inform the system about the appropriate amount of insulin to be delivered. Integrating these data with glucose trends permits more timely and precise insulin delivery. By iteratively updating an automated insulin delivery algorithm, glycemic control can not only be maximized in a truly personalized way that few HCPs or PWD could otherwise achieve. AI- and ML-driven algorithms are putting us on the cusp a fully closed-loop artificial pancreas.

SD5-2 THE ADVANCE OF A.I. FROM RETINA TO WHOLE BODY IN FUTURE HEALTH INDUSTRY

YIH-SHIOU HWANG, MD, PHD

Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou and Taipei.

Background: Retinal imaging has been applied for detecting eye diseases and cardiovascular risks using deep learning–based methods. However, a deep learning–based method using retinal images for detecting other systemic diseases has not yet been well studied.

Aim: Our works aimed to develop and evaluate a deep learning model for detecting other systemic disease using retinal fundus images.

Methods: This retrospective study enrolled patients who underwent renal function tests with color fundus images captured at any time between January 1, 2001, and August 31, 2019. A deep learning model was constructed. Model performance was evaluated with respect to the receiver operating characteristic curve and area under the curve (AUC).

Conclusions: The deep learning model can be used to enable the detection of some systemic diseases.

SD5-3 POST -PANDEMIC ERA-DIGITALIZATION FLIPS HEALTH EDUCATION OF DIABETES

SHI-YU CHEN

Tri-Service General Hospital, Taipei, Taiwan RN, CDE

In the early 1980, continuous blood glucose monitor and insulin pump completely changed the paradigm of diabetes self-management. Diabetes management emphasis on preventive, predictive, personalized and involvement of patient and their families’ participatory which is the core of treatment decision-making (4P medical care). With high-tech wearable products providing instant and accurate blood glucose readings, the trends of blood glucose fluctuation combined with the use of precise model to calculate the demand for insulin dose and basal insulin delivery in a segmented manner. In the literature review, the use of high-tech products such as continuous blood glucose monitors are relatively good in terms of physical and psychological risks to the future. Somehow, there is still people quit using it after trying. At present, most of the research on the use of these high-tech products including continuous blood glucose monitors are for system development, refinement, and scientific proof of accuracy, safety and effectiveness. Fewer studies considering patients' thoughts or expected responses to these high-tech systems, and even underestimate the central role played by psychosocial factors in diabetes management. The purpose of the course is to further investigate the post-pandemic era-digitalization flips health education of diabetes, the patient adoption, utilization and continuance to use the complex process of successful implementation of continuous blood glucose monitoring, and the insight into the human factors of high-tech management of diabetes, reminding the basic literacy and ability of diabetes professionals to improve.

SD6-1 THE PERSPECTIVE OF ISLET TRANSPLANTATION ON THE TREATMENT OF TYPE 1 DIABETES

J-H JUANG

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

For patients with type 1 diabetes, isolation of islets from a deceased donor pancreas with intrahepatic transplantation of allogeneic islets can ameliorate problematic hypoglycemia, stabilize glycemic lability, and maintain on-target glycemic control, consequently with improved quality of life. Recent progress in techniques for islet isolation, islet culture, and peritransplant management of the islet transplant recipient has resulted in substantial improvements in metabolic and safety outcomes for patients. Multiple islet infusions are often required to achieve and maintain insulin independence. Many challenges remain in clinical islet transplantation, including substantial islet loss early and late after islet infusion. Contributions to graft loss include the instant blood-mediated inflammatory reaction (IBMIR), potent host auto- and alloimmune responses, and β cell toxicity from immunosuppressive agents. Protective strategies are being tested to circumvent several of these events including exploration of alternative transplantation sites, alternative islet cell sources, co-transplantation with mesenchymal stem cells or exploration of novel immune protective agents.

Extrahepatic sites have included the renal subcapsular space, striated muscle, pancreas, omentum, eye chamber, and testis. Thus far, all attempts have remained elusive to be superior to the intraportal site. Current work has focused on two potential sources for islets, namely xenogeneic islets and stem cell-derived islets. Pig islets provide an attractive source. The opportunity to genetically manipulate the pig genome initially with knock-out constructions for decay accelerating factor, and Gal epitopes, and more recently the potential to humanize the pig genome using CRISP-Cas9 technologies, offers great potential. Human embryonic stem cell (hESC) and induced pluripotent stem cells (iPSC) are being intensively investigated for their ability to differentiate into insulin producing cells. Two clinical trials utilize hESC-derived pancreatic endoderm cells contained in a macroencapsulation device. Ongoing research is determining the utility of generating patients’ own β cells with the iPS approach.

SD6-2 ENGINEERING OF MICROCAPSULES FOR OVERCOMING BARRIERS FOR ISLET TRANSPLANTATION.

KUN-HO YOON M.D.

Professor, Department of Endocrinology & Metabolism, The Catholic university Medical college, Seoul, Korea

One of the strategies for overcoming lifelong immunosuppression after islet transplantation is the incorporation of encapsulation technology, which can provide a physical immune barrier by keeping out high molecular weight immune system components, while still allowing low molecular weight oxygen, insulin and nutrients to pass through. Encapsulated islet transplantation approaches that have been studied so far include macroencapsulation, microencapsulation, conformal coating and nanoencapsulation. Among these methods, microencapsulation technology already translated into clinical practice. However, we still need to overcome the barriers such as incomplete function as an immune barrier, fibrosis on the surface and hypoxic damage on the encapsulated islets. To overcome these problems, our group has been developed surface coating capsules with various immunosuppresants to suppressed surface fibrosis. We also try to incorporate the perfluorodecalin to improve oxygen delivery to encapsulated islets and observed reduction of islet death in hypoxic environments in vivo and in vitro. With immune isolation with microencapsulation of the islets, we could incorporate the wide and genetically modified pig islets into the microcapsules and transplanted in small and large animals including dogs and monkeys. In this talk, I will present our recent results of pig islet transplantation on monkeys.

SD6-3 CURRENT PROGRESS IN STEM CELL THERAPY FOR DIABETES MELLITUS

1CHIA-NING SHEN, PH.D.; 1EDWARD PO-FAN CHU, PH.D.; 2CHIA-HUNG LIN, M.D.,

PH.D.; 1I-FEN CHENG, PH.D; 1CANDY HSIN-HUA CHO, PH.D.; TZU-CHIEN KUO, M.SC.; 1FANG-PEI CHANG, PH.D.; 3I-TE LEE, M.D., PH.D.; 3WAYNE H-H SHEU, M.D., PH.D.

1Genomics Research Center, Academia Sinica, 115 Taipei, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; 3Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Islet transplantation is a potential way to sustainably control blood sugar levels of patients with Type 1 diabetes mellitus (T1DM). However, the shortage of donor islets and poor islet graft survival limit the potential use of islet transplantation to treat T1DM patients. Recent research progress had demonstrated that stem cells hold potentials to be used for the treatment of DM patients. For example, both induced pluripotent stem cells and mesenchymal stem cells have been used to generate insulinproducing cells for the purpose of treating T1DM. In addition, we recently demonstrate beta-like cells derived from hepatocyte reprogramming could not only ameliorate autoimmune diabetes but can also significantly suppress autoreactive T cells. The findings raise the possibility of developing cell therapeutic strategies for autoimmune diabetes utilizing reprogramming approaches. Indeed, deficits of β-cell functional mass are now recognized as hallmarks for both T2DM as well as type 1 diabetes. Therefore, it is important to preserve β-cell functional mass in the management of diabetes. Development of strategies that can either induce β-cell regeneration or increase β-cell functional mass would be important for both types of diabetes. Induced pluripotent stem cells (iPSCs) generated from patients’ cells have been utilized for studying disease mechanisms and validating drug response. To derive diabetic patient-specific induced pluripotent stem cells (iPSCs) for purpose of modeling diseases causes and for evaluating therapeutic efficacy, we have then established methodologies to generate iPSCs from PBMCs of patients with T1DM and T2DM. To identify novel insulin secretagogues and/ or discover novel therapeutic target that can promote β-cell differentiation, we developed a reliable method that allows high-throughput identification of compounds that would enable to enhance betacell differentiation based on combining a calcium flux indicator together with insulin-luciferase fusion protein. We used the platform to assess a number of drugs that target various pathways to enhance β-cell differentiation. For example, we discovered that the use of IBMX as agent to increases Ca2+ influx through voltage-dependent Ca2+ channels could largely enhance the efficiency of iPSCs to differentiate into beta-cells. Importantly, we also utilized iPSCs to dissect mechanism involved in development of diabetic retinopathy. Based on establishment of protocols to differentiate of T2DM patients’ iPSCs into retinal pigment epithelial (RPE) cells and endothelial cells, we determined the

role of miRNAs in pathogenesis of diabetic retinopathy and identified RPE cells derived from iPSCs of DM-PDR patients had lower levels of phagocytic activity in high glucose condition. The findings possibly unravel the clues to the risk of DM patients to develop diabetic retinopathy. Hopefully, our findings would lead to developing novel cellular therapeutics for DM patients soon.

SD7-1 CAN WE RELY ON NUTRITION SCIENCE FOR DIABETES AND CARDIOVASCULAR DISEASE?

PEY RONG CHEN

Dietetic Department of National Taiwan University Hospital, Taiwan, R.O.C.

Due to factors such as the collection method of dietary intake, experimental design, selection and number of subjects on nutrition research, the degree of reliability of the research results will vary. Exploring the relationship between diet and disease, including cohort or retrospective studies. Such studies involve the completeness and accuracy of dietary intake, the length of collection time, the frequency of collection during the research period, consideration of seasonal factors, etc.; collection of dietary information Tools also have very important influencing factors, such as food weighing, food records, and dietary recall; subjects self-reported or interviews by trained interviewers, etc. The collection of dietary data is the most challenging part of nutrition research. For the complex content of human diets and time-consuming and labor-intensive issues, various dietary questionnaires have been developed to study the relationship between dietary habits and diseases, such as the Mediterranean diet.

Nutritional intervention research, the outcome is easily affected by whether other diet component is properly controlled, and the research results are also easily questioned. The collection of outcome parameters and the verification of results are also a university question. This also includes that with the advancement of medical research, the pathogenic mechanism and risk factors also keep pace with the times. For example, the risk of cardiovascular disease in the past has been based on total cholesterol, then, shift to LDL, LDL/HDL, and inflammatory markers, but now it may depends on the intestinal microbiota. Nutrition-related research on DM or CVD should focus on individualized considerations when

applied to the clinical fields; if the multiple situation of the case is not carefully evaluated, such as medication, exercise, work and life style, nutrigenomics or metabolomics, the results will be limited. The nutritional treatment of chronic diseases should be refined towards a new model as precision nutrition.

SD7-2 INTERMITTENT FASTING IN PATIENTS WITH DIABETES MELLITUS

W-L CHUANG

Department of Endocrinology, Lukang Christian Hospital, Taiwan, R.O.C.

Although more and more drugs developed to help patient to control blood glucose, nutrition therapy is still a popular method and issue in the News, internet discussion, and Youtube videos. Intermittent fasting is one of recent popular diet approaches for treating or preventing diabetes mellitus. But is intermittent fasting effective for treating or preventing diabetes mellitus and is it safe ? Is there sufficient evidence to support this diet approach?

SD7-3 PARADIGM SHIFTS IN NUTRITION THERAPY FOR TYPE 2 DIABETES

楊宜瑱

中山附設醫院 內分泌新陳代謝科

Nutrition therapy is the initial treatment for diabetes. However, recommended nutrition therapies tend to be largely based on consensus among experts rather than on scientific evidence. The principles of nutrition therapy have been inherited from the pioneers of diabetes research, but they lack current updates reflecting advances in nutrition science. Nutrition science is a constantly advancing field, just like other fields of science, and the accepted knowledge base changes over time. This session will review the evolution history of nutrition therapy for diabetes and then the future directions will be discussed.

SD8-1 ACCUMULATED CV DATA FROM SGLT2I OUTCOME TRIALS

SHIH-HSIEN SUNG

Attending Physician, Division of Cardiology, Taipei Veterans General Hospital, Taiwan Associate Professor, National Yang-Ming University

Cardiovascular (CV) diseases are the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (DM). Therefore, there has been an increasing endorsement from diabetic associations across the globe for the use of anti-diabetic drugs, which not only provide not only glycemic control but also have cardioprotective effects. Recent clinical trials have shown that sodium glucose co-transport 2 inhibitors (SGLT2i) have dramatic beneficial cardiovascular outcomes, independent of glycemic control. These include a reduced incidence of cardiovascular death, heart failure hospitalization, deterioration of renal function in people with and without diabetes, and those with and without prevalent heart failure or chronic kidney disease. The actual mechanisms responsible for these beneficial effects are not completely clear. Several potential mechanisms have been proposed to explain the cardioprotective and renal protective effects of SGLT2 inhibition, which include diuresis/natriuresis, blood pressure reduction, erythropoiesis, resume of tubuloglomerular feedback, improved cardiac energy metabolism, inflammation reduction, inhibition of the sympathetic nervous system, prevention of adverse cardiac remodeling, prevention of ischemia/reperfusion injury, inhibition of the Na+/H+-exchanger, inhibition of SGLT1, reduction in hyperuricemia, increasing autophagy and lysosomal degradation, decreasing epicardial fat mass, increasing erythropoietin levels, increasing circulating pro-vascular progenitor cells, decreasing oxidative stress, and improving vascular function.

Although the published trials have enrolled type 2 DM patients with varied baseline characteristics in terms of age, BMI, sex, glomerular filtration rate, or history of existing renal diseases, the SGLT2i were found generally to be beneficial by significantly reducing all-cause mortality, CV death, and risk of major CV events. Therefore, the clinical application of SGLT2i might be critical for specific populations and specific purposes. We have to understand the subtle differences between the SGLT2i to maximize the clinical benefits to our patients.

SD8-2 ACCUMULATED CARDIOVASCULAR DATA FROM GLP-1 RECEPTOR AGONIST CARDIOVASCULAR SAFETY TRIALS

1H-Y LI,

1Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital.

GLP-1 receptor agonists are incretin mimetic drugs that act on the GLP-1 receptor. It can stimulate pancreatic beta-cells to secrete insulin, inhibit pancreatic alpha cells for glucagon secretion, decrease appetite, and enhance satiety. Therefore, it is effective in lowering hyperglycemia and reducing body weight. In recent years, many cardiovascular safety studies have been published, such as The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial for liraglutide, The Harmony Outcome trial for albiglutide, The Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial for dulaglutide, The Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial for lixisenatide, The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial for one-weekly exenatide, The Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6) for semaglutide, and the Peptide Innovation for Early Diabetes Treatment (PIONEER) 6 for oral semaglutide. Among these trials, liraglutide, albiglutide, dulaglutide, and semaglutide have been shown to reduce cardiovascular events in subjects with type 2 diabetes significantly. In this talk, data from these cardiovascular safety trials will be reviewed.

SD8-3 OPTIMIZING DELIVERY OF GUIDELINE-BASED CARE IN PATIENTS WITH TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE

JENNIFER B. GREEN, MD

Department of Medicine, Division of Endocrinology and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA

Cardiovascular and kidney disease are common causes of premature death and disability for patients with type 2 diabetes mellitus (T2DM). Many agents in the SGLT2 inhibitor (SGLT2i) and GLP-1 receptor agonist (GLP-1RA) classes have demonstrated cardiovascular risk reduction and kidney function benefits which appear additive to traditional risk reduction strategies and also largely independent of the medications’ glucose lowering effects. Care guidelines from cardiovascular, kidney, and diabetes care societies have changed dramatically in response to this information; however, these beneficial medications are significantly underutilized in patients at high risk for adverse cardio-renal complications. There are numerous barriers to the adoption of evidence‐based therapies, including patient, clinician, and system‐level obstacles. Lack of clinician familiarity, inconsistencies in society guidelines, clinical inertia, cost considerations, and fragmentation of care all contribute to this evidence‐to‐practice gap. Primary care physicians, cardiologists and nephrologists will need to play key roles in the implementation of effective care strategies; fortunately, highly practical care pathways have been developed to facilitate appropriate use of SGLT2i and GLP-1RA medications in those clinical settings.

SD9-1 RISK FACTOR CONTROL IN DIABETIC PATIENTS WITH CARDIOVASCULAR AND KIDNEY DISEASES - TAIWAN DIABETES REGISTRY STUDY

1S-Y LIN, 2WAYNE H-H SHEU

on behalf of Taiwan Diabetes Registry Study

Objectives: We aimed to examine the achievement of guideline-recommended targets and medication use in diabetic patients enrolled from October 2015 to August 2018 in Taiwan Diabetes Registry.

Results: Among all 1201 participants (52.8% males), they had a mean age 65.7 ±11.7 years, and disease duration 15.2 ±7.7 years. The prevalence of cardiovascular diseases (CVD), including coronary artery disease, stroke, and peripheral arterial disease, was 11.5%, and 48.7 % for diabetic kidney disease (DKD), as defined by estimated glomerular filtration rates (eGFR) <60 ml/min/1.73 m2 or spot urine albumin to creatinine ratio (UACR) ≥30 mg/g. Among the patients with CVD, the control rates for glycated hemoglobin (HbA1c)<7% were 26.1%, 63.8% for blood pressure (BP)<140/90mmHg (35.5% for BP <130/80mmHg), and 73.2% for TC <160 mg/dL or LDL-C <100 mg/dL. In participants with DKD, the control rates were 31.2% for HbA1c <7%, 34.6% (BP <140/90mmHg), 62.6% (<130/80mmHg), and TC <160 mg/dL or LDL-C <100 mg/dL was 69.7%. In participants with CVD, all three risk factor control rates were 7.3% (BP <130/80 mmHg), and 13.8% (BP <140/90 mmHg), and in those with DKD, the control rates of all three risk factors were 10.3 % (BP <130/80 mmHg), and 16.3% (BP <140/90 mmHg). For those with CVD, the use of statin was 48.6%, and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) were prescribed in 43.9 % of patients with DKD.

Conclusion: In the TDR, suboptimal proportions of patients achieved composite targets. Care quality of diabetic patients remained to be improved.

SD9-2 FACTORS ASSOCIATED WITH QUALITY OF LIFE AMONG PATIENTS WITH DIABETES: THE TAIWAN DIABETES REGISTRY STUDY

1YI-JING SHEEN, 1SHIH-YI LIN, 2WAYNE H-H SHEU

1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taiwan, R.O.C.

OBJECTIVE A higher risk of depression and anxiety have been observed among T2DM patients. Disease severity, physical condition, economic factors, medication use, and psychosocial well-being could be factors that play a role in the complex interaction between T2DM and quality of life. Despite a growing appreciation for the quality of life and psychosocial well-being, there are limited studies exploring these complex issues among patients with diabetes in Taiwan. In the present study, we aimed to investigate factors associated with quality of life and measures depression in patients with diabetes using data from the Taiwan Diabetes Registry Study.

METHODS Study source: Taiwanese Diabetes Registry (TDR), a web-based platform, was launched in 2015. A total of 14 medical centers, 44 regional, local hospitals, and 37 general practice clinics participated in the TDR. Data were collected from 2015 Oct to 2018 Aug. The study subjects comprise groups including those who ever participated in “quality control study by Taiwan Association of Diabetes Educators” in 2006 and 2011 (group 1); newly diagnosed type 2 diabetes within 6 months (group 2). Outcome measurement: Quality of life was evaluated by the EuroQol- 5 Dimension (EQ5D), patients will be divided into two groups EQ-5D <1 vs. EQ-5D =1. The severity of depression was evaluated by the PHQ-9 (Patient Health Questionnaire: a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders).

RESULTS Proportions of patients with poor quality of life evaluated by EQ-5D were 38% and 31% in group 1 and group 2, respectively. Multiple logistic regression analyses revealed independent risk factors of poor quality of life of group 1 patients were: aged, female, abnormal PHQ-9; among patients in group 2, independent risk factors were aged, female, abnormal PHQ-9, and those who under insulin treatment for glycemic control. The proportions of depression detected by PHQ-9 rates were 23% and 20% among patients in group 1 and group 2, respectively. Multiple logistic regression analyses revealed that in group 1, independent risk factors of depression were: young, female, higher fasting glucose value; independent risk factors of group 2 were young, female, eGFR< 30, and ever experienced hypoglycemia events. In addition, there was a significant correlation between EQ-5D and PHQ-9 among both patients in group 1 and group 2 (AUC of ROC were 0.72 and 0.71 in group 1 and group 2, respectively).

CONCLUSIONS Type 2 diabetic patients with depressive situations also had a lower diabetes-

specific quality of life. Aged patients were associated with poor quality of life; however, young patients have a higher depression risk. Insulin injection is an independent risk factor of poor quality of life among newly diagnosed type 2 diabetes, however, it seems didn’t affect patients with a long duration of diabetes significantly. Monitoring for depression is needed while patients with poor quality of life among patients with type 2 diabetes. Awareness of depression in young female patients is also important.

SD9-3 TREATMENT GOAL ACHIEVEMENT AND ASSOCIATION WITH 10YEAR AND 30-YEAR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISKS IN PATIENTS WITH TYPE 1 DIABETES MELLITUS IN TAIWAN

1HSUAN-WEI LIN, 2TSUNG-HUI WU, 2CHII-MIN HWU

1Department of Internal Medicine, Taipei Veterans General Hospital Hsinchu Branch, Hsinchu County, Taiwan, R.O.C.; 2Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.

OBJECTIVE This study evaluated the status of attainment of treatment goals in patients with type 1 diabetes mellitus (T1D) in Taiwan and its association with 10-year and longer-term (30-year) risks for atherosclerotic cardiovascular disease (ASCVD).

METHODS Between 1 October 2015 and 31 August 2018, 1083 patients with T1D enrolled in the Taiwan Diabetes Registry were analyzed. The 10-year and 30-year ASCVD risk estimates were calculated respectively for patients aged 40-79 years with Pooled Cohort Equations and for those aged 20-59 years with the prediction algorithms based on the Framingham Offspring cohort. Multiple linear regression was used to examine the associations between ASCVD risk estimates and potential risk factors that were not included in risk calculations.

RESULTS The estimated 10-year ASCVD risk decreased with greater achievement of treatment goals (from none to all three goals: geometric mean [95% confidence interval] 4.6% [3.19-6.64], 3.39% [2.76-4.16], 2.09% [1.67-2.61], and 1.68% [1.11-2.55]). Similar declines in estimated 30year ASCVD risks with goal attainment were found. In addition, the waist circumference showed a significant association with 10-year ASCVD risk independently of other potential risk factors in multivariable regression analysis (β coefficient 0.24; P=0.002).

CONCLUSION Attainment of two or more treatment goals is associated with lower shortterm and longer-term estimated ASCVD risks in patients with T1D compared to those with lesser goal achievement.

SD9-4 THE EPIDEMIOLOGIC INVESTIGATION AND RISK FACTOR ANALYSIS OF DIABETIC KIDNEY DISEASE AMONG TYPE 1 DIABETES PATIENTS IN TAIWAN

1TJ CHANG, 2YB LIN,

3LM CHUANG

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

OBJECTIVE To identify risk factors of diabetic kidney disease (DKD) in type 1 DM patients.

METHODS We conducted a cross-sectional study by obtaining questionnaires from type 1 DM patients who has registered in Taiwan Diabetes Registry Study from 2015 to 2018. The definition of DKD is based on clinical guideline for diabetic management in chronic kidney disease (KDIGO 2020). Student’s t-test and Chi-square test were used to compare the difference of various parameters between patients with and without DKD. Pearson correlation was used to identify the association of various continuous variables with eGFR. Logistic regression was applied to identify DKD risk factors, and multivariable linear regression was conducted to identify the factors associated with eGFR.

RESULTS A total of 1086 type 1 DM patients were enrolled in our study, and 459 (42.3%) were defined as DKD, with median age 32 years (interquartile range, 22 to 41 y/o) and female predominant (57.3%). The type 1 DM patients with DKD had higher BMI, higher SBP & DBP, higher waist and HbA1C, longer disease duration, lower education level, higher percentage with family history of DM & hypertension, higher percentage with diabetes retinopathy, inpatient history within 3 years, and higher percentage of using ACEI/ARB. According to logistic regression model, lower education level, family history of DM, higher DBP, diabetes retinopathy and use of ARB were independent risk factors associated with DKD. According to multiple regression model, age, sex, use of ARB, education level, HbA1c, diabetes retinopathy, inpatient history within 3 years, and SBP were independently associated with eGFR. We also found only 3.1% and 10.3% T1DM patients with DKD receiving ACEI or ARB, respectively.

CONCLUSION In the Taiwan type 1 diabetes cohort, the presence of diabetic retinopathy, lower level of education and higher blood pressure were independently associated to with both DKD and lower eGFR. The administration of ACEI or ARB will be strongly recommended in patients with DKD to fulfill the standard of care in DKD patients.