SD：Symposium-Diabetes (1-8

SD1-1 OVERVIEW OF EVIDENCE-BASED MEDICINE

JIH-I YEH

Department of Family Medicine, Tzu-Chi General Hospital, Hualien County, Taiwan

The application of clinical epidemiology principles to clinical practice is the foundation of evidence-based medicine. Evidence-based medicine (EBM) is an essential topic in medical school curriculum, resident training program and accreditation of hospitals and training programs.

The aims of this talk is to give an overview of levels of evidence pyramid in clinical medicine and the steps to practice EBM. We will focus on the strength of evidence based on randomize controlled trials and meta-analyses. For the steps to practice EBM, we will describe the structure of the PubMed and useful strategies to conduct literature search in PubMed. The strategies include using medical subject headings, title search, and clinical queries.

SD1-2 THE KEY CONCEPTS OF CLINICAL TRIAL

KUOMENG LIAO

Department endocrinology and metabolism, Taipei City Hospital, Zongxiao branch, Taiwan

Randomized double blind placebo control studies are considered the “gold standard” of epidemiologic studies. If well-blinded and designed, they provide the strongest possible evidence of causation. However, how to interpretate the clinical trial data remains a challenge to many clinical doctors. So, in this lecture, we try to elucidate some concepts which frequently misunderstood but very important, by using recently published outcome trials, including EMPA-REG, CAVAS, DECLARE, and CREDENCE trials as examples . These concepts including: 1. Blindness, randomization, controls 2. Superiority trial vs. non-inferiority trial 3. Efficacy trial vs. safety trial 4. Intention-to-treat vs. Ontreat analysis 5. Primary endpoint, secondary endpoint, other pre-specified endpoint 6. Subgroup analysis, and test of heterogeneity 7. RCT vs. RWE 8. Interim analysis, and early termination criteria. And we will provide an overview of RCT, including aims, designs, methods, results and interpretations.

SD1-3 SUPERIOR OR NON-INFERIOR? CRITICAL APPRAISAL OF THREE GLP-1 RECEPTOR AGONIST CARDIOVASCULAR OUTCOME TRIALS FROM A METHODOLOGICAL POINT OF VIEW

CHIA-HSUIN CHANG

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Large placebo-controlled randomized clinical trials have shown that in addition to SGLT2 inhibitor, GLP-1 receptor agonist is another class of hypoglycemic agent that can significantly reduce the risk of cardiovascular adverse events. This presentation will focus on the three large GLP1 receptor agonist cardiovascular outcome trials – “Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER)”, “Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes (EXSCEL)”, “Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial”, and have an in-depth discussion about the similarities and differences in their study designs, conduct, analyses, and results. From the documents of the US FDA Endocrinologic and Metabolic Drugs Advisory Committee Meeting, we can learn about what should be considered to approve liraglutide for the reduction the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease. We will further talk about whether there is one GLP-1 receptor agonist superior to others in terms of cardiovascular protection, and emphasize “rational drug use”, that is, physicians need to consider both the risks and benefits of treatment for each individual type 2 diabetic patient.

SD2-2 HEART FAILURE TREATMENT UPDATE IN THE DIABETICS

TSUNG-HSIEN LIN

Division of cardiology, Department of internal medicine, Kaohsiung medical university hospital,Taiwan

The diabetics have not only higher risk of developing cardiovascular disease (CVD) but also heart failure. For heart failure with reduced ejection fraction (HFrEF), conventional treatment agents including renin-angiotensinogen system inhibitors, β blockers and sacubitril/valsartan work similarly in those with and without the diabetes. Although intensive glycemic lowering by various drugs or strategies could reduce the risk of CVD, it might increase the risk of heart failure. Furthermore, mortality in diabetic patients with heart failure have up to 6-fold risk compared with those without heart failure in major clinical trials. Although new anti-diabetic therapy with GLP1-RA has neutral effect on heart failure outcomes, cardiovascular outcome trials found SGLT2 inhibitors reduce the risk of cardiovascular death and heart failure hospitalization in the diabetics. Recently, DAPA-HF trial shows the risk of worsening heart failure or death was lower among those who received dapagliflozin, regardless of the presence or absence of diabetes among patients with heart failure and a reduced ejection fraction. Further studies will clarify the role of SGLT2 inhibitors on the heart failure with preserved ejection fraction.

SD2-3 GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONIST AND CARDIOVASCULAR OUTCOMES TRIALS

YU-YAO HUANG

Department of Medical Nutritional Therapy, Chang Gung Memorial Hospital at Linkou, Taiwan

Not until the publish of major cardiovascular outcome trials (CVOTs) with sodium glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in recent 5 years did the anti-diabetic medication can demonstrate their cardiovascular safeties and benefits in patients with type 2 diabetes. The potential cardioprotective effect of incretin-based therapies is attributed to their glycemic-lowering and multiple non-glycemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on inflammations and possible mechanisms on vascular plague stabilization. Liraglutide, Semaglutide, Albiglutide and Dulaglutide have been demonstrated to reduce the risk of major adverse cardiac event (MACE), whereas Lixisenatide and extended-release Exenatide had a neutral effect. Thus, it is conceivable that there are some class-effects and some different drug-specific properties across the class of GLP-1 RAs.

In this talk, we will discuss the results of the published major CVOTs between GLP-1 RAs and SGLT2i. Understanding the pros and cons of these drugs on individual component of MACE, along with the different action and mechanism of each drug may give lights for personalized treatment to achieve cardiovascular benefits.

SD3-1 DIABETES FATIGUES SYNDROME AND SARCOPENIA IN DIABETES PATIENTS

KUO-CHIN HUANG

Department of Family Medicine, National Taiwan University Hospital, Taipei, Taiwan

Diabetes Fatigues Syndrome (DFS) is commonly encountered in diabetic patients. DFS may be caused by lifestyle, nutritional, medical, and psychological factors. Fatigue could impair physical and mental function then lead to muscle weakness, impaired mobility, functional limitation, fall, sarcopenia, and frailty. Eventually, it will cause disability, reduce the quality of life, and increase mortality. The clinical characteristics of fatigue can be divided into psychological aspects related to cognitive function and physiological aspect related to muscle weakness. Patients may show reduced activity, low energy, decreased concentration, and depression. Hyperglycemia, chronic inflammation and vascular or neurological complications are possible underlying causes of fatigue in diabetic patients. Studies have shown that 61% of newly diagnosed diabetes patients have symptom of fatigue; nearly 70% of the 18-70-year-old type 2 diabetes patients of industrial workers have suffered from fatigue. Furthermore, it has been found that blood sugar levels are associated with the severity of fatigue in type 2 diabetic patients. Therefore, the diabetic patients with fatigue symptom should be carefully evaluated and then adopt therapeutic lifestyle modification, mental support, and adequate comorbidities management. Good sleep, regular exercise, healthy eating and better blood sugar control with reduced glycemic variability can improve DFS, reduce muscle loss, and may improve the sarcopenia and frailty in diabetic patients.

SD3-2 DIABETES PATIENT LIFESTYLE THERAPY

HUNG-YU CHANG

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

The American Diabetes Association and the Diabetes Association of the Republic of China recommend that all patients with type 2 diabetes should undergo lifestyle therapy, including medical nutrition therapy. The current guidelines emphasize “Pyramid of Risk” (postprandial blood glucose, fasting blood glucose and glycosylated hemoglobin) as three important glycemic targets that should be controlled in diabetes care. However, more and more studies have disclosed that blood glucose variability (GV) also plays an important role in glycemic control. Compared with healthy people, diabetic patients have more unstable glucose fluctuation, which means that blood glucose variability is greater. Guidelines recommend that when patients with type 2 diabetes are diagnosed, medical nutrition therapy should be listed as the first-line treatment. Research also pointed out that medical nutrition intervention such as meal replacements can significantly improve blood glucose fluctuations in patients with type 2 diabetes. This method can be regarded as an effective treatment to reduce blood GV; at the same time, it can significantly reduce the postprandial blood glucose of type 2 diabetic patients, significantly increase the secretion of GLP-1, and promote satiety, thereby achieving the goal of weight loss. Type 2 diabetes is a progressive disease and studies have shown that the sooner a patient receives medical nutrition treatment after being diagnosed with type 2 diabetes, the greater the improvement of glycemic control.

SD3-3 NUTRITION INTERVENTION FOR PATIENTS WITH DIABETES AND OBESITY

YI-SUN YANG

Chung Shan Medical University Hospital, Taichung, Taiwan

The nutrition therapy goals for the individual with diabetes have evolved and have become more flexible and patient centered. The goals from the American Diabetes Association (ADA) 2020 include the following: to promote and support healthful eating patterns, emphasizing a variety of nutrient dense foods in appropriate portion sizes in order to improve overall health and achieve and maintain body weight goals、attain individualized glycemic, blood pressure, and lipid goals、delay or prevent complications of diabetes; to address individual nutrition needs based on personal and cultural preferences, health literacy and numeracy, access to healthful food choices, willingness and ability to make behavioral changes, as well as barriers to change; to maintain the pleasure of eating by providing nonjudgmental messages about food choices, to provide an individual with diabetes the practical tools for day-to-day meal planning rather than focusing on individual macronutrients, micronutrients or single foods. Knowledge and individual application to improve adherence to the core foundational nutrition principles is one of the most important aspects of diabetes lifestyle management. There is no longer such a thing as a 1200 or 1800 calorie ADA diet! The dietary goals covered here, along with other lifestyle changes, if consistently applied, can help to improve metabolic profiles and ultimately help prevent long-term complications associated with diabetes. Motivating the persons with diabetes to make changes by working with a diabetes management team to implement an individualized program may help to elicit positive outcomes.

SD4-1 THE TRANSCRIPTION NETWORK IN COMPENSATION FOR THE LOSS OF β-CELL FUNCTION AND IDENTITY

YAU-SHENG TSAI

Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan

Rationale: Subjects unable to sustain β-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that deficiency of EGR-1 might influence β-cell compensation in response to metabolic overload.

Methods: Mice deficient in EGR-1 (Egr1−/−) were used to investigate the in vivo roles of EGR-1 in regulation of glucose homeostasis and beta-cell compensatory responses.

Results: In response to a high-fat diet, Egr1−/− mice failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and attenuated hypertrophic response of islets. High-fat feeding caused a dramatic impairment in glucose-stimulated insulin secretion and downregulated the expression of genes encoding glucose sensing proteins. The cells co-expressing both insulin and glucagon were dramatically upregulated in islets of high-fat-fed Egr1−/− mice. EGR1-deficient islets failed to maintain the transcriptional network for β-cell compensatory response. In human pancreatic tissues, EGR1 expression correlated with the expression of β-cell compensatory genes in the non-diabetic group, but not in the diabetic group.

Conclusion: These results suggest that EGR-1 couples the transcriptional network to compensation for the loss of β-cell function and identity. Thus, our study highlights the early stress coupler EGR-1 as a critical factor in the development of pancreatic islet failure.

SD4-2 NOVEL APPROACHES FOR THYROID CANCER THERAPY

SHU-FU LIN

Division of Endocrinology and Metabolism, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation)

Anaplastic thyroid cancer (ATC) is a rare but very aggressive human malignancy, occurring in 1-2% of all thyroid cancers but contributing to 14-39% of thyroid cancer mortality. The disease is typically fatal, with a median survival of 3 to 5 months for ATC patients. Recently, the US Food and Drug Administration (FDA) approved dabrafenib (BRAF inhibitor) plus trametinib (MEK inhibitor) for locally advanced, metastatic ATC with BRAFV600E mutation. However, many patients develop refractory disease or discontinue treatment due to adverse effects of these drugs. There is an urgent need for novel therapies with different mechanisms of activity for patients with ATC.

Our preclinical work demonstrates therapeutic efficacy of small molecules targeting different pathways: PI3K/AKT/MTOR (BEZ235), cyclin-dependent kinases (roniciclib), heat shock protein 90 (ganetespib); polo-like kinase 1, and Wee1 kinase against ATC, with promising safety profiles.These findings reveal potential approaches in the treatment of patient with ATC.

SD5-1 EPIDEMIOLOGY OF DIABETES AND TRENDS IN ANTIDIABTIC MEDICAL TREATMENT FROM 2005 TO 2014 IN TAIWAN

CHIH-HSUN CHU

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

From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20-79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged > 65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20-39 years (p < 0.001). The standardized incidence of T1DM slightly decreased by 11% (p = 0.118) and standardized prevalence of T1DM increased from 0.04% to 0.05%. Number of T1DM accounted for 0.51-0.59% of the entire diabetic population during the observation period.

Several new antidiabetic drugs have been introduced in Taiwan. We studied data from the Taiwan National Health Insurance Database to identify outpatient prescriptions for antidiabetic drugs from 2005 to 2014. The total and mean prescriptions gradually increased during the study period. Prescription of oral antidiabetic drugs (OADs) only or insulin-only therapy decreased slightly. Prescriptions of monotherapy and dual therapy decreased, whereas those of triple or higher order combinations increased. Prescriptions of sulfonylureas (SUs) decreased, whereas those of metformin and dipeptidyl peptidease-4 (DPP4) inhibitors increased. Insulin prescriptions increased but accounted for only 13.07% of prescriptions in 2014. Among monotherapy prescriptions, SU prescriptions decreased, but metformin and DPP4 inhibitor prescriptions increased. Among dual OAD prescriptions, those including SUs decreased, and those of metformin and DPP4 inhibitors increased. Although prescriptions of the metformin-SU combination decreased, they remained the most common among all dual OAD prescriptions, followed by the metformin-DPP4 inhibitor combination. Prescriptions of human insulin decreased and those of insulin analogs increased considerably; those of basal insulin increased, and those of mixed insulin decreased. However, mixed insulin was prescribed more than basal-bolus insulin. In conclusion, antidiabetic treatment has become complex in Taiwan. Although combination therapy would become the major treatment strategy gradually, the underuse of insulin therapy must improve.

SD5-2 ACCOUNTABILITY AND UTILIZATION AND PAY FOR PERFORMANCE FOR DIABETES CARE FROM 2005 TO 2014 IN TAIWAN

I-TE LEE

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

Background/Purpose: Comprehensive and continuous care is crucial for patients with diabetes. The diabetes pay-for-performance (P4P) program launched by the National Health Insurance (NHI) administration in Taiwan provides a financial incentive to facilitate this goal. In this study, we explored the characteristics of patients in the P4P program between 2005 and 2014.

Methods: Data of patients with diabetes enrolled in the NHI program between 2005 and 2014 were extracted from the NHI research database. Patients were classed as having diabetes if they had three or more outpatient visits within 365 calendar days with an International Classification of Diseases, 9th Revision, Clinical Modification diagnostic code of 250 or hospitalization one or more times with such a diagnosis. The trends of participating in the P4P program were analyzed.

Results: Participation rate of the P4P program increased from 12.1% to 19% between 2005 and 2014. Participants were younger and more likely to be female than those not participating in the program. Lower risks of cancer-related mortality, annual mortality and heart failure were seen in patients participating in the P4P program than in those not participating.

Conclusion: Older, male patients with a high disease severity may be less likely to enroll in the P4P program. Although participation rate is increasing, a broad enrollment is expected. (Adapted from Lee IT, et al. J Formos Med Assoc. 2019;118 Suppl 2:S122-S129)

SD5-3 HOSPITALIZATION AND TRENDS OF MORTALITY IN DIABETIC PATIENTS: A NATIONWIDE SURVEY FROM 2005 TO 2015 IN TAIWAN

HUNG-YUAN LI

Department of Internal Medicine, National Taiwan University Hospital, Taiwan

Diabetes mellitus has become a major cause of death and hospitalization worldwide. In 20052014, the number of diabetic patients increased from 1.3 to 2.2 million in Taiwan. Meanwhile, the rate of hospitalization among patients with type 2 diabetes mellitus decreased from 395.4 per 1000 person-years in 2005 to 336.96 per 1000 person-years in 2014, which is in contrast to the fact that the hospitalization rates of non-diabetic patients was stable during this period. An increase in hospitalization rates for malignancies and sepsis/infection was observed from 2005 to 2014 in patients with and without type 2 diabetes. The risk of hospitalization for heart diseases, cerebrovascular diseases, malignancies, respiratory diseases other than pneumonia, sepsis/infection other than pneumonia in patients with type 2 diabetes (vs. without diabetes) decreased from 2005 to 2014. However, the risk of hospitalization for pneumonia in patients with type 2 diabetes increased during these years.

In 2005-2014, all-cause mortality in patients with diabetes decreased continuously across sexes and age groups in Taiwan. The diabetic patients exhibited a shorter life expectancy than the entire population. The differences decreased from 2005 to 2014 and were greater when diabetes was diagnosed early in life. In 2014, the estimated loss of life was 2.6 and 3.2 years in the women and men, respectively, when diabetes was diagnosed at 40 years of age. The top five causes of death in diabetic patients were malignancy, diabetes, heart diseases, cerebrovascular diseases, and pneumonia.

In conclusion, there were continuous improvement in diabetes care in Taiwan, which resulted in a significant reduction in the rate of hospitalization and mortality from 2005 to 2014.

SD5-4 PREVALENCE OF DIABETIC MACRO- AND MICROVASCULAR COMPLICATIONS AND RELATED FACTORS FROM 2005 TO 2014 IN TAIWAN: A NATIONWIDE SURVEY

CHIEN-HSING LEE

Songshan Banting ChienHsing Clinic, Taipei, Taiwan; Division of Endocrinology and Metabolism, Tri-Service General Hospital, Taipei, Taiwan

Background/Purpose: Patients with diabetes have a higher risk of developing chronic complications and cause a huge burden to the public health care system as well as on patients and their families. Diabetic macrovascular complications contribute to nonignorable causes of morbidity and mortality in patients with diabetes mellitus (DM). In this study, the trends of risk factors, microvascular and macrovascular complications were examined in patients with DM in Taiwan.

Methods: Health care information and International Classification of Diseases, Ninth Revision diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files between 2005 and 2014. Using these data, the number of cases and annual prevalence of diabetic microvascular and macrovascular complications in individuals with DM were stratified by age and sex.

Results: The prevalence of DM with either stroke or cardiovascular disease (CVD) showed a decreasing trend in enrolled patients with DM (p for trend < 0.005), but that of DM with peripheral vascular diseases (PVDs) showed an increasing trend (p for trend < 0.001). Notably, the trend of changes in the prevalence of heart failure (HF) was similar to that of changes in the prevalence of stroke, although the decrease in prevalence was not statistically significant (p for trend 0.053). The prevalence of diabetic kidney disease (DKD) significantly increased from 10.49% to 17.92% from 2005 to 2014. The prevalence rate of diabetic foot significantly decreased from 1.34% to 1.05% from 2005 to 2014, and the rate of severe infection also significantly decreased from 50.69% to 45.85%. The amputation rate significantly decreased from 24.91% to 17.47% among all patients with diabetic foot.

Conclusion: From this nationwide study, we observed a decrease in the prevalence of diabetic macrovascular complications, such as stroke, CVD, and HF, but an increase in the prevalence of PVDs in the past decade in Taiwan. The trends in DKD and dialysis prevalence were similar to those of the 2012 report. The rate of increase in dialysis prevalence is lower in this study than in the 2012 report. The prevalence of diabetic foot, severe infection, and amputation in this report exhibited significantly decreasing trends. This improvement may be attributable to care from multidisciplinary teams.

SD6-2 THE NEW APPLICATION OF A.I. IN DIABETIC RETINOPATHY

YI-TING HSIEH

Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan

Diabetic retinopathy (DR) is one of the major microvascular complications in diabetes mellitus. Almost all patients who have type 1 diabetes for 20 years or more develop DR; among them, 20 to 30% suffer visual loss. During the lifetime, over 60% of patients with type 2 diabetes develop DR, which is also the main cause for legal blindness among the population within 20 to 74 years of age. The American Diabetes Association suggests that patients of type 1 diabetes should receive fundus examinations for DR within 5 years after diagnosis, and patients of type 2 diabetes should receive DR screening at the time of diagnosis. However, not all diabetic patients receive DR screening regularly. In Taiwan, only 45.5% of patients with diabetes received fundus examinations for DR screening in 2019. This results in delayed diagnosis of DR in many patients, to whom adequate referral or treatment cannot be given in time.

One of the reasons for the poor DR screening rate is that many general practitioners or internal physicians are not confident in diagnosing DR with retinal fundus photography by themselves. In recent years, artificial intelligence (AI) with deep learning has been developed for the diagnosis of DR, and previous studies have demonstrated its applicability, while most of them used open-access datasets only for the development and validation of their algorithms. National Taiwan University Hospital and Acer Inc. cooperated in developing a computer-aided diagnosis system Verisee™ for the diagnosis of DR. We used an open-access dataset as well as a local dataset collected in Taiwan to train the Verisee™ for diagnosing DR, and to validate its efficacy by comparing the precision rate of diagnosis with those made by internal physicians and ophthalmologists.

Our study found that the AUCs for VeriSee™ in diagnosing any DR, referable DR and proliferative diabetic retinopathy (PDR) were 0.955, 0.955 and 0.984, respectively. VeriSee™ had better sensitivities in diagnosing any DR and PDR (92.2% and 90.9%, respectively) than internal physicians (64.3% and 20.6%, respectively) (P < 0.001 for both). VeriSee™ also had better sensitivities in diagnosing any DR and referable DR (92.2% and 89.2%, respectively) than ophthalmologists (86.9% and 71.1%, respectively) (P < 0.001 for both), while ophthalmologists had better specificities. VeriSee™ has been proved to have good sensitivity and specificity in grading the severity of DR from color fundus images. Now it is under the application for the approval in DR screening by the TFDA. We hope in near future VeriSee™ can offer clinical assistance to non-ophthalmologists in DR screening with nonmydriatic retinal fundus photography.

SD6-3 THE 2020 CONSENSUS OF CGM AND CSII IN TAIWAN

CHIA-HUNG LIN

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

Continuous glucose monitoring (CGM) has been greatly implicated in clinical practice for various parts of diabetic management. The CGM could be set as professional or blinded and unblinded in different clinical application.The standardized reading and reporting disciplines are developed in this 2020 consensus in Taiwan.

Continuous subcutaneous insulin infusion (CSII) or insulin pump therapy is the promising paradigm for intensive therapies in diabetes (DM). The basal insulin is supplied in the form of a continuous infusion (comprising between 40 and 60 percent of the total daily dose) with pre-meal bolus doses given to minimize postprandial glucose excursions. The adjustment of dose and device maintenance are discussed and advised in the context.

The latest sensor-augmented pump therapy composed of CSII and real-time CGM is the perfect paradigm to cure not only type 1 but type 2 diabetes. The suspension of insulin before low blood glucose and automatic increase in basal insulin delivery are the main characteristics of this smartguarded insulin pump. Further automatic basal insulin adjustment and bolus infusion corresponding to high glucose are well developed and implicated in the clinical care of diabetes.

SD7-3 NEW PARADIGM IN THE MANAGEMENT OF DIABETES KIDNEY DISEASE

KUN-DER LIN

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

Diabetic Kidney Disease (DKD) is the major cause of end-stage renal disease (ESRD) in Taiwan and is associated with many kinds of chronic complications such as stroke, ischemic heart disease and congestive heart failure (CHF) in patients with diabetes mellitus. It is a serious problem to prevent the incidence and progression of DKD both in family and public health issues.

In recent years, several kinds of anti-diabetic agents including injection and oral forms, showed the great glucose lowering effects and additional kidney protection effects on patients of type 2 diabetes. These large random control trials showed the solids evidences and would affect our treatment of DKD in patients of diabetes. There was also some evidence on the limitations about metformin treatment on patients with DKD. About SGLT2i, in the different stages of DKD, there were different limitations of kidney function on each SLGT2i agent based on their own clinical studies. Empagliflozin is the first one to show the heart and kidney protection effects on patients with DKD. Dapagliflozin and canagliflozin also showed the similar effects after on. However, there were some tiny differences among these trials including the sides effects especially about amputation. GLP-1 injection also provides the great glucose lowering effects on patients with type 2 diabetes and it’s random control trials also showed additional cardiovascular protection and kidney protection in patients with diabetes. However, the protection effects of GLP-1 on DKD seems different from SLGT2i. Based on the different mechanism, further discussion on these two classes of anti-diabetic agents should be dressed more and need more random control trials to prove the effects of combination of these two classes.

There are more and more kinds of anti-diabetic agents and we needs more data on the clinical use of these new generation agents. We should emphasize on the new clinical experiences of these new agents and pay more attention to the updated guidelines to treat our patients with DKD.

SD8-1 DIABETIC FOOT CARE: THE CHANG GUNG EXPERIENCE AND UPDATED STATUS IN TAIWAN

CHENG-WEI LIN

Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital at Linkou, Taoyuan City, Taiwan

Diabetic foot ulcer (DFU) was the leading cause of non-traumatic lower-extremity amputation (LEA). The annual population-based prevalence of DFU is 1 to 11%, and the estimated lifetime risk is 25% for diabetic patients. Among the diabetic foot complications, diabetic foot infection (DFI) is the leading threatening problem for limb loss and sepsis, and is the most common cause of hospital admissions and costly expenditure in diabetic populations. Among the in-hospital DFU cases, 82% have been reported to have DFIs in Europe and 94% in Taiwan. According to the current study, diabetic foot complications continue to remain a major medical and public health issue as we face patients in increased numbers, age, and comorbidities. The annual incidence of LEAs in Taiwan decreased from 2.85 to 2.06 per 1000 type 2 diabetic population from 2007 to 2014. Commensurately, the proportion of people receiving peripheral artery intervention increased from 6.2 to 19.5% over the same time period. In Chang Gung, the annual amputation rate also decreased along with the dramatic increasing cases of peripheral artery intervention. Despite the success in revascularization for limb preservation, nevertheless, we are facing a trend of more patients with higher associated comorbidities, particularly the ESRD. That’s a big challenge in DFU treatment for such patients, whether in limb or life salvage.

SD8-2 ENDOVASCULAR INTERVENTION IN LOWER EXTREMITY ARTERY DISEASE: NEW TOOLS, TECHNIQUES, AND INDICATIONS

JEN-KUANG LEE

Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Advances in endovascular therapies during the past decade have broadened the options for treating peripheral vascular disease percutaneously. Endovascular treatment offers a lower risk alternative to open surgery in many patients with multiple comorbidities. Noninvasive physiological tests and arterial imaging precede an endovascular intervention and help localize the disease and plan the procedure. The timing and need for revascularization are broadly related to the 3 main clinical presentations of claudication, critical limb ischemia, and acute limb ischemia. Many patients with claudication can be treated by exercise and medical therapy. Endovascular procedures are considered when these fail to improve quality of life and function. In contrast, critical limb ischemia and acute limb ischemia threaten the limb and require more urgent revascularization. In general, endovascular treatments have greater long-term durability for aortoiliac disease than femoral popliteal disease. Infrapopliteal revascularization is generally reserved for critical and acute limb ischemia. Balloon angioplasty and stenting are the mainstays of endovascular therapy. New well-tested innovations include drug-eluting stents and drug-coated balloons. Adjunctive devices for crossing chronic total occlusions or debulking plaque with atherectomy are less rigorously studied and have niche roles. Patients receiving endovascular procedures need a structured surveillance plan for follow-up care. This includes intensive treatment of cardiovascular risk factors to prevent myocardial infarction and stroke, which are the main causes of death. Limb surveillance aims to identify restenosis and new disease beyond the intervened segments, both of which may jeopardize patency and lead to recurrent symptoms, functional impairment, or a threatened limb.

SD8-3 CLINICAL APPLICATION OF CELL THERAPY IN TREATMENT OF CHRONIC DIABETIC FOOT ULCERS

NAI-CHEN CHENG

Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan

Among the devastating complications related with diabetes, these patients are particularly susceptible to poor wound healing, especially chronic foot ulcer. Diabetic patients were estimated to have a lifetime risk of 25% to develop a foot ulcer, and 14–24% of them will have progressive disease that necessitates amputation. As the prevalence of diabetes keeps on increasing, the medical and socioeconomic burden of diabetic wounds is expected to increase accordingly. Therefore, the diabetesassociated wound complications have emerged as important clinical problems nowadays, but current treatments have their limitations.

In recent years, cell therapy has become an emerging practice in the international medical community to promote diabetic wound healing. Among the various options of cell, stem cell therapy shows great potential for clinical application considering its unique biological properties. Particularly, mesenchymal stem cells (MSCs) have gained increased attention because they can contribute to tissue repair and regeneration through differentiation and paracrine effects. For example, adipose-derived stem cell (ASC) is a potential source of abundant mesenchymal stem cells, which can be applied to promote tissue regeneration. The mechanism underlying the ASC-associated tissue regeneration has yet been thoroughly understood, but it probably involves increased collagen deposition, reduction of inflammatory states, and several paracrine effects of ASCs.

In September 2018, the Ministry of Health and Welfare Taiwan issued the Regulations Governing Specific Cellular Therapeutic Technology, which conditionally allowed clinical application of six cell therapy technologies with ascertained safety and efficacy. For example, the clinical use of ASCs has been included for five indications: chronic wound, large-area burn injury, subcutaneous/soft tissue deficiency, osteoarthritis/knee cartilage defect and adjuvant superficial minimally invasive techniques. Through this talk, we will discuss about the new developments of cell-based regenerative therapy in diabetic wound healing. Moreover, we will give a brief overview regarding the necessary steps to perform such a cell therapy in compliance with the current regulations in Taiwan.