Ching-Ling LinDr. Taiwan

• Brain Remodeling of Appetite Centers in Obesity - Results from Murine Omics Studies and Human Brain Imaging
  Tomohiro TanakaJapan Speaker Brain Remodeling of Appetite Centers in Obesity - Results from Murine Omics Studies and Human Brain ImagingBody weight is regulated by functional interplay between multiple organs, among which the hypothalamus plays a critical role through its modulatory functions on energy intake and expenditure. In early 1900s, professors Joseph Babinski and Alfred Frolich reported a case of acquired hypothalamic obesity, whose obesity was secondary to hypothalamic damage by brain tumor. The case provides the first evidence that the hypothalamus plays a key role in the maintenance of body weight in humans. In the 1970s and 1980s, experimental injury or electrical stimulation of the hypothalamic nuclei in rodents further led to an elucidation of its vital role in body weight regulation. Mechanistic insight has been addressed when the discovery of leptin followed by an elucidation of anorexigenic effect of GLP-1 has cast limelight on the endocrinologic aspect of body weight regulation. In fact, more than a dozen genetic forms of obesity has been reported, each of which is caused by mutations of a single gene with indispensable functions within leptin-hypothalamus axis. However, in routine clinical practice, tumors or genetic abnormalities in the hypothalamus are rarely observed in patients with obesity disease. The question, then, is whether the hypothalamus is functioning normally in such patients with primary obesity disease? In 2012, professor Joshua Thaler and colleagues reported that mice fed a high-fat diet exhibit early activation and proliferation of microglia and astrocytes within the hypothalamus - histologic changes suggestive of "hypothalamic inflammation". Subsequent pharmacologic and knockout mouse studies have demonstrated that this hypothalamic inflammation is not merely a result but a critical cause of obesity. We have studied the molecular landscape and its alterations during the development or the improvement of the obesity disease. Methodologically, our research involves transcriptomic and lipidomic analyses of hypothalamic nuclei in mice, with the aim of elucidating the molecular basis of hypothalamic remodeling observed in obese animal models. We have identified obesity-induced biochemical changes in the hypothalamus, such as inflammation-related transcriptome and region-specific accumulation of arachidonic acid esters. More clinically, we are investigating a potential reverse remodeling of the hypothalamus during weight loss in mouse models. Of note, in human subjects with obesity disease, reversible hypothalamic inflammation has been demonstrated using T2 relaxation time measurements in MRI studies. As such, hypothalamic inflammation, a common feature of hypothalamic pathology in rodents and humans, is attracting more attention as a focus of obesity research. In this session, I would like to discuss more of the status quo and future perspectives of the neuropathologic basis of the obesity disease.
• Obesity Management: What's New?
  Alice KongHong Kong, China Speaker Obesity: What Clinicians Should KnowRapid changes in technology, human behavior and lifestyle over the past few decades have resulted in a dramatic increase in the prevalence of obesity worldwide. Besides social stigmata and psychological consequences, obesity is associated with escalated risks of type 2 diabetes, coined the term "Diabesity", hypertension, dyslipidemia, sleep apnoea, metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome, cancers, cardiovascular diseases and increased mortality. Body mass index (BMI) is a commonly adopted tool to identify people with obesity. Clinicians should note that the cutoff points of BMI for clinical actions are different between people with obesity from the East and the West, as well as the limitations of BMI in diagnosing obesity. Recently, the Lancet Diabetes and Endocrinology Commission proposed a new definition of obesity which differentiates excess adiposity with obesity-related illness (clinical obesity) from those without obesity-related diseases (pre-clinical obesity). Also, people with clinical obesity have many unmet needs requiring personalized treatment regimens, intensive counselling and emotional support. The 5 A's framework including Ask, Assess, Advise, Agree and Assist, provide a patient-centred approach to promote lasting behavioral change in obesity management. In addition to lifestyle modifications and behavioral changes, pharmacological agents for weight reduction, bariatric and metabolic surgeries are therapeutic options requiring careful selections for the appropriate patients with adequate counselling of the risks and benefits. Through case sharing approach, the use of weight reducing drugs and surgical strategies for people with preclinical and clinical obesity will be discussed in this session. Acknowledgement: The work described in this lecture was partially supported by funding from Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong SAR, China (Reference number:21223391), Matching Grant from Research Grants Council (reference number: 8601556), and Area of Excellence Scheme, Research Grants Council, Hong Kong SAR, China (Reference number: AoE/M-401/24-R). Obesity Management: What's New?Obesity is a global health hazard with rising prevalence in most parts of the world. Weight reduction by lifestyle modification remains the cornerstone in the prevention and treatment of obesity. However, weight management by lifestyle therapy alone is difficult to sustain in many obese individuals with rebound of body weight being observed as a common phenomenon. Given the invasiveness of bariatric and metabolic surgeries which are not accepted by many people with obesity, the use of pharmacological agents in weight management is increasingly popular. In 2025, the Lancet Diabetes and Endocrinology Commission proposed a new definition of obesity which differentiates excess adiposity with obesity-related illness (clinical obesity) from those without obesity-related diseases (pre-clinical obesity). Among the various obesity complications, diabetes is well recognized to be closely related to obesity, with the term 'Diabesity' coined to show the strong link between these two important modifiable risk factors of cardiovascular disease and premature death. In recent decades, many new generation anti-diabetic drugs are developed and found to have weight reducing properties. Looking ahead, more new drugs are in the pipeline of clinical trials, and the results may eventually change the landscape of obesity management. Acknowledgement: The work described in this lecture was partially supported by funding from Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong SAR, China (Reference number:21223391), Matching Grant from Research Grants Council (reference number: 8601556), and Area of Excellence Scheme, Research Grants Council, Hong Kong SAR, China (Reference number: AoE/M-401/24-R).
• The Hidden Barrier: Understanding and Overcoming Weight Bias
  Hai-Hua ChuangTaiwan Speaker The Hidden Barrier: Understanding and Overcoming Weight Bias

• Diabetes and Heart Failure: A Dual Epidemic
  Kuo-Meng LiaoTaiwan Speaker Diabetes and Heart Failure: A Dual EpidemicDiabetes mellitus (DM) and heart failure (HF) are tightly interconnected disease states that interact through complex and bidirectional cardio-metabolic mechanisms. Among HF phenotypes, heart failure with preserved ejection fraction (HFpEF) shows the strongest association with DM, reflecting shared pathophysiological pathways beyond traditional ischemic heart disease. Epidemiologically, DM confers a two- to four-fold increased risk of incident HF, with a disproportionate burden of HFpEF. Patients with HFpEF exhibit a high prevalence of DM and insulin resistance, accompanied by worse exercise intolerance, higher hospitalization rates, and increased mortality. These observations support the concept that DM is not merely a comorbidity but a central contributor to HFpEF pathogenesis. Mechanistically, chronic hyperglycemia and insulin resistance initiate a cascade of systemic and myocardial abnormalities. Endothelial dysfunction, coronary microvascular inflammation, and impaired nitric oxide–cyclic GMP–protein kinase G signaling promote cardiomyocyte stiffness and diastolic dysfunction. Metabolic inflexibility, characterized by excessive fatty acid utilization and impaired glucose oxidation, reduces myocardial energetic efficiency. In parallel, advanced glycation end products, oxidative stress, mitochondrial dysfunction, and lipotoxicity drive myocardial fibrosis and adverse extracellular matrix remodeling. These myocardial changes are further amplified by extracardiac factors common in DM—obesity, chronic kidney disease, systemic inflammation, and autonomic imbalance—creating the multi-organ HFpEF syndrome. Conversely, HF exacerbates insulin resistance through neurohormonal activation, inflammation, and skeletal muscle hypoperfusion, reinforcing a vicious cycle between metabolic and cardiac dysfunction. Recognition of this cross-talk has important therapeutic implications, as exemplified by sodium–glucose cotransporter 2 inhibitors, which improve HF outcomes through mechanisms extending beyond glucose lowering. In summary, DM and HFpEF are linked through shared mechanistic pathways involving metabolism, microvascular dysfunction, and inflammation. A mechanistic understanding of this interaction is essential for developing integrated, phenotype-specific cardio-metabolic strategies.
• Metabolic Dysfunction and Brain Health: Diabetes as a Risk Factor for Dementia
  Jong-Ling FuhTaiwan Speaker Metabolic Dysfunction and Brain Health: Diabetes as a Risk Factor for DementiaType 2 Diabetes Mellitus (T2DM) is no longer confined to glucose dysregulation—it is a systemic accelerator of brain aging and a major modifiable risk factor for dementia. Epidemiologic and mechanistic studies reveal that poor glycemic control, including both hyper- and hypoglycemia, significantly increases dementia risk. Data from Taiwan’s National Health Insurance Database show that pronounced glycemic fluctuations more than double this risk, while meta-analyses identify prolonged diabetes duration, elevated HbA1c, hypertension, and insulin resistance as key predictors of cognitive decline. Pathophysiological evidence links chronic hyperglycemia and insulin resistance to neuroinflammation, oxidative stress, and tau pathology. Neuroimaging studies show hippocampal atrophy and white matter degradation in patients with poorly controlled diabetes. Cardiovascular comorbidities amplify this burden: diabetes combined with coronary artery disease doubles the risk of vascular dementia. Encouragingly, therapeutic innovation offers hope. Glucose-lowering agents such as GLP-1 Receptor Agonists (GLP-1RAs) and SGLT2 Inhibitors (SGLT2is) may extend their cardiometabolic benefits to the brain. GLP-1RAs have shown a 45% reduction in dementia risk in real-world and trial-based analyses, reinforcing the interconnectedness of metabolic, vascular, and neurodegenerative pathways. In East Asia, where diabetes and dementia are surging, the clinical imperative is clear: brain health must be a core outcome of metabolic care. Early glycemic optimization, vascular protection, and neuroprotective therapies may define the next frontier in dementia prevention.
• Sleep Apnea in Diabetes: A Silent Aggravator
  Li-Pang ChuangTaiwan Speaker Sleep Apnea in Diabetes: A Silent AggravatorObstructive sleep apnea (OSA) is a highly prevalent clinical disease affecting more than 10% of the adult population. It is characterized by repetitive episodes of partial or total upper airway obstruction during sleep, resulting in subsequent sleep fragmentation and intermittent hypoxia. Accumulating studies reveal that OSA is an independent risk factor for consequent cardiovascular morbidities, such as myocardial infarction, heart failure, nocturnal dysrhythmias and pulmonary hypertension. Currently, OSA can be treated by means of positive airway pressure therapy, pharmacological therapy and surgical intervention. OSA is a silent aggravator of diabetes because it worsens glucose metabolism and insulin resistance through mechanisms like intermittent hypoxia, sleep fragmentation, and sympathetic nervous system activation. This creates a bidirectional relationship where OSA increases the risk and severity of diabetes, and diabetes can worsen OSA. Treating OSA may improve glycemic control, and screening for it is crucial, especially in individuals with type 2 diabetes, particularly those who are obese.