Prof. Ji Linong: Status and Prospects of Precision Diabetes Therapy

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Diabetes is a disease group characterized by hyperglycemia. The causes of hyperglycemia are highly heterogeneous. The method of classification is used to describe heterogeneity. Dividing diabetes into more homogeneous subtypes can be further clarifiedThe root cause of heterogeneity is the basis for identifying methods to cure diabetes.Professor Ji Linong pointed out that different subtypes of diabetes have different natural course of hyperglycemia and different clinical treatment strategies. Different subtypes have different natural course of diabetes complications and different clinical treatment strategies.Changes in the classification of diabetes Our cognition of diabetes is gradually increasing, and there is also an evolutionary process regarding the classification of diabetes.In 1936, Himsworth divided patients with diabetes into insulin resistance patients (Ⅰ) and sensitive patients (Ⅱ) according to their response to insulin therapy.In 1959, Yalow detected free insulin, and since then diabetes has been divided into two categories, insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM).In 1997, WHO / ADA officially defined the type of diabetes as type 1, type 2, GDM and special types of diabetes.The clinical and scientific value of the current diabetes typing system. The type of diabetes (immunity-mediated and idiopathic) in the type of diabetes (WHO / ADA) we currently adopt accounts for approximately <5%, and 95% of patientsIt belongs to type 2 diabetes, and in addition, 1% -2% are other special types of diabetes.These special types of diabetes have inherited defects in islet β-cell function, people with inherited defects in insulin action, pancreatic exocrine diseases and some endocrine diseases caused by hyperglycemia. For special types of diabetes, it is necessary to screen for diabetes-causing gene mutations based on clinical phenotype.And choose a drug.The clinical needs that the current diabetes typing system fails to meet. Professor Ji Linong pointed out that typing according to the cause of the single feature of the disease (hyperglycemia) is important for the etiology and treatment strategy of the subtype of diabetes with clinical features that are only hyperglycemia.Value can prevent microvascular disease.The new subtypes increase slowly, which affects the corresponding pathophysiology research, research and implementation of precise treatment strategies, and cannot meet the needs of precise clinical sugar control.The current classification system does not classify according to diabetes, and it does not help the pathophysiological abnormalities other than hyperglycemia and the etiology and treatment strategies of its causes, and it cannot prevent macrovascular disease.Therefore, the clinical outcome of most patients with type 2 diabetes cannot be improved.At present, only a few patients can receive precise hypoglycemic treatment, such as abnormal blood glucose caused by HNF-1a mutation, which is a type of insulin secretion deficiency and needs to be treated with low-dose secretagogues; GCK mutations are glucose-sensing defects and do not require treatment becauseIt does not respond to hypoglycemic drugs; the KCNJ11 mutation belongs to the K-ATP channel defect and is treated with high-dose sulfonylureas; PPARγ / LMNA belongs to ectopic fat accumulation and is treated with insulin sensitizers.The MODY3 gene mutation causes hyperglycemia to be more sensitive to sulfonylureas, and is the first-line medication for these patients.China's 500,000 cohort study shows that diabetes increases the risk of death from macroangiopathy and kidney disease.And many large-scale clinical studies of hypoglycemic agents lack evidence that intensified glucose control significantly reduces the risk of kidney outcomes.Metformin and intensive lifestyle (including weight management and exercise) are the first-line treatment options in the current diabetes drug treatment pathway. If the glycated hemoglobin does not meet the standard, then the treatment plan is further adjusted, that is, blood glucose-centric + postmortem treatmentStrategy.How can we achieve precise treatment according to the specific conditions of patients?Attempts to Establish New Types of Diabetes ANDIS research uses artificial intelligence diabetes cluster analysis to divide newly diagnosed patients with diabetes into five subtypes based on different indicators.Relevant indicators are: GAD65 antibody level, HbA1c, BMI and age at diagnosis, C-peptide level, insulin sensitivity calculated based on HOMA-IR, and islet β-cell function calculated based on HOMA-B.This new type of diabetes not only focuses on hyperglycemia, but also focuses on patient weight, age, antibody-positive status, and multiple indicators of insulin secretion and insulin sensitivity. Using artificial intelligence to analyze diabetes, it is finally divided into five subgroupsType, of which the first three subtypes belong to severe diabetes and the latter two subtypes are mild diabetes.The first SAID type is GAD antibody positive, the latter four are antibody negative.Each type of diabetes has different changes in blood glucose (HbA1c) levels.Among them, autoimmune and severe insulin deficiency blood glucose fluctuates greatly.. In addition, in terms of the difficulty of blood glucose control, autoimmune and severe insulin deficiency are the most difficult to control, and age-related hyperglycemia is relatively easy to control.In addition, the researchers conducted some drug trials to observe the response of different groups of patients to different hypoglycemic agents, which helped guide the patients' medication. Therefore, this new classification helps us to refinetreatment.Layering before treatment is a clinical study of outcome-driven precision therapy.The above content is only authorized by for exclusive use, please do not reprint without authorization of the copyright party.


The author ouyangshaoxia