Editor’s note:With the development and research of immunology and molecular genetics With the deepening of the research, some of the causes of diabetes have been relatively clear, and accordingly, the precise classification of diabetes has also made considerable progress. At the 2022 Annual Meeting of Endocrinology and Metabolism Physicians of the Chinese Medical Doctor Association, Professor Zhou Zhiguang, Department of Metabolic Endocrinology, Second Xiangya Hospital of Central South University, and National Clinical Research Center for Metabolic Diseases, gave a wonderful presentation on the topic of “Consensus and Thinking on Accurate Diabetes Classification”. The various reports are now sorted out for the readers.
diabetes mellitus is a highly heterogeneous group of genetic and Environmental factors and their interactions can affect a variety of mechanisms (eg, autoimmunity, decreased beta cell numbers, insulin secretion defects, inflammation, health care disorders, etc.), resulting in different occurrence and progression of diabetes in each patient. These individual differences lead to heterogeneity among diabetes types, such as early-onset TIDM, LADA, and KPD. It is also the case that the heterogeneity of pathophysiology promotes the development of precision medicine in diabetes.
reviewdevelopment of the diagnosis of diabetes Stage
With the gradual deepening of the exploration and understanding of diabetes, the classification of diabetes is also evolving, and it has mainly experienced three stages of development: classification based on clinical characteristics (1965 ~1996), classification based on etiology, pathogenesis and clinical characteristics (1997~2019), classification based on etiology and precision medicine (2020 to present). In different stages, the recommendations of different academic organizations on diabetes classification are constantly changing while seeking common ground while reserving differences. Currently, there are slight differences in the classification of diabetes between different guidelines (Table 1).
Table 1. Recommendations for diabetes classification by different guidelines
Important: “Chinese Expert Consensus on Diagnosis of Diabetes Types” released
With the accumulation of clinical evidence and the advancement of detection technology, the way of diagnosis of diabetes is constantly updated. Accurate etiology classification is the basis and key to individualized precision treatment. In view of this, the Endocrinology and Metabolism Branch of the Chinese Medical Doctor Association and the National Clinical Research Center for Metabolic Diseases (Changsha) organized experts to formulate and publish the “Chinese Expert Consensus on Diagnosis of Diabetes Types” (hereinafter referred to as the “Consensus”), in order to standardize the classification of diabetes mellitus. Type diagnosis process, early identification of diabetic individuals with clear etiology, and promotion of precise treatment. In the consensus, diabetes is divided into 6 types according to the etiology, including T1DM, monogenic diabetes, secondary diabetes, GDM, indeterminate diabetes, and T2DM, in order to achieve individualized and precise treatment.
Source: Diagnosis of Etiology and Types of DiabetesBased on
- History and physical examination: span>It has important prompting value for the diagnosis of diabetes etiology, and clinical history and physical examination should be inquired in detail and comprehensively analyzed.
- islet β-cell function:serum C-peptide is the main indicator for clinical evaluation of islet β-cell function. important reference. C-peptide <200pmol/L after stimulation, indicating poor islet function, high possibility of T1DM; <600pmol/L, indicating impaired islet function, should be alert to the possibility of T1DM or monogenic diabetes affecting islet development and secretion; ≥600pmol/ L, suggesting that the islet function is acceptable, and it is highly possible to consider T2DM.
- Islet autoantibodies: a key indicator reflecting the autoimmune attack of islet beta cells for autoimmune T1DM For diagnosis, the internationally recognized radioligand method and enzyme-linked immunosorbent assay (ELISA) are recommended.
- Genetic testing: the gold standard for diagnosing monogenic diabetes.
- Other indicators:Including serum insulin, glycated hemoglobin, blood/urine amylase, high-sensitivity C-reactive protein, Lactate detection, antinuclear antibodies and other autoantibodies, fundus examination, electrical audiometry, acoustic impedance, electromyography, etc. The corresponding significance is shown in Table 2.
Table 2. Indicators and significance of diabetes classification and diagnosis
Characteristics of six types of diabetes diagnosis /span>
1, T1DM span> >From the perspective of etiology, according to whether the islet antibody is positive, it can be divided into autoimmune or idiopathic.
- Autoimmune T1DM:Can manifest as fulminant, classic, Latency (delayed – differentiated between LADA and LADY based on age of onset). Specifically, LADA diagnostic criteria: (1) age of onset of diabetes ≥ 18 years old; (2) positive islet autoantibodies or islet autoimmune T cells; (3) insulin-independent treatment for at least half a year after diagnosis of diabetes. LADY diagnostic criteria: (1) age of onset <18 years old; + (2) and (3) above.
- idiopathic T1DM: It can manifest as fulminant, classic, and is a subtype of unknown etiology , the mechanism of pancreatic β-cell destruction is unclear. Has typical clinical features of T1DM. However, islet autoantibodies are negative, and it is very important to explore its etiology.
According to the onset, it can be divided into classic, fulminant or slow-onset.
- Classic TIDM:Age of onset is usually <20 The symptoms of "one little" are obvious, the onset is ketosis or ketoacidosis, the body type is not obese, dependent on insulin treatment, the serum C-peptide is significantly reduced, and most of them have islet autoantibodies.
- Fulminant T1DM:It is more common in East Asian populations, accounting for 10% of new T1DM in my country. The diagnostic criteria are: (1) ketosis or ketoacidosis developed within 1 week after the onset of hyperglycemia symptoms; (2) the blood glucose level at the first diagnosis is ≥16 mmol/L, and HbA< sub>1c<8.7%; (3) Fasting blood C-peptide <100pmol/L and/or post-loading blood C-peptide <170pmol/L.
- Delayed-onset TIDM:In Chinese adults, delayed-onset T1DM (i.e. LADA) accounts for approximately 2/3 of T1DM.
II. Monogenic diabetes
more than 70 causes of monogenic diabetes found so far Most of the genes are caused by affecting the function of pancreatic islet β cells (diabetes caused by mutations at different sites of the same gene, the clinical phenotype can be of different types). It accounts for 1% to 5% of all diabetes mellitus, and is divided into two types: pancreatic β-cell function defect and insulin action defect. Islet beta cell dysfunction monogenic diabetes: mainly including neonatal diabetes mellitus (NDM), MODY, mitochondrial diabetes, genetic syndrome monogenic diabetes, autoimmune monogenic diabetes. Insulin action-deficient monogenic diabetes: manifested as marked hyperinsulinemia, with acanthosis nigricans, polycystic ovary, and ovarian hyperandrogenism, which can be divided into severe insulin resistance monogenic diabetes, lipoatrophy Monogenic diabetes.
III. Secondary diabetes
4. Gestational diabetes mellitus (GDM) GDM refers to abnormal glucose metabolism related to pregnancy status, but does not meet the diagnostic criteria for diabetes in non-pregnant people, and is related to physiological insulin in the second and third trimesters of pregnancy. resistance related. GDM accounts for about 75% to 90% of hyperglycemia in pregnancy. It needs to be differentiated from gestational overt diabetes. Although this disease was discovered during pregnancy, it has reached the diagnostic criteria for diabetes in non-pregnant people, and most of its glucose metabolism disorders will not return to normal after pregnancy.
V. Undiagnosed diabetes According to their symptoms, signs and the above-mentioned results of islet function, islet autoantibodies and genetic testing but still can not be classified, “unconfirmed” emphasizes the necessity of follow-up and future etiology diagnosis.
VI. T2DMThe Groop team proposed six variables based on big data + AI analysis: age, BMI, GAD antibody, HbA1c, beta cell function and insulin It is recommended to classify diabetes into severe autoimmune diabetes mellitus (SAID), severe insulin deficiency diabetes mellitus (SIDD), severe insulin resistance diabetes mellitus (SIRD), mild obesity-related diabetes mellitus (MOD), and mild age-related diabetes mellitus (MARD). Five types, of which SIRD, MOD, MARD consider subtypes that can be classified as T2DM. In addition, some scholars have proposed a β-cell-centered classification of diabetes.
Clarify: the diagnostic process of diabetes typing
standardize diabetes typing The diagnostic process helps to identify individuals with diabetes with a clear etiology at an early stage, and facilitates the realization of precise treatment. The consensus recommends using the following standardized diagnostic process to classify diabetes (Figure 1).
Figure 1. Diagnosis process of diabetes classification /strong>
Conclusion
Diagnosis of Diabetes Types Based on etiology and precision medicine, the Chinese Expert Consensus divides diabetes into six types: T1DM, monogenic diabetes, secondary diabetes, gestational diabetes, undetermined diabetes, and T2DM. In the consensus, the diagnostic basis for medical history collection, physical examination, basic and auxiliary examinations, islet β-cell function, islet autoantibodies, and genetic testing (selection) is clarified, and a diagnostic flow chart with good operability is provided to guide clinical individuals with diabetes. precision medicine.
References:
Chinese Expert Consensus on Type Diagnosis” Chinese Journal of Diabetes, 2022, 14(2) : 120-139
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(Source: International Diabetes Editor)
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