An Overview of the Pathogenesis of Diabetes
In the clinical study of diabetes has been in the exploratory stage, so far the pathogenesis of diabetes is still no definite structure, which is mainly in vivo glycogen caused by high body function changes as a fundamental, that is how it affects The following for everyone to describe the pathogenesis of diabetes.
Pathogenesis
It is generally believed that the incidence of type 1 diabetes is mainly mediated by cellular immunity. (Eg, nutrition, viruses, chemicals, IL-1, etc.) will result in the release of B cell antigens or viral antigens expressed in B cells or with B cell antigens, which are similar to B cell antigens, The antigen may be ingested by antigen-presenting cells (macrophages) located on the islets and processed into a sensitized antigen peptide to further activate the antigen-presenting cells, resulting in the production and secretion of large amounts of cytokines (IL-1 and TNF, etc.) , A receptor that specifically recognizes the sensitized antigen peptide of T helper cells (CD8 lymphocytes) that appear on the islets and induces a series of lymphokine gene expression, one of which, such as TNF, will increase the number of feedback - stimulated antigen - presenting cells Histocompatibility complex (MHC) subclass molecules, IL-1 and TNF expression. In addition, other cells outside the macrophage lineage (outside the islet) also lead to cytokine release. IL-1, which is enhanced by TNF and interferon (IFN), exhibits cytotoxic effects on B cells by inducing free radical production within the islets. With the damage (degeneration) of B cells, more allergenic antigens are presented to the immune system, appear vicious cycle, showing self-induced and self-limiting form. IL-1, interferon-γ (INF-γ) and TNF-α are also responsible for the increase in free radical production (superoxide anion, hydrogen peroxide, hydroxyl radical, etc.) Induced NO production of nitric oxide (NO) synthase, resulting in a large number of NO production (NO derivative of nitrous acid on B cells also has significant toxic effects), combined with human islet B cells have the lowest oxygen free radicals The ability to selectively remove B cells is particularly sensitive to the destruction of oxygen free radicals. Oxygen free radicals damage B cell DNA, activating polyglycol synthase to repair damaged DNA, which accelerates the depletion of NAD, and finally B cell death. In addition, free radicals on the cell membrane lipid, intracellular carbohydrates and proteins also have a great damage. In addition, in the above process, lymphokines and free radicals also lead to CIM4T lymphocytes tend to damage the site and activation, while macrophages also presented virus antigens or damaged B cells of the autoantigen to CD4 lymphocytes, activated CD4 cells Further activation of B lymphocytes to produce antiviral antibodies and anti-B cell autoantibodies, but also to promote the destruction of B cells.
It is now clear that l-type diabetes is caused by immunological-mediated selective destruction of islet B cells. (ICA), insulin antibody (IAA), glutamate decarboxylase antibody (GAD antibody), and anti-idiopathic antibodies against B cells, such as islet cell antibody (ICA), insulin antibody (IAA), glutamate decarboxylase antibody (GAD antibody), and Insulin-related protein antibodies.
1. Islet cell antibody Bottazzo is equal to 1974 first described the presence of anti-islet cell antigen in patients with type 1 diabetes, and can be detected by immunofluorescence, this method in addition to minor changes, has been in use today, recently also by radioimmunoassay And enzyme-linked immunosorbent assay. Clinical study report: general non-diabetic ICA positive rate of less than 3%, while the newly diagnosed type 1 diabetes patients ICA positive rate of 60% to 90%. ICA is divided into islet cytoplasmic antibodies and islet cell surface antibodies. However, the detection of islet cells on the surface of the antibody is rarely used in clinical, clinical difficult to obtain fresh islet or insulinoma cell specimens, and islet cytoplasmic antibody examination is relatively simple and standardized, and thus widely used in clinical practice. The positive rate of islet cell antibodies decreased with the prolongation of diabetes mellitus, and 80% to 90% of patients with type 1 diabetes mellitus did not disappear after 2 years of onset; 10% to 15% of patients persisted for more than 3 years. In the case of similar course of disease, antibody positive often accompanied by: ① thyroid and stomach autoantibodies; ② other autoimmune endocrine disease; ③ have a strong family history of other autoimmune diseases; ④ more common; ⑤ and HLA-DR3 / B8 is strongly related. However, there are reports of type 1 diabetes 3 years after onset of 62% of patients with ICA positive in the body, did not find the difference.
The detection rate of ICA in the first-degree relatives of type 1 diabetes was significantly higher than that of the general population, and the detection of ICA was associated with an increased risk of subsequent clinical type 1 diabetes, and the predicted value of high titers (eg> 80 JDF units) Is significantly higher than the low titer (eg <20jdf ica = "" 1 = "" "" "" "" "" "" "" "" "" "" "" "" 10 = "" 60 = "" 79 = "" ica = "" 1 = "" icas = "" b = "" ica = "" 1 = "" 10 = "" "=" "Ica =" "ica =" "ica =" "lada =" "1 =" "1 =" "5 =" "spiddm =" "gad =" "> 15 years old; Non-insulin-dependent diabetes mellitus; ③ early onset of diet or oral hypoglycemic drug control treatment; ④ often 1 to 4 years of oral hypoglycemic drug failure or susceptibility to diabetic ketosis need to rely on insulin; ⑤ICA positive, GAD-Ab positive, low C peptide level and HLA-DR3 / 4, etc. For the "LADA" patients are more consistent opinion is the early use of insulin therapy to delay the destruction of islet B cells in the body.
2. Anti-GAD antibody glutamic acid decarboxylase (GAD) is a biosynthesis of the inhibitory neurotransmitter γ-aminobutyric acid, which is present in the brain and islet tissues of humans and animals. In recent years, it has been found that there are two isomeric forms with relative molecular weights of 65,000 (GAD65) and 67000 (GAD67), respectively, and show that GAD has many common physicochemical properties in islet 64000 protein antigens. Some studies have demonstrated that type 1 diabetes is associated with disease-related autoantigens. 64,000 proteins are GAD, and GAD is considered to be the primary autoantigen of autoimmune response in type 1 diabetes mellitus. GAD antibody (GAAs) determination method is far more practical than anti-64000 protein, which is gradually widely used clinically. Its clinical value and ICA similar, but its positive rate and specificity than ICA high. GAAs and IAA were sometimes negative in individuals with type 1 diabetes mellitus type 1 diabetes mellitus, and the positive rate of GAAs was 75% to 90% in newly diagnosed type 1 diabetes mellitus, ~ 10 years) of type 1 diabetes in the positive rate of up to 60% to 80%. The detection of GAA is of great value in the diagnosis of type 1 diabetes, particularly in the early identification of LADA, and predicts the risk of diabetes in relatives of type 1 diabetes. At present, the methods used for GAA detection are immunoprecipitation, radioimmunoassay, enzyme-linked immunosorbent assay and immunofluorescence.
3. Insulin autoantibodies (IAAs) IAA, autoantibodies that bind to insulin, can be found in patients with type 1 diabetes without exogenous insulin and in preclinical patients. The newly diagnosed type 1 diabetes in patients with type 1 diabetes has a positive rate of IAA For 40% to 50%. The existing method is not yet able to distinguish IAA from insulin-induced insulin antibodies. At the same time, the diagnosis of type 1 diabetes, IAAs natural history has not been investigated. IAA production may be primary, from the B lymphocyte abnormal cloning, or caused by the destruction of islet B cells. Injury of pancreatic islet B cells may lead to structural changes in insulin release and are treated as foreign bodies by the body's immune system; or progesterone or earlier biosynthetic precursors are released as antigen when B cells are destroyed; reports of insulin immunoreaction Active (possibly proinsulin progenitor) is present on the B-cell plasma membrane, and the similarity of extrinsic antigen molecules independent of insulin can also lead to IAAs in vivo. Like ICAs and GAAs, IAAs are also important in predicting type 1 diabetes. IAA titer is part of the formula for predicting the onset of type 1 diabetes mellitus, which takes into account the first phase of insulin secretion in high-risk populations, the time at which type 1 diabetes mellitus occurs = 1.50.03 × intravenous glucose tolerance (1 min Insulin and insulin at 3 min) -0.008 (IAA titer), but a large series of prospective studies were needed to evaluate this formula. Age was negatively correlated with IAAs, IAAs were common in children, and often high titer. It has been shown that IAAs appear in younger non-diabetic individuals that are more likely to reflect pancreatic islet B cell destruction faster and faster progress in type 1 diabetes than in adults. IAA associated with type 1 diabetes is predominantly IgG, occasionally IgM. IAAs can generally be determined by radioimmunoassay and enzyme-linked immunosorbent assay. Some studies have reported that radioimmunoassay of IAAs can improve the value of ICAs in predicting the subsequent occurrence of type 1 diabetes in individuals with type 1 diabetes and the general population, whereas IAAs with enzyme-linked immunosorbent assays have no predictive value for type 1 diabetes. Therefore, the International Diabetes Symposium that only liquid radioimmunoassay evaluation of diabetes-related autoantibodies is more practical.
For diabetic patients to understand the pathogenesis of diabetes is also a way to treat, in life must avoid the impact of induced and stimulate the pathogenesis of diabetes, which is the best way to control the disease. Also pay attention to their own diet. Do not take too much intake of carbohydrates.
Pathogenesis
It is now clear that l-type diabetes is caused by immunological-mediated selective destruction of islet B cells. (ICA), insulin antibody (IAA), glutamate decarboxylase antibody (GAD antibody), and anti-idiopathic antibodies against B cells, such as islet cell antibody (ICA), insulin antibody (IAA), glutamate decarboxylase antibody (GAD antibody), and Insulin-related protein antibodies.
1. Islet cell antibody Bottazzo is equal to 1974 first described the presence of anti-islet cell antigen in patients with type 1 diabetes, and can be detected by immunofluorescence, this method in addition to minor changes, has been in use today, recently also by radioimmunoassay And enzyme-linked immunosorbent assay. Clinical study report: general non-diabetic ICA positive rate of less than 3%, while the newly diagnosed type 1 diabetes patients ICA positive rate of 60% to 90%. ICA is divided into islet cytoplasmic antibodies and islet cell surface antibodies. However, the detection of islet cells on the surface of the antibody is rarely used in clinical, clinical difficult to obtain fresh islet or insulinoma cell specimens, and islet cytoplasmic antibody examination is relatively simple and standardized, and thus widely used in clinical practice. The positive rate of islet cell antibodies decreased with the prolongation of diabetes mellitus, and 80% to 90% of patients with type 1 diabetes mellitus did not disappear after 2 years of onset; 10% to 15% of patients persisted for more than 3 years. In the case of similar course of disease, antibody positive often accompanied by: ① thyroid and stomach autoantibodies; ② other autoimmune endocrine disease; ③ have a strong family history of other autoimmune diseases; ④ more common; ⑤ and HLA-DR3 / B8 is strongly related. However, there are reports of type 1 diabetes 3 years after onset of 62% of patients with ICA positive in the body, did not find the difference.
The detection rate of ICA in the first-degree relatives of type 1 diabetes was significantly higher than that of the general population, and the detection of ICA was associated with an increased risk of subsequent clinical type 1 diabetes, and the predicted value of high titers (eg> 80 JDF units) Is significantly higher than the low titer (eg <20jdf ica = "" 1 = "" "" "" "" "" "" "" "" "" "" "" "" 10 = "" 60 = "" 79 = "" ica = "" 1 = "" icas = "" b = "" ica = "" 1 = "" 10 = "" "=" "Ica =" "ica =" "ica =" "lada =" "1 =" "1 =" "5 =" "spiddm =" "gad =" "> 15 years old; Non-insulin-dependent diabetes mellitus; ③ early onset of diet or oral hypoglycemic drug control treatment; ④ often 1 to 4 years of oral hypoglycemic drug failure or susceptibility to diabetic ketosis need to rely on insulin; ⑤ICA positive, GAD-Ab positive, low C peptide level and HLA-DR3 / 4, etc. For the "LADA" patients are more consistent opinion is the early use of insulin therapy to delay the destruction of islet B cells in the body.
2. Anti-GAD antibody glutamic acid decarboxylase (GAD) is a biosynthesis of the inhibitory neurotransmitter γ-aminobutyric acid, which is present in the brain and islet tissues of humans and animals. In recent years, it has been found that there are two isomeric forms with relative molecular weights of 65,000 (GAD65) and 67000 (GAD67), respectively, and show that GAD has many common physicochemical properties in islet 64000 protein antigens. Some studies have demonstrated that type 1 diabetes is associated with disease-related autoantigens. 64,000 proteins are GAD, and GAD is considered to be the primary autoantigen of autoimmune response in type 1 diabetes mellitus. GAD antibody (GAAs) determination method is far more practical than anti-64000 protein, which is gradually widely used clinically. Its clinical value and ICA similar, but its positive rate and specificity than ICA high. GAAs and IAA were sometimes negative in individuals with type 1 diabetes mellitus type 1 diabetes mellitus, and the positive rate of GAAs was 75% to 90% in newly diagnosed type 1 diabetes mellitus, ~ 10 years) of type 1 diabetes in the positive rate of up to 60% to 80%. The detection of GAA is of great value in the diagnosis of type 1 diabetes, particularly in the early identification of LADA, and predicts the risk of diabetes in relatives of type 1 diabetes. At present, the methods used for GAA detection are immunoprecipitation, radioimmunoassay, enzyme-linked immunosorbent assay and immunofluorescence.
3. Insulin autoantibodies (IAAs) IAA, autoantibodies that bind to insulin, can be found in patients with type 1 diabetes without exogenous insulin and in preclinical patients. The newly diagnosed type 1 diabetes in patients with type 1 diabetes has a positive rate of IAA For 40% to 50%. The existing method is not yet able to distinguish IAA from insulin-induced insulin antibodies. At the same time, the diagnosis of type 1 diabetes, IAAs natural history has not been investigated. IAA production may be primary, from the B lymphocyte abnormal cloning, or caused by the destruction of islet B cells. Injury of pancreatic islet B cells may lead to structural changes in insulin release and are treated as foreign bodies by the body's immune system; or progesterone or earlier biosynthetic precursors are released as antigen when B cells are destroyed; reports of insulin immunoreaction Active (possibly proinsulin progenitor) is present on the B-cell plasma membrane, and the similarity of extrinsic antigen molecules independent of insulin can also lead to IAAs in vivo. Like ICAs and GAAs, IAAs are also important in predicting type 1 diabetes. IAA titer is part of the formula for predicting the onset of type 1 diabetes mellitus, which takes into account the first phase of insulin secretion in high-risk populations, the time at which type 1 diabetes mellitus occurs = 1.50.03 × intravenous glucose tolerance (1 min Insulin and insulin at 3 min) -0.008 (IAA titer), but a large series of prospective studies were needed to evaluate this formula. Age was negatively correlated with IAAs, IAAs were common in children, and often high titer. It has been shown that IAAs appear in younger non-diabetic individuals that are more likely to reflect pancreatic islet B cell destruction faster and faster progress in type 1 diabetes than in adults. IAA associated with type 1 diabetes is predominantly IgG, occasionally IgM. IAAs can generally be determined by radioimmunoassay and enzyme-linked immunosorbent assay. Some studies have reported that radioimmunoassay of IAAs can improve the value of ICAs in predicting the subsequent occurrence of type 1 diabetes in individuals with type 1 diabetes and the general population, whereas IAAs with enzyme-linked immunosorbent assays have no predictive value for type 1 diabetes. Therefore, the International Diabetes Symposium that only liquid radioimmunoassay evaluation of diabetes-related autoantibodies is more practical.
For diabetic patients to understand the pathogenesis of diabetes is also a way to treat, in life must avoid the impact of induced and stimulate the pathogenesis of diabetes, which is the best way to control the disease. Also pay attention to their own diet. Do not take too much intake of carbohydrates.
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