Islet cell destruction

Introduction Diabetes mellitus is a metabolic disorder caused by a decrease in the biological effect of insulin deficiency and (and) insulin. It is a common disease characterized by persistent high blood sugar elevation and the appearance of diabetes. The incidence rate is 1% to 2%. Diabetes refers to primary diabetes, which can be divided into insulin-dependent diabetes mellitus (type I diabetes) and non-insulin-dependent diabetes mellitus (type II diabetes) according to its etiology, pathogenesis, pathology, clinical manifestations and prognosis. ). Insulin-dependent diabetes mellitus can occur at any age, but it usually occurs in children or adolescents. It accounts for less than five percent of all diabetes, but its impact on life is far greater than that of common non-insulin-dependent diabetes. The exact cause of insulin-dependent diabetes is not very clear. It is more certain that the body's immune system is out of order and is against the tissues of the body. The body's immune system creates certain substances that fight insulin in the pancreas. When these cells are destroyed, they cannot secrete insulin.

Cause

Causes of islet cell destruction:

Insulin-dependent diabetes mellitus (IDDM), also known as type I diabetes, accounts for 10% to 20% of diabetes. Most of the patients are adolescents. The age at onset is less than 20 years old, and the islet B cells are significantly reduced. Insulin is significantly reduced, complicated with ketosis and even coma, treatment depends on insulin. It is currently believed that the disease is based on the genetic susceptibility, and the islets are infected with viruses (such as mumps virus, rubella virus and Coxsack B4 virus) or by toxic chemicals (such as pyridoxine). Injury of islet B cells, release of allergenic proteins, causing autoimmune reactions (including cellular immunity and humoral immunity), leading to autoimmune inflammation of islets, further causing severe destruction of islet B cells.

The main basis of genetic susceptibility is that one of the ovarian twins is sick, and 50% of the other is also ill; there is a clear relationship with the HLA type. The frequency of DR3 and DR4 is significantly increased in this type of Chinese patients. The population of -DR3 or DR4 is 5 to 7 times more likely to develop the disease than others. These people have immunodeficiency, on the one hand, the resistance to the virus is reduced, on the other hand, the inhibitory T cells are low in function and prone to autoimmune reactions (see toxic goiter in this chapter).

The main basis of the autoimmune response is: a large number of lymphocytic infiltrates (insulinitis) in the early islets of patients, including CD4+ T cells, consistent with the animal model of type I diabetes, CD4+T extracted from type I diabetic animals. Transfer of cells to normal animals can cause the disease; 90% of patients can detect anti-islet cell antibodies in the blood within one year after onset; 10% of patients have other autoimmune diseases at the same time. Insufficient insulin secretion, dysfunction or two factors are the main causes of hyperglycemia.

an examination

Related inspection

SST receptor imaging C-peptide glucagon insulin antibody pancreatic CT examination

Examination and diagnosis of islet cell destruction:

1. Symptoms of insulin-dependent diabetes can occur rapidly and severely. Symptoms include frequent urination, thirst, hunger, blurred vision, and fatigue. Because insulin-dependent diabetes patients lack insulin, the blood glucose is getting higher and higher, and the kidneys will excrete a part of the blood's glucose. This process will cause a lot of water and electrolytes to be discharged together, thus forming frequent urination and thirst. .

Because the body can't use glucose as energy, it turns to decomposing protein and fat to get energy. Because the body uses a lot of protein and fat, it produces weight loss. The metabolism of fat produces some acidic substances. If this acidic substance is produced too much, it will evolve into diabetic ketoacidosis, which is an emergency and needs to be sent to the hospital immediately.

Since the discovery of insulin in 1921, the life of insulin-dependent diabetes patients has been extended from a few weeks to several decades. Although insulin has a life-saving effect, diabetes is still a chronically fatal disease. Diabetes can produce some chronic complications after many years of onset. These complications mainly affect the heart, eyes, kidneys and nerves. The main cause of damage to these organs is that the small blood vessels of the whole body are caused by diabetes. It has been found that insulin-dependent diabetes patients can reduce these complications if they control blood sugar.

2. Other organizational changes and complications:

(1) Arterial disease: 1 atherosclerosis, earlier and more severe than non-diabetic patients; 2 glassy arteriolar degeneration, manifested as thickening of basement membrane, substance rich in type IV collagen, due to permeability Increased protein leakage increased, so protein deposition in the arterial wall, resulting in narrow lumen, causing tissue ischemia. This change is more pronounced in patients with hypertension.

(2) nephropathy: 1 glomerular sclerosis, there are two types, one is diffuse glomerulosclerosis (diffuse glomerulosclerosis), glomerular capillary basement membrane diffuse thickening, vascular mesangial cell proliferation and matrix increase The other is nodular glomerulosclerosis, which is characterized by a large amount of transparent substance deposition on the part of the mesangial axis, forming a nodular shape, and the periphery of the nodule is capillary vasospasm. 2 arteriosclerosis and arteriosclerotic nephrosclerosis. 3 acute and chronic pyelonephritis, prone to renal papillary necrosis, the latter is more sensitive to bacterial infection on the basis of ischemia. 4 The renal epithelial cells of the proximal convoluted tubule have glycogen deposition.

(3) Diabetic retinopathy. There are two types, one is background retinopathy, the basement membrane of the retinal capillaries is thickened, the venules are dilated, often there are small hemangiomas, followed by edema and hemorrhage; the other is caused by vascular disease. Retinal hypoxia, stimulation causes angiogenesis and fibrous tissue hyperplasia, called proliferative retinopathy. Retinopathy is prone to blindness. In addition to retinopathy, diabetes is associated with cataracts.

(4) Neurological diseases: peripheral nerves including motor nerves, sensory nerves and autonomic nerves can cause ischemic injury due to vascular changes, and various symptoms such as limb pain, numbness, loss of sensation, muscle paralysis and foot drop, wrist Drooping, gastrointestinal and bladder dysfunction, etc.; brain cells can also undergo extensive degeneration.

(5) Other organ lesions: glycogen deposition in the nucleus of the liver cells; yellow tumor nodules or plaques may occur due to hyperlipidemia.

(6) Diabetic coma: the cause is 1-ketoacidosis; 2 hyperglycemia causes dehydration and high osmotic pressure.

(7) Infection: Due to metabolic disorders and vascular lesions, tissue ischemia is easy to combine with various infections.

Differential diagnosis

Symptoms of islet cell destruction confusing:

Insulinitis is seen early in type I diabetes, and there are a large number of lymphocytes infiltrating in and around the islets, occasionally eosinophils. The islet cells undergo progressive destruction and disappearance, and the number of A cells in the islets increases relatively, and the islets become smaller and the number is reduced. Some islet fibrosis; when type II diabetes is examined by conventional methods, there is little change in the early stage, and then the islet B cells are visible. Reduced. A common change is islet amyloidosis, where there is amyloid deposition around the B cells and between the capillaries, which may be a breakdown of the insulin B chain.

Non-insulin dependent diabetes mellitus (NIDDM), also known as type II diabetes, is more than 40 years old. There is no islet inflammation and the number of islets is normal or slightly reduced. Insulin in the blood does not start to rise, or even increase, no anti-islet cell antibody, no other autoimmune response. Although this type is also familial, more than 90% of all cases of ovarian twins have not been found to be directly related to the HLA gene. Its pathogenesis is not as clear as type I diabetes, which is generally thought to be caused by a relative lack of insulin associated with obesity and tissue insensitivity to insulin (insulin resistance).

Obesity is an important factor in the occurrence of this type of disease. More than 85% of patients are obviously obese. As long as they eat less and lose weight, blood sugar can be reduced and the disease can be controlled. There are two important links in causing the disease: 1 relative lack of insulin and abnormal secretion. Long-term high-calorie foods stimulate islet B cells, causing hyperinsulinemia, but compared with non-diabetic people who are equally obese, blood insulin levels are lower, so insulin is relatively insufficient. In addition, for glucose and other stimuli, insulin has a delayed response in the early stage, indicating that the islet B cells themselves are also defective. Long-term excessive load can cause islet B cell failure, so there may be an absolute lack of insulin secretion in the late stage of the disease, but it is much lighter than type I. 2 tissue insulin resistance, the greater the fat cells, the less sensitive to insulin, the decreased insulin receptors of fat cells and muscle cells, so the response to insulin is poor, which is the performance of insulin receptor negative regulation caused by hyperinsulinemia; Substance excess cells also have a defect of postreceptor signaling by insulin, so that glucose and amino acids cannot enter the cell through the cell membrane. In fact, excess nutrients (including liver cells and muscle cells) have lost their normality. The ability to handle nutrients in the blood. In patients with non-obese type II diabetes, early insulin response to glucose is worse than that of obese patients, suggesting that islet B cell defects are more severe, and tissue is also insulin resistant, the cause of which is unknown, may be related to genetic abnormalities.

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