Type 1 diabetes, also known as insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes, is prone to diabetic ketoacidosis (DKA). it often develops before the age of 30 and accounts for less than 10% of diabetes. type 1 diabetes is insulin-dependent, meaning that patients need to be treated with insulin from the onset and for life. The reason for this is that the insulin-producing cells of the pancreas in type 1 diabetes have been completely damaged, thus completely losing the function of insulin production. When there is an absolute lack of insulin in the body, it causes a continuous increase in blood glucose levels and the development of diabetes.
Signs and Symptoms
Type I diabetes produces absolutely no insulin on its own and therefore requires lifelong treatment with foreign insulin; Type I diabetes has been described as an autoimmune disease – the body’s immune system attacks the islet cells in the pancreas and eventually destroys their ability to make insulin. Without insulin, the body cannot convert glucose into energy, so people with type I diabetes must take insulin injections to survive.
The symptoms of diabetes can be divided into two categories: one is the manifestations related to metabolic disorders, especially the “three polydipsia” associated with hyperglycemia; the other is the manifestations of various acute and chronic complications.
Polyuria is due to high blood sugar, exceeding the renal sugar threshold (8,89~10,0mmol/L), and the glucose filtered out by the glomerulus cannot be completely reabsorbed by the renal tubules, forming osmotic diuresis. The higher the blood glucose, the more urinary sugar excretion, the more urine volume, 24h urine volume up to 5000 ~ 10000ml, but the elderly and people with kidney disease, the renal glucose threshold increased, urinary sugar excretion is impaired, in a mild to moderate increase in blood sugar, polyuria may not be obvious.
2.Drinking Mainly due to high blood sugar, plasma osmolarity increases significantly, and with polyuria, water loss is excessive, intracellular dehydration occurs, which aggravates hyperglycemia and further increases plasma osmolarity significantly, stimulating the thirst center, leading to thirst and drinking. Polydrinking further aggravates polyuria.
3, polyphagia The mechanism of polyphagia is not very clear. Most scholars tend to be the result of reduced glucose utilization (difference in glucose concentration in arterial and venous blood before and after entering and leaving tissue cells). Normal people fasting when the glucose concentration difference between arterial and venous blood narrowing, stimulating the feeding center, resulting in hunger; ingestion of food after the rise in blood sugar, arterial and venous blood concentration difference increased (greater than 0, 829mmoL / L), the feeding center is inhibited, satiety center excitement, feeding requirements disappear. However, in diabetic patients, due to absolute or relative lack of insulin or insulin insensitivity of tissues, the ability of tissues to take in and use glucose is reduced. In addition, the body can not make full use of glucose, a large amount of glucose excretion from the urine, so the body is actually in a semi-starvation state, lack of energy also caused by hyperphagia.
4, weight loss Diabetic patients, despite normal appetite and food intake, or even increase, but weight loss, mainly due to absolute or relative lack of insulin or insulin resistance, the body can not make full use of glucose to produce energy, resulting in the strengthening of fat and protein decomposition, excessive consumption, a negative nitrogen balance, weight loss gradually, and even wasting. Once the diabetes is reasonably treated and well controlled, weight loss can be controlled and even regained. If a diabetic patient continues to lose weight or lose weight significantly during the treatment process, it suggests that the metabolism may be poorly controlled or combined with other chronic wasting diseases.
5.Lack of energy is also common in diabetic patients, because glucose can not be fully oxidized, that is, the body can not fully utilize glucose and effectively release energy, while tissue water loss, electrolyte imbalance and negative nitrogen balance, etc., and therefore feel general weakness, depression.
6, vision loss Many diabetic patients complain of vision loss or blurred vision when they visit the clinic in the early stage, which may be mainly due to the change of crystal osmolarity caused by hyperglycemia, resulting in the change of crystal refraction. In the early stage, most of the changes are functional, and once the blood sugar is well controlled, the vision can return to normal sooner.
Treatment with medication
The main objectives of diabetes treatment include: correcting metabolic disorders, eliminating symptoms, guaranteeing normal growth and development (in pediatric patients), maintaining the ability to learn, live and work well; preventing various acute or chronic complications and concomitant diseases, prolonging life expectancy, and reducing the rate of disability and death. While obtaining the above objectives, the quality of life of patients should not be excessively restricted. The principles of diabetes treatment are: perseverance and comprehensive management. The treatment of diabetes includes not only the control of hyperglycemia, but also the comprehensive treatment of some complications (such as hypertension, lipid metabolism disorders, etc.) and various complications. The treatment of diabetes mellitus hyperglycemia generally includes reasonable use of diabetes education, diet therapy, exercise therapy, drug therapy and self-monitoring and other means to make the glucose metabolism control as normal or close to normal as possible. ①Glucose control is good: fasting blood glucose <6,0mmol/L, 2h postprandial blood glucose <8,0mmoL/L, HbA1c <7,0%< span="">or 6,5%; ②Glucose control is better: fasting blood glucose 6-8mmol/L, 2h postprandial blood glucose 8-10mmol/L, HbA1c <9,0%; ③< span="">more than the above Values are poor glycemic control. 2015 ADA recommended treatment goals HbA1c<7,5%< span="">
1.Insulin therapy
(1) Types
According to the type and duration of action of insulin, it can be divided into short-acting insulin (RI), medium-acting pearl protein insulin (NPH), long-acting fisetin insulin (PZI) and insulin analogues. If better control is achieved requires 3-4 times daily intensive therapy or pump therapy.
(2) Dose adjustment: adjust insulin dose as needed according to blood glucose (whole blood glucose in the morning fasting, 2h after breakfast, 2h after lunch, 2h after dinner and before bedtime can be measured in units with conditions) and urine glucose test results.
(3) Injection site: the abdominal wall, the front and outside of both upper arms, and the front and outside of the thighs are suitable. Injections should be given in rows in order, with each row of needles spaced 2cm apart, to prevent fibrosis or atrophy of the local subcutaneous tissues from occurring in the same area for a long time.
2.Planned diet The principle of diabetic children’s diet plan is that it should meet the needs of their growth and development and daily activities. Appropriate restrictions and flexibility should be made according to the dietary habits of the child’s family.
Daily calorie requirement = 4184 + age x (290 to 420) kJ [1000 + age x (70 to 100) kca1]. Younger and thinner children should choose higher calories, <3< span="">year-old children use 418,4kJ (100kcal) per year, decreasing with age; while older and fatter, especially adolescent girls should use lower calories, which can be 209,2~251,0kJ (50~60kcal) per year, with total calories ≤8368kJ/d (≤ 2000kcal/d). Higher calories are available for those who exercise extraordinarily, and the distribution of calories is as follows: carbohydrates account for 50% to 55%; proteins 15% to 20%, and fats account for 25% to 30%.
Protein in the food composition should be mainly animal protein; fat should be selected with vegetable oils containing unsaturated fatty acids. It is best to consume enough vegetables or foods with more fiber every day. The daily calorie allocation of each meal should be basically fixed, which can be divided into 1/5 for breakfast and 2/5 for lunch and dinner, leaving a small amount for snacks between meals, and eating on time. If you cannot eat on time, you must measure the blood sugar before meals to adjust insulin or meal quantity.
3. Exercise therapy In the stage of glucose metabolism disorder, children with diabetes who are first diagnosed must arrange appropriate programs according to their age and exercise ability and exercise regularly and quantitatively every day under the condition of good blood sugar control. It is necessary to make good adjustment of insulin dosage and diet or add meals before exercise (such as during the 4th period of physical education class) to prevent the occurrence of hypoglycemia during exercise. Any exercise should not be performed during ketoacidosis.
Exercise can improve insulin sensitivity, lower blood glucose, increase energy consumption, reduce the occurrence of obesity, regulate blood lipids, and enhance physical fitness, etc., which are significant to the treatment of diabetes and prevention of complications.
4. Education and psychological treatment of children with diabetes should be carried out throughout the whole process of diabetes diagnosis and treatment, and the knowledge of diabetes and psychological education should be popularized to children with diabetes. To make the child establish confidence to overcome the disease.
Pathogenesis
The exact etiology and pathogenesis of type 1 diabetes are not well understood, but the cause is a combination of genetic and environmental factors. It is mainly due to immune-mediated selective destruction of pancreatic islet B cells.
Autoimmune system defects: Because a variety of autoimmune antibodies can be detected in the blood of type 1 diabetes patients, such as glutamic acid decarboxylase antibodies (gad antibodies) and islet cell antibodies (ica antibodies), these abnormal autoantibodies can damage the insulin-secreting b cells of human pancreatic islets, making them unable to secrete insulin normally.
Genetic factors: (1) Family history: Type 1 diabetes has a certain degree of family aggregation. Some studies have reported a history of diabetes in both parents, and the incidence of type 1 diabetes in their children is 4% to 11%; the incidence of family aggregation of type 1 diabetes among siblings is 6% to 11%; the consistency of type 1 diabetes in identical twins is less than 50%.
(2) HLA and type 1 diabetes: The human leukocyte antigen (HLA) gene is located on the short arm of the 6th chromosome pair and is a group of closely interlocked genes, HLA is encoded by 3 types of genes: I, II and III. The class I gene region includes HLA-A, HLA-B, HLA-C and some other genes with unknown functions and pseudogenes, which encode antigen molecules present on the surface of all nucleated cells and are responsible for the delivery of foreign antigens to CD8+ T lymphocytes; the class II gene region mainly includes three subregions, HLA-DR, HLA-DQ and HLA-DP, which encode DR, DQ and DP, respectively. The class III gene region encodes a number of soluble proteins, including certain complement components, such as C2C4A, C4B, tumor necrosis factor (TNF) and heat shock protein (HSP), etc. HLA is involved in T lymphocyte recognition of antigens and other immune cells through the major tissue soluble complex (MHC) restriction. HLA plays an important role in the recognition of antigens and other immune cell interactions, as well as in the formation and maintenance of self-tolerance, and in the recognition of self and foreign bodies and the induction and regulation of immune responses. It is evident that HLA plays a very important role in the development and progression of many autoimmune diseases, including type 1 diabetes.
A strong correlation between certain HIAs and the development of type 1 diabetes has been demonstrated. In a family with type 1 diabetes, siblings with identical HLA antigens have a 5% to 10% chance of developing diabetes, while non-HLA-identical siblings have less than a 1% chance of developing diabetes. In the Caucasian population, 95% of type 1 diabetics have HLA-DR3 or HLA-DR4 compared to 45%-50% of non-diabetics; HLA-DR2 is protective against the development of type 1 diabetes. the HLA-DQ gene is a more specific marker of type 1 diabetes susceptibility and determines the susceptibility and resistance of B cells to autoimmune destruction. HLA-DQw3,2 has been reported to be found in almost 70% of patients with concomitant type 1 diabetes HLA-DDR3, while the protective gene HLA-DQw3,1 was found in DR4 controls. It was found that if position 57 of the two allelic DQβ chains were occupied by aspartate, they would generally be less susceptible to autoimmune diabetes, and if both alleles were non-aspartate they would be strongly susceptible to type 1 diabetes, and arginine at position 52 of the HLA-DQA1 chain was also a susceptibility gene for type 1 diabetes. 57 positions of the HLA-DQβ1 chain were non-aspartate pure and HLA-DQA1 The relative risk of developing type 1 diabetes is highest in individuals with a pure amino acid at position 52 of the HLA-DQA1 chain. 45 amino acids in the DQβ chain immunorecognize the antigenic determinant cluster as DQw3,2 rather than DQw3,1. The above findings may explain the higher risk of type 1 diabetes with the combined presence of the HIA-DQ and HLA-DR loci than with their separate manifestations.
Viral infections may be causative: Perhaps surprisingly, many scientists suspect that viruses can also cause type i diabetes because people with type i diabetes often have had viral infections for some time prior to the onset of the disease, and because the “epidemic” of type i diabetes often occurs after a viral epidemic. Viruses, such as those that cause mumps and rubella, and the coxsackievirus family, which causes poliomyelitis, can play a role in type i diabetes.
Other factors: such as milk, oxygen free radicals, some rodenticides, etc. Whether these factors can cause diabetes is being studied by scientists.
Screening methods
1.Urine examination
(1) urine sugar: normal people from the renal tubular filtration of glucose is almost completely absorbed by the renal tubules, only a trace of glucose excreted from the urine every day (32 ~ 90mg), general glucose qualitative test can not be detected. Diabetes usually refers to the daily urinary excretion of glucose > 150mg. urinary glucose can be detected when blood glucose exceeds 8,9-10mmol/L (160-180mg/dl) in normal people, and this blood glucose level is called the renal glucose threshold. Older people and people suffering from kidney disease, the renal sugar threshold increases, blood glucose more than 10mmol/L, or even 13, 9 ~ 16, 7mmol/L can be no diabetes; On the contrary, women in pregnancy and some renal tubular or interstitial lesions, the renal sugar threshold is reduced, and diabetes can occur when blood glucose is normal. Commonly used tests for diabetes are the Ban method (with the help of copper sulfate reduction reaction) and glucose oxidase. Ban method is often affected by lactose, fructose, pentose, ascorbic acid, vincristine, isoniazid and salicylate in urine, showing false positives, and the operation is relatively inconvenient, has been gradually eliminated; glucose oxidase method because the enzyme only positive reaction to glucose, specificity is stronger, but when taking large doses of ascorbic acid, salicylic acid, methyldopa and levodopa can also appear false positives. Urine glucose is not used as a diagnostic indicator of diabetes mellitus, but only as an indicator to monitor the control of diabetes mellitus and as an indicator of possible diabetes mellitus requiring further testing. In addition to the renal sugar threshold and the interference of certain reducing substances, the influence of urine sugar is often affected by the amount of urine and the emptying of the bladder.
(2) Urine ketones: Urine ketone body measurement provides an indicator of insulin deficiency, warning that ketoacidosis is imminent or may already exist in diabetic patients, suggesting the need for further blood ketone body measurement and blood gas analysis. Urine ketone bodies are determined using the reaction of sodium nitrate with acetoacetic acid, forming a purple substance that suggests positive urine ketone bodies. However, the reaction based on sodium nitroprusside does not measure β-hydroxybutyric acid, which is quantitatively the major part of the ketone bodies (acetone, acetoacetic acid and β-hydroxybutyric acid). False positives have been reported with sulfhydryl-containing drugs such as captopril (mercaptopropionic acid); and false negatives can be produced if urine specimens are exposed to air for a prolonged period of time.
Urine ketone body testing should be performed in patients with diabetes mellitus, especially type 1 diabetes mellitus, when combined with other acute illnesses or severe stress, and during pregnancy, or when there are unexplained gastrointestinal symptoms such as abdominal pain, nausea, and vomiting.
(3) Urine albumin: Urine albumin measurement can sensitively reflect the damage of diabetic kidney and its degree. In the early stage of diabetic nephropathy, 24h urine protein is usually <150mg< span=""> and intermittent. Strict control of blood glucose can make urine protein disappear. Mogensen believes that exercise test is a sensitive test for early diagnosis of diabetic nephropathy.
2.Blood test
(1)Blood glucose: blood glucose is increased, mostly 16,65~27,76mmol/L (300~500mg/dl), sometimes up to 36,1~55,5mmol/L (600~1000mg/dl) or more, blood glucose 36,1mmol/L can often be accompanied by hypertonic coma.
(2) Blood ketones: Qualitative positive ketone body formation. However, since ketone bodies in blood are often dominated by β-hydroxybutyric acid, whose blood concentration is 3 to 30 times higher than that of acetoacetic acid and parallels the ratio of NADH/NAD, if ketoacidosis occurs clinically and blood is dominated by β-hydroxybutyric acid while qualitative test is negative, further specific enzyme test should be performed to directly determine the level of β-hydroxybutyric acid.
(3) Acidosis: mainly associated with increased ketone body formation. Ketone bodies include β-hydroxybutyric acid, acetoacetic acid and acetone. Acetoacetic acid and acetone can react with sodium nitroprusside, while β-hydroxybutyric acid does not react with sodium nitroprusside. In most cases, there is a large amount of acetoacetic acid in the serum that reacts with sodium nitroprusside in DKA. In this metabolic acidosis, the pH may be within the normal range during the compensatory period, but when it is not compensated, the pH is often below 7.35 and sometimes below 7.0. CO2 binding is often below 13.38 mmol/L (30% volume), and in severe cases below 8.98 mmol/L (20% volume), and HCO3- may fall to 10-15 mmol/L. The residual base on blood gas analysis is increased, and the buffered base is significantly reduced. The buffered base is significantly reduced (<45mmol/L), and SB and BB are also reduced.
(4) Electrolytes: The measurement of sodium, potassium, phosphorus and magnesium should be noted.
(6) Blood creatinine and urea nitrogen: often elevated due to water loss, circulatory failure (prenephrosis) and renal insufficiency. It can be restored after rehydration.
Other ancillary tests
Diabetic retinopathy is part of diabetic microangiopathy and often coexists with diabetic nephropathy, so once retinopathy is detected on fundus examination, we should be alert to the presence of renal microangiopathy. Ultrasound and electrocardiogram are optional depending on the condition.
Complications
The most important complications of type 1 diabetes are retinopathy and nephropathy caused by microangiopathy, which can lead to blindness and renal failure in severe cases.
The future of prevention intervention trials
Many new immunotherapeutic drugs for type 1 diabetes are under clinical research and practice, such as immunosuppressive drugs, T-cell monoclonal antibodies, and immune vaccines. Also pancreatic, islet, and stem cell transplantation are being investigated.