Turns out, insulin-dependent diabetes mellitus, contrary to popular belief, is not synonymous with type 1 diabetes. Insulin-dependent patients can be either type 2 diabetics or pregnant women with gestational diabetes. In turn, patients diabetes mellitus Type 1 patients may cease to be insulin dependent for a certain period of time (during the “honeymoon” of their disease).
Insulin dependent diabetes
Insulin-dependent diabetes mellitus (as well as juvenile or juvenile diabetes) - These are outdated names for type 1 diabetes- this is what this disease is now called. It occurs when the pancreas stops secreting insulin due to the destruction of beta cells. Insulin cannot be taken orally in the form of tablets, so the patient is forced to inject himself with insulin. Insulin must be taken regularly throughout your life to avoid high blood sugar levels.
The main function of insulin is to unblock cells to allow glucose to enter them, a source of energy that is produced from food that enters our body. Dietary sources of carbohydrates, once in the body, are broken down into glucose, and insulin delivers glucose to the cells.
With insulin-dependent diabetes, patients use different insulin treatment regimens. Previously, the so-called traditional insulin therapy was popular, in which insulin injections were given 3 times a day before meals. The doses of insulin were the same; the patients were only advised to eat the same portions of food each time in order to meet the prescribed dose of the medicine.
Over time, a basal-bolus (intensified) diabetes treatment system was developed, in which patients use two types of insulin - short-acting and long-acting.
Insulin-dependent diabetics inject short-acting insulin (regular or ultra-short-acting insulin) before meals (to “coat” the food), and its dosage may vary depending on the amount of carbohydrates eaten.
Long-acting insulin has serious help insulin-dependent patients, because it mimics the function of a healthy pancreas, which produces natural human insulin. Patients administer it 1-2 times a day to create a “background” (basal) concentration of insulin in the body, which protects against surges and dips in blood sugar levels.
Insulin-dependent diabetes type 2
Occurs in 3-9% of all pregnancies depending on the population studied. Most often it occurs in the third trimester. This type of diabetes affects only 1% of women under the age of 20, but 13% of those who become pregnant over the age of 44.
They are treated in different ways. Initially, diet, exercise and oral medications are prescribed, and if this is not enough to control blood sugar levels, insulin therapy is prescribed. Thus, People with gestational diabetes may also have insulin-dependent diabetes, albeit temporarily.
The difference between diabetes in pregnancy and types 1 and 2 is that after the birth of the child, diabetes subsides and insulin treatment is stopped.
We can conclude that the inaccuracy of the term “insulin-dependent diabetes” is manifested in the fact that the first and second types of diabetes are, in fact, different diseases, but patients of each of these types can be insulin dependent. Pregnant women who are diagnosed are also treated with insulin. Therefore, when talking about insulin-dependent patients, it is impossible to immediately understand what type of diabetes we are talking about.
Insulin dependent children
It primarily affects children, adolescents and young adults. Sometimes diabetes occurs from birth, although such cases are quite rare.
Raising an insulin-dependent child - a difficult test not only for the patient, but also for his parents. Parents should study this disease in depth to teach their child how to properly inject insulin, count carbohydrates and bread units, measure their blood sugar levels and adapt to normal life.
Parents of insulin-dependent children should discuss the following important issues with their endocrinologist:
- How often should I measure my child's blood sugar?
- Which insulin therapy is better: use a basal-bolus system or an insulin pump?;
- How to recognize and treat hypoglycemia and high blood sugar?
- How to detect the presence of ketonuria in a child and stop it?
- How do carbohydrates affect blood sugar levels?
- How to count bread units?
- How does physical activity affect blood sugar levels in an insulin-dependent child?
- How to learn to live painlessly with diabetes - study at school, stop being ashamed of having this disease, go to summer camps, go hiking, etc.?
- How often do you visit an endocrinologist and other diabetes treatment specialists?
Honeymoon with type 1 diabetes or turning an insulin-dependent patient into an insulin-independent one
With type 1 diabetes, a situation may arise when the remaining pancreatic cells begin to intensively produce insulin, which leads to the cancellation or significant reduction of prescribed insulin therapy. Many patients during this period think that they have been cured of diabetes, but, unfortunately, the “honeymoon” period of diabetes is only a temporary lull.
Why does temporary remission of diabetes occur? develops against the background of the body’s destruction of its own insulin-producing pancreatic cells. When a patient begins to take insulin injections (becomes insulin dependent), part of the burden of producing its own insulin is removed from the pancreas. This rest period, provided by insulin injections, stimulates the pancreas to produce insulin from the remaining beta cells.
However, after a few months, the vast majority of these remaining beta cells will be destroyed. The honeymoon period ends when the pancreas no longer produces enough insulin to maintain optimal level blood glucose.
A study was conducted “Honeymoon in children with type 1 diabetes mellitus: frequency, duration and impact on it” various factors» (PubMedPMID: 16629716). It writes that the honeymoon period of type 1 diabetes is characterized by a reduction in insulin requirements while maintaining good glycemic control. Clinical significance This phase is a potential opportunity for pharmacological intervention to slow or stop the ongoing self-destruction of the remaining beta cells.
A group of 103 children with diabetes mellitus under the age of 12 years was examined and the frequency, duration and factors influencing partial remission of diabetes mellitus were assessed. According to the results of the study, it was revealed that 71 children experienced partial remission of diabetes mellitus, and complete remission in three. The duration of remission ranged from 4.8 to 7.2 months.
Non-insulin-dependent diabetes mellitus (diabetes of the elderly or type 2)
It should be noted that there is also non-insulin dependent diabetes, which doctors today call type 2 diabetes. In this type of diabetes, the pancreas secretes normal amounts of insulin, but the cells cannot process it properly.
The main problem of people with type 2 diabetes is overweight and (metabolic syndrome), which prevents cells from interacting properly with insulin.
Unlike the insulin-dependent type of diabetes mellitus, only patients with type 2 of this disease can be insulin-independent (except for cases of temporary remission of type 1 diabetes). There is also diabetes insipidus, but this is a completely different disease that has nothing in common with traditional diabetes mellitus.
Resume:
The terms “insulin-dependent” and “non-insulin-dependent” diabetes mellitus are completely incorrect and outdated. Not only patients with type 1 diabetes, but also type 2 diabetics, as well as women with gestational diabetes, can be insulin dependent. While not only people with type 2 diabetes can be insulin-independent, but also people whose type 1 diabetes has temporarily subsided (during the honeymoon period).
Type 1 insulin-dependent diabetes is a dangerous endocrine disease of a chronic nature. It is caused by a deficiency of pancreatic hormone synthesis.
As a result, the presence of glucose in the blood increases. Among all the cases of the disease in question, this type is not so common.
As a rule, it is diagnosed in people of young and young age. On at the moment The exact cause of this disease is unknown. But, at the same time, there are several certain factors that contribute to its development.
These include genetic predisposition, viral infectious diseases, exposure to toxins and autoimmune reactions of cellular immunity. The main pathogenetic link of this dangerous and serious disease of the first type is the death of approximately 91% of pancreatic β-cells.
Subsequently, a disease develops that is characterized by insufficient insulin production. So what is insulin-dependent diabetes, and what leads to it?
This form of the disease accounts for approximately 9% of the incidence, which is associated with increased glucose levels in the blood plasma.
However, the total number of diabetics is increasing every year. It is this type that is considered the most severe and is often diagnosed in people at an early age.
So what should every person know about insulin-dependent diabetes mellitus in order to prevent its development? First, you need to understand the terms. Diabetes mellitus is a disease of autoimmune origin, which is characterized by a complete or partial cessation of the formation of a pancreatic hormone called insulin.
This dangerous and fatal process subsequently leads to an unwanted accumulation of sugar in the blood, which is considered the so-called “energy raw material” necessary for the smooth functioning of many cellular and muscle structures. In turn, they cannot receive the vital energy they need and begin to break down the existing reserves of protein and fat for this.
Insulin production
It is insulin that is considered the only hormone of its kind in the human body that has the ability to regulate. It is produced by certain cells located on the islets of Langerhans of the pancreas.
But, unfortunately, in the body of every person there is huge number other hormones that have the ability to increase sugar levels. For example, these include adrenaline and norepinephrine.
The subsequent appearance of this endocrine disease is influenced by many factors, which can be found out later in the article. It is believed that the current lifestyle has a tremendous impact on this disease. This is due to the fact that people of the modern generation increasingly suffer from the presence and do not want to lead.
The most popular types of the disease are the following:
- insulin-dependent diabetes type 1;
- non-insulin dependent type 2;
The first form of the disease is considered a dangerous pathology, in the presence of which insulin production almost completely stops. Large quantity modern scientists believe that the main reason for the development of this type of disease is considered to be a hereditary factor.
The disease requires constant scrupulous monitoring and remarkable patience, because at the moment there are no medications that could completely cure the patient.
Treatment
As for effective therapy, there are two main tasks: a radical change in the current lifestyle and competent treatment with the help of certain medications.
It is very important to constantly comply special diet, which implies .
You also shouldn’t forget about sufficient physical activity and self-control. An important stage is individual selection.
Any additional sports activities and meals must be taken into account when calculating the amount of insulin administered.
There is a simple regimen of insulin therapy, a continuous subcutaneous infusion of pancreatic hormone, and multiple subcutaneous injections.
Consequences of disease progression
During subsequent development, the disease has a strong negative impact to all systems of the body.This irreversible process can be avoided thanks to timely diagnosis. It is also important to provide specific supportive treatment.
The most devastating complication is.
For this state Symptoms such as dizziness, attacks of vomiting and nausea, as well as fainting are typical.
An additional complication in people with diabetes is a decrease in the body's protective functions. It is for this reason that they often suffer from colds.
Video on the topic
All about insulin-dependent diabetes mellitus in:
Type 1 diabetes is not a death sentence. The most important thing is to know everything about this disease. This is what will help you be armed and promptly detect any changes in the performance of your own body. When the first alarming symptoms appear, you should immediately contact a qualified endocrinologist for examination, examination and appropriate treatment.
Despite the fact that patients with type II diabetes mellitus are prescribed insulin medications, insulin-dependent diabetes is still considered to be a type I disease. This is due to the fact that with this disease the body stops producing its own insulin.
The pancreas of people diagnosed with insulin-dependent diabetes is virtually devoid of cells that produce this protein hormone.
In type II diabetes, the pancreas produces too little insulin and the body cells do not have enough of this hormone for normal functioning. Often, correct physical activity and a well-designed diet can normalize insulin production and improve metabolism in type II diabetes.
If this is the case, then insulin administration to these patients will not be required. For this reason, type I diabetes is also commonly referred to as insulin-dependent diabetes mellitus.
When a patient with type II diabetes has to be prescribed insulin, the disease is said to have entered the insulin-dependent phase. But, fortunately, this does not happen very often.
Type I diabetes develops very rapidly and usually occurs in childhood and adolescence. This is where another name for this diabetes comes from – “juvenile”. Full recovery only possible with a pancreas transplant. But such an operation entails lifelong use of medications that suppress the immune system. This is necessary to prevent pancreatic rejection.
Injecting insulin does not have such a strong negative effect on the body, and with proper insulin therapy, the life of a patient with type I diabetes is no different from life healthy people.
How to notice the first symptoms
When type I diabetes just begins to develop in the body of a child or teenager, it is difficult to identify immediately.
- If a child constantly asks for a drink in the summer heat, then most likely the parents will consider this natural.
- Visual impairment and high fatigue of primary school students are often attributed to high school loads and the body’s unfamiliarity with them.
- There is also an excuse for weight loss, they say that hormonal changes occur in the teenager’s body, which again affects fatigue.
But all these signs may be the beginning developing diabetes according to type I. And if the first symptoms go unnoticed, then the child may suddenly develop ketoacidosis. By its nature, ketoacidosis resembles poisoning: abdominal pain, nausea, and vomiting occur.
But with ketoacidosis, the consciousness becomes confused and falls asleep all the time, which is not the case with food poisoning. The smell of acetone from the mouth is the first sign of illness.
Ketoacidosis can also occur with type II diabetes, but in this case, the patient’s relatives already know what it is and how to behave. But ketoacidosis that appears for the first time is always unexpected, and this makes it very dangerous.
The meaning and principles of insulin treatment
The principles of insulin therapy are very simple. After a healthy person has eaten, his pancreas releases the required dose of insulin into the blood, glucose is absorbed by the cells, and its level decreases.
In people with diabetes mellitus types I and II, this mechanism is disrupted for various reasons, so it has to be imitated manually. To correctly calculate the required dose of insulin, you need to know how much and with what foods the body receives carbohydrates and how much insulin is needed to process them.
The amount of carbohydrates in food does not affect its calorie content, so counting calories makes sense unless type I and II diabetes is accompanied by excess weight.
Type I diabetes does not always require a diet, which cannot be said about insulin-dependent type II diabetes. This is why every person with type I diabetes should measure their blood sugar levels and calculate their insulin doses correctly.
People with type II diabetes who do not use insulin injections also need to keep a self-monitoring diary. The longer and more clearly the records are kept, the easier it is for the patient to take into account all the details of his disease.
The diary will provide invaluable assistance in monitoring nutrition and lifestyle. In this case, the patient will not miss the moment when type II diabetes turns into the insulin-dependent form of type I.
“Bread unit” - what is it?
Diabetes I and II require constant calculation of the amount of carbohydrates consumed by the patient in food.
For type I diabetes mellitus, this is necessary to correctly calculate the insulin dose. And in type II diabetes - in order to control therapeutic and dietary food. When calculating, only those carbohydrates are taken into account that affect glucose levels and the presence of which forces the administration of insulin.
Some of them, for example, sugar, are absorbed quickly, others - potatoes and cereals, are absorbed much more slowly. To facilitate their calculation, a conventional value called a “bread unit” (XU) has been adopted, and a unique one makes life easier for patients.
One XE is equal to approximately 10-12 grams of carbohydrates. This is exactly as much as is contained in a 1 cm thick piece of white or black “brick” bread. It doesn’t matter what foods are measured, the amount of carbohydrates will be the same:
- in one tablespoon of starch or flour;
- in two tablespoons of ready-made buckwheat porridge;
- in seven tablespoons of lentils or peas;
- in one medium potato.
Those suffering from type I diabetes and severe type II diabetes should always remember that liquid and cooked foods are absorbed faster, which means they increase blood glucose levels more than solid and thick foods.
Therefore, when preparing to eat, the patient is advised to measure his sugar. If it is below the norm, then you can eat semolina porridge for breakfast, but if the sugar level is above the norm, then it is better to have scrambled eggs for breakfast.
On average, one XE requires from 1.5 to 4 units of insulin. True, in the morning you need more of it, and in the evening – less. In winter, the dosage increases, and with the onset of summer it decreases. Between two meals, a person with type I diabetes can eat one apple, which is equal to 1 XE. If a person controls his blood sugar level, then he will not need an additional injection.
Which insulin is better
For diabetes I and II, 3 types of pancreatic hormones are used:
- human;
- pork;
- bullish.
It is impossible to say exactly which one is better. The effectiveness of insulin treatment depends not on the origin of the hormone, but on its correct dosage. But there is a group of patients who are prescribed only human insulin:
- pregnant women;
- children diagnosed with type 1 diabetes for the first time;
- people with complicated diabetes mellitus.
Based on their duration of action, insulins are divided into short-acting, medium-acting and long-acting insulins.
Short insulins:
- Actropid;
- Insulrap;
- Iletin P Homorap;
Any of them begins to work 15-30 minutes after the injection, and the duration of the injection is 4-6 hours. The drug is administered before each meal and between them if the sugar level rises above normal. People with type 1 diabetes should always carry extra injections with them.
Intermediate acting insulins
- Semilente MS and NM;
- Semilong.
They begin their activity 1.5 - 2 hours after the injection, and the peak of their action occurs after 4-5 hours. They are convenient for those patients who do not have time or do not want to have breakfast at home, but do it at work, but are embarrassed to administer the drug in front of everyone.
You just need to take into account that if you don’t eat food on time, your sugar level may drop sharply, and if your diet contains more carbohydrates than it should, you will have to use an additional injection.
Therefore, this group of insulins is acceptable only for those who, when eating out, know exactly what time they will eat and how many carbohydrates it will contain.
Long-acting insulins
- Monotard MS and NM;
- Protafan;
- Iletin PN;
- Homophan;
- Humulin N;
- Lente.
Their action begins 3-4 hours after injection. For some time, their level in the blood remains unchanged, and the duration of action is 14-16 hours. For type I diabetes, these insulins are injected twice a day.
Where and when are insulin injections given?
Compensation for type I diabetes is carried out by combining insulins of different durations. The advantages of such schemes are that with their help you can most closely imitate the work of the pancreas, plus you need to know
PREFACE
Diabetes mellitus is one of the most serious problems, the scale of which continues to increase and which affects people of all ages and all countries.
Diabetes mellitus ranks third among the direct causes of death after cardiovascular diseases and cancer, therefore, the solution of many issues related to the problem of this disease has been placed at the level of government tasks in many countries.
There is now growing evidence worldwide that effective control of diabetes can minimize or prevent many of its complications.
A critical role in the management of diabetes mellitus, along with drug provision played by a team consisting of well-trained medical personnel (doctor, nurse, nutritionist, psychologist) and a patient who is well trained and motivated to achieve their goals.
This manual was developed for the professional training of general practitioners, endocrinologists, and diabetologists and is the fruit of international cooperation between the Russian Ministry of Health, the WHO European Bureau and Novo-Nordisk. We believed that combining efforts would allow us to obtain the most significant results, which fully corresponds to the objectives defined by the St. Vincent Declaration and, of course, corresponds to the main directions of the National Program to Combat Diabetes Mellitus.
Chief diabetologist of the Ministry of Health of the Russian Federation
Professor A.S. Ametov
PATHOGENESIS OF NON-INSULIN DEPENDENT DIABETES MELLITUS
Important research and findings over the past 10 years have significantly improved the quality of life for many people with diabetes. However, along with further improvements in metabolic control, the task of understanding the fundamental principles of the disease, determining risk and understanding the causes of complications remains urgent.
Non-insulin-dependent diabetes mellitus (NIDDM) or type II diabetes mellitus is a group of heterogeneous disorders of carbohydrate metabolism. And this explains, first of all, the absence of a single generally accepted theory of pathogenesis of this disease, Although modern achievements understanding of the pathophysiology of NIDDM and its many complications has led to remarkable changes in the management of this common disease. Thanks to the contribution of world biological science, many aspects of the pathogenesis of NIDDM have been clarified and some ways have been found to normalize metabolic processes in this disease.
Genetic basis of non-insulin-dependent diabetes mellitus. At present, the genetic basis of NIDDM is not in doubt. Moreover, it should be noted that genetic determinants in NIDDM are even more important than in type 1 diabetes. The genetic basis of NIDDM is confirmed by the fact that in identical twins, NIDDM almost always develops (95-100%) in both. At the same time, the genetic defect that determines the development of NIDDM has not been fully deciphered. From the perspective today two options are being considered. First: two independent genes are involved in the pathogenesis of NIDDM, one is responsible for impaired insulin secretion, the second causes the development of insulin resistance. The possibility of a general defect in the glucose recognition system by B cells or peripheral tissues is also being considered, resulting in either a decrease in glucose transport or a decrease in the glucose-stimulated response of B cells.
The risk of developing type II diabetes increases from 2 to 6 times if your parents or immediate family have diabetes.
The relationship between non-insulin-dependent diabetes mellitus and obesity. The risk of developing NIDDM increases twofold with class 1 obesity, 5-fold with moderate obesity, and more than 10-fold with obesity. III degree. Moreover, abdominal fat distribution is more closely associated with the development of metabolic disorders (including hyperinsulinemia, hypertension, hypertriglyceridemia, insulin resistance and type II diabetes mellitus) than peripheral fat distribution or distribution of fat in typical body parts.
The “deficit” phenotype hypothesis. IN recent years The hypothesis of a “deficient” phenotype is of particular interest. The essence of this hypothesis is that insufficient nutrition during fetal development or the early postnatal period is one of the main reasons for the delayed development of endocrine pancreatic function and predisposition to NIDDM.
It may seem doubtful that phenomena that develop in the first two years of a child's existence are capable of causing changes endocrine functions to 50-70 years of life. However, it should be noted that a fertilized egg develops into a full-fledged fetus, going through 42 cycles of cell division, while after birth and throughout our entire life, only 5 further cycles of division occur. Moreover, the number of cell divisions varies in different tissues. A full-fledged newborn has a full set of neurons in the brain, glomeruli of the kidneys, and only 50% of the set of beta cells in the pancreas of an adult. Therefore, the influence of various harmful factors may affect beta cell morphology and function with increasing age.
"Depletion" of the pancreas. According to one of the leading experts in the field of pathogenesis of NIDDM, R. A. de Fronzo, non-insulin-dependent diabetes mellitus occurs as a consequence of an imbalance between insulin sensitivity and insulin secretion. Numerous studies on this issue have shown that the most early sign NIDDM is a disruption of the body's ability to respond to insulin. As long as the pancreas is able to increase insulin secretion to overcome insulin resistance, glucose tolerance remains normal. However, over time, beta cells lose the ability to maintain a sufficient level of insulin secretion, relative insulinopenia leads to impaired glucose tolerance and, gradually, to overt diabetes mellitus. The reason for the “exhaustion” of the pancreas is not fully understood, as well as the reason for the loss of the first phase of insulin secretion in NIDDM.
Mechanisms of development of hyperglycemia.
It is well known that there are two main sources of glucose entering the blood:
- fasting glucose is directly produced by the liver,
- After eating, glucose is absorbed from food in the intestines.
In addition, hepatic glucose production is controlled by glucagon and catecholamines, which stimulate hepatic glucose release and therefore act as antagonists of insulin action.
Similar to the action of insulin, in this case glucose acts, which, according to the principle of internal feedback, itself suppresses the production of glucose by the liver.
Thus, knowing the main sources of glucose entering the blood and the main mechanisms of glycemic regulation, we can conclude that disruption of glucose homeostasis in NIDDM is possible as a result of pathology at at least three different levels:
- the pancreas, where a disruption of the glucose recognition mechanism and, as a result, disruption of insulin secretion may occur;
- peripheral tissues, where cells can become insulin resistant, leading to insufficient glucose transport and metabolism;
- the liver, where glucose production increases, caused by a disruption of the normal mechanism (feedback) of its suppression by insulin or glucose, or, on the contrary, due to excessive stimulation by glucagon or catecholamines.
Causes of impaired insulin secretion:
1) decrease in the mass of beta cells of the pancreas,
2) dysfunction of beta cells with their number unchanged,
3) a combination of a decrease in beta cell mass with their dysfunction.
The etiology of loss of beta cell mass in NIDDM is not completely known. Autopsy studies have shown a decrease in the size of the islets of Langerhans and beta cell mass by 40-60% of normal. Considering the various causes of loss of B-cell mass and impairment of their function, it is necessary to dwell on the phenomenon of “glucotoxicity”. It has been shown that chronic hyperglycemia itself can cause structural disorders of the islets and a decrease in insulin secretion, while hyperglycemia reduces the ability of insulin to stimulate glucose uptake into peripheral tissues. It is no coincidence that one of the outstanding diabetologists of our time, Dr. Harold Rifkin, proposed including the term “glucotoxicity” in the everyday vocabulary of a diabetes physician.
In recent years, some attention from diabetes scientists has been drawn to studies that have noted changes in beta cell morphology, including islet fibrosis and amyloid accumulation. Relatively recently, it was discovered that amyloid consists of a specific protein called amylin, the structure of which is 37 amino acids. In vitro studies have shown that amylin reduces glucose uptake and suppresses insulin secretion in isolated beta cells. It has been hypothesized that due to the primary defect at the level of beta cells in NIDDM, characterized by impaired conversion of proinsulin to insulin, amylin (a normal participant in this process) is deposited in beta cells and further reduces insulin secretion.
One of the most controversial areas of the pathogenesis of NIDDM is the question of insulin secretion in this disease. Unlike healthy people, in whom glucose administration causes a transient increase in glycemia and insulinemia, in patients with NIDDM, basal insulin levels are more often within the normal range or elevated, and glucose-stimulated insulin release is impaired. Below, the table provides an analysis of 32 publications relating to basal insulin secretion and the response of B cells to a glucose load. Most researchers note that in NIDDM there is a loss of the so-called first phase of insulin secretion in response to intravenous stimulation with glucose.
Insulin response to glucose load in non-obese NIDDM patients (analysis of 32 publications)
Although the early insulin response is “lost” when plasma glucose levels exceed 6.33 to 6.66 mmol/L, basal insulin concentrations are normal or even increased, thus reflecting an increase in the rate of insulin secretion in response to the increase. fasting glucose. At fasting blood glucose levels of 6.66 to 9.99 mmol/L, the total insulin response may be normal, elevated, or decreased, but is usually inversely related to basal hyperglycemia. At plasma glucose levels of 9.99-16.65 mmol/l, both (early and late) phases of insulin secretion become markedly weakened.
So, the absolute response to glucose in NIDDM is very different - from excessively elevated, especially in overweight patients, to significantly reduced in patients with a severe form of the disease. Assessment of insulin production and secretion can only be carried out by comparing the levels of insulinemia and glycemia. With significantly elevated glucose levels, it becomes clear that insulin release in response to glucose stimulation in NIDDM is in fact severely impaired.
In this regard, it has been suggested that a decrease in the response of beta cells to glucose is the primary disorder in this pathology. Any factor, such as obesity, that increases demands on beta cells can potentially cause impaired glucose tolerance and diabetes mellitus, mainly through progressive impairment of insulin release.
There is an opinion that a decrease in insulin response to glucose is an early, possibly genetic, marker of NIDDM. Moreover, the secretory response of beta cells to arginine, glucagon and catecholamines is usually within normal limits, which indicates a selective change in the glucose-sensing mechanism in NIDDM.
Radioimmunoassay of immunoreactive insulin. Despite the extreme popularity of radioimmunoassay of immunoreactive insulin, there is an opinion that modern methods of immunochemical determination of insulin levels do not provide a complete picture of the secretion of the hormone, while its true level is significantly reduced.
The insulin radioimmunoassay is believed to determine the sum of all insulin- and proinsulin-like molecules in plasma.
Decreased insulin activity in the periphery and in the liver. This is one of the latest concepts underlying the pathogenesis of NIDDM. It lies in the fact that, along with a decrease in secretion, there is a decrease in insulin activity in the periphery and in the liver. In patients with moderate hyperglycemia, the main defect is a decrease in insulin sensitivity at the level of peripheral tissues, mainly in muscles. With significant fasting hyperglycemia, an additional factor is increased glucose production by the liver.
Insulin resistance. Not all diabetes scientists share the opinion that a decrease in the functional activity of beta cells in relation to insulin secretion is the main distinctive feature NIDDM, many of them believe that the resistance of peripheral tissues to the action of insulin plays a major role in the pathogenesis of this disease. It is known that in some patients with type II diabetes mellitus, normal basal insulin levels do not affect blood glucose levels, and in some cases, even elevated insulin levels cannot normalize glycemia. This phenomenon is called insulin resistance.
It is known that the main target organs for insulin action are the liver, muscle and adipose tissue. The first step in the way insulin acts on a cell is to bind it to specific molecules located on the outer surface of the cell membrane, called receptors. The receptor activated by insulin includes a chain of intracellular processes typical of the insulin response (triggering tyrosine kinase activity, enhancing phosphorylation processes).
A cell can become resistant at two levels: at the level of the insulin receptor and at the level of the post-receptor pathways. In addition, insulin resistance may be due to the production of an altered insulin molecule, on the one hand, and the phenomenon of incomplete conversion of proinsulin to insulin, on the other.
The production of a defective insulin molecule is based on a mutation in the structural insulin gene, and in this case we're talking about about just one violation of the amino acid sequence in the insulin molecule. At position 24 of the B chain, leucine is present instead of phenylalanine, which leads to a decrease in biological activity, with normal levels of immunoreactive insulin.
As a result of a defect in the structural gene of proinsulin, its conversion into insulin is not fully realized. An excess of proinsulin is formed, which has a lower biological activity than insulin. Proinsulin has a pronounced cross-reaction with insulin, and radioimmunoassay of insulin gives the impression of its excess.
Considering the phenomenon of insulin resistance in NIDDM, you should also pay attention to the group called - insulin antagonists in the blood circulation. This group should include: 1) counter-insular hormones; 2) antibodies to insulin; 3) antibodies to insulin receptors.
With regard to counter-regulatory hormones, it should be noted that their list is well known (growth hormone, cortisol, thyroid hormones, thyrotropin, placental lactogen, prolactin, ACTH, glucagon, catecholamines), and the mechanism of their counter-regulatory action has been sufficiently studied, although there are still a number of questions need clarification. First of all, we are talking about insulin resistance, causing disruption control of glucose production by the liver. In NIDDM, liver glucose production does not decrease, which leads to hyperglycemia. Disruption of the mechanisms regulating glucose production in the liver can occur at different levels:
- insufficient suppression of glucose production by insulin, reflecting the role of the liver in general insulin resistance;
- resistance to the physiological suppressive effect of glucose due to prolonged hyperglycemia;
- absolute or relative increase in the activity of counter-regulatory hormones.
It is appropriate to recall the theory of reserve receptors, according to which in a given unit of time only 10% of receptors participate in the interaction of insulin with the receptor, the remaining 90% are in a “free” state. Moreover, which of the receptors in given time interacts with insulin - a statistical accident.
A significant number of studies have demonstrated that insulin binding to monocytes and adipocytes in NIDDM patients is reduced by an average of 30%. Decreased insulin binding occurs as a result of a decrease in the number of insulin receptors, while at the same time, the force of attraction of insulin does not change. In addition to a decrease in the number of insulin receptors on the cell surface, various defects in the internalization of receptors are possible. However, these phenomena should be assessed with caution. There are facts indicating that a decrease in insulin binding to the receptor cannot fully explain the defect in the action of the hormone in NIDDM. In particular, a decrease in the number of insulin receptors was found in only 2/3 of NIDDM patients, especially in patients with significant fasting hyperglycemia.
It should be noted that in individuals with impaired glucose tolerance, most likely there is only minor defect binding of insulin to the receptor, while in patients with NIDDM with moderate and severe fasting hyperglycemia, the development of insulin resistance is due to a defect in the post-receptor action of insulin.
Thus, a decrease in the number of insulin receptors plays a role, but is not the only factor contributing to the development of insulin resistance.
In peripheral tissues, glucose uptake is reduced by more than 55%. This disorder is based, on the one hand, on processes that result in a decrease in the number of insulin receptors, on the other hand, on the other hand, a decrease in the number of glucose transporters - proteins located on inner surface cell membranes and ensuring the transport of glucose into the cell.
Currently, there are 2 classes of glucose transporters - GluT:
1 - Na+ - cotransporters that transport glucose against a concentration gradient by coupling Na+ uptake and glucose uptake.
II - lightweight transporters that transport glucose by enhancing passive transport mechanisms.
Glucose transporters have been the subject of intense research over the past five years. It was possible to decipher their DNA sequence and determine their function. 5 glucose transporters have been described with a clear distribution at the level various organs and fabrics. In particular, GluT.1 and GluT.3 are responsible for the main, or constituent, uptake of glucose, GluT.2 - transport of glucose to the hepatocyte and, partially, to epithelial cells small intestine and kidneys, GluT.4 - is responsible for insulin-stimulated glucose uptake into muscle and adipose tissue, GluT.5 - intercellular transport to epithelial cells.
The activity of glucose transport in NIDDM has been widely studied, and many studies have shown that it decreases in adipocytes and muscles.
Thus, in insulin-resistant states, maximally stimulated glucose transport activity is reduced. This resistance is associated with an apparent reduction in glucose transporters in muscle and adipose tissue and a reduction in transporter translocation in response to insulin.
Despite the presence of compensatory fasting hyperinsulinemia, in the post-absorptive state, hepatic glucose output remains unchanged or increased, while the efficiency of glucose uptake into tissues decreases. Glucose production by the liver increases due to increased gluconeogenesis. IN muscle tissue Impaired insulin action is associated with changes in insulin receptor tyrosine kinase activity, decreased glucose transport, and decreased glycogen synthesis. In the early stage of NIDDM, the main defect is the inability of insulin to stimulate the uptake of glucose and its deposition as glycogen.
Other potential mechanisms to explain insulin resistance include increased lipid oxidation, changes in skeletal muscle capillary density, impaired insulin transport across vascular endothelium, increased amylin levels, and glucose toxicity.
CLINICAL AND DIAGNOSIS OF NIDSD
As a rule, NIDDM develops in people over 40 years of age. The onset of the disease in most cases is gradual. Except rare cases hyperglycemic hyperosmolar conditions, uncomplicated type 2 diabetes mellitus does not manifest itself with classic symptoms and is not diagnosed for a long time. Detection of impaired glucose tolerance occurs either accidentally during routine screening or during clinical examination of patients with diseases often combined with NIDDM. When collecting anamnesis, the first symptoms of the disease are retrospectively revealed: polydipsia, polyuria, weight loss, increased fatigue, decreased exercise tolerance, increased appetite, muscle cramps, transient refractive errors, susceptibility to infectious diseases (skin, urinary tract), itching, sensory disturbances, decreased libido and impotence.
The heterogeneity of NIDDM determines the nature of the onset of the disease:
- hyperglycemia, increased levels of free fatty acids in the blood serum - 100%,
- obesity - 80 %,
- fasting hyperinsulinemia - 80 %,
- essential hypertension - 50 %,
- dyslipidemia (increased triglycerides, decreased HDL cholesterol) - 50%,
- cardiovascular diseases - 30%,
- diabetic retinopathy, neuropathy - 15 %,
- nephropathy - 5 %.
Threatened in terms of the development of NIDDM are:
1) patients with the above symptoms,
2) patients with a high risk of developing diabetes mellitus - persons who have one of their parents with diabetes; the second of twins, if one has diabetes; mothers whose children had a birth weight of more than 4500 g or a congenital malformation; women with a history of spontaneous abortions,
3) patients with diseases that are often associated with diabetes (obesity, arterial hypertension, polycystic ovary syndrome),
4) patients with pancreatitis, hyperthyroidism, acromegaly, pheochromocytoma, Cushing's syndrome,
5) patients receiving diabetogenic therapy for a long time (synthetic estrogens, diuretics, corticosteroids).
If, during the examination, the fasting blood glucose level exceeds (or is equal to) 140 mg% (7.8 mmol/l) with two measurements, diabetes mellitus is diagnosed. Otherwise, an oral glucose tolerance test is required. Based on recommendations World Organization healthcare, the methodology for conducting a glucose tolerance test is as follows: in the morning on an empty stomach, after examining glycemia, the patient takes 75 g of glucose orally, then 1 hour and 2 hours after the load they examine capillary blood for glucose content.
Classification of oral glucose tolerance test results according to WHO recommendations (data must be confirmed by two consecutive tests)
MANAGEMENT OF NON-INSULIN DEPENDENT DIABETES MELLITUSMain tasks:
1. Achieve good metabolic and biochemical control.
2. Prevent the development of vascular complications.
Solutions:
diet therapy,
exercise,
drug treatment.
Goals of therapy for NIDDM
Depending on age:
1) in young and middle-aged patients - relief of symptoms of diabetes mellitus and improvement of long-term prognosis,
2) in the elderly (patients over 65 years of age) - relief of symptoms of the disease.
According to the criteria proposed by the European NIDDM Policy Group:
Long-term diabetes management includes attentive attitude to nutrition, energy expenditure and drug treatment. The success of therapy depends on how involved the patient is in the treatment program. The patient's motivation and behavior are critical factors when drawing up a therapeutic plan.
DIET THERAPY NIDSD
The main goals of diet therapy:
- prevention of postprandial hyperglycemia,
- reduction of excess body weight,
- correction of concomitant dyslipidemia,
- reducing the risk of late complications,
- providing necessary nutrients, vitamins and microelements.
1) reducing calorie intake,
2) fractional meals (5-6 times a day),
3) exclusion of mono- and disaccharides from the diet,
4) limiting the consumption of saturated fats,
5) reducing cholesterol intake (less than 300 g per day),
6) consumption of foods high in dietary fiber,
7) reducing alcohol intake (less than 30 g per day).
The calorie content of food is calculated depending on body weight and the nature of energy expenditure. Patients with NIDDM are recommended to be prescribed a diet with a calorie content of 20 - 25 kcal per kilogram of actual body weight. In the presence of obesity, daily caloric intake is reduced according to the percentage of excess body weight to 15 - 17 kcal per kilogram (1100 - 1200 kcal per day).
Dependency indicators daily requirement body in energy from body weight (at absolute rest).
When calculating daily calorie intake, it is necessary to take into account the nature of the patient’s work activity.
Calculation of daily caloric intake taking into account energy costs for labor activity.
* daily caloric intake in a state of absolute restThe composition of daily calories should be as follows:
carbohydrates 50%, proteins 15-20%, fats 30-35%. The diet of a NIDDM patient should always provide positive influence on lipid metabolism. The basic principles of a lipid-lowering diet according to the recommendations of the European Society of Atherosclerosis are presented below:
| Recommendations | Main sources |
| 1. Reduce fat intake | Butter, margarine, whole milk, sour cream, ice cream, hard and soft cheeses, fatty meats. |
| II. Reducing saturated fat intake | Pork, duck meat, sausages and sausages, pates, cream, coconuts. |
| III. Increased intake of foods high in protein and low in saturated fatty acids | Fish, chicken, turkey, game, veal. |
| IV. Increased consumption complex carbohydrates, fiber from cereals, fruits and vegetables. | All types of fresh and frozen vegetables, fruits, all types of grains, rice. |
| V. Slight increase in the content of simple unsaturated and polyunsaturated fatty acids. | Sunflower, soybean, olive, rapeseed oils. |
| VI. Reduced cholesterol intake. | Brain, kidneys, tongue, eggs (no more than 1-2 yolks per week), liver (no more than twice a month). |
The distribution of fat in the diet should be as follows:
1/3 - saturated fats (fat of animal origin)
1/3 - simple unsaturated fatty acids ( vegetable oils)
1/3 - polyunsaturated fatty acids (vegetable oils, fish).
It is advisable to include in the diet foods rich in dietary fiber (18-25 g per day), since this improves the utilization of carbohydrates by tissues, reduces the absorption of glucose in the intestines, and significantly reduces glycemia and glycosuria. To monitor the adequacy of diet therapy, it is recommended to use a system for counting “carbohydrate units”, the use of which allows you to strictly control the amount of carbohydrates the patient receives and will facilitate self-control.
It is believed that reducing dietary calories by reducing saturated fat may have a positive effect on lipid and lipoprotein profiles, even in the absence of weight loss in individuals without diabetes. Information about the role of such changes in diet therapy in patients with NIDDM is contradictory. The controversy concerns the question of which foods should reduce the consumption of saturated fats: carbohydrates, mono- or polyunsaturated fats. According to the famous diabetologist H.E. Lebovitz, only 5 - 8% of patients with NIDDM can control glycemia with a combination of diet and exercise, the remaining 92% of patients require sulfonamide drugs.
PHYSICAL ACTIVITY IN THE TREATMENT OF NIDSD
- intensity
- duration
- frequency
- energy consumption
age, initial physical activity and general condition patient.
Patients with NIDDM are recommended daily, same type, dosed, adequate physical activity, taking into account the condition cardiovascular system, blood pressure level and tolerance to them. The higher the initial blood pressure, the lower the exercise tolerance in patients with NIDDM.
It is known that physical exercise reduces glycemia when the initial blood glucose concentration is no more than 14 mmol/l, causes its increase and enhances ketogenesis when glycemia is more than 14 mmol/l at the start of exercise. Carrying out physical activity requires careful monitoring of glycemia before, during and after exercise, and in patients with concomitant cardiovascular diseases, also ECG monitoring.
The effect of physical activity on metabolism, hormonal regulation and circulation system.
Metabolism and blood coagulation system.
- increasing glucose tolerance
- reduction in triglyceride levels
- increased HDL cholesterol levels
- increased fibrinolytic activity of the blood
- decreased blood viscosity and platelet aggregation
- decreased fibrinogen levels
- reduction of insulin resistance and hyperinsulinemia
- reduction of stress hormones
- increased endorphin levels
- testosterone increase
- increasing cardiac output efficiency
- increasing the electrical stability of the myocardium
- decreased oxygen consumption by the heart muscle
- lowering blood pressure
- improved blood circulation in muscles
Lifestyle changes for NIDDM include diet, exercise, and stress reduction.
REDUCE STRESS:
- change of situation
- changing perceptions
- relaxation
Drug treatment should be prescribed to a patient with NIDDM if good or satisfactory levels of glycemic control cannot be achieved through a combination of diet and exercise.
Oral glucose-lowering drugs or insulin?
The pharmacological alternative depends on the following factors:
- severity of the disease (degree of hyperglycemia, presence or absence of its clinical symptoms),
- the patient’s condition (presence or absence of concomitant diseases),
- patient preference (if he is well informed regarding the use, expected therapeutic and possible side effects of both oral drugs and insulin),
- patient motivation,
- patient's age and weight.
New therapeutic options have emerged with the discovery of alpha-glucosidase inhibitors, which slow down the absorption of carbohydrates in small intestine. Acarbose pseudo-tetrasaccharide - glucobay (Bayer, Germany) is an effective inhibitor of alpha-glucosidase, slows down the absorption of glucose in the small intestine, prevents a significant postprandial increase in glycemia and hyperinsulinemia.
Indications for acarbose therapy in NIDDM:
- unsatisfactory glycemic control due to diet,
- “failure” on PSM in patients with sufficient levels of insulin secretion,
- unsatisfactory control during treatment with metformin,
- hypertriglyceridemia in patients with good glycemic control on a diet,
- severe postprandial hyperglycemia during insulin therapy,
- reducing the dose of insulin in insulin-requiring patients.
Acarbose is particularly effective as monotherapy in NIDDM patients with low fasting blood glucose levels and high postprandial glycemia. Clinical studies showed a decrease in fasting glucose levels by 10%, after meals by 20-30%, and glycosylated hemoglobin levels by 0.6-2.5% after 12-24 weeks. treatment. Our experience with the use of acarbose in patients with diabetes mellitus showed a significant decrease in postprandial glycemia from 216.5 +/- 4.4 to 158.7 +/- 3.9 mg%, glycosylated hemoglobin from 10.12 +/- 0.20 to 7.95 +/- 0.16%, cholesterol levels - by 9.8% of the original and triglycerides - by 13.3%.
An important therapeutic effect of acarbose is the reduction of postprandial hyperinsulinemia and triglyceride levels in the blood. Its significance is great, since lipoproteins saturated with triglycerides in patients with NIDDM aggravate insulin resistance and are an independent risk factor for the development of atherosclerosis.
The advantage of the drug is the absence of hypoglycemic reactions, which is especially important in elderly patients.
Side effects of acarbose:
- bloating,
- diarrhea,
- increased transaminase activity,
- decrease in serum iron.
Sulfonylurea derivatives and acarbose. In case of unsatisfactory glycemic control during therapy with sulfonamide drugs, the combination is most often used maximum dose glibenclamide and acarbose at a dose of 0.3 g per day. Acarbose does not change the pharmacokinetics of glibenclamide. The combination of PSM/acarbose can reduce the average daily glycemic level by 10-20%, the HbA1c level by 1-2%.
Insulin and acarbose. In insulin-requiring NIDDM patients, improvement in glycemic control and reduction in the dose of exogenous insulin during combination therapy with insulin/acarbose have been convincingly demonstrated. Alpha-glucosidase inhibitors are particularly effective in cases where postprandial hyperglycemia is not controlled by monoinsulin therapy.
Sulfonylureas.
Main indications to the prescription of glucose-lowering sulfonylurea drugs (SMU) are:
1) lack of compensation for carbohydrate metabolism in patients with newly diagnosed NIDDM against the background of diet therapy and rational physical activity;
2) NIDDM in persons with normal or overweight in cases where compensation of carbohydrate metabolism was achieved by prescribing insulin in a dose of no more than 20-30 units. per day.
Characteristics underlying the choice of PSM:
- internal anti-diabetic power,
- speed of onset of action,
- duration of action,
- metabolism and excretion,
- positive and negative side effects,
- age and mental state sick.
1. PSMs are not effective in patients with significant or complete loss of B cell mass.
2. For reasons that are still unclear, in some patients with NIDDM, PSMs do not exhibit their antidiabetic effect.
3. PSM does not replace diet therapy, but complements it. Their treatment is ineffective if diet is ignored.
STARTING SULPHONYLUREA THERAPY
1/3 - great effect
1/3 - good effect
1/3 - unsatisfactory effect
After 5 years of therapy, about 50% of patients from subgroups 1 and 2 still have a good response to SM drugs.
Contraindications to the use of PSM:
1) insulin-dependent diabetes mellitus, pancreatic diabetes,
2) pregnancy and lactation,
3) ketoacidosis, precoma, hyperosmolar coma,
4) decompensation against the background infectious diseases,
5) hypersensitivity to sulfonamides,
6) predisposition to severe hypoglycemia in patients with severe pathology liver and kidneys,
7) major surgical interventions.
Relative contraindications are cerebral atherosclerosis, dementia, alcoholism.
Mechanism of action of PSM. Sulfonylurea derivatives have a hypoglycemic effect due to pancreatic and extrapancreatic effects.
- The pancreatic effect is to stimulate the release of insulin from the beta cell and enhance its synthesis, restoring the number and sensitivity of beta cell receptors to glucose. Sulfonamides exert their insulinotropic effect by closing ATP-dependent potassium channels, which in turn leads to cell depolarization, the entry of calcium ions into the B cell and increased insulin secretion. Sulfonamides bind to receptor-like structures on the B cell. The binding capacity of various sulfonylurea derivatives determines their insulin-stimulating activity.
- Extrapancreatic action
1. Potentiation of stimulation of insulin-mediated glucose transport in skeletal muscle and adipose tissue.
2. Potentiation of insulin-mediated translocation transport.
3. Potentiation of insulin-mediated activation of glycogen synthesis.
4. Potentiation of insulin-mediated hepatic lipogenesis.
II. Possibly related to antidiabetic effects.
1. Direct effect on the liver.
a) increase in fructose-2,6 diphosphate,
b) stimulation of glycolysis,
c) suppression of gluconeogenesis.
2. Direct action on skeletal muscles.
a) increased transport of amino acids,
b) increase in fructose-2,6-diphosphate.
3. Suppression of insulinase.
III. Unlikely to be associated with antidiabetic effects.
1. Direct action on adipose tissue.
a), activation of 3"-5"AMP diesterase and suppression of lipolysis.
2. Direct effect on the myocardium.
a) increased contractility and oxygen saturation, increased glycogenolysis,
b) decrease in glycolysis, decrease in phosphofructokinase activity.
3. Increased synthesis and secretion of plasminogen activator in endothelial cells.
Pharmacokinetics of sulfonamides. Sulfonylureas are weak acids. They are intensively bound to proteins (more than 90%), metabolized by the liver and excreted by the kidneys or intestines. There are marked differences in absorption, metabolism and elimination between various representatives of this group of drugs (Table 1).
Table 1.
Pharmacokinetics of sulfonylurea derivatives.
1. Strengthening the hypoglycemic activity of PSMs by changing their pharmacokinetics:
- clofibrate,
- salicylates,
- some sulfa drugs.
- salicylates,
- guanitidine,
- MAO inhibitors,
- beta blockers,
- alcohol.
1. Shortening the half-life, accelerating metabolism:
- chronic alcohol consumption,
- rifampicin,
- diuretics (thiazides, furosemide),
- epinephrine,
- estrogens,
- glucagon,
- glucocorticoids,
- indomethacin,
- isolanide,
- nicotinic acid,
- phenytoin,
- L-thyroxine.
Table 2.
Characteristics of sulfonamide drugs.
| Name intl. | Name commercial | Contents of the drug in 1 tab. (G) | Highest daily dose (g) | Duration of action (hours) |
| 1 | 2 | 3 | 4 | 5 |
| First generation drugs | ||||
| Tolbutamide | butamide orabeth orinase | 0,5 | 2,0 | 6-10 |
| Carbutamide | bukarban wounded midozol diaboral | 0,2 | 2,0 | 6-12 |
| Tolazamide | tolinase norglycine | 0,1; 0,25; 0,5 | 1,0 | 16-24 |
| Chlorpropamide | diabinosis diabatoral | 0,1; 0,25 | 0,5 | 24-60 |
| Second generation drugs | ||||
| Glibenclamide | Maninil daonil euglucone glucobene | 0,001; 0,005 | 0,02 | 20-24 |
| Glipizide | glibinez minidiabe | 0,005 | 0,02 | 8-12 |
| Gliclazide | Diabeton diamicron predian | 0,08 | 0,32 | 8-10 |
| Gliquidone | glyurenorm beglinor | 0,03 | 0,075 | 8 |
Typically, sulfonamide antihyperglycemic drugs are well tolerated and the incidence of side effects is low. Skin reactions nonspecific and rare. Hematological complications such as thrombocytopenia, agranulocytosis and hemolytic anemia, have been described mainly with chlorpropamide and tolbutamide. Abnormal liver function tests and jaundice may occur during treatment with any sulfonylurea derivatives.
SIDE EFFECTS AND TOXICITY OF PSM
- hypoglycemia
- skin reaction (rash, erythema, itching)
- gastrointestinal disorders (anorexia, nausea)
- blood disorders (agranulocytosis, thrombocytopenia)
- disulfiram-like reaction (Antabuse)
- hyponatremia
- hepatotoxicity (cholestatic jaundice)
Pharmacological action. It has a hypoglycemic effect when taken orally by stimulating insulin secretion by pancreatic B cells and increasing the sensitivity of peripheral tissues to insulin. Extrapancreatic action is aimed at suppressing gluconeogenesis in the liver and lipolysis in adipose tissue. The sugar-lowering effect appears after 1.5 hours, reaches a maximum after 3-4 hours, duration effective action 6-10 hours. 95% bound to plasma proteins and metabolized in the liver. Metabolites have weak hypoglycemic activity. Excretion is carried out by the kidneys.
Application. The initial daily dose is usually 1-1.5 g, depending on the blood glucose level. The therapeutic effect of the drug appears no earlier than the first 10-14 days from the start of treatment, and if there is no effect of the therapy, the dose can be increased to 2 g per day no earlier than 2 weeks from the start of treatment. Further increase in dose above 2 g (maximum permissible) does not lead to an increase in effect. When glucosuria is eliminated and blood glucose is normalized, the dose can be reduced by 0.25 - 0.5 g in the evening.
In the absence of compensation of carbohydrate metabolism within 4 weeks of treatment with maximum doses, the appointment of sulfonamide drugs of the second generation, or, in a combination of diabetes mellitus and obesity, is indicated - combination of tolbutamide with biguanides.
Carbutamide - bukarban, oranil.
Pharmacological action. Has a hypoglycemic effect when taken orally, stimulating the release of endogenous insulin by B cells insular apparatus pancreas and increasing the sensitivity of peripheral tissues to insulin. The presence of an amino group in the drug molecule causes a more powerful insulinotropic effect than butamide. The hypoglycemic effect appears an hour after administration, reaches a maximum after 5 hours, and lasts up to 12 hours.
Application. The initial dose is 0.25 g, 2 times a day. The daily dose of carbutamide at the beginning of treatment should not exceed 0.75 g. In this case, it is recommended to take 0.5 g of the drug before breakfast and 0.25 before dinner. If the effectiveness is insufficient, a further increase in the dose to 1.5 g per day (1.0 g in the morning and 0.5 g in the evening) may be recommended no earlier than 10 days from the start of treatment, which is due to the duration of the response metabolic transformations in the body during taking carbutamide. The maximum dose should not exceed 2 g per day. Insufficient compensation of carbohydrate metabolism when using the maximum dose of the drug for 4 weeks is an indication for the prescription of second generation sulfonamide drugs.
Tolazamide- tolinase.
Pharmacological action. The hypoglycemic effect is due to stimulation of insulin secretion by B cells. It has an extrapancreatic effect, increasing the sensitivity of peripheral tissues to insulin, inhibiting gluconeogenesis in the liver and lipolysis in adipose tissue. Rapidly absorbed in the small intestine, achieving maximum hypoglycemic effect after 3-4 hours. The peak concentration lasts for 7 hours, the duration of action is up to 16 hours. Has a weak diuretic effect.
Application. The initial dose should not exceed 0.25 g per day. The frequency of administration is 2 times a day. Due to the rapid and pronounced hypoglycemic effect of tolazamide, its therapeutic effect is manifested already in the first week of treatment and further dose adjustment can be made after 7 days from the start of treatment with mandatory monitoring of glycemia and glucosuria. The maximum daily dose is 1.0 g. Compared to tolbutamide and carbutamide, it has a greater hypoglycemic effect; when replacing drugs, 1.0 g of carbutamide and/or tolbutamide corresponds to 0.25 tolazamide.
Chlorpropamide - Apotex, Diabinez, Diabetoral.
Pharmacological action. Despite long period half-life (up to 35 hours), absorbed relatively quickly. It has the longest duration of action - up to 60 hours. Subject to intense hepatic metabolism, the main metabolites have hypoglycemic activity and are excreted by the kidneys. Plasma concentrations depend more on renal elimination than on absorption. The onset of the hypoglycemic effect is observed 2 hours after administration, reaching a maximum after 4-6 hours.
An additional effect of chlorpropamide is the potentiation of the action of antidiuretic hormone, which may be accompanied by fluid retention.
Application. The dose is selected individually. The initial daily dose should not exceed 0.25 g, taken once, during breakfast. In cases of severe hyperglycemia and glycosuria, and the ineffectiveness of previous therapy with other sulfonamides, it is possible to prescribe 0.5 g per day, also once, during breakfast.
For patients over 65 years of age, the initial dose is 0.1 g per day, with a maximum of 0.25 g per day due to slower urinary excretion. Glycemia and glucosuria are monitored 3-5 days after the start of treatment. In case of insufficient metabolic effect, the dose can be increased to 0.5 g per day.
To avoid cumulation of the drug, in all situations of achieving compensation for carbohydrate metabolism, it is recommended to reduce the dose of chlorpropamide by 0.1 g per day, under glycemic control. The potentiating effect on the action of antidiuretic hormone makes it possible to use chlorpropamide in the treatment of diabetes insipidus. It can be prescribed in cases of refractoriness to the action of adiurecrine and in case of intolerance to other pituitary drugs. The dose in the absence of carbohydrate metabolism disorders should not exceed 0.1 g per day.
In all cases of long-term use of the drug (more than 5 years), a decrease in sensitivity to its action develops.
Glibenclamide - daonil, maninil, euglucon, glucobene, glucored, antibet.
Pharmacological action. It has a pronounced pancreatic and extrapancreatic effect. It has a hypoglycemic effect due to stimulation of insulin synthesis - enhancing its secretion from insulin-containing granules of beta cells and increasing the sensitivity of beta cells to glucose, increases the number and sensitivity of insulin receptors, as well as the degree of binding of insulin to glucose and target cells. Glibenclamide is well absorbed from the gastrointestinal tract. The onset of the hypoglycemic effect is observed 40 minutes after administration, the peak concentration is reached after 2 and persists for 6 hours, the duration of action is 10-12 hours. The ability to bind to plasma proteins prolongs the effect of the drug, but the short half-life of up to 5 hours causes its low toxicity. Metabolized in the liver, excreted in bile and urine in the form of inactive metabolites.
The above features of the action of glibenclamide determine it as the drug of choice in the treatment of type II diabetes mellitus. The initial dose is 5 mg in the morning or 0.25 mg in the morning and evening. Monitor carbohydrate metabolism indicators - after 5-7 days and, if necessary, increase the dose by 0.25-0.5 mg per week to the maximum (20 mg). It should be noted that a dose of more than 15 mg per day does not increase the hypoglycemic effect. The frequency of administration is 1-2 times a day and depends on daily dose: if metabolic control is effective against the background of 5 mg/day, take 1 time in the morning; a dose of 10 mg can be distributed evenly in 2 doses in the morning and evening; if it is necessary to use 15 mg per day, it is recommended to use 10 mg in the morning and 5 mg in the evening; when using the maximum permissible daily dose of 20 mg, it is divided into 2 doses.
In the absence of compensation within 4-6 weeks, combination therapy with second generation sulfonylurea derivatives of another group, biguanide or insulin therapy is possible.
Glipizide - glibenez, minidiab.
Pharmacological action. The drug has pancreatic and extrapancreatic effects. It has a hypoglycemic effect by stimulating the secretion of insulin and increasing the sensitivity of pancreatic B cells to glucose. At the extrapancreatic level, it improves the post-receptor effect of insulin in liver cells and muscle tissue. It has a slight lipid-lowering effect, improves fibrinolytic activity and inhibits platelet aggregation. It is quickly absorbed in the intestine, providing the onset of a sugar-lowering effect 30 minutes after administration. The maximum concentration is observed after 1.5 hours, the duration of action is 8-10 hours. The drug is quickly excreted in the urine in the form of practically inactive metabolites.
The initial dose for patients with newly diagnosed diabetes mellitus should not exceed 7.5 mg in 2-3 doses. Further increases in the dose are made under glycemic control after 5-7 days. Maximum single dose 10 mg, daily - 20 mg. There are reports of the possibility of using 30 mg per day without side effects, however, such an increase in dose is not accompanied by an increase in the sugar-lowering effect.
Glipizide may be used in combination with other sulfonylureas.
Glyurenorm - Gliquidone.
Pharmacological action. It has pancreatic and extrapancreatic effects. According to the mechanism of hypoglycemic action, it is close to gliclazide and is able to stimulate phase 1 of insulin secretion. The features of this drug are its rapid and short-term action, preferential excretion through the intestines (95%), which makes it possible to use it in the treatment of patients with NIDDM with kidney damage. Absorbed quickly, the onset of hypoglycemic action is after 40 minutes, the peak concentration is after 2 hours, the half-life is 1.5 hours. Duration active action- 6-8 hours. Like other sugar-lowering sulfonamides of the second generation, it has a positive effect on insulin receptors and enhances its post-receptor interaction in cells, stimulating the utilization of glucose in the liver and muscles and suppressing lipolysis.
The initial dose is 30 mg 1-2 times a day. If there is no effect, the dose is increased after 5-7 days to the maximum, which is 120 mg. The drug is taken within 30-60 minutes. before meals, frequency of administration is 2 times at a dose of 60 mg, when used large doses- 3 times during the day.
Can be used in elderly patients due to the low incidence of hypoglycemia. Glurenorm does not damage dialyzer membranes and can be used in patients undergoing chronic hemodialysis.
We assessed the effect of the drug on lipid and carbohydrate metabolism in 25 patients with newly diagnosed NIDDM. During therapy with glurenorm, there was an improvement in the secretory function of pancreatic B cells. This effect of the drug was most pronounced at week 12 of treatment: in response to a food stimulus, the secretion of C-peptide reached the control value of 211% compared to 245% in the healthy group. For 120 min. food stress test, persistent hyperinsulinemia was noted, indicating persistent peripheral insulin resistance.
The hypocholesterolemic effect of glurenorm therapy appeared already at week 6 of the study: cholesterol levels decreased to control values, largely due to VLDL cholesterol (the decrease in this indicator was 30% from the initial level). It should be noted that in patients with initially lower cholesterol levels (less than 250 mg/dl), there was an increase in the ratio of HDL cholesterol/cholesterol - HDL cholesterol from 0.25 to 0.40, which indicated an improvement in the cholesterol transport system during therapy with glurenorm ( table 3). The effect of the drug on the apoprotein composition was inconsistent: having decreased by 20% by week 6 of therapy, the level of atherogenic apoprotein B reached the initial value by week 12.
Table 3.
Dynamics of lipid and apoprotein profiles in patients with newly diagnosed NIDDM treated with glurenorm in the group with initial cholesterol<250 мг/дл.
| Researched indicators stages research | HS mg/dl | TG mg/dl | HS HDL mg/dl | HS VLDL mg/dl | HS LDL mg/dl | Apo A 1 mg/dl | Apo B mg/dl | Apo B/ Apo A 1 | HS LDL/ HDL cholesterol | HS HDL/ Apo A 1 |
| 1. after 3 weeks. diet therapy | 13,1 100% | 146,3+/- 27,9 100% | 47,0+/- 5,5 100% | 29,3+/- 5,6 100% | 141,2+/- 5,0 100% | 136,8+/- 16,9 100% | 105,8+/- 19,7 100% | 0,8+/- 0,2 100% | 3,2+/-0,5 | 0,3+/-0,001 |
| 2. after 6 weeks. treatment | 194,0+/- 16,7 89% | 99,2+/- 15,7 68% | 45,4+/- 5,2 97% | 19,8+/- 3,2 68% | 128,8+/- 15,4 91% | 138,4+/- 13,9 101% | 86,0+/- 13,9 81% | 0,6+/- 0,1 75% | 3,0+/-0,5 | 0,3+/-0,02 |
| 3. after 12 weeks treatment | 180,0+/- 22,6 83% | 108,3+/- 49,9 74% | 52,3+/- 4,8 111% | 21,7+/- 10,0 74% | 106,0+/- 5,5 R<0,01 1-3 75% | 156,3+/- 15,0 114% | 56,7+/- 17,4 54% | 0,4+/- 0,2 50% | 2,1+/-0,3 | 0,3+/-0,01 |
| practically healthy faces | 205,4+/- 0,3 | 100,7+/- 0,5 | 50,9+/- 0,1 | 20,1+/- 0,3 | 134,4+/- 0,3 | 143,0+/- 4,0 | 117,0+/- 3,0 | 0,8+/- 0,1 | 2,6+/-0,2 | 0,3+/-0,01 |
| P<0,001 k-3 | P<0,01 k-3 |
The effect of glurenorm on the level of triglycerides in plasma was noted in patients with a cholesterol concentration of more than 250 mg/dl - this indicator reached the control value by the 12th week of therapy (Table 4).
Table 4.
Dynamics of lipid and apoprotein profiles in patients with newly diagnosed NIDDM treated with glurenorm in the group with initial cholesterol>250 mg/dl.
| Researched indicators stages research | HS mg/dl | TG mg/dl | HS HDL mg/dl | HS VLDL mg/dl | HS LDL mg/dl | Apo A 1 mg/dl | Apo B mg/dl | Apo B/ Apo A 1 | HS LDL/ HDL cholesterol | HS HDL/ Apo A 1 |
| 1. after 3 weeks. diet therapy | 273,2+/- 20,7 100% | 206,5+/- 13,7 100% | 38,7+/- 3,4 100% | 41,3+/- 2,2 100% | 193,2+/- 25,6 100% | 137,8+/- 6,8 100% | 126,0+/- 12,1 100% | 0,9+/- 0,1 100% | 5,1+/-0,7 | 0,3+/-0,02 |
| 2. after 6 weeks. treatment | 227,3+/- 11,9 83% | 120,7+/- 33,1 58% | 41,7+/- 2,9 108% | 23,9+/- 6,6 58% | 161,7+/- 13,2 84% | 131,8+/- 4,2 96% | 100,0+/- 16,5 79% | 0,8+/- 0,1 89% | 3,9+/-0,2 | 0,3+/-0,02 |
| 3. after 12 weeks treatment | 239,7+/- 7,7 88% | 145,0+/- 42,1 70% | 44,3+/- 4,4 114% | 28,9+/- 8,5 70% | 166,3+/- 11,8 86% | 141,5+/- 7,4 103% | 131,2+/- 11,6 104% | 0,9+/- 0,1 100% | 3,9+/-0,4 | 0,3+/-0,02 |
| practically healthy faces | 205,4+/- 0,3 | 100,7+/- 0,5 | 50,9+/- 0,1 | 20,1+/- 0,3 | 134,4+/- 0,3 | 143,0+/- 4,0 | 117,0+/- 3,0 | 0,8+/- 0,1 | 2,6+/-0,2 | 0,3+/-0,01 |
| P<0,05 1-k P<0,01 3-k | P<0,001 1-k | P<0,01 1-k P<0,05 2-room | P<0,001 1-k | P<0,05 1-k | P<0,01 1-k P<0,01 2-room P<0,05 3-k |
Pharmacological action. Like other sulfonylurea derivatives of the second generation, diabeton has pancreatic and extrapancreatic effects, however, the mechanism of its influence has a number of features. Diabetes restores the early peak of insulin secretion. The early phase of insulin secretion plays an important role in increasing the readiness of target organs for insulin in the second phase of insulin secretion. The latter leads to a decrease in the total amount of insulin required for glucose utilization and avoids hyperinsulinemia caused by prolonged stimulation of B cells. Diabetes increases the effectiveness of insulin, reducing insulin resistance, increases the utilization and accumulation of glucose in muscles and reduces hepatic glucose synthesis.
Gliclazide may improve insulin-mediated glucose utilization by improving the action of insulin on skeletal muscle glycogen synthetase.
As studies conducted in our clinic have shown (N.L. Vinnitskaya, 1995), diabeton, along with an active hypoglycemic effect, has a pronounced positive effect on the lipid and apoprotein spectrum of plasma. The use of the drug at an average dose of 160 mg per day for six weeks in patients with newly diagnosed NIDDM led to a significant decrease in cholesterol levels, VLDL cholesterol (by 15 and 30%, respectively, p<0,05). Уровень атерогенного аполипопротеина В снизился на фоне лечения на 20% от исходного. Достоверное снижение показателя загруженности ЛПВП холестерином (соотношение ХС ЛПВП/Апо А1) свидетельствовало о положительных сдвигах в соотношении липопротеидов, транспортирущих холестерин. Гипотриглицеридемический эффект диабетона (уровень триглицеридов достоверно снизился к шестой неделе терапии на 50% от исходного), по-видимому, был обусловлен улучшением чувствительности к инсулину на уровне жировой ткани, снижением липолиза и доступа НЭЖК в печень как основного субстрата для синтеза триглицеридов.
The second distinctive effect of diabeton is its effect on platelets and fibrinolysis. By inhibiting the aggregation and adhesion of platelets and erythrocytes, it restores the process of physiological parietal fibrinolysis, prevents the development of microthrombosis and increased vascular response to adrenaline in microangiopathies.
The onset of the sugar-lowering effect is observed after 40-60 minutes. after administration and its maximum is reached after 2 hours. Duration of action is up to 12 hours. In most cases, two tablets per day (160 mg) are sufficient. If necessary, the dose can be increased under glycemic control to 320 mg per day (maximum permissible dose). If it is necessary to use 240 mg of the drug during the day, a larger dose - 2 tablets - is taken in the morning.
Diabeton can be used in combination with other sulfonamide antihyperglycemic drugs for the prevention and treatment of hemorheological disorders.
Resistance to sulfonamide drugs.
PRIMARY AND SECONDARY FAILURE:
- "primary failure"
- "secondary failure"
As NIDDM progresses, insulin resistance reaches a critical level in many patients. Even therapy with maximum doses of sulfonamides with an optimal dietary regimen and adequate physical activity is not effective. This phenomenon is called "secondary failure" of oral therapy, and 5-10% of all patients with NIDDM experience this phase of the disease each year. The failure rate reaches its maximum 12-15 years after the onset of the disease. Due to the decreased anabolic effect of insulin, poor metabolic control, severe glycosuria, and decreased tissue glucose utilization, body weight decreases to normal or subnormal in most of these patients.
While “primary failure” of sulfa drugs is usually due to misuse in IDDM, the reasons for “secondary failure” are less clear. It is also unknown whether “secondary failure” is an obligatory phenomenon that develops in all patients with NIDDM.
"SECONDARY FAILURE" FOR PSM occurs in 5 - 10% of patients per year
What is the basis?
- disease progression?
- decreased response to therapy?
- obesity?
- overeating and weight gain,
- decreased physical activity,
- stress,
- intercurrent diseases,
- poor doctor-patient contact.
- inadequacy of the dose of PSM,
- decreased sensitivity to PSM due to long-term use,
- impaired absorption of the drug due to hyperglycemia,
- unsuccessful combination with other drugs.
- further decrease in B cell mass,
- increased insulin resistance.
The following main factors determine the presence of “secondary failure” in patients with NIDDM:
1. Satisfactory control with diet and PSSP for at least 4 years after diagnosis.
2. The level of fasting glycemia with repeated determinations exceeds 10-11 mmol/l, postprandial - 13-15 mmol/l.
3. Lack of effect from taking the maximum dose of glucose-lowering drugs against the background of a subcalorie diet, an optimal physical activity regimen and the exclusion of other causes of unsatisfactory metabolic control.
4. Absence of autoantibodies to pancreatic islet cells and insulin, or their inconsistent presence.
5. Basal concentration of C-peptide is more than 0.3 nmol/l; the integrated level of C-peptide during the oral glucose tolerance test is more than 3.3 nmol/l, the daily excretion of C-peptide in urine is more than 6.6 nmol/l.
It is known that some patients with NIDDM who have autoantibodies to islet cells or to insulin slowly develop insulin dependence over several years (from 1 to 4 years), which is apparently associated with autoimmune damage to pancreatic islet cells. The above characteristics allow for a differential diagnosis between “secondary failure” in patients with NIDDM and slowly progressive IDDM. Specific immunological and genetic markers are indicators of a high risk of having slowly progressive IDDM in patients with a previously established diagnosis of NIDDM. The most accessible indicators for establishing a diagnosis are the duration of the period of therapy with glucose-lowering drugs before the occurrence of “secondary refusal” to them and the level of C-peptide secretion.
Biguanides
Indications:
1. Obesity in patients with NIDDM.
2. Lack of effect of PSM monotherapy.
3. The prospect of combined treatment with PSM.
CHARACTERISTICS OF BIGUANIDES
| preparation | Name | single dose (mg/day) | days dose (mg/day) | T 1/2 (hour) | action (hour) |
| Phenformin | DBI DBI TD | 25 50 | 25-150 | 3 | 6 12 |
| Metformin | Glucophage | 500 | 250-1500 | 3 | 6 |
| Buformin | Silubin | 100 | 100-300 | 2 | 6 |
BIGUANIDES MECHANISM OF ACTION:
- increasing glucose utilization through anaerobic glycolysis
- decreased liver glucose production
- decreased glucose absorption in the gastrointestinal tract
- increased glucose consumption in muscle and fat tissue
- enhancing insulin action
- increase in the number of insulin receptors on the cell surface
- increase in the number of glucose transport sites in insulin-sensitive tissues
gastrointestinal disorders (anorexia, nausea, vomiting, diarrhea, metallic or bitter taste), weight loss, lactic acidosis.
Contraindications to the use of biguanides are:
- insulin-dependent diabetes mellitus (IDDM),
- diabetic ketoacidosis,
- liver and kidney diseases,
- pulmonary heart failure,
- pregnancy,
- acute infectious diseases,
- alcoholism.
Studies conducted in our clinic showed that therapy with metformin (Glucophage) in combination with maninil for 4 weeks in patients with secondary resistance to sulfonamide drugs led to a significant decrease in insulinemia to control levels. At the same time, a significant decrease in the concentration of total cholesterol was noted due to the fraction of LDL cholesterol (LDL cholesterol) and VLDL cholesterol (VLDL cholesterol), the level of triglycerides decreased by 40%.
A decrease in the ratio of atherogenic and antiatherogenic apoB/apoA1 apoproteins and an improvement in the phospholipid composition of erythrocyte membranes in this study indicated the effectiveness of combination therapy with metformin and sulfonamides on atherogenic dyslipidemia.
Dynamics of the lipid profile in patients with NIDDM, with “secondary failure”.
Insulin therapy for NIDDM
Insulin therapy still remains the most controversial aspect of treatment for patients with NIDDM. This is due, on the one hand, to the lack of a unified concept regarding the etiology and pathogenesis of NIDDM and the ongoing debate about where the primary defect is located - at the level of insulin secretion or its activity at the peripheral level, whether it is logical to treat patients with insulin who are obese and hyperinsulinemic, on the other hand, there are no criteria to guarantee the effectiveness of this type of therapy.
There are situations when it is easy to talk about the need to prescribe exogenous insulin for a long period or temporarily.
Long-term insulin therapy for NIDDM is indicated for:
- the presence of contraindications to the prescription of sulfonylureas and biguanides,
- primary or secondary resistance to hypoglycemic sulfonamide drugs,
- severe late complications of diabetes (high degree of retinopathy, severe peripheral neuropathy, especially its painful form, progressive nephropathy).
Indications for temporary insulin therapy for NIDDM are as follows:
- surgical interventions accompanied by general anesthesia,
- concomitant corticosteroid therapy,
- severe infectious diseases with fever, intercurrent illnesses or stress, leading to an increase in counter-insular hormones and the need for insulin,
- malabsorption due to long-term use of oral hypoglycemic drugs,
- the need to achieve normoglycemia with obvious signs of insulin deficiency (polyuria, thirst, weight loss) or symptoms of severe neuropathy.
- 110-140 mg%,
- 141-200 mg%,
- 201-240 mg%,
- more than 240 mg%.
If there is doubt about the advisability of insulin therapy, it is necessary to ensure that the insulin secretory activity of B cells decreases in response to glucagon stimulation. The test cannot be performed against the background of decompensated diabetes, since hyperglycemia has an additional toxic effect on B cells. This may lead to a spurious decrease in the secretory response to stimulation. Insulin therapy for several days to correct the metabolic imbalance will not affect the C-peptide level on the test. Evaluation of the glucagon test (1 mg of glucagon intravenously with a study of the level of serum C-peptide before and 6 minutes after injection): fasting C-peptide concentration above 0.6 nmol/l and above 1.1 nmol/l after stimulation indicates sufficient secretory activity. A glucagon-stimulated plasma C-peptide level of 0.6 nmol/L or less indicates an unconditional need for exogenous insulin. However, the glucagon test does not allow us to judge the degree of insulin resistance. This means that despite the presence of sufficient endogenous insulin production, exogenous insulin therapy may become necessary. Contraindications to the glucagon test: pheochromocytoma, severe hypertension.
Insulin therapy strategy for NIDDM. Clinical experience shows that after long-term “failed” therapy with sulfonamides, a fairly long period of insulin therapy is required to correct metabolic disorders, especially dyslipidemia. Typically, a combination of highly purified animal insulin preparations and long- and short-acting human insulins is used (Table 5). In addition to conditions requiring long-term hospitalization, patients with NIDDM without obesity can receive insulin therapy twice a day. Typically, insulin is administered before breakfast and dinner. The initial dose of basal insulin is determined at the rate of 0.2-0.5 units/kg of body weight, and is subsequently adjusted according to fasting glycemia (1 unit of insulin for every 1.1 mmol/l exceeding 7.7 mmol/l). If necessary, the second injection of basal insulin can be postponed to a later time (22.00). The dose of short-acting insulin is determined at the rate of 1 unit. for every 1.7 mmol/L postprandial glycemia above 7.8 mmol/L (J.A. Galloway). In simpler cases, combination insulin preparations with a fixed ratio of long-acting and short-acting insulin can be used.
Table 5.
Insulin preparations.
| Drug name | Species specificity | Nature of action (hours) | ||
| start | Max. | total duration | ||
| 1 | 2 | 3 | 4 | 5 |
| Short-acting insulin preparations | ||||
| Actrapid ActrapidChM Actrapid ChM (penfill) Alt-N-insulin Velosulin (Penfill) Insulrap Insuman-RapidChM Insuman-Rapid World Cup (penfill) Iletin regular I Iletin regular II Maxirapid VO-S N-Insulin N-Insulin (penfill) Hoorup (penfill) Humulin R | pork human human human human pork human human mixed pork pork human human human human | 0,5 0,5 0,5 0,5 0,5 0,5 0,3 0,3 0,5 0,5 0,5 0,5 0,5 0,5 0,5 | 2-3 1-3 1-3 2-3 1-3 2-3 3-4 3-4 2-3 2-3 2,5-5 1-2 1-2 2-3 1-3 | 6-8 6-8 6-8 6-8 5-8 6-8 6-8 6-8 6-8 6-8 7-8 5-8 5-8 6-8 5-7 |
| Intermediate-acting insulin preparations | ||||
| Insuman-BazalChM Insuman-Basal World Cup (penfill) Insulong Insulatard Insulatard (penfill) Lente Lente VO-S Monotard MK MonotardChM ProtafanChM Protafan ChM (penfill) Semilente MK Semilente VO-S Huminsulin Basal (NPH) Humulin N (isophane) Humulin L | human human mixed human human beef+mixed pork pork human human human pork pork human human human | 0,5-1,5 0,5-1,5 1,5-2,0 1,0-1,5 1,0-1,5 1,5-2,0 2,0 1,5-2,0 2,0-2,5 1,0-1,5 1,0-1,5 1,5-2,0 1,0-1,5 0,5-1,0 1,0 2,5-2,0 | 8-10 8-10 8-16 4-12 4-12 8-16 6-12 8-12 7-15 4-12 4-12 6-8 4-7,5 2-10 2-8 4-16 | 20-22 20-22 20-22 16-24 16-24 20-22 24 18-24 18-24 16-24 16-24 8-12 8-12 18-20 18-20 24 |
| Long-acting insulin preparations | ||||
| Ultralente Ultralente VO-S UltratardChM Humulin U | beef pork human human | 6-8 1-3 3-4 3 | 12-18 12-17 8-24 3,5-18 | 24-26 24-30 24-28 24-28 |
| Mixed insulin preparations | ||||
| Depo-N15-Insulin (15/85)* Depo-N-Insulin (25/75) Insuman-Combe World Cup (50/50) Insuman-Combe World Cup (50/50) (penfill) Insuman-Combe World Cup (25/75) Insuman-Combe World Cup (25/75) (penfill) Insuman-Combe World Cup (15/85) Insuman-Combe World Cup (15/85) (penfill) Mixtard World Cup 10 (10/90) (penfill) Mixtard World Cup 20 (20/80) (penfill) Mixtard World Cup 30 (30/70) (penfill) (Aktrafan World Cup) Mixtard World Cup 40 (40/60) (penfill) Mixtard World Cup 50 (50/50) (penfill) Humulin M1 (10/90) Humulin M2 (20/80) Humulin M3 (30/70) Humulin M4 (40/60) | human human human human human human human human human human human human | 0,5-1 0,5-1 0,3-0,5 0,3-0,5 0,5-1,5 0,5-1,5 1,5 1,5 0,5 0,5 0,5 0,5 | 1-6 3-6 3-5 3-5 4-6 4-6 4-8 4-8 2-8 2-8 2-8 2-8 | 11-20 12-18 12-14 12-14 14-16 14-16 18-220 18-20 12-24 12-24 12-24 12-24 |
However, practice has shown that achieving near- or normoglycemia in NIDDM is often an illusory goal. Only 10-20% of patients on twice-daily insulin have blood glucose levels recommended by the NIDDM Policy Group. This task is especially difficult with a long duration of the disease and the development of secondary sulfonamide resistance. Multiple insulin injection regimen in short-term or long-term use it is most attractive. The advantages of this type of insulin therapy are a relatively free distribution of meals, fast and optimal glycemic control. This type of therapy acts on the main pathogenetic anomalies of NIDDM; in addition, the fastest and most effective glycemic control interrupts the vicious circle of “hyperglycemia - glucose toxicity - insulin resistance - hyperglycemia”. Numerous studies have shown a significant decrease in basal glucose production by the liver and an improvement in glucose utilization by peripheral tissues, both against the background of both short and long-term use of an intensified insulin therapy regimen in patients with NIDDM. At the same time, short-term three-week insulin therapy has the most pronounced positive reactions that persist after discontinuation of insulin therapy: a decrease in liver glucose production by 32-75%, an increase in the rate of peripheral glucose utilization by 70%, an increase in the average 2-hour insulin response to glucose by 6 times. A significant barrier to the use of this regimen is chronic hyperinsulinemia, which is associated with an increased risk of atherosclerosis. Basal and postprandial hyperinsulinemia is a clear outcome of many studies that have evaluated this insulin therapy regimen with the determination of the level of free IRI, or using the clamp technique. However, it remains unclear whether hyperinsulinemia resulting from the administration of exogenous insulin is the same risk factor for atherogenesis as endogenously elevated insulin levels in patients with NIDDM.
In this regard, it is interesting to evaluate the effect of intensive insulin therapy on atherogenic parameters of lipid metabolism. According to the literature, the regimen of multiple insulin injections causes antiatherogenic changes in the plasma lipoprotein spectrum in patients with NIDDM: the level of VLDL and triglycerides decreases. Studies of the effectiveness of short-term (3 weeks) and long-term (12 weeks) intensive insulin therapy in NIDDM patients with “secondary failure” on the PSM, conducted in our clinic (L.P. Ivanova, 1994, V.Z. Topchiashvili, 1995), showed the possibility of optimal correction of atherogenic dyslipidemia: reducing the level of triglycerides, total cholesterol, LDL and VLDL cholesterol, restoring the normal ratio of plasma apoproteins.
Combination therapy insulin/PSM. In the early 1980s, interest in combination therapy with insulin and sulfonamides increased significantly as an alternative to insulin monotherapy in patients with NIDDM with “secondary failure” on the PSM. The theoretical basis for this type of therapy was the following:
- endogenous insulin, stimulated by sulfonamides, is transported directly to the liver;
- small doses of insulin required during combination therapy do not lead to hyperinsulinemia;
- the risk of hypoglycemia for patients is reduced;
- sensitivity to PSM is restored in patients at the initial stages of “secondary failure”;
- Patients' motivation for insulin therapy improves with a one-time insulin injection regimen.
There is no consensus on the benefits of using a particular type of insulin supplement in combination with sulfonylureas. Some authors recommend the use of a single injection of extended-acting insulin at a dose of 0.2-0.3 units/kg and an average therapeutic dose of PSM, but no advantages of morning or evening insulin injections have been identified. Although theoretically, administering basal insulin before bed allows you to achieve maximum suppression of glucose production by the liver and normalize fasting glycemia. Our short-term studies of the effectiveness of various insulin therapy regimens in combination with PSM showed the advantages of administering short-acting insulin before main meals in terms of improving stimulated insulin secretion and peripheral glucose utilization.
According to H.E. Lebovitz, the increase in the cost of combination treatment by 30% and its modest clinical difference from monoinsulin therapy limits the use of this type of glucose-lowering therapy in patients with NIDDM. Combination treatment with insulin/PSM should be used in cases of unsatisfactory glycemic control with twice-daily administration of insulin at a dose of 70 units/day. or more than 1 unit/kg. Improvement in glycemic control will be achieved in 30% of these patients. Combination therapy is not justified if glycemia is less than 10 mmol/l and the daily insulin requirement is less than 40 units.
Monitoring and self-monitoring of the course of diabetes mellitus and therapy.
SELF-CONTROL -
the basis for successful treatment, prevention of decompensation and complications of diabetes mellitus.
Self-monitoring system includes
- patient knowledge of the clinical manifestations and treatment of the disease,
- diet control,
- control over glycemia, glucosuria and body weight,
- correction of glucose-lowering therapy.
Only complex treatment of patients with NIDDM using diet therapy, adequate physical activity, drug hypoglycemic therapy and self-control methods can help prevent late complications of diabetes, preserve the ability to work and prolong the life of patients.
This is a severe endocrine disease caused by insulin deficiency or cell insensitivity to this hormone. Diabetes mellitus is a systemic pathology that affects blood vessels and many organs, inhibits metabolic processes in tissues and often leads to disability. However, with adequate treatment, the patient's quality of life can be high.
Signs of diabetes
There are several options for classifying the disease. In everyday medical practice, endocrinologists distinguish the following main types of diabetes mellitus: insulin-dependent (I) and non-insulin-dependent (II). In the first case, the disease occurs because the pancreas produces too little insulin. In the second, because the cells are not able to use it and also experience a glucose deficiency.
Both types of diabetes have many similar symptoms. They differ mainly in degree of expression. Signs of type I disease are more intense, brighter and appear suddenly and rapidly. People suffering from type II disease often do not realize for a long time that they are sick. General malaise can easily hide the true diagnosis. However, diabetes mellitus is known for its triad of classic symptoms. This:
- unquenchable thirst;
- increased urine formation;
- persistent feeling of hunger.
The disease may manifest itself with additional symptoms. These ailments are numerous; adults often experience:
- sore throat;
- “iron” taste in the mouth;
- dryness and flaking of the skin, fungal infections;
- wounds that do not heal for a long time;
- debilitating itching in the groin;
- headaches;
- pressure changes;
- insomnia;
- weakened vision;
- susceptibility to colds;
- weight loss;
- muscle weakness;
- loss of strength.
Reasons
Why does the pancreas stop producing a vital hormone? Insulin-dependent diabetes mellitus is a consequence of the pathological action of the immune system. It perceives gland cells as foreign and destroys them. Insulin-dependent diabetes develops rapidly in childhood, adolescents, and young adults. The disease occurs in some pregnant women, but goes away after childbirth. However, such women may subsequently develop type II disease.
For what reasons does this happen? For now there are only hypotheses. Scientists believe that serious reasons for the insulin-dependent type of disease may include:
- viral infections;
- autoimmune diseases;
- severe liver pathologies;
- hereditary predisposition;
- sweet tooth;
- overweight;
- prolonged stress, depression.
Diagnosis of type I diabetes
Determining the insulin-dependent variant of the disease is not a difficult task for an endocrinologist. The patient's complaints and characteristics of the skin provide the basis for making a preliminary diagnosis, which is subsequently, as a rule, confirmed by laboratory tests. Diagnosis of the disease is carried out using blood and urine tests.
Blood is donated:
– for sugar (on an empty stomach and 2 hours after eating);
– glycosylated hemoglobin;
– glucose tolerance (insulin-dependent diabetes must be differentiated from prediabetes);
Urine is analyzed:
– for sugar;
– acetone.
Complications
The disease significantly undermines the immune system. The patient becomes very vulnerable to infections. The consequences of the disease can be acute, but transient, and chronic. The most acute complications are ketoacidosis and hypoglycemia. Cells, in search of an energy source, break down fats instead of glucose. The increased acidity of the blood in conditions of a lack of fluids causes a critical condition of the diabetic - up to ketoacidosis coma with a fatal outcome. The patient suffers from dizziness, thirst, vomiting, and his breath smells of acetone.
If the amount of food you eat and the amount of insulin in the body are not balanced, the blood glucose level drops sharply (below 3.3 mmol/l). In this case, the development of a dangerous hypoglycemic syndrome is inevitable. The body experiences an energy deficiency and reacts to this very sharply. The patient is tormented by an attack of severe hunger, he breaks into sweat, and his body trembles. If you don't eat sweets right away, a coma will occur.
Transient complications can be prevented. Chronic consequences are difficult to treat. However, if left untreated, the insulin-dependent type of pathology can dramatically shorten a person’s life. The most common chronic complications:
- atherosclerosis;
- hypertension;
- stroke;
- myocardial infarction;
- trophic ulcers, diabetic foot, gangrene of the extremities;
- cataract, retinal damage;
- kidney degeneration.
How to treat diabetes
A person who has been diagnosed with this must realize that the insulin-dependent version of the disease cannot be completely cured. Medicines alone will not help either - you need proper nutrition. Treatment should become a new way of life for a person. The most important condition is to maintain sugar levels within optimal limits (not higher than 6.5 mmol/l), otherwise serious complications cannot be avoided.
You should check your condition with a glucometer several times a day. Monitoring sugar levels helps to quickly adjust the dosage of medications and diet. At the initial stage of insulin-dependent diabetes mellitus, treatment often begins with glucose-lowering tablets. However, over time, it is often necessary to switch to hormone injections or a combination of both.
Insulin therapy
The treatment tactics for type II diabetes mellitus are chosen exclusively individually. Insulin therapy today is an effective method of blocking the pathological process thanks to effective medications. These are hypoglycemic tablets Gliformin, Glucobay, Dibikor and Eslidin. Insulin for injection - Actrapid, Rinsulin, Insuman, etc. - is available in fast-acting and long-acting forms. The patient must learn to give himself injections himself. Injections can be replaced by an insulin pump. Dosed administration of the hormone through a subcutaneous catheter is much more convenient.
Authorized Products
The principle of the diet is to get the optimal amount of calories from carbohydrates while consuming little fat. Then fluctuations in glucose in insulin-dependent diabetes mellitus will not be sharp. An absolute ban on all high-calorie and sweet foods. If you follow this nutritional rule, the disease progresses minimally.
You need to eat little by little, but often, in 5-6 meals. The following foods are safe and healthy:
- vegetable cabbage soup, soups, beetroot soup, borscht, okroshka;
- porridge (limited);
- lean meat, poultry;
- fish and seafood;
- vegetables (potatoes – a little at a time);
- low-fat dairy and fermented milk products;
- inconvenient flour products;
- sweet and sour fruits;
- drinks – with sweeteners;
Folk remedies
Traditional medicine recipes and available home remedies may be useful:
- Jerusalem artichoke is effective for insulin-dependent diabetes mellitus. Tubers are best eaten raw.
- Chicken egg, beaten with juice of 1 lemon (on an empty stomach).
- Infusion of walnut leaves (brewed like regular tea).
- Millet ground in a coffee grinder. A tablespoon of powder is washed down with milk on an empty stomach (a recipe that is especially popular among patients with insulin-dependent diabetes mellitus).
