Diabetes mellitus ranks third in the world in terms of mortality in developed countries. Today, there are about 150 million people on the planet suffering from this disease, and, according to forecasts of the world health organization, this figure may grow to 300 million by 2025. While diabetes is incurable, modern medical science is able to improve the quality of life of patients and make them able to live and work normally. This medicine and public health says the doctor of medical Sciences, head of Department of endocrinology and diabetology of the Russian medical Academy of postgraduate education of the Ministry of health of Russia, Professor Alexander Sergeevich Ametov. New methods of controlling and treating diabetes, which are discussed in the article, will be presented at the international specialized exhibition of goods and services “Life without the power of diabetes”, which will be held in April this year in Moscow at the all-Russian exhibition center.
The proinsulin molecule produced in the beta cells of the pancreas consists of 84 amino acids.
With diabetes, the regulation of blood glucose levels is disrupted.
80% of patients with insulin-independent diabetes are obese.
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The world health organization has called diabetes a problem of all ages and all countries.
The mechanism and causes of diabetes still remain a mystery “behind seven seals”. The word “diabetes” comes from the Greek “diamino” – I pass through. And through with diabetes passes all the liquid you drink. The main symptoms of the disease are debilitating thirst and a huge amount of daily urine (in some patients-up to 40 liters).
Diabetes occurs when the body lacks the most important hormone-insulin, without which the cells do not absorb the glucose coming from carbohydrate food. There is another variant of diabetes: the amount of insulin is sufficient, but for a number of reasons, the body’s cells lose sensitivity to it, and this also affects the utilization of glucose, primarily by muscle and fat tissues. As a result, the concentration of glucose in the blood increases, but it does not enter the tissues at all. Glucose is the main” fuel ” of the body, without it, cells do not produce the main molecule that accumulates living energy – adenosine triphos fat (ATP). Brain cells that die without glucose within 5 minutes are particularly sensitive to glucose deficiency.
The hormone insulin, or rather, its predecessor – proinsulin, is produced by cells of the pancreas, which are called Langerhans Islands. But not all cells synthesize it, but only a part of them – the so-called beta cells. Proinsulin, a short – chain protein molecule, is converted to insulin as it passes through the cell membrane. The more insulin you need to produce, the more beta cells are involved in this process. It should be emphasized that the human body has a background, so-called “basal”, insulin production and peak, associated with food intake.
Currently, there are two main types of diabetes mellitus (DM): insulin-dependent diabetes mellitus (DM 1) and insulin – independent diabetes mellitus (DM 2). type 1 diabetes mellitus is characterized by absolute insulin deficiency-the pancreas does not produce a hormone at all. In this case, insulin injections are required in order to save the patient’s life.
In type 2 diabetes, the level of insulin in the blood is normal or even elevated, but the body’s tissues lose sensitivity to it, or the hormone itself is in a “non-working” state for various reasons. There is also a variant of not absolute, but relative insufficiency of insulin secretion – the pancreas produces too little insulin. As a rule, the diagnosis of DM 2 is made in 85-90% of cases of diabetes. This type of diabetes mainly affects people over 40 years of age, about 80% of these patients are obese. In most cases, patients with DM 2 do not need regular insulin injections and can control their condition by following a diet, exercising and taking hypoglycemic tablets.
Why does a person get diabetes?
It is hardly possible to give an unambiguous answer to this question today, but some of the causes of diabetes are already clear. Thus, in patients with DM 1, almost all insulin-producing beta cells of the pancreas are destroyed. What is the reason for these violations? As a result of some “breakdown” of the immune system, the body begins to produce antibodies not only against foreign proteins and cells, but also against its own “native” beta cells. Such an irreversible “failure” in the immune system can in principle be caused by a viral disease or stress. Fortunately, in most people the flu does not end with the destruction of the beta cells. As with many other diseases, a person’s genetic predisposition to diabetes is important.
According to one of the leading experts in this field, Professor Ralph de Fronzo (USA), DM 2 occurs as a result of a violation of the balance between insulin sensitivity and its production in the body. Numerous studies on this issue have shown that first of all, DM 2 develops a decrease in the sensitivity of cells to insulin.
Experts believe that the mechanism of occurrence of DM 2 is also based on a genetic predisposition, and it is even more important than in the case of DM 1. Failure in the” work ” of the insulin-glucose system can occur at various levels: glucose transport to the cell, glucose phosphorylation, binding of insulin to cell receptors, and many others, depending on which protein gene the “harmful” mutation occurred. So it turns out: beta cells are safe and sound, there is insulin, but the body is not able to use it. Mutations accumulate with age. But this does not mean that if you have a genetic predisposition, diabetes is inevitable. Prevention measures are simple: do not abuse high-calorie food, monitor weight, and actively engage in physical education.
So, if there is not enough insulin in the body, then the glucose consumed with food is not absorbed by the cells, but accumulates in the blood. Excess glucose is excreted by the kidneys, and dehydration occurs. Cells try to find new sources of energy that replace glucose-fats, but when they are not fully broken down, toxic substances – ketone bodies-begin to accumulate in the blood, which directly threatens the patient’s life. Debilitating thirst and dehydration are not all the consequences of diabetes. Most patients with both type 1 and type 2 diabetes suffer from vascular, neurological, and organ-specific disorders. The frequency and severity of many diabetes complications are related not only to the duration of the disease, but also to the degree of increased glucose levels. There are other factors that affect the occurrence of complications.
In recent years, the results of advances in medical and biological science have finally begun to be widely implemented in medical practice.
Which of them are most important? Undoubtedly, the main task of modern diabetology is to maintain the physiological level of glucose in the blood of patients. This is a top priority for patients with both type 1 and type 2 diabetes.
It should be emphasized that in cases of DM 1, the glucose concentration at the desired level is maintained exclusively by subcutaneous administration of insulin. What are the sources of insulin for injection?
Until recently, due to the lack of insulin, the diagnosis of “diabetes” sounded like a death sentence. You can’t extract enough of it from the human pancreas, and it’s difficult to synthesize such a long protein molecule chemically. A method has been developed for isolating insulin from the pig’s pancreas, which differs from the human one by only one amino acid. The ” pig “hormone was chemically modified to produce a “human” protein. Modern science has found a new way to produce insulin – genetically engineered: the hormone is produced by bacteria with the built-in insulin gene. And today, almost all the insulin used by patients is a product of genetic engineering, which in its chemical structure does not differ from human.
Currently, short -, medium-and long-acting insulins are available. Thus, by combining these different drugs, it is possible to reproduce the physiological secretion of insulin: maintain the background concentration of insulin (long-acting insulins) and simulate the peaks associated with food intake (short-acting insulins). Ideally, short-acting insulin should give a peak of activity, quickly disappearing at the end of the meal. In contrast, the task of long-acting insulin is to maintain activity at the same level for a long time.
More than 20 years of experience in using genetically engineered insulin preparations has shown that despite the fact that they have the chemical structure of human insulin, genetically engineered proteins differ in their action in the human body from insulin produced by the pancreas and do not meet the requirements listed above.
Therefore, ultrashort analogs of insulin were developed. They start acting faster, and their duration of action is shorter than conventional commercial short-acting insulins, whose molecules are complexes of six monomers. One of these ultra – short-acting insulins is the drug “Humalog” produced by the company “Eli Lilly” (USA), registered in our country in 1996.
Significant efforts have also been made to create forms of insulin that are active for 24 hours. New long-acting insulin analogs are obtained by chemical modification of individual amino acids, which leads to a change in the total electric charge of the protein, and this, in turn, can slow down the absorption of insulin and ensure its long-term constant activity. The drug is made as a solution (rather than a suspension, as usual), and it has more reproducible uniform activity profiles. For example, such long-acting insulin is developed and implemented by Aventis Pharma (France). It is registered in most countries under the name “Lantus”. In our country, the drug is undergoing clinical trials.
New ways of injecting insulin are also being developed. Today, along with conventional syringe pens, so-called insulin pumps are used, in which the dose of insulin and the time of administration are set using special dispensers. There are devices with a programmed dose and time of administration. The time is not far off when people with diabetes will use syringes equipped with special glucose sensors, and the program of insulin administration will be implemented taking into account the level of glucose in the blood in the “feedback”mode.
In the meantime, the level of insulin in the blood of patients can only be maintained by injections. But scientists have never given up trying to come up with other-alternative ways to supply the body with insulin. One of them is the use of an aerosol form in the form of a nasal spray-nasal insulin. The rate of absorption of insulin with this method of administration is higher than with subcutaneous injections. But only 10-20% of the administered dose is absorbed, and this is very small. Pharmaceutical companies continue to work on improving the characteristics of the nasal drug. It remains unclear what the level of insulin absorption will be under various conditions (upper respiratory diseases, low and high humidity, hot and cold weather), however, it can be expected that in the near future nasal insulin will be used as an adjunct to injections.
Interesting are the results of joint efforts of two pharmaceutical companies – Pfizer (USA) and Aventis Pharma, which realized a long – standing dream of scientists-the introduction of insulin aerosols through the lungs. Inhaling insulin is very effective – the surface area of the lungs is not comparable to the surface area of the nasal mucosa. Preliminary studies with the participation of volunteers showed that aerosol forms of insulin in doses of 0.2 Units of insulin per 1 kg of body weight are absorbed in quantities sufficient to normalize glucose levels in patients with DM 2. There is already accumulated data on the effective use of inhaled insulin even in patients with DM 1. Insulin inhalation, according to most doctors, is the most promising method of treatment.
It would seem that the simplest thing is to swallow a pill, and the right dose of insulin is provided. But so far, almost all attempts to create insulin in tablets have failed: the hormone is quickly destroyed by the action of enzymes contained in gastric juice. In recent years, attempts have been made to integrate the insulin molecule into the lipid environment – liposomes. The idea was partly successful: some amount of insulin is absorbed in the gastrointestinal tract, but it was not enough to reduce blood sugar to the required level. And the technology of obtaining liposomes itself requires large expenditures, and therefore such work is considered unpromising.
I would especially like to mention the research of our scientists – academician N. A. plate and Professor L. I. Valuev (Institute of petrochemical synthesis of the Russian Academy of Sciences), who created an insulin preparation in the form of a gel for oral administration. Insulin is included in a polymer hydrogel and a substance is added to this mixture that blocks enzymes (proteinases) that destroy insulin in the stomach. The blocker of insulin breakdown simultaneously increases the rate of penetration of the hormone into the bloodstream. In an experiment, scientists have shown that taking insulin in the form of a gel leads to the same decrease in blood glucose levels as with intramuscular injections.
The result of these studies is insulin tablets. Now, based on the decision of the Pharmacological Committee of the Ministry of health of the Russian Federation, they are undergoing the first stage of clinical trials in three leading endocrinological clinics in the country. There is also evidence that such insulin tablets can be used as immunomodulators that protect beta cells from destruction by antibodies at the “prediabetes” stage.
Certain hopes in the treatment of DM 1 are associated with complete or partial pancreatic transplantation. However, in order to avoid rejection of the transplanted organ, after such surgery, patients need to take large doses of immunosuppressive drugs. And organs for transplantation are not always available.
One of the areas of current research in many countries is the search for various ways to protect pancreatic islet cells from attack by their own antibodies. To do this, combine artificial membranes, or capsules, with “live” islet cells. For example, beta cells are encapsulated in porous tubes made of biocompatible material to protect them from antibodies, while not disrupting the interaction of cells with glucose. What are the advantages of this method? First of all-the availability of the operation, since it is possible to use islet cells of animals, then-the ease of implantation, which in this case is a small surgical operation. However, it has not yet been determined how many islet cells need to be encapsulated in order to obtain the desired insulin response over a long period of time.
The original technique of microencapsulation of islet cells was developed by American Professor Saudek: the cells are placed in balls made of special biological material, which are then injected intravenously or into the peritoneum. A significant advantage of this approach is the ability to inject microspheres into the portal vein, that is, direct delivery of insulin to the liver.
Unfortunately, there is no consensus on the need and effectiveness of beta-cell transplantation among doctors yet. Indications for transplant surgery, special training programs for patients, and criteria for evaluating clinical effectiveness and impact on the course of diabetes are not yet fully defined. Issues related to the development of postoperative complications, repeated transplantation, its timing and effectiveness also need to be clarified.
The most promising method for the treatment of dM1, in my opinion, is the use of so-called pseudolite cells. They are obtained by genetic engineering, embedding the insulin gene in them, and when the concentration of glucose in the blood increases, they “give out” insulin. An important task is to develop a cell line that responds to glucose and secretes insulin in the same way as cells in a healthy body. Ideally, the pseudocells are not rejected. This is the dream of all doctors and patients, which may soon come true. Such work is being carried out at Rockefeller University (USA).
In the meantime, the main task is still to develop measures for the prevention of DM 1.here, the most important step is to examine people with a high risk of developing the disease. How do I identify “at-risk” patients? First of all, the analysis for genetic predisposition should ideally be performed by all the closest relatives of patients with DM 1, including newborns. If this is not possible, then it is necessary to conduct an immunological analysis for the presence of antibodies to islet cells, the enzyme – glutamate det carboxylase or insulin.
Some of these immunological markers are detected long before the development of the clinical picture of the disease. For example, antibodies to glutamate decarboxylase are detected for 10-12 years, and according to some data, even 15 years before the onset of diabetes symptoms.
In the US, they are working on a special vaccine against type 1 diabetes for people from the “risk group”.
How to treat patients with insulin-dependent diabetes mellitus? It is necessary to limit the consumption of high-calorie food, increase physical activity, and try not to get into stressful situations. Medications recommended include sulfonylureas, alpha-glucosidase inhibitors, biguanides, glitazones, prandial regulators, and insulin therapy. Within a relatively short time, the regimen and treatment can normalize many metabolic disorders in most patients with DM 2.
It should be noted that the risk of developing DM 2 increases twice in the presence of grade I obesity, five times in the presence of grade II obesity, and more than 10 times in the presence of grade III obesity.
Repeat: today, it is impossible to cure insulin-dependent diabetes mellitus, but the disease can be managed and live a full life, maintaining working capacity and good health for many years. An integrated approach can prevent the appearance of late complications of DM 2.
Self-control is the basis for successful treatment and prevention of diabetes complications. The system of self-control includes: the patient’s knowledge of the features of clinical manifestations and therapy of the