Diabetes is ranked third in the world in mortality in developed countries. Today, there are about 150 million people suffering from this disease all over the world, and, according to the World Health Organization, this figure could increase to 300 million by 2025. While diabetes is incurable, but to improve the quality of life of patients, to make it so that they can live and work normally, modern medical science can do.
The World Health Organization has called diabetes mellitus a problem of all ages and all countries.
The mechanism and causes of diabetes mellitus still remain a secret “sealed.” The word “diabetes” comes from the Greek “diabayno” – pass through. And diabetes goes through all the fluid you drink. The main symptoms of the disease are exhausting 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 glucose coming from carbohydrate foods. There is another option for diabetes: the amount of insulin is enough, but due to a number of reasons, the cells of the body lose sensitivity to it, and this also affects the utilization of glucose, primarily muscle and fatty tissues. As a result, the concentration of glucose in the blood rises, but it does not enter the tissue at all. Glucose is the main “fuel” of the body, without it, the cells do not produce the main molecule that accumulates the living energy – adenosine triphosphate (ATP). Brain cells are especially sensitive to the lack of glucose, dying without it after 5 minutes.
The hormone insulin, or rather, its predecessor, proinsulin, produces pancreatic cells called the islets of Langerhans. But not all cells synthesize it, but only a part of them – the so-called beta cells. Proinsulin, a short-chain protein molecule, is transformed into insulin as it passes through the cell membrane. The more insulin you need to produce, the greater the number of beta cells involved in this process. It should be emphasized that in the human body there is a background, the 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 non-insulin-dependent 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 mellitus, the level of insulin in the blood is within the normal range or even elevated, but the tissues of the body lose sensitivity to it or the hormone itself is in a “non-working” state for various reasons. There is also the option of not absolute, but relative insufficiency of insulin secretion – the pancreas produces insulin too little. As a rule, diabetes mellitus 2 is diagnosed in 85-90% of diabetes mellitus cases. This type of diabetes mainly affects people after 40 years, about 80% of these patients are obese. In most cases with diabetes, 2 patients do not need regular injections of insulin and can control their condition by following a diet, doing physical exercises and taking hypoglycemic pills.
Why does a person get diabetes? It’s hardly possible to give an unequivocal answer to this question today, but some of the causes of diabetes are already clear. Thus, in patients with type 1 diabetes, almost all insulin-producing beta cells of the pancreas are destroyed. What is the cause of these violations? As a result of some kind of “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, stress. Fortunately, for most people, the flu does not end with the destruction of beta cells. As in the case of 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), diabetes mellitus 2 occurs as a result of the imbalance between insulin sensitivity and its production in the body. Numerous studies on this issue have shown that, first and foremost, in case of diabetes mellitus, a decrease in insulin sensitivity of cells develops.
Experts believe that the basis for the onset of diabetes is also genetic predisposition, and it is even more important than in the case of diabetes 1. Failure in the “work” of insulin-glucose can occur at different levels: glucose transport to the cell, glucose phosphorylation, insulin binding to cellular receptors, and many others, depending on which protein gene has the “harmful” mutation. So it turns out: beta cells are safe and sound, insulin is, and its body is not able to use it. Mutations accumulate with age. But this does not mean that in the presence of a genetic predisposition, diabetes is inevitable. Prevention measures are simple: do not abuse high-calorie foods, keep an eye on weight, actively engage in physical exercise.
So, if there is not enough insulin in the body, then glucose consumed with food is not absorbed by the cells, but accumulates in the blood. Excess glucose excreted by the kidneys, dehydration occurs. The cells are trying to find new sources of energy, replacing glucose, fats, but if they are not fully broken down, toxic substances, ketone bodies, begin to accumulate in the blood, which directly threatens the patient’s life. Exhausting thirst and dehydration are not all the effects of diabetes. The majority of diabetic patients of both type 1 and type 2 suffer from vascular, neurological and organ-specific disorders. The frequency and severity of many complications of diabetes are associated not only with the duration of the disease, but also with the degree of increase in glucose levels. There are other factors that influence the occurrence of complications.
In recent years, the results of advances in medical and biological science have finally begun to be widely introduced into medical practice.
Which ones 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 the primary task for patients with diabetes mellitus as the 1st and 2nd type.
It should be emphasized that in cases of diabetes mellitus 1, the concentration of glucose at the right level is maintained solely by subcutaneous insulin. What are the sources of insulin for injection?
More recently, due to the lack of insulin, the diagnosis of diabetes sounded like a death sentence. You cannot select it in sufficient quantities from the human pancreas, it is difficult to chemically synthesize such a long protein molecule. A method has been developed for isolating insulin from the pancreas of a pig, which differs from the human one by only one amino acid. “Pork” hormone is chemically modified and received “human” protein. Modern science has found a new way to get insulin – genetically engineered: the hormone is accumulated by bacteria with an embedded insulin gene. And today almost all insulin used by patients is a product of genetic engineering, which by its chemical structure does not differ from human.
Currently available short, medium and long-acting insulins. Thus, by combining these various drugs, it is possible to reproduce the physiological secretion of insulin: maintain the background concentration of insulin (long-acting insulin) and simulate peaks associated with food intake (short-acting insulin). Ideally, short-acting insulin should give a peak of activity that quickly disappears at the end of the meal. And, on the contrary, the task of long-acting insulin is to maintain activity at the same level for a long time.
More than 20 years of experience with the use of genetically engineered insulin preparations has shown: despite the fact that they have the chemical structure of human insulin, genetically engineered proteins differ from insulin produced by the pancreas in their effects on the human body and do not meet the above requirements. .
Therefore, ultrashort insulin analogues have been developed. They begin to act faster, and their duration is less than the usual commercial short-range insulin, the molecules of which are complexes of six monomers. One of these ultrashort-acting insulins is the drug Humalog, produced by Eli Lilly (USA), registered in our country in 1996.
Considerable effort has also been made to create insulin forms that would be active for 24 hours. New long-acting insulin analogues were obtained by chemical modification of individual amino acids, which leads to a change in the total electrical charge of the protein, and this, in turn, allows to slow down the absorption of insulin and ensure its long-term constant activity. The drug is made in the form of a solution (rather than a suspension, as usual), and it has more reproducible uniform activity profiles. For example, such long-acting insulin was developed and introduced 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 insulin administration are also being developed. Today, along with conventional syringe pens, so-called insulin pumps are used, in which the insulin dose and 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 in the daily life of diabetics there will be syringes equipped with special sensory glucose sensors, and the insulin program will be implemented taking into account the level of blood glucose in the “feedback” mode.
In the meantime, the level of insulin in the blood of patients can be maintained exclusively by injection. But scientists have never given up trying to think of others — alternative ways of supplying the body with insulin. One of them is the use of an aerosol form in the form of a nasal insulin spray for the nose. Insulin absorption rate with this method of administration is higher than with subcutaneous injections. But only 10-20% of the injected dose is absorbed, which is very small. Pharmaceutical firms continue to work on improving the characteristics of the nasal preparation. It remains unclear what the level of insulin absorption will be under various conditions (diseases of the upper respiratory tract, 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.
The results of the joint efforts of the two pharmaceutical companies, Pfizer (USA) and Aventis Pharma, which realized the scientists’ long-held dream of administering insulin aerosols through the lungs, are interesting. Insulin inhalation is very effective – the surface area of the lungs cannot be compared with the surface area of the nasal mucosa. Preliminary studies with the participation of volunteers showed that insulin aerosol forms in doses of 0.2 U insulin per 1 kg of body weight are absorbed in quantities sufficient to normalize glucose levels in patients with DM 2. Already accumulated data on the effective use of inhaled insulin even in patients with type 1 diabetes. Insulin inhalation, as most physicians believe, is the most promising treatment option.
It would seem that the simplest thing is to swallow a pill, and the required insulin dose is provided. But while almost all attempts to create insulin tablets have failed: the hormone is quickly destroyed by the action of enzymes contained in the gastric juice. In recent years, an insulin molecule has been attempted to be inserted into the lipid environment — liposomes. Partly the idea was a success: some amount of insulin is absorbed in the gastrointestinal tract, but it was not enough to lower the blood sugar to the required level. Yes, and the technology of obtaining liposomes is costly, in connection with which 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 the insulin preparation in the form of a gel for oral administration. Insulin is incorporated into 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 hormone penetration into the bloodstream. In the experiment, scientists have shown that taking insulin in the form of a gel leads to the same decrease in the level of glucose in the blood, as with intramuscular injections.
The result of these studies – insulin tablets. Now, on the basis of 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, protecting beta cells from being destroyed by antibodies in the “pre-diabetes” stage.
Certain hopes in the treatment of diabetes mellitus 1 are associated with a full or partial pancreas transplant. However, in order to avoid the rejection of the transplanted organ, after such a surgical intervention, patients need to take large doses of immunosuppressive drugs. Yes, and organs for transplantation is not always available.
One of the directions of today’s research in many countries is the search for various ways to protect pancreatic islet cells from attack with their own antibodies. For this purpose, artificial membranes, or capsules, are combined with live islet cells. For example, beta-cells are encapsulated into porous tubes of biocompatible material in order to protect them from antibodies, without at the same time 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 the islet cells of animals, then – the simplicity 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 to obtain the desired insulin response for a long time.
The original technique of microencapsulation of islet cells was developed by American professor Saudek: cells are placed into balls of special biological material, which are then injected intravenously or into the peritoneum. A significant advantage of this approach is the possibility of injecting 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 physicians. The indications for transplantation operations, special training programs for patients, criteria for evaluating clinical efficacy and the impact on the course of diabetes are not fully defined. Issues related to the development of postoperative complications, re-transplantation, its timing and effectiveness also need to be clarified.
The most promising method of treating diabetes mellitus 1, in my opinion, is the use of so-called pseudo-beta cells. They are obtained by genetic engineering, embedding the insulin gene in them, with an increase in the concentration of glucose in the blood, they “give out” insulin. An important task is to develop a cell line that would react to glucose and secrete insulin in the same way as the cells of a healthy organism. Ideally, pseudo-cells should not be rejected. This is the dream of all doctors and patients, which, perhaps, will soon come true. Such work is carried out at Rockefeller University (USA).
In the meantime, the development of diabetes prevention measures 1 remains the main one. Here the most important step is the examination of people with a high risk of developing the disease. How to identify patients at risk? First of all, the analysis of genetic predisposition should ideally be carried out by all the immediate relatives of patients with type 1 diabetes, including newborns. If this is not possible, an immunological analysis should be carried out for the presence of antibodies to islet cells, the enzyme – glutamatedecarboxilase 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 10–12 years, and according to some data, even 15 years before the onset of diabetes symptoms.
In the USA, they are working on a special vaccine against diabetes mellitus type 1 for people from the “risk group”.
How to treat patients with non-insulin dependent diabetes mellitus? It is necessary to limit the consumption of high-calorie foods, increase physical activity, try not to fall into stressful situations. Among the drugs, sulfonylurea preparations, alpha-glucosidase inhibitors, biguanides, glitazones, prandial regulators and insulin therapy are recommended. For a relatively short time, the regimen and treatment can normalize many metabolic disorders in the majority of patients with diabetes 2.
It should be noted that the risk of developing diabetes mellitus doubles in the presence of grade I obesity, five times in cases of grade II obesity and more than 10 times in grade III obesity.
We repeat: today, it is impossible to cure insulin-dependent diabetes mellitus, but the disease can be managed and lead a full life, while retaining its working capacity and well-being. An integrated approach can prevent the occurrence of late complications of diabetes 2.
Self-control is the basis for successful treatment and prevention of diabetes complications. The system of self-control includes: patient’s knowledge of the features of clinical manifestations and treatment of the disease; monitoring diet and weight, for indicators of glucose in the blood and urine. Excessive emotions, excessive physical exertion, errors in diet, infections, stress – those factors that are foreseen in advance and cannot be taken into account. The patient must be able and able to examine blood sugar before and after meals in any situation; analyze subjective feelings, evaluate the results obtained and take appropriate therapeutic measures.
Modern devices for self-monitoring – blood glucose meters – allow you to analyze for sugar in seconds, and almost under any circumstances. The latest-generation glucometers are comparable in accuracy to laboratory analyzers, yet they are easy to handle and compact. Self-control provides a high level of education of patients with diabetes. This is possible only if there is an established and well-developed system of training patients in outpatient and inpatient diabetes care facilities.