Treatment of diabetes mellitus using innovative technologies. Moscow.

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10.13.2021 The article was checked by an endocrinologist, Ph.D. Mirna S.S. , is for general informational purposes only and does not replace specialist advice. For recommendations on diagnosis and treatment, consultation with a doctor is necessary.

At the Clinical Hospital on Yauza, the diagnosis and treatment of diabetes mellitus is worked out to the smallest detail - diet correction, prescribing insulin or tablets. We also offer innovative methods for the prevention and treatment of microvascular complications of diabetes mellitus - methods of extracorporeal hemocorrection. With its help, you will reduce the risk of vascular complications and significantly improve your quality of life. Our hospital is a participant in international medical research on diabetes.

387 million people worldwide suffer from diabetes mellitus (DM) and the number of new cases continues to rise steadily, according to WHO
5.7% prevalence of diabetes mellitus in Russia (9 million people)
A history of diabetes increases the likelihood of stroke and heart attack by 2–3 times.

About diabetes

Among the causes of diabetes mellitus, autoimmune aggression, genetic predisposition, as well as the influence of stress, poor lifestyle, nutrition, and obesity play an important role. Diabetes can be a consequence of various diseases of the pancreas (pancreatitis, large cysts, surgical interventions accompanied by the removal of a significant part of the organ) and certain physiological conditions (pregnancy).

There are two types of diabetes:

Type 1 diabetes: the human body produces insufficient amounts of insulin, causing a steady increase in blood glucose levels. Most often, this form of diabetes develops in people under 40 years of age and is accompanied by a clear clinical picture (progressive weight loss, muscle weakness, diabetes and thirst). At the same time, the only treatment for such patients is insulin injections.
Type 2 diabetes (90% of all diabetes cases): when the body develops a condition in which insulin is produced initially in sufficient quantities, but insulin-dependent organs (fat, liver and muscles) are unable to use it due to the development of a specific condition called insulin resistance. Over time, cells lose the ability to produce insulin and its production decreases in the same way as in type 1 diabetes. At the same time, the level of glucose in the blood, which increases after eating, does not decrease, which leads to the formation of serious vascular complications that cause disability and increase the risk of death. This pathology most often occurs in patients over 40 years of age and those suffering from obesity. In some cases, patients do not have any complaints at all and the diagnosis is established by chance, during the study of a biochemical blood test, in which an increase in glucose levels appears.

Choosing an insulin therapy regimen for type 2 diabetes mellitus

In recent years, indications for insulin therapy in patients with type 2 diabetes mellitus (DM) have expanded significantly. According to the British Prospective Diabetes Study (UKPDS), every year 5–10% of patients with newly diagnosed type 2 diabetes require insulin therapy [12], and after 10–12 years, about 80% of patients require constant insulin therapy. Over time, in patients with type 2 diabetes, glycemic control worsens, due to an increasing decrease in residual secretion of β-cells. Peripheral insulin sensitivity remains relatively preserved, which determines the need to select optimal therapy at each stage of disease development [4, 6, 10]. Monotherapy with oral hypoglycemic drugs (OHLDs) is usually effective in the first 5–6 years of the disease; subsequently, it becomes necessary to use a combination of two or more drugs with different mechanisms of action, correcting both insulin deficiency and insulin resistance. At the same time, treatment with diet, exercise, sulfonylureas or metformin does not have a significant effect on the progressive decrease in the secretory function of β-cells. According to UKPDS, 40% of patients already have a marked decrease in the secretory function of β-cells by the time they are diagnosed with type 2 diabetes. The duration of the period from the onset of type 2 diabetes to the prescription of constant insulin therapy depends primarily on the decrease in the functional activity of β-cells and the worsening of insulin resistance. A state of chronic hyperglycemia significantly shortens the duration of this period. Patients with type 2 diabetes have a number of parameters that increase insulin resistance: concomitant diseases, use of drugs with negative metabolic effects, low physical activity, weight gain, depression and frequent stress. Along with glucose and lipotoxicity, they accelerate the decline in the functional activity of β-cells in patients with type 2 diabetes.

With a progressive decrease in the residual secretion of β-cells and the ineffectiveness of PSSP therapy, insulin is prescribed, the preparations of which are presented on the Russian market by both foreign and domestic manufacturers (actrapid, protophan, humulin, biosulin, etc.), both in the form of monotherapy and in combination with tableted hypoglycemic drugs. According to conservative estimates, about 40% of patients with type 2 diabetes mellitus need insulin therapy, but less than 10% of patients actually receive insulin. Analysis of clinical practice in the treatment of type 2 diabetes indicates a late start of insulin therapy, as well as unsatisfactory metabolic compensation of diabetes, even against the background of insulin therapy (low doses of insulin). This can happen either through the fault of the doctor - due to fear of weight gain and the development of hypoglycemia, or due to the patient’s negative attitude towards this type of therapy - in the absence of regular self-monitoring of glycemia. Typically, insulin therapy is prescribed to patients who have had diabetes mellitus for more than 10–15 years and severe vascular complications.

The main advantage of insulin therapy as a method of treating type 2 diabetes is its impact on the main pathophysiological defects inherent in this disease [6, 8, 10]. First of all, this concerns compensation for the lack of endogenous insulin secretion against the background of a progressive decline in β-cell function.

Indications for insulin therapy in patients with type 2 diabetes

Signs of insulin deficiency (ketosis, weight loss).
Acute complications of diabetes.
Newly diagnosed diabetes with high levels of glycemia on an empty stomach and during the day, without taking into account age, expected duration of the disease, body weight.
Acute macrovascular diseases, the need for surgical treatment, severe infections and exacerbation of chronic diseases.
Newly diagnosed type 2 diabetes in the presence of contraindications to the use of oral hypoglycemic drugs (impaired liver function, kidney function, allergic reactions, hematological diseases).
Severe dysfunction of the liver and kidneys.
Pregnancy and lactation.
Lack of satisfactory glycemic control during therapy with maximum doses of PSSP in acceptable combinations along with adequate physical activity.

Recently, doctors have realized the need for insulin therapy to eliminate glucose toxicity and restore the secretory function of β-cells with moderate hyperglycemia. In the early stages of the disease, β-cell dysfunction is reversible and endogenous insulin secretion is restored with a decrease in glycemia. Early insulin therapy in patients with type 2 diabetes, although not traditional, seems to be one of the possible options for drug treatment in case of poor metabolic control at the stage of diet therapy and physical exercise, bypassing the PSSP stage. This option is most justified in patients who prefer insulin therapy to other glucose-lowering drugs, patients with underweight, and also in cases of latent autoimmune diabetes of adults (LADA).

Successful reduction of hepatic glucose production in type 2 diabetes requires inhibition of two processes: gluconeogenesis and glycogenolysis. Since insulin administration can reduce gluconeogenesis and glycogenolysis in the liver and improve peripheral insulin sensitivity, it becomes possible to optimally correct the main pathogenetic mechanisms of type 2 diabetes. The positive effects of insulin therapy in patients with type 2 diabetes mellitus are:

reduction of fasting and postprandial hyperglycemia;
decreased gluconeogenesis and glucose production by the liver;
increased insulin secretion in response to food intake or glucose stimulation;
suppression of lipolysis in the postprandial period;
suppression of glucagon secretion after eating;
stimulation of antiatherogenic changes in the profile of lipids and lipoproteins;
reduction of nonspecific glycation of proteins and lipoproteins;
improvement of aerobic and anaerobic glycolysis.

Treatment of patients with type 2 diabetes is primarily aimed at achieving and long-term maintenance of target levels of HbA1c and glycemia both on an empty stomach and after meals, which leads to a reduction in the risk of development and progression of vascular complications.

Before starting insulin therapy for type 2 diabetes, it is necessary to teach patients methods of self-control, review the principles of diet therapy, and inform patients about the possibility of developing hypoglycemia and methods for its relief [1, 4, 15]. Insulin therapy, depending on the indications, can be prescribed to patients with type 2 diabetes for both short and long periods of time. Short-term insulin therapy is usually used for acute macrovascular diseases (myocardial infarction, stroke, CABG), operations, infections, exacerbation of chronic diseases due to a sharp increase in the need for insulin during these periods, which usually occurs when tableted glucose-lowering drugs are discontinued [7, 9, 15]. In acute situations, the use of insulin quickly reverses the symptoms of hyperglycemia and the adverse effects of glucose toxicity.

Currently, there are no clear recommendations regarding the choice of initial dose of insulin. Basically, the selection is made based on an assessment of the clinical condition, taking into account the daily glucose profile and the patient’s body weight. The need for insulin depends on the insulin secretory ability of β-cells, reduced against the background of glucose toxicity, and the degree of insulin resistance. Patients with type 2 diabetes and obesity with varying degrees of insulin resistance may require 1 or more units of insulin per 1 kg of body weight per day to achieve metabolic control. The most commonly prescribed bolus insulin therapy is when short-acting insulin (or a human insulin analogue) is used several times a day; a combination of short-acting and intermediate-acting insulin (at bedtime or twice a day) or a long-acting insulin analogue (at bedtime) is possible. The number of injections and the daily dose of insulin depend on the level of glycemia, diet and general condition of the patient.

Temporary long-term insulin therapy (2–3 months) is prescribed in the following situations [9, 13]:

if there are temporary contraindications to taking oral glucose-lowering drugs;
during long-term inflammatory diseases;
in case of glucose toxicity and the need to restore the secretory function of β-cells.

In such cases, short-acting insulin (2-3 times) and long-acting insulin are prescribed at bedtime or twice a day under glycemic control, and PSAPs are usually discontinued.

After elimination of glucotoxicity, with stable normalization of glycemic indicators, a decrease in HbA1c levels, positive dynamics in the general somatic status of the patient and preserved endogenous insulin secretion against the background of temporary insulin therapy, PSSPs are gradually prescribed under the control of glycemia, and the daily dose of insulin is slowly reduced. Another option is combination therapy with insulin and PSSP.

With reduced endogenous insulin secretion, insulin monotherapy is prescribed.

In the treatment of type 2 diabetes, there are several treatment options, both combined with tablet drugs and insulin monotherapy. The choice, accordingly, is made on the basis of the doctor’s clinical experience, taking into account the characteristics of the patient’s somatic status, concomitant diseases and their drug therapy. Most often, for type 2 diabetes, combination therapy with insulin and tableted glucose-lowering drugs is used, when oral monotherapy does not achieve adequate glycemic control. Options for combination therapy are the following combinations: sulfonylurea derivatives and insulin, meglitinides and insulin, biguanides and insulin, thiazolidinediones and insulin [2, 11, 14].

The advantages of combination therapy include better patient motivation, rapid resolution of glucose toxicity, improved sensitivity of peripheral tissues to insulin, and increased endogenous insulin secretion.

The positive effect of combination therapy for diabetes is not only the achievement of glycemic control, but also a reduction in the daily dose of tablet drugs, the possibility of using small doses of insulin and, accordingly, less weight gain [7]. The insulin therapy regimen for combination treatment may include, in addition to the previous oral therapy, one injection of intermediate-acting insulin before bedtime, which effectively suppresses excess glucose production by the liver and normalizes fasting glycemia. According to our data and the literature, the average insulin requirement during combination therapy is 0.2–0.5 U/kg body weight in patients with normal weight and reaches 1 U/kg body weight or more in overweight patients. It is necessary to follow certain steps in carrying out insulin therapy in patients with type 2 diabetes [8]. At the first stage, a starting dose is prescribed in the form of a single injection of intermediate-acting insulin 0.2–0.3 IU/kg body weight (in the elderly 0.15 IU/kg body weight), on average 8–12 IU before bedtime, if necessary, administering insulin before breakfast. The next step is to titrate the insulin dose every 3-4 days to achieve individual metabolic control parameters. It is recommended to increase the dose by 6-8 IU of insulin for fasting glycemia of more than 10.0 mmol/l, by 4-6 IU for glycemia of more than 8.0 mmol/l, and by 2 IU for glycemia of more than 6.5 mmol/l . The duration of the titration period is usually 6–12 weeks, during which time weight dynamics are regularly assessed; if the dynamics are negative, the caloric content of the diet is reduced and, if possible, physical activity is increased. If a single injection of insulin does not provide adequate glycemic control, a double injection of long-acting insulin or ready-made insulin mixtures in a two- or three-fold administration mode can be recommended [14]. At the next stage, the tactics of further treatment are determined, the abolition of insulin therapy and monotherapy of PSSP or the continuation of combination therapy. In cases of unsatisfactory metabolic control and an increase in the daily dose of insulin by more than 30–40 units, insulin monotherapy is indicated.

Insulin monotherapy in patients with type 2 diabetes is carried out both in the mode of traditional insulin therapy and intensified insulin therapy (basal-bolus). Significant progress in diabetology is associated with a wide arsenal of different types of insulin, and practitioners have the opportunity to choose treatment, meeting the needs and capabilities of the patient. In the treatment of type 2 diabetes, any insulin therapy regimen is applicable that can successfully control hyperglycemia and avoid unwanted hypoglycemia.

Possible options for insulin therapy regimens

One injection of intermediate-acting insulin or long-acting insulin analogue at bedtime or before breakfast; a ready-made mixture of insulin in a ratio of 30:70 in one injection mode (before breakfast or before dinner) or 2-3 injections (before breakfast and before dinner, or before breakfast, before lunch and before dinner).
A combination of intermediate insulin (in 1-2 injections) or long-acting analogues and short-acting insulin or ultra-short-acting analogues, administered before main meals.

The most important component of insulin therapy is the use of adequate doses of insulin to ensure the achievement and long-term maintenance of target glycemic levels, and not the choice of one or another treatment regimen.

The advantage of insulin over PSSP is that early insulin therapy in patients with type 2 diabetes better preserves endogenous insulin secretion and provides more complete metabolic control (table).

The most effective prandial regulator is short-acting insulin. Subcutaneous administration of short-acting insulin preparations before meals can prevent a sharp rise in glucose levels after meals.

A significant decrease in endogenous insulin secretion during type 2 diabetes with the ineffectiveness of other previously used insulin therapy regimens requires the need for basal-bolus insulin therapy. An intensive insulin therapy regimen is possible only in patients with intact intelligence, without significant cognitive impairment, after appropriate training and subject to regular monitoring of glycemia throughout the day, including mandatory monitoring at 3 am [14]. Intensive insulin therapy is not indicated for patients who have suffered a myocardial infarction, acute cerebrovascular accident, or for persons with unstable angina [7, 9].

We have already mentioned above the revision of the indications for insulin therapy for type 2 diabetes, or more precisely, the need to expand them. As a rule, the need for insulin therapy is directly proportional to the duration of diabetes; According to some data, 10–12 years after the onset of the disease, almost 80% of patients need such treatment. Many patients who require insulin therapy but are not candidates for intensive insulin therapy can achieve good compensation with a twice-daily basal-bolus regimen.

In such cases, preference should be given to a ready-made insulin mixture in a ratio of 30: 70. The use of such a ready-made insulin mixture provides a rational and “physiological” proportion of short-acting insulin (1: 3) and medium-acting insulin (2: 3), which covers the need for both “bolus” and “basic” insulin in patients with type 2 diabetes.

The use of a ready-made mixture in a ratio of 30:70, administered using a syringe pen, seems rational, especially for elderly patients with type 2 diabetes. This insulin has an advantage over basal insulin, since treatment with basal insulin alone, in the absence of short-term insulin, is not enough to effectively control glycemia after meals. Therapy with ready-made mixtures in a ratio of 30: 70 begins with a daily dose of 0.4–0.6 U/kg body weight, usually divided equally into 2 injections - before breakfast and dinner, in some patients 2: 3 daily doses are prescribed before breakfast and 1 : 3 - before dinner. Then, if necessary, the insulin dose is gradually increased every 2–4 days by 4–6 units until target control levels are achieved.

Side effects of insulin therapy include weight gain, which is also common with all glucose-lowering drugs except metformin, and hypoglycemia. The increase in body weight observed in patients with type 2 diabetes who are on insulin therapy is primarily due to the elimination of the consequences of chronic hyperglycemia: glycosuria, dehydration, energy consumption. Other reasons include restoring a positive nitrogen balance, as well as increasing appetite. At the beginning of therapy, the need for a higher dose of insulin in some patients is due to severe insulin resistance. Methods for preventing weight gain in patients with type 2 diabetes who are on insulin therapy include patient education, keeping a food diary, reducing calorie intake, limiting salt intake and increasing physical activity.

Combination therapy with insulin and metformin has a significant advantage in limiting weight gain in overweight patients with type 2 diabetes, which is characterized not only by an additional decrease in fasting glycemia, but also by a decrease in the need for exogenous insulin (17–30%), as well as low risk of hypoglycemia, lipoprotective effect.

Severe hypoglycemia occurs much less frequently in patients with type 2 diabetes who are on insulin therapy compared to patients on intensive insulin therapy for type 1 diabetes. They occur much more often and in some cases have a relapsing course during the treatment of type 2 diabetes with certain long-acting sulfonylurea derivatives than during insulin therapy.

The main criterion for the adequacy of the insulin dose in patients with type 2 diabetes is the level of glycemia. At the beginning of insulin therapy, large doses of insulin may be required to achieve compensation for diabetes, which is mainly due to decreased sensitivity to insulin due to chronic hyperglycemia and insulin resistance. When normoglycemia is achieved, the need for insulin decreases.

The main parameters of metabolic control of type 2 diabetes are fasting and postprandial glucose levels and HbA1c level. According to the Federal Target Program "Diabetes Mellitus", the main goal of insulin therapy for type 2 diabetes is to achieve the following parameters: fasting glycemia - ≤6.5 mmol/l, glycemia 2 hours after meals - <9.0 mmol/l and HbA1c - 7 % [1].

Early and reasonable administration of insulin therapy is the main factor contributing to long-term maintenance of target glycemic levels.

The bulk of patients with type 2 diabetes are elderly people, who are characterized by decreased visual acuity, impaired motor coordination, sedentary behavior, multimorbidity and polypharmacy [5, 7, 11]. Long-term decompensation of type 2 diabetes in elderly patients predisposes to the development of acute diabetic complications, leads to the progression of vascular complications, activation of catabolic processes, decreased immunity, and worsens the course of concomitant chronic diseases and the effectiveness of their therapy [3]. In elderly patients, compensation criteria may be less stringent, given the risk of poorly recognized hypoglycemia and its adverse consequences [1, 11]. For elderly patients, glycemic targets should be strictly individualized. With an expected life expectancy of more than 10 years and intact intelligence, one should strive to achieve target glycemic levels. With a low life expectancy, the criteria for compensation for type 2 diabetes are less stringent - elimination of clinical manifestations of hyperglycemia and maintaining fasting glycemia < 9.0 mmol/l, after meals - < 11.0–13.0 mmol/l and HbA1c level - < 9 %.

The progressive deterioration of metabolic status and tolerance to improved β-cell function justify more aggressive treatment tactics for type 2 diabetes, which is justified already in the early stages of the disease. Timely and adequate insulin therapy in the form of monotherapy or in combination with tableted glucose-lowering drugs in patients with type 2 diabetes opens up broad prospects for achieving the main goals of diabetes treatment - maintaining long-term metabolic control and preventing or delaying vascular complications.

For questions regarding literature, please contact the editor.

A. M. Mkrtumyan, Doctor of Medical Sciences, Professor E. V. Biryukova, Candidate of Medical Sciences, Associate Professor N. V. Markina MGMSU, Moscow

Clinical picture of diabetes mellitus

Symptoms of this disease appear almost immediately. The range of symptoms varies greatly depending on the type of diabetes. The most pronounced signs are:

Copious and frequent urination: occurs as a consequence of the “ability” of glucose molecules to surround themselves with water molecules.
Constant thirst: large fluid losses (see point above) and high concentrations of glucose in the blood contribute to the development of this symptom.
The feeling of hunger (polyphagia) is associated with energy starvation of cells.
Weight loss is caused by the breakdown of fat and protein molecules.

After a few months, the patient begins to experience itching of the skin and mucous membranes, weakness, increased fatigue, dry mucous membranes, headache, decreased memory and attention, blurred vision, the smell of acetone from the mouth, and pustular skin lesions.

Separately, it is worth mentioning the complications of diabetes mellitus that develop when the disease is untreated or difficult to correct:

Diabetic ulcerative defects of the lower extremities
Diabetic damage to the retina of the eye, quickly leading to blindness - diabetic retinopathy
Diabetic damage to nerve endings, leading to a decrease in all types of sensitivity, the appearance of pain in the legs, palpitations, diarrhea, and movement disorders - diabetic neuropathy;
Diabetic damage to the blood vessels of the kidneys, quickly leading to the inability of the kidneys to remove toxic waste products from the body - diabetic nephropathy.

Treatment of diabetes

A decrease in the level of glycated hemoglobin by 1% reduces the likelihood of complications overall by 21%, myocardial infarction by 16%, and cerebral hemorrhage (stroke) by 44%.
It is enough to undergo a course of vascular therapy 2 times a year to stop the development of complications of diabetes mellitus.
The use of extracorporeal hemocorrection methods increases the bioavailability of prescribed medications, thereby reducing their dosage and increasing the effectiveness of therapy.

Therapy for this pathology should be comprehensive and pursue the achievement of individual goals set by the doctor depending on the length of the disease, age, existing complications or concomitant diseases, especially cardiovascular ones:

Regular self-monitoring of glucose levels, which should correspond to the set goals
Prevention and regression of blood vessel lesions.
Restoring full blood supply to organs and tissues of the body.
Prevention of complications.

At the Yauza Clinical Hospital, treatment of diabetes mellitus and its complications is carried out using carefully selected drug therapy (prescription of insulin or drugs that improve the uptake of glucose by cells, symptomatic treatment depending on the clinical picture) and regulation of the patient’s diet. And also with the help of innovative methods of extracorporeal hemocorrection (EG), which make it possible to prevent, stop the progression or even reduce the severity of vascular complications of diabetes - the main cause of its other consequences (pathologies of the heart, kidneys, eyes, feet).

Extracorporeal hemocorrection in the treatment of diabetes mellitus

EG allows:

cleanse the plasma of substances that damage the vascular wall and nerve fibers in diabetes, and also reduce the concentration of these substances in tissues,
reduce blood viscosity and its tendency to form blood clots,
restore red blood cell membranes and their properties for delivering oxygen to tissues,
activate blood microcirculation in tissues and internal organs, restoring their normal functioning,
improve the impaired sensitivity of body tissues to insulin.

Two methods are used:

Cryoapheresis: blood plasma is exposed to low temperatures in the presence of a certain substance (heparin), causing the appearance of cryoprecipitate, which includes a whole range of harmful substances; then it is removed, and the purified plasma is returned to the patient.
Cascade plasma filtration: plasma passes through a filter that has a membrane with a certain pore size. This filter removes harmful substances from the plasma, and the purified plasma is returned to the patient's body.

After the first session of the chosen procedure, experts note an improvement in the state of health in most patients, and the course of treatment provides the following effects:

The progression of diabetic changes in the retina, glomeruli of the kidneys, blood vessels of the heart, brain, lower extremities, and peripheral nerves is inhibited.
The pain syndrome associated with ischemia and neuropathy loses its intensity or disappears altogether.
Trophic ulcers heal or decrease in size.
Blood glucose levels decrease.
Signs of diabetic nephropathy become less pronounced, kidneys work better.
Vision improves.
Working capacity may be restored.

Extracorporeal hemocorrection is not a panacea, but this technique reduces the risk of developing complications such as diabetic foot, retino- and nephropathies, disruption of the nervous system, and patient disability. And comprehensive treatment of diabetes mellitus returns the patient the opportunity to do what he loves and lead an active lifestyle.

NEW TREATMENT METHODS FOR TYPE 1 DIABETES

Combination therapy eliminates the need for insulin replacement therapy.*

Below is information for specialists, information for patients in the section: “Make an appointment.” Guarantees, as in all medical institutions, are provided only for the quality of medical procedures performed in a hospital/day hospital setting within the framework of a license to practice medicine.

For the treatment of type 1 diabetes mellitus, only insulin replacement therapy has been used for a long time. The goal of such therapy is to imitate as accurately as possible the normal functioning of the pancreas, which is difficult to achieve in full, especially before the age of 18. At the same time, the issue of restoring normal pancreatic function was not considered; therefore, such therapy cannot be called treatment. Recent publications in reputable scientific publications show that compensation alone is not enough, so we suggest familiarizing yourself with diabetes treatment methods, which consist of two important components:

COMPENSATION (included in the cost of the initial consultation).

SUBSCRIPTION SERVICE (leading to the cancellation of replacement therapy against the background of normoglycemia, it is necessary to conclude an additional agreement).

*This is not a public offer, there are contraindications, consultation with a specialist and an interclinical consultation are required. Guarantees for the provision of medical services. There are no 100% guarantees of cures in medicine; we do not create false hopes. We recommend getting a “second opinion” first.

SPECIAL REGISTRATION PROCEDURE FOR THOSE WHO HAVE AN ILLNESS EXPERIENCE OF UP TO 120 DAYS

There is such a thing as the “immunological window of opportunity,” when intervention is most effective in treating the disease.

For those whose illness history (from the moment of manifestation) is less than 120 days, a special procedure for conducting a consultation without a queue applies. The biological features of the immune response and the insulin synthesis algorithm have a certain time dependence, which makes it possible to use this in the therapy process. They try to admit such patients within 30 days after submitting documents, subject to availability, since the effectiveness of therapy is much higher.

Some may think that treatment in the honeymoon phase masks the results of treatment because there are still viable B cells present at the onset of the disease, but this is not the case. It has been proven that some of the B cells persist after manifestation even for 10 years!

Our task is to help not only restore the number of capable B cells, but also stop the body’s autoimmune reaction - that is, eliminate the very cause of diabetes.

SCIENCE CONFIRMED - TYPE 1 DIABETES IS NO LONGER A “WAY OF LIFE”, BUT A DISEASE THAT IS CURED In January 2021, the authoritative scientific journal Nature published a study that confirms and explains the direction of work of Yu.A. Zakharov. It is interesting that over the past three years this is not the only publication mentioning the results of earlier works and explaining the principle of operation of certain proposed methods. An international team of researchers has described a new approach to treating diabetes. According to experts, in the future the human body, “with the right settings,” will be able to cope with the disease itself. In the human pancreas there are alpha, beta and delta cells, united in clusters. Each of the three types is responsible for the production of “its own” hormone to regulate blood sugar levels. Alpha cells produce glucagon, which increases sugar levels. Beta cells produce insulin, which reduces glucagon levels. Delta cells produce somatostatin, which controls the secretion of both glucagon and insulin. Patients with diabetes have impaired beta cell function, which means their blood sugar is constantly elevated. To restore balance, you have to resort to insulin injections. It turned out that if beta cells are completely removed, their neighbors - alpha cells - take over the function of producing insulin. The number of such “helpers” is small, only 1-2%. But this was enough to maintain normal blood sugar levels. It is noteworthy that alpha cells do not provide a similar service if the body has about half of beta cells working. According to the researchers, this suggests that the so-called change in cellular “personality” is not a passive process, but rather the result of processing signals coming from other cells. In other words, signaling from beta cells prevents alpha cells from producing insulin: the latter probably “think” that in this case the help of neighboring cells is not required. Based on this, scientists have suggested that the process of intercellular signaling can be influenced. For this they developed a special drug. Preclinical trials confirmed the guess: the drug was shown to increase insulin-producing cells by up to 5%. Thus, the authors of the work proved that “self-healing” of the body from diabetes is quite possible. However, experts have discovered that the alpha cells in the pancreas, which produce glucagon, can change their “personality” and adapt to perform the tasks of their neighbors, the beta cells. www.nature.com/articles/s41556-018-0216-y

WHY ARE PATIENTS WHO MANIFESTED WITHIN THE LAST 120 DAYS ACCEPTED WITHOUT A QUEUE? There are so-called “WINDOWS OF OPPORTUNITY” for immunological interventions, see:

www.ncbi.nlm.nih.gov/pmc/articles/PMC6105696/

MONOCLONAL ANTIBODIES in type 1 diabetes Many patients with diabetes mellitus (both type 1 and type 2) require therapy to maintain normal fasting glucose levels. Biophysical studies with cultured cells expressing human INSR showed that XMetA acts allosterically and does not compete with insulin for binding to its receptor. XMetA was found to function as a specific partial agonist of INSR, causing tyrosine phosphorylation of INSR but not IGF-IR. Although this antibody activated metabolic signaling, leading to increased glucose uptake, it did not activate Erk or induce cancer cell proliferation. In an insulin-resistant, insulinopenic model of diabetes, XMetA markedly reduces elevated fasting blood glucose levels and normalizes glucose tolerance. After 6 weeks, there was a significant improvement in HbA1c, dyslipidemia, and other diabetes features. It should be noted that hypoglycemia and weight gain were not observed during these studies. In summary, these studies indicate that allosteric monoclonal antibodies may be novel, ultra-long-acting agents for regulating hyperglycemia in diabetes.

The author of the method, YURI ZAKHAROV, IS NOT THE ONLY WHO CONSIDERS IMMUNOTHERAPY FOR THE TREATMENT OF TYPE 1 DIABETES IN CHILDREN AS THE MOST PROMISING DIRECTION . Domestic scientists have long ago (2005) published works and even defended dissertations on the immunotherapy of type 1 diabetes in children and adolescents. Moreover, there is no secret in this. It’s just that the conventional majority stubbornly tries not to notice obvious things. Yes, there are new targeted drugs for IL1, 6, 18, etc. But there are also proven “ancient” regimens: • Methotrexate 10 mg/m2, once a week; start - 1 month before the first infliximab infusion; further - throughout the entire course of therapy; • Infliximab 3 mg/kg, as an intravenous infusion (according to the instructions for use of the drug): weeks 0, 2 and 6, and then every 6 weeks. CONCLUSIONS: Combination therapy with infliximab and methotrexate leads to restoration of the mass and functional activity of B cells in children suffering from type 1 diabetes, as determined by an increase in the level of C-peptide. Reduced insulin requirements by 6 months. therapy; Increase in C-peptide level or maintain it at the initial level (but not less than 0.1 pmol/l) by 6 months. therapy.

www.dissercat.com/content/immunosuppressivnaya-terapiya-v-kompleksnom-lechenii-sakharnogo-diabeta-1-go-tipa-u-detei-0

A MORE STRICTURE APPROACH TO CALCULATIONS IS CONFIRMED BY YURIY ZAKHAROV NUTRITION FEATURES IN DIABETES MELLITUS In this case we are talking about both type 1 and type 2 diabetes. There are publications that prove that when preparing a diet and calculating the dose of insulin drugs, it is necessary to take into account not only carbohydrates, although we have been recommending this to our patients since 2000, some clinicians sincerely do not understand why. The fact is that here the process can be viewed from two sides: the body’s reaction to neglect of counting, say, protein and fats (fish/poultry/meat and cheese) - it has been proven that in the long term this leads to decompensation and an increase in the level of glycated hemoglobin. And the reaction of increasing insulin levels in response to this or that food. Here are data on increases in different types of protein and fats. An illustrative comparison: the reaction to beef is similar to the reaction to brown rice.

www.ncbi.nlm.nih.gov/pubmed/20060863

ncbi.nlm.nih.gov/pubmed/18249201

www.ncbi.nlm.nih.gov/pubmed/9356547

ncbi.nlm.nih.gov/pubmed/9356547

idp.u.washington.edu/idp/profile/SAML2/Redirect/SSO;jsessionid=C287D03CB04AA95E48FCFCAF0C12C13F.idp01?execution=e1s1

Do not listen to those who say that insulin administered “from the outside” (exogenous) will “kill” all remaining B-cells and calmly carry out the insulin therapy prescribed at the place of hospitalization. Otherwise, you will be able to maintain a more or less normal glycemic level for only a few months, but then a state of decompensation will set in and it will be more difficult for us to work with you.

Do not refuse insulin therapy under any circumstances - there is no problem in compensating for your condition and later reducing and then possibly canceling insulin therapy. Strictly follow all orders of endocrinologists-diabetologists at the place of primary observation!

Do not try to “brew herbs” or exhaust yourself with physical activity with dietary restrictions (ketogenic/low-carb diet) - this will also lead to decompensation and serious consequences after several months of compensation.

There are a large number of websites offering glycemic reduction through a low-carb diet (according to Dr. Bernstein). This gives a short-term effect and threatens complications. Especially if it is a low-carbohydrate, high-fat diet, which in some cases can be used by adults, but is completely unsuitable for children, moreover, as the latest (2021) publications show, it is harmful.

We will introduce you only to safe, scientifically proven methods. For many years, we have been in contractual relations with hospital centers in the Russian Federation and three clinics outside the Russian Federation, which have all the necessary documentation to provide high-tech medical care, but no matter how effective and high-quality this care is, the patient must be observed and actively helped in the process recovery for a long time, which is impossible in the conditions of even the best hospital.

We will help you:

until entering the “controlled honeymoon” state (stable remission without the use of insulin therapy) and at least five years after entering this state;
We organize the closest contact with the attending physician (clinic), transfers, air ambulance, translators.

The information presented is not a public offer; there are contraindications and age restrictions; all recommendations must be agreed upon with the attending physician at your place of residence. There are no 100% guarantees, cures, or unreasonable hopes. This is a very long and serious work.

“Managed Honeymoon” method (RF Patent), in addition to achieving stable compensation, normalizing carbohydrate metabolism and preventing complications:

Allows you to prevent the development of an autoimmune reaction against B cells in individuals with a high genetic risk of insulin-dependent diabetes mellitus (close relatives), especially HLA-DQA1/DQB1, in addition to the INS genes (marker-23HphI) and PTPN22 (marker R620W) and block the already begun autoimmune reaction in patients diagnosed with type 1 diabetes mellitus;

Restores normal activity of the endocrine pancreas and immunity (control of glycated hemoglobin, C-peptide, autoantibodies to insulin, to isoforms of glutamate decarboxylase with a molecular weight of 65,000 and 67,000 and to phosphotyrosine phosphatase);
In the case of normalization of the level of glycemia and metabolic processes in the body, restoration of the level of basal C-peptide to normal, reduction of autoantibody titers, increase in the intensity of CD95 expression and a decrease in the intensity of CD95L expression on lymphocytes (special studies), in the absence of complications and emerging systematic conditions of hypoglycemia, a decrease is carried out dosage of externally administered insulin followed by complete withdrawal.

In the photo: Dr. Lewis collects adipose tissue for subsequent mobilization of mesenchymal stem cells.
This is achieved:

A more thorough approach to the differential diagnosis of diabetes, not only with the maximum possible study of the HLA genotype, but also the markers: -23HphI (rs689) of the INS gene and R620W of the PTPN22 gene;
In some cases, against the background of cell therapy with autologous stem cells, an experimental model of extracellular regulation (using EMR) leading to endogenous stimulation of insulin in B cells due to increased expression of the cathelicidin LL-37 peptide gene group was the first to draw attention to this was the group of Prof. Fraser Scott (Canada);
The use of a pharmacological drug, used in clinical practice for a long time in the territory of the Russian Federation, (certified), which has a mild, controlled effect regulating autoimmune processes so that it practically neutralizes the destructive reaction of one’s own immunity to B cells (Confirmed by the scientific group of Nepton S. ( Toronto) and “transforming” duct-lining precursor cells into alpha, and then into B-like cells (The mechanism was studied by the research group of the PAR INSERM Institute France;
The use of special domestic equipment of a new generation, entered into the register of medical equipment and having the appropriate certificates to achieve rapid compensation and active treatment of complications of diabetes mellitus, targeted stimulation of betatrophin in the liver (recommended for strict indications);
Prevention of autoimmune attack by HLA (capsid protein 1 (VP1));
Active control using a pharmaceutical drug that controls the level of TXNIP, approved in the Russian Federation and used for more than 10 years;
Strict control of lifestyle, nutrition, glycemic levels;
An individual approach to the treatment of diabetes mellitus (in addition to replacement therapy), the manifestation of which arose due to various factors (stress, viral infection, food poisoning, routine vaccination, nutrition, parasitic infestations, regardless of age;
An individual approach when prescribing some traditional methods of scientific medicine;
The use of experimental methods for persons over 18 years of age in the Russian Federation (Moscow) and under 18 years of age in a representative clinic in Thailand (Bangkok, Pattaya) of cell therapy with various lines of stem cells, controlled gene expression, immunotherapy, which significantly speeds up the process of discontinuing insulin therapy (clinics consist with us in official contractual relations and have all the necessary permits).

It has been established that intensive immunosuppressive therapy followed by transplantation of autologous stem cells (ASCTs) leads to an increase in immunological tolerance and, thus, increases the production of intrinsic insulin in type I diabetes mellitus. More details in the new book by Yuri Zakharov and the work of: K. Рrata, G De Santis, MC Oliveira et al. Mobilisation, collection, infusion and granulocyte recovery of PBSC in early onset type 1 diabetes mellitus submitted to autologous haematopoietic cell transplantation - update of outcome results // Bone Marrow Transplantation, Vol. 39, Supl. 1, p. 19.

Immunotherapy of diabetes mellitus for persons over 18 years of age with drugs: Ustekinumab – regulating IL12, 13. Interleukin-12 is produced by B cells and macrophages. Its ability to induce THO cells into inflammatory T cells (TH1) is directly related to the formation of the immune system. IL-13 is a cytokine that can inhibit the functions of macrophages and is produced in CD4+, CD8+ T cells, neutrophils and some non-immune cells. IL-13 blocks the production of anti-inflammatory cytokines by macrophages, as well as nitric oxide molecules, which are an important component of the cytotoxic effects of these cells. At the same time, IL-13 stimulates the differentiation of T cells and the secretion of immunoglobulins by plasma cells*. *Recommended on a limited basis for strict indications. GABA (Gamma-aminobutyrate or gamma-aminobutyric acid, GABA) is one of the most important neurotransmitters in the brain, GABA restores β-cell mass and modifies the course of the disease. Suppresses insulitis and systemic inflammation by suppressing cytokine production. The regenerative function of β-cells due to the regulation (suppression) of autoimmune reactions makes GABA a promising drug for clinical use in type 1 diabetes.
Outpatient targeted therapy in the presence of HLA-DQ8 in the Russian Federation;
Inpatient immunotherapy is strictly performed in a day hospital setting and is performed in the Kingdom of Thailand.
The use of teplizumab (a humanized mAb against CD3), as well as antibodies to CD20, CD2, rituximab, CD80, CD86 and abatacept.

Drugs that target CD3, which is a T cell coreceptor and plays an important role in antigen recognition. CD3 antibodies target the T cell receptor (TCR)-CD3 complex on regulatory T cells, resulting in internalization of the complex. This process temporarily creates “silent” T cells and halts the immune response. In activated effector T cells, CD3 antibodies serve as triggers for the apoptotic signaling cascade, resulting in the depletion of about 25% of T cells. Teplizumab, a humanized monoclonal antibody (mAb) against CD3, promotes insulin production and increases HbA1c levels. In 2019, a clinical trial determined that treatment with teplizumab slowed the progression of T1DM by two years in a high-risk T1DM population, leading the FDA to designate teplizumab's breakthrough therapy as the first immune therapy for T1DM. Additional drugs to suppress the T-cell immune response have been tested for the treatment of T1DM. These include antibodies to CD20, CD2, rituximab, as well as CD80, CD86 and abatacept. These drugs had a positive effect on C-peptide levels.

The individual approach and personalized therapy is the main problem of the possibility of disseminating and replicating this methodology in clinical practice. For therapy using our method, it is necessary to know not only the consequence (complete or partial failure of the endocrine part of the pancreas), but also the possible cause of the manifestation, which is a trigger mechanism that triggers a cascade of reactions, the result of which is an absolute deficiency of endogenous insulin. Today, in clinical practice, virtually only replacement therapy with insulin drugs is performed; our task is to restore the normal activity of the endocrine part of the pancreas and prevent/stop the body’s autoimmune reaction.

What does a long-term subscription service of three years with subsequent dispensary observation for at least five years imply?

Achieving a long-term state of stable compensation and, if necessary, reducing the dosage of insulin medications to prevent hypoglycemia;
In the event of prolonged episodes of hypoglycemia against the background of stable compensation in the absence of complications and normalization of the body's metabolic processes, discontinuation of replacement therapy drugs (insulin therapy);
Long-term dynamic observation of patients who do not use replacement therapy to exclude relapse.

Warning (on the issue of terminology, the concept: “cure of diabetes mellitus”), the average duration of observation is at least three years, if during the specified period the patient is in a state of stable compensation without insulin replacement therapy, then at the place of residence, in most cases cases, disability is removed, but the diagnosis and dispensary registration are not removed, despite the cessation of insulin replacement therapy and normoglycemia. As a result, it was decided to replace the phrase: “cure of diabetes” with another term: transfer to a “Managed honeymoon” state.

Please be careful, we do not offer: “instant and miraculous healings.” We adhere to the principles of evidence-based medicine.

We have been working since 1995. Over the past ten years, we/our partners have not had any negative dynamics. That is, the vast majority of patients do not use insulin therapy for more than 5 years.

NOTE: Video images (interviews), links to scientific publications are posted on the site for SPECIALISTS and are not intended for patients, in order to avoid unreasonable motivation for using such technologies. There are strict indications and contraindications. Consultation with the attending physician and an interclinical consultation are required.

In connection with the declared conflict of interest, Yu.A. Zakharov reports the following: paid “reviews” of our fictitious patients or slanderous messages periodically appear on the Internet, which will be consistently prosecuted within the law. For an example, see the attachment of the Court's decision.

Why us

Doctors. Specialists of the highest qualification category, with academic degrees and extensive experience in practical and scientific work.
Accurate diagnosis. Informative and painless examination: ultrasound of the abdominal organs, blood vessels, the whole range of necessary laboratory tests - determination of blood glucose levels and the amount of glycated hemoglobin, diagnosis of metabolic disorders and the presence of signs of atherosclerosis, etc.
Complexity. Comprehensive treatment developed specifically for you, taking into account the full clinical picture with the participation of all necessary specialists: endocrinologist, nutritionist, therapist, cardiologist, ophthalmologist, etc.
High tech. High-tech treatment using extracorporeal hemocorrection methods, which reduces the risk of developing microangiopathies (diabetic foot, visual impairment, renal failure) and makes it possible to increase tissue sensitivity to insulin and reduce the dosage of medications.
Diabetes Check-up. The opportunity to be examined yourself and have your loved ones checked using the “Diabetes Check-up” program in order to eliminate even the slightest chance of developing this pathology in your loved ones.
Convenience and comfort. All diagnostic and treatment units are located in a single complex of our hospital, which significantly saves the time and effort of our patients.