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The use of metformin: from diabetes, old age and not only ...

I was interested in the topic of type 2 diabetes for a long time. It so happened that a close relative died of diabetes caused by stress.

Then my grandmother got sick with diabetes at the age of 80, and my mother at 52 with the onset of menopause. I did not avoid this fate even though I never loved sweets, never took strong alcoholic drinks and, of course, did not smoke. So I did not want to believe that my life would begin with this chronic disease.

Of course, the first thing I began to refresh the knowledge of herbs to reduce blood sugar levels. Deeper began to delve into the mechanism of action of drugs for diabetics, to get acquainted with new research about them. Then I learned a lot about metformin, a popular, long-known sugar-lowering drug in pills. I must say that his fame is growing every day.

Metformin was opened in 1922, and was widely used only in the late 90s. Endocrinologists prescribe it for the treatment of type 2 diabetes. Also known destination with overweight, obesity, with polycystic ovaries and infertility.

The World Health Organization has recognized metformin as one of the most effective medicines.

And although his popularity is high, the effect of metformin is not yet fully understood: and today, studies are being conducted that reveal new facets of his "talent". This and wanted to pay a little attention today.

Known mechanisms of action of metformin

The most important action of metformin is the suppression of glucose production by the liver.

Metformin activates the secretion of liver enzyme AMPK, which is responsible for the metabolism of glucose and fat. This activation leads to the effect of suppressing glucose production in the liver. That is, extra glucose due to metformin is not formed.

In addition, metformin increases sensitivity to its own insulin and increases peripheral glucose uptake (with insulin, glucose is delivered to all cells of the body and becomes a source of energy), increases fatty acid oxidation, reduces glucose absorption in the gastrointestinal tract.

Delaying metformin glucose absorption in the gastrointestinal tract allows you to maintain lower levels of glucose in the blood after a meal, as well as to increase the sensitivity of target cells to their own insulin. This property of metformin allows its use in pre-diabetes - to prevent diabetes with a propensity to such.

After oral administration, metformin is absorbed in the gastrointestinal tract, its active action begins after 2.5 hours. Metformin is eliminated by the kidneys after some 9-12 hours. It should be noted that metformin can accumulate in the liver, kidneys and muscles.

The use of metformin start with taking 500-850 mg 2-3 times a day during or after meals. A further gradual increase in dose is possible depending on the results of analyzes of glucose concentration in the blood.

Maintenance dose of metformin is usually 1500-2000 mg / day.

To reduce the side effects of the gastrointestinal tract, the daily dose is divided into 2-3 doses. The maximum daily dose of 3000 mg / day, divided into 3 doses.

The original drug is Metformin French Glyukofazh.

Generic Glyukofazha: Metformin firms Ozon (Russia), Siofor, etc.

Still, to reduce the side effects of metformin (gastrointestinal disorders) and improve the quality of life of patients with type 2 diabetes in France, a long-acting metformin was developed and released under the name Glucophage Long with delayed absorption of active metformin. Glucophage long can be taken 1 time per day, which of course is much more convenient for patients.

The absorption of prolonged metformin is in the upper gastrointestinal tract.

Side effects of metformin

• With long-term administration of metformin, a decrease in the absorbability of vitamin B12 may be observed. If megablastic anemia is detected, additional intramuscular administration of vitamin B12 is necessary.
• There are often problems with the gastrointestinal tract (nausea, vomiting, diarrhea (diarrhea), abdominal distension, abdominal pain, change in taste, loss of appetite). In this case, metformin should be taken with food to reduce irritation of the gastrointestinal tract.
• With prolonged use, as well as when taking metformin with large doses of alcohol, lactoacidosis can occur - a high level of lactic acid in the blood, which can threaten the patient's life. Occurs more often with an overdose of metformin and in patients with renal insufficiency.
• Very rarely, skin reactions - erythema, rash, pruritic dermatosis.
• Very rarely, liver dysfunction, hepatitis, disappearing when the drug is canceled.

Metformin is prescribed only by a doctor’s prescription, and his leave is assumed only by prescription.

Unique properties and new uses of Metformin

Metformin is being researched in many countries: the Internet is replete with reports of its newly discovered unique properties. So, what are the uses of metformin and cautions today?

• Metformin prevents and controls type 2 diabetes.
• Metformin does not reduce sugar immediately after taking the first dose. Its action begins after 2.5 hours. Decrease in blood glucose occurs in a few days - from 7 to 14 days.
• Does not cause hypoglycemia in therapeutic doses, with overdose - extremely rare.
• Metformin can be combined with insulin, mannil, etc.
• Dr. R. Bernstein (USA) claims that metformin reduces the risk of cancer and also suppresses the hormone of hunger, thereby helping to stabilize the weight.
• According to research by Craig Kerry, metformin can be successfully used in complex treatment of oncology and cardiovascular diseases.
• Metformin promotes the growth of new neurons in the brain and spinal cord.
• In Alzheimer's disease, the number of nerve cells in the hippocampus, the part of the brain where new memories are formed, is significantly reduced. Experience shows that taking 1000 mg of metformin per day for people weighing 60 kg significantly improves the ability to create new memories.
• There is also an opposite opinion that metformin itself increases the risk of dementia. Taiwanese researchers under the direction of Dr. Ichun Kuan conducted a study of 9,300 patients with type 2 diabetes, analyzing the effects of metformin on the control group of patients. Their conclusion: the longer the patient took Metformin and the higher the dose, the higher the likelihood of developing dementia. This opinion is questioned by many experts.
• Metformin suppresses systemic inflammation - one of the causes of aging, protects the heart and blood vessels from aging.
• The drug improves cholesterol, reducing low-density harmful cholesterol.
• Metformin reduces elevated levels of liver enzymes and can treat non-alcoholic fatty liver in patients with diabetes mellitus.
• Reduces the risk of mortality from a bunch of diabetic complications by about 30%.
• Metformin has no absolute contraindications for diseases of the kidneys, liver, chronic heart failure. If there are any, the doctor adjusts the dose, and the patient continues to take Metformin. However, the decision of the doctor in severe pathologies of the heart, liver and kidneys of the patient may not be in favor of taking this drug.
• Metformin is able to reduce the level of vitamin B12, so when it is used it is necessary to monitor blood parameters.
• It is used in the absence of ovulation in patients with infertility.
• Metformin stabilizes weight when recruiting, caused by antipsychotic drugs.
• Can not be combined with alcohol in order to avoid complications such as lactic acidosis (a deadly complication).
• Metformin is a candidate for becoming a cure for old age.
• It is being studied as a potential drug for the possible treatment of rheumatoid arthritis in patients with type 2 diabetes.

From this list, new uses of metformin (except for type 2 diabetes), which have been investigated by scientists, are highlighted. For the sake of justice, I must say that many of these new indications for use disproved the work of other researchers. So, experts are still arguing - reduces the weight of metformin or not. Some studies indicate successful stimulation of ovulation with metformin, while others tell about the minor effects of the drug on the reproductive system.

Therefore, it is impossible to take this drug as an absolutely healthy remedy for aging and from aging, although the media advertise metformin as an old drug that is ready to become a new "rejuvenating apple." Metformin has its own list of indications, which in our country (as well as all over the world) mainly consists in the treatment of type 2 diabetes.

Metformin prolongs life

In people and animals with insulin resistance and high blood pressure, old-fashioned medicine Metformin protects the brain from aging, reduces the level of senile inflammation, slows down the aging of the heart and blood vessels, reduces the likelihood of some types of cancer, reduces weakness in old age, promotes weight loss, reduces the level of depression, prevents nephropathy of the kidneys, improves male potency, prevents osteoporosis in overweight patients, helps reduce infectious diseases of the respiratory tract , improves the effectiveness of complex therapy for rheumatoid arthritis, reduces the size of small solid thyroid nodules, reduces the increased thyroid stimulating hormone, prevents an increase in thyroid gland size, reduces liver enzymes, improves cholesterol and atherogenic index, reduces inflammatory and fibrous conditions in the lungs, significantly reduces mortality and prolongs a life. Metformin has a good safety profile if prescribed by a doctor and not used for self-medication.

A cure for old age, metformin, as scientists believe, is the prototype of the future cure for aging. This is a well-studied research tool that retards the development of many senile diseases.

Metformin protects the brain of animals from aging

As a result of aging, a variety of senile problems develop in the brain. For example, in Alzheimer's disease, the number of nerve cells in the hippocampus is significantly reduced. In experiments on rodents, as well as with humans, it was shown that metformin activates the AMPK signaling pathway, which affects aPKC / CBP and stimulates stem cells, giving rise to new neurons (brain, spinal cord, etc.). The stem cells of rodents who use the drug Metformin, produce neurons 2 (!!!) times more intense. This leads to a noticeable increase in the number of new neurons in the hippocampus by 30%. The hippocampus is the part of the brain in which new memories are formed. And indeed, the experiments demonstrated that the ability to create new memories in experimental mice is greatly enhanced. In order to notice this effect, it is enough to consume only about 1000 mg of metformin per day for people weighing 60 kg. However, more research is needed to determine the effectiveness of the drug for the same purpose in humans.

However, the use of old-age medication metformin, as shown in the graph, reduces the absorption of vitamin B12 by 19% in 10-30% of patients, which may increase the risk of Alzheimer's disease. This fact was shown in randomized controlled trials for 4 years. Therefore, when taking metformin, it is necessary to control the level of vitamin B12 in the blood and replenish it.

The old-age cure metformin reduces the manifestations of multiple sclerosis in animals.

Metformin suppresses senile inflammation in people with insulin resistance - one of the causes of aging

The old-age cure metformin suppresses chronic inflammation as a result of increased C-reactive protein in diabetic patients. And C-reactive protein is a marker of inflammation, the high value of which is associated with increased mortality from many age-related (senile) diseases.

2016, Shandong University, China. Metformin significantly reduced the level of inflammatory markers of interleukin 6 in the blood as a result of clinical studies in people with insulin resistance.

Metformin protects the heart and blood vessels from aging in animals and people with insulin resistance

Aging of the cardiovascular system begins with vascular atherosclerosis. Then high blood pressure may develop, which overloads the heart and causes it to wear out faster. Due to overloading of the heart, hypertrophies of the heart muscle, blockade of the heart, arrhythmias and ultimately heart failure develop. The old-age medicine, metformin, slows down the development of all these manifestations of cardiac and vascular aging in mice and people with insulin resistance, slows down the development of such senile diseases as chronic heart failure, atherosclerosis, atrial fibrillation, increased arterial pressure, aortic aneurysms, peripheral arterial disease, vascular calcification.

A cure for old age metformin prevents the development of chronic heart failure. The old-age cure metformin improves cardiac function in non-diabetic rats after a heart attack, as well as in heart failure. And in patients with diabetes, it reduces all-cause mortality after a heart attack.

The old-age cure metformin inhibits the progression of atherosclerosis in mice, regardless of cholesterol metabolism. A heart attack is basically the consequences of atherosclerosis.

Old-age cure Metformin reduces the risk of Atrial Fibrillation of the heart (a type of arrhythmia) in patients with type 2 diabetes and improves heart function in people.

Metformin can reduce pulmonary hypertension, high blood pressure associated with hypertrophy of the right ventricle of the heart in mice, and also significantly weakens the hypertrophy of cardiomyocytes (heart cells) - one of the signs of aging of the heart muscle.

Metformin reduces the risk of developing an aortic aneurysm, and is also potentially useful for the treatment of peripheral arterial disease.

Metformin prevents vascular calcification in animals. The calcification of the vessels makes the arteries stiff, old and unable to stretch effectively, overloading the heart.

Metformin warns and controls type 2 diabetes

Diabetes today is seen as a model of accelerated aging. As a result, blood sugar rises, insulin sensitivity is disturbed, the liver, kidneys, nervous system, blood vessels, etc. are affected. Metformin is the number one medication in the world for treating insulin resistance.

The old-age cure metformin inhibits the end products of glycation, which arise as a result of protein glycation, one of the aging processes (glycation is active in diabetes mellitus and affects vessels).

Metformin improves cholesterol levels in diabetes, lowers elevated triglycerides, lowers LDL (bad cholesterol), increases HDL (good cholesterol), and improves atherogenic index.

Old-fashioned medicine Metformin reduces the risks of many types of cancer in mice and rats, and also suppresses the development of cancer tumors in experiments on human cell cultures and on human implants

The combination of metformin and aspirin significantly inhibits the growth of pancreatic cancer cells, inhibiting anti-apoptotic proteins Mcl-1 and Bcl-2. Caspas (caspse) are enzymes primarily responsible for cell death. The combination of metformin and aspirin significantly inhibits the growth of pancreatic cancer cells through caspse-3 activation. Metformin reduces TNF alpha STAT3 (signal transducer and activator of transcription 3) —signal protein and transcription activator from the STAT protein family. Metformin effectively inhibits STAT3 and can block the precancerous stages of bladder cancer and squamous cell carcinoma of the esophagus. Tyrosine kinase 2 is an enzyme that is involved in IL-6, IL-10 and IL-12 signaling. May play a role in antiviral immunity. A mutation in the TYK2 gene was associated with hyperimmunoglobulin E syndrome [en] (HIES) - a primary immunodeficiency characterized by an increased level of immunoglobulin E. Metformin inhibits the growth of prostate cancer by suppressing Tyrosine kinase 2. Mutations and overexpression of β-catenin are associated with many types of cancer, including hepatocellular carcinoma, colorectal cancer, lung cancer, with malignant tumors of the breast, ovaries and endometrial cancer. Metformin dose-dependently inhibits the β-catenin in breast cancer PPAR-γ - Peroxisome proliferator-activated receptor gamma. PPAR-γ regulates fat metabolism and glucose storage. PPAR-γ knockout mice do not have adipose tissue when fed on foods high in fat. Many insulin sensitizing drugs used to treat diabetes activate PPAR-γ, reducing serum glucose without increasing insulin secretion by the pancreas).

PPAR-γ metformin agonist negatively affects neuroblastoma growth. EGFR is a transmembrane protein. His hyperactivation is associated with a number of oncological diseases: squamous cell lung cancer (80% of cases), rectal cancer, glioblastoma, head and neck tumors. This protein is involved in 30% of all cancers (epithelial tissue tumors). Metformin inhibits EGFR in glioblastoma. AKT1 kinase is a key enzyme of the PI3K / AKT signaling pathway and is involved in the regulation of cell proliferation, growth and survival. The study of the functions of this enzyme pays great attention due to the fact that it acts as an oncogene in many malignant diseases. Metformin inhibits AKT1. Metformin reduced the risks of oncology and prolonged life, reducing the incidence of many types of cancer in various strains of mice prone to various cancers.

Metformin reduces the risk of many types of cancer in people with insulin resistance

After 40 years, the probability of getting cancer is growing exponentially. Insulin-like growth factor 1 (IGF-1) stimulates angiogenesis (the growth of new blood vessels), which improves the blood supply to cancer tumors. And suppression of IGF-1 hampers the growth and survival of cancerous tumors. And metformin proven decreases IGF-1. 3-4 weeks of treatment with metformin (500 mg 3 times a day) reduces IGF-1 in patients diagnosed with endometrial cancer to normal. 2016, Xi'an Transport University, China.

Today, the third stage of clinical trials in Canada (National Cancer Institute) for the treatment of metformin in breast cancer at a dose of 850 mg 2 times a day in humans is underway.

Metformin enhances standard treatment for breast cancer and glioblastoma multiforme.

Therapy with small doses of metformin in clinical trials after 1 month showed a significant decrease in rectal aberrant foci of crypts.

A meta-analysis of 2016 showed that the use of metformin in patients with insulin resistance was associated with better survival of diabetic patients with liver cancer.

If cancer is hormone-dependent and her2, and also, if it is patients with insulin resistance, then the effectiveness of treatment with metformin for this type of cancer is comparable to hormone therapy or chemotherapy (see the graph on the left). Increased expression of the HER2 gene plays an important role in the progression of aggressive types of breast cancer. Patients who receive the old-fashioned metformin for breast cancer (with a positive HER2 status) and who have diabetes mellitus have a better prognosis and a better survival. Also, metformin can overcome the resistance of breast cancer with a positive HER2 status to treatment with tamoxifen. Aspirin increased the effectiveness of metformin in the treatment of breast cancer only with a positive HER2 status.

Old-age cure metformin increased survival in patients with endometrial cancer with insulin resistance. It is important that diabetic patients who were not treated with metformin, and also had endometrial cancer, had the same mortality as endometrial cancer patients who did not have diabetes. In other words, metformin quite possibly can improve the prognosis of patients with endometrial cancer not only in patients with diabetes mellitus, but also in people who do not have diabetes.

Old-age cure Metformin improves sexual function in male mice after long-term treatment (potency)

With age, as a result of vascular atherosclerosis, many men suffer an erection. The medicine for old age metformin improves erection in mice and thus treats for impotence, which occurs as a result of vascular atherosclerosis. And this is the most common cause of impotence. Only the effect of metformin is gradual - after the course of treatment. American experts from the University of Georgia showed that the old age medicine metformin is able to dilate the blood vessels of the circulatory system. This causes the fact that the blood in the vessels of the penis begins to actively circulate and awakens a good erection.

Metformin is a potential drug for the possible treatment of rheumatoid arthritis in diabetic patients

Metformin reduces the level of inflammatory markers and reduces inflammation of the joints in rheumatoid arthritis in patients with diabetes.

Metformin improves the condition of the thyroid gland in people with insulin resistance

Metformin reduces thyroid-stimulating hormone TSH only if it is elevated, and not below normal, and also reduces the size of small, solid nodules of the thyroid gland. It also prevents an increase in thyroid volume. Meta-analysis concluded that metformin reduces the level of TSH in overt and subclinical hypothyroidism. In contrast, no change in TSH levels was found in euthyroid people.

Metformin reduces elevated liver enzymes and can treat non-alcoholic fatty liver (NAFLD) in diabetic patients

How often to hear that metformin "puts the liver." But here a series of clinical trials show that given the metabolic effects and a good safety profile, metformin looks like a promising drug in the treatment of NAFLD, especially in patients with components of the metabolic syndrome. Metformin reduces elevated liver enzymes, reduces liver insulin resistance, improves the results of liver ultrasound.

Metformin protects the kidneys from aging in nephropathy in people with insulin resistance

Nephropathy is a disease of the kidneys with diabetes mellitus, can also be considered as aging of the kidneys. Over time, this disease turns into chronic renal failure, which is extremely dangerous for life and is not treated, but is only controlled. And metformin protects the kidneys from such conditions.

Metformin protects strengthens the immune system and protects the respiratory system

Metformin helps to reduce the number of infectious diseases of the respiratory tract. Suppresses inflammatory and fibrotic processes in the lungs, and also reduces the risk of obstructive chronic lung disease (COPD). But COPD is also one of the frequent senile lung diseases that is not treated, but is only controlled.

Metformin prolongs life and reduces mortality in people with insulin resistance and in mammals

2012, University of Gothenburg, Gothenburg, Sweden. The old age cure metformin reduces mortality in humans by about 30%. What was shown in the study on 51 675 patients with type 2 diabetes.

Metformin must be started from a youth; then the effect is greater.

A cure for old age metformin prolongs life. Patients with diabetes who use metformin have lived longer than people of the same age in the control group.

Metformin is a medication for the treatment of insulin resistance, which is also a PPAR gamma receptor agonist. A 2014 human study conducted by the University of Texas Health Science Center (see left) in San Antonio (USA) showed that the main effect of reducing mortality by metformin is due to the reduced risk of senile weakness due to muscle contraction and other causes of weakness . Researchers studied 2415 patients with type 2 diabetes mellitus aged from 65 to 89 years from 1999 to 2006. Patients were considered who were prescribed only metformin for the treatment of diabetes mellitus (without any other hypoglycemic agents) for at least 180 days. Also excluded patients with diseases of the kidneys, liver, with oncology. It turned out that the reduction in mortality by 23% in receiving metformin was associated precisely with the prevention of the onset of infirmity. So for people who already had weakness at the time of prescribing metformin, this medicine did not reduce mortality. This means that the extension of life by metformin was mainly due to the prevention of the development of infirmity.

After such promising results from the use of metformin, a clinical trial of metformin was initiated to prevent the reduction of muscle mass in diabetic patients. A clinical trial is conducted by the University of Kentucky in the United States (see figure to the left). The fact is that in a number of patients with diabetes mellitus at an advanced age, training of muscle mass does not give results, and sometimes even the other way around, the size of muscle mass decreases. But it was hypothesized that metformin could block muscle insensitivity to training in a number of diabetics. Aged patients receive 1700 mg of metformin per day or placebo. At the same time, patients are trained on simulators. As planned by scientists, a cure for old age metformin should increase the effectiveness of training. The results will be ready in 2017-2018.

Life extension (NRM) of long-lived mice with low doses of metformin starting at 12 months of age, as well as an NRM by 38% in spontaneously hypertensive mice.

The old-age cure metformin prolongs life by mitogormesis in animals and humans. In female mice, by 26% prolonged the maximum lifespan, and in spontaneously hypertensive rodents - by 38%.

Old Age Medicine Metformin - instructions for use

Sources: Any dosage form of metformin with the active ingredient - metformin. Sold in pharmacies.

Instructions for use to prolong life: taking Metformin 1-2 times a day, 500 mg.

If the doctor prescribed metformin, you can buy it at any pharmacy in the Russian Federation.

Warning: the cure for old age metformin is dangerous at the most severe stage of renal failure, but has a high safety profile for people with healthy kidneys!!! Alcohol intake should be no later than 48 hours before taking metformin and not earlier than 48 hours after its use.

Those using metformin need to take vitamin B12 at the same time. You can not combine the use of metformin with diuretics, with the drug Danazol, and you can not use metformin during pregnancy. Methformin is a drug with a high level of safety, but it cannot be used like any other medicine without a prescription.

Diabetes

Diabetes mellitus (DM) is an endocrine-metabolic disease characterized by chronic hyperglycemia, accompanied by a violation of all types of metabolism, which are caused by absolute or relative insulin deficiency, which develops as a result of a genetic predisposition to the effects of many endogenous and exogenous factors.

The first information about diabetes appeared in the III century BC. er The doctors of ancient Egypt, Greece, Rome and medieval Europe were familiar with him. Roman doctor Aretius (II century AD) described the disease in this way: "Diabetes is a terrible suffering, not very frequent among men, dissolving flesh and limbs in urine. Patients, without ceasing, emit water in a continuous stream, as through open water pipes. Life is short, unpleasant and painful, thirst is insatiable, fluid intake is excessive and not commensurate with the huge amount of urine due to even greater diabetes. Nothing can keep them from taking fluid and excreting urine. If for a short time they refuse to take fluids, their mouth dries up, the skin and mucous membranes become dry. Patients have nausea, are agitated, and die within a short time. " Treatment of diabetes mellitus depended on the severity of the disease and the age of the patient. If the patient was a child or a young man with insulin-dependent diabetes mellitus, then he was doomed to a quick death from diabetic coma. If the disease developed in an adult 40–45 years old and older (according to the modern classification, it is insulin-dependent diabetes mellitus), then such a patient was treated, or rather, life was maintained in it with the help of diet, exercise and herbal medicine.

In 1776, an English doctor Dobson (1731–1784) determined that the sweetish taste of the urine of patients was due to the presence of sugar in it, from that date diabetes began to be called diabetes. In 1841, the method for determining sugar in the urine was first developed. Then they learned to determine the level of sugar in the blood, and in 1921 they managed to get the first insulin. In 1922, insulin was used to treat a patient with diabetes. In 1956, the properties of some sulfonylurea drugs capable of stimulating insulin secretion were studied. In 1960, the chemical structure of human insulin was established. In 1979, the complete synthesis of human insulin was carried out by genetic engineering.

Types of diabetes

The first type of diabetes mellitus is associated with insulin deficiency and is called insulin-dependent diabetes mellitus (IDDM). A damaged pancreas cannot cope with its responsibilities: it either does not produce insulin at all, or it produces it in such small quantities that it cannot process even the minimal amount of glucose coming in, resulting in an increase in blood glucose. Patients can be of any age, but most people with diabetes mellitus type 1 suffer from people under 30, they are usually thin and, as a rule, they notice the sudden onset of signs and symptoms of the disease. Patients with this type of diabetes have to additionally inject insulin to prevent ketoacidosis (an increase in the content of ketone bodies in the urine) and to maintain life.

The second type of diabetes mellitus is called insulin-independent (NIDDM), since it produces a sufficient amount of insulin, sometimes even in large quantities, but it can be completely useless because the tissues lose sensitivity to it. The diagnosis of type 2 diabetes mellitus is usually made in patients older than 30 years. They are obese, with relatively few classic symptoms. They have no tendency to ketoacidosis, except during periods of stress. They are not dependent on exogenous insulin. For the treatment of this form of the disease, drugs from diabetes mellitus in pills that reduce the resistance (resistance) of cells to insulin or stimulate the pancreas to insulin secretion are used.

There are other types of diabetes and impaired glucose tolerance. In some cases, diabetes for the time being does not make itself felt. Sometimes the patient may not have any signs of diabetes mellitus at all, and the disease is determined, for example, when referring to an ophthalmologist when examining the fundus.

There is a complex of symptoms, with diabetes mellitus, characteristic of both types. The severity of symptoms depends on the degree of reduction of insulin secretion, the duration of the disease and the individual characteristics of the patient:

• frequent urination and an unquenchable thirst;
• rapid weight loss, despite the constant feeling of hunger;
• feeling weak or tired;
• blurred vision ("white veil" before the eyes);
• difficulty with sexual activity;
• numbness and tingling in the limbs;
• feeling of heaviness in the legs;
• dizziness;
• slow cure of infectious diseases;
• slow wound healing;
• drop in body temperature below average;
• fast fatiguability;
• cramps of the gastrocnemius muscles;
• pruritus and itching in the perineum;
• furunculosis;
• pain in the heart.

Currently, diabetes is equated with a non-infectious epidemic and is one of the global problems of mankind. In 2010, there were about 285 million people suffering from diabetes worldwide, and according to the International Diabetes Federation (IDF), in less than 20 years, this number will increase to 439 million people. Both throughout the world and in Russia, the main increase in the number of patients is due to type 2 diabetes (NIDDM). According to official data, the number of patients with diabetes in Russia is about 3 million people, of which more than 2.7 million are patients with type 2 diabetes. The pandemic of diabetes and the projected steady increase in the frequency of its occurrence in the future represent a serious problem for national health systems around the world.

Complications and consequences of diabetes

Acute complications of diabetes mellitus - hypo-and hyperglycemia. Chronic complications appear 10–15 years after the onset of the disease, develop unnoticed and at first do not affect the state of health. Due to the high blood sugar levels, diabetes-specific complications from the eyes, kidneys, legs, and also non-specific ones from the cardiovascular system gradually arise and progress very quickly.

Hypoglycemia - lowering blood sugar levels below 3.3 mmol / l. The following phases are distinguished:

• Phase 1: feeling of hunger, weakness, drowsiness, rapid heartbeat, headache, incoordination, tremors, sweating;
• Phase 2: double vision, pale and wet skin, sometimes numbness of the tongue, inadequate behavior (the patient begins to "flog crap"), aggression appears;
• Phase 3: inhibition, loss of consciousness, hypoglycemic coma.

Causes of hypoglycemia is an overdose of a glucose-lowering drug; skipping meals or less carbohydrates (bread units) in food intake, a large interval between insulin injection and food; greater compared to normal physical activity (especially sports); alcohol intake.

Hyperglycemia - an increase in blood sugar levels above 5.5–6.7 mmol / l. It is accompanied by the following symptoms:

• polyuria (frequent urination), glycosuria (sugar excretion in the urine), a large loss of water in the urine;
• polydipsia (intense persistent thirst);
• drying of the mouth, especially at night;
• weakness, lethargy, fatigue;
• weight loss;
• nausea, vomiting, headache.

The cause of hyperglycemia is a lack of insulin, and, as a result, increased sugar. High glucose in the blood causes a dangerous acute violation of the water-salt metabolism and hyperglycemic (hyperosmolar) coma.

Ketoacidosis is a clinical disorder caused by the influence of ketone bodies and tissue hypoxia (oxygen starvation) on the cells of the central nervous system, is a consequence of hyperglycemia. This condition leads to ketoacidosis coma.

Symptoms:

1. the smell of acetone from the mouth (similar to the smell of sour fruit);
2. rapid fatigue, weakness;
3. headache;
4. loss of appetite, and then - aversion to food;
5. stomach ache;
6. nausea, vomiting, diarrhea are possible;
7. noisy, deep, rapid breathing.

Prolonged hyperglycemic condition leads to chronic complications of the eyes, peripheral nerves, cardiovascular system, as well as damage to the feet - this is one of the most common chronic complications in diabetics.

Diabetic Nephropathy

Nephropathy - the defeat of small vessels in the kidneys, causes the following symptoms:

• proteinuria (the appearance of protein in the urine);
• swelling;
• general weakness;
• thirst, dry mouth;
• decrease in the amount of urine;
• discomfort or heaviness in the lumbar region;
• loss of appetite;
• rarely - nausea, vomiting, bloating, and loose stools;
• unpleasant taste in the mouth.

Diabetic neuropathy

Neuropathy - peripheral nerve damage.

Possible damage to not only the peripheral, but also the central structures of the nervous system. Patients concerned about:

1. numbness;
2. goose bumps;
3. cramps in the limbs;
4. pains in the legs, worse at rest, at night, and lessening when walking;
5. decrease or absence of knee reflexes;
6. decrease in tactile and pain sensitivity.

Diabetic foot

Diabetic foot - skin changes, changes in the joints and nerve endings on the feet.

The following lesions of the foot are possible:

• accidental cuts, abrasions. Combing, blistering after burns;
• scratches, cracks associated with fungal infections of the skin of the feet;
• corns on the joints of the fingers and on the foot, caused by uncomfortable shoes or orthopedic reasons (one leg shorter than the other, flat feet, etc.).

With loss of sensation and angiopathy, any of these lesions can develop into a trophic ulcer, and the ulcer develops into gangrene. The most dangerous thing in this situation is that the patient does not see his foot, and if the innervation is poor, sensitivity to pain is lost, as a result of which the ulcer may exist for a long time and go unnoticed. Most often this occurs in the part of the foot, which when walking accounts for the bulk. If an infection gets there, all the prerequisites for the formation of purulent ulcers are created, which can affect the deep tissues of the foot, up to the tendons and bones.

Medical procedures for patients with type 2 diabetes

1. Diet for diabetes mellitus type 2 is more rigid than for IDDM. Diet can be quite free in time, but you need to strictly avoid foods containing sugar, fats and cholesterol.
2. Moderate exercise.
3. Daily intake of glucose-lowering drugs according to doctor's prescriptions.
4. Control of blood sugar several times a week, preferably 1 time per day.

Therapy for type 2 diabetes includes a fairly large number of drugs.

Oral hypoglycemic agents (PSP)

Sulfonylurea preparations (CM):

Gliclazide is a derivative of SM generation II. It stimulates insulin secretion by the pancreas, increases the insulin-secreting effect of glucose and the sensitivity of peripheral tissues to insulin. Activates intracellular enzymes - muscle glycogen synthase. Reduces the time from eating to the start of insulin secretion. Restores the early peak of insulin secretion. Reduces postprandial hyperglycemia decreases platelet adhesion and aggregation, retards the development of membrane thrombosis, normalizes vascular permeability and prevents the development of atherosclerosis and mikrotromboza, facilitates the process of membrane physiological fibrinolysis counteracts increased vascular response to epinephrine at microangiopathies. It slows down the development of PD at the non-proliferative stage; with DN on the background of long-term use, a significant decrease in proteinuria is noted. It does not lead to an increase in body weight, as it has a predominant effect on the early peak of insulin secretion and does not cause hyperinsulinemia; leads to weight loss in obese patients, while maintaining an appropriate diet. It has anti-atherogenic properties, reduces the concentration of cholesterol in the blood;

Glibenclamide is a derivative of the second generation of SM. It stimulates insulin secretion by lowering the threshold for stimulating glucose of b-cells of the pancreas, increases insulin sensitivity and its binding to target cells, increases insulin release, enhances the effect of insulin on glucose absorption by muscles and liver, inhibits lipolysis in adipose tissue. Acts in the second stage of insulin secretion. It has a lipid-lowering effect, reduces blood thrombogenic properties. The hypoglycemic effect develops after 2 hours and lasts 12 hours;

glimepiride - stimulates insulin secretion by pancreatic β-cells, increases insulin release. Increases the sensitivity of peripheral tissues to insulin;

glykvidon - stimulates the secretion (secretion) of insulin b-cells of the islets of Langerhans of the pancreas. A fast-acting drug, is prescribed in cases where the regulation of carbohydrate metabolism is not achieved by the diet, and the insulin-producing cells are capable of secreting insulin.

Meglitinides:

Repaglinide - reduces the amount of glucose in the blood, stimulating the secretion of insulin by the pancreas. It binds on the β-cell membrane to a receptor protein specific to this drug. This leads to the blocking of ATP-dependent potassium channels and depolarization of the cell membrane, which contributes to the opening of calcium channels. Calcium ingestion of β-cells stimulates insulin secretion. In patients with type 2 diabetes, the insulinotropic reaction is observed within 30 minutes after taking the drug inside, the decrease in the glucose content is dose-dependent.

Biguanides:

Metformin - reduces the concentration of glucose in the blood by inhibiting gluconeogenesis in the liver, reducing the absorption of glucose from the gastrointestinal tract (GIT) and increasing its utilization in the tissues; reduces the serum concentration of TG, cholesterol and LDL (determined on an empty stomach) and does not change the concentration of lipoproteins of other densities. Stabilizes or reduces body weight. In the absence of insulin in the blood, the therapeutic effect does not appear. It improves blood fibrinolytic properties by suppressing tissue-type inhibitor of profibrinolysin activator (plasminogen).

Thiazolidinedione:

Pioglitazone - reduces insulin resistance, increases the consumption of insulin-dependent glucose and reduces the release of glucose from the liver. Reduces the average TG, increases the concentration of HDL and cholesterol. Selectively stimulates gamma receptors activated by peroxisome proliferator (PPAR). The activation of PPAR nuclear receptors modulates the transcription of a number of insulin-sensitive genes involved in the control of blood glucose concentrations and in lipid metabolism. Does not stimulate insulin secretion.

Α-glucosidase inhibitors:

acarbose - inhibits intestinal a-glucosidase, reduces the enzymatic conversion of di-, oligo- and polysaccharides to monosaccharides, thereby reducing the absorption of glucose from the intestine and postprandial hyperglycemia. The development of hypoglycemia when taking this drug for diabetes is not typical.

Combined preparations:

glibenclamide + metformin - a fixed combination of glibenclamide and metformin is a rational combination of two active substances, optimally combining their properties.

Incretomimetry

GPP-1 agonists

The potential of representatives of the class of GLP-1 receptor agonists is widely discussed in the clinical and scientific environment as a new stage in the treatment of type 2 diabetes. Exendin-based therapy has already been introduced into clinical practice: Exenatide is a synthetic GLP-1 receptor agonist isolated from the saliva of the giant lizard Gila Monster.

Lyraglutide is an analogue of human GLP-1 for administration once a day. The liraglutide molecule is 97% homologous in amino acid composition to the native human GLP-1 and is obtained by modifying human GLP-1 by replacing one amino acid (arginine with lysine) at position 34 and adding palmitic acid to lysine at 26th position C16. These changes contribute to the binding of liraglutide to serum albumin, oligomerization to heptamers, and also provide resistance to DPP-4-mediated inactivation, which leads to a prolongation of the half-life of the drug. Mechanisms of drug action:

• glucose-dependent stimulation of insulin secretion and glucose-dependent suppression of glucagon secretion, however, at normal or low glycemic values, insulin secretion is not stimulated, and glucagon secretion increases (this mechanism prevents the development of hypoglycemic states);
• slowing the evacuation of food from the stomach (which reduces postprandial hyperglycemia);
• acceleration of the saturation process (which leads to a decrease in food intake and a significant reduction in body weight, mainly due to visceral fat);
• decrease in systolic blood pressure, reduction of myocardial infarction in the experiment (this action is carried out by binding liraglutide with GLP-1 receptors in the cardiac muscle);
• improving the function of β-cells (assessed by the HOMA-B index and the ratio of proinsulin / insulin). The equilibrium plasma concentration of liraglutide is maintained for 24 hours after a single subcutaneous injection.

Exenatide is a stimulator of incretin (GLP-1), enhances glucose-dependent insulin secretion and improves b-cell functions, and suppresses inadequately increased glucagon secretion. The amino acid sequence of exenatide partially corresponds to the sequence of human GLP-1, as a result of which it binds and activates its receptors, which leads to increased glucose-dependent synthesis and secretion of insulin from pancreatic b-cells with the participation of cyclic adenosine monophosphate (AMP) and / or other intracellular signaling pathways . Exenatide stimulates insulin release from b-cells in the presence of elevated glucose concentrations. In hyperglycemic states, exenatide enhances glucose-dependent insulin secretion from pancreatic b-cells, which stops as the concentration of glucose in the blood decreases and approaches normality, thereby reducing the potential risk of hypoglycemia. Insulin secretion during the first 10 min. (first phase of the insulin response) is absent in patients with type 2 diabetes; loss of the first phase of the insulin response is an early dysfunction of b-cells in this type of diabetes. The introduction of exenatide restores or significantly enhances both the first and second phase of the insulin response in these patients. Against the background of hyperglycemia, administration of exenatide suppresses excessive secretion of glucagon, while the normal glucagon response to hypoglycemia is not disturbed. The introduction of exenatide leads to a decrease in appetite and a decrease in food intake, suppression of gastric motility (slowing its emptying).

Dipeptidyl peptidase type 4 inhibitors (DPP-4):

vildagliptin - causes an increase in both basal and food-stimulated secretion of GLP-1 and glucose-dependent insulinotropic polypeptide (HIP) from the intestine into the systemic circulation throughout the day. By increasing levels of GLP-1 and HIP, vildagliptin causes an increase in the sensitivity of β-cells of the pancreas to glucose, which leads to an improvement in glucose-dependent insulin secretion. Increases the level of endogenous GLP-1, increases the sensitivity of α-cells to glucose, which leads to an improvement in glucose-dependent regulation of glucagon secretion. It reduces the level of excess glucagon during a meal and causes a decrease in insulin resistance. An increase in the insulin / glucagon ratio due to hyperglycemia due to increased levels of GLP-1 and HIP causes a decrease in glucose production by the liver both in the prandial period and after a meal, which leads to a decrease in the level of glucose in the blood plasma. In addition, against the background of the use of vildagliptin there is a decrease in the level of lipids in the blood plasma;

Sitagliptin is an active oral inhibitor of the enzyme DPP-4. By inhibiting DPP-4, sitagliptin increases the concentration of GLP-1 and HIP. A decrease in glucagon concentration on the background of an increase in insulin levels contributes to a decrease in glucose production by the liver, which ultimately leads to a decrease in glycemia. Sitagliptin prevents hydrolysis of incretins by the enzyme DPP-4, thereby increasing the plasma concentrations of the active forms of GLP-1 and HIP. By increasing the level of incretins, sitagliptin increases glucose-dependent insulin release and contributes to a decrease in glucagon secretion. Reduces HbA1c level and decreases plasma glucose concentration, determined on an empty stomach and after a stress test;

Saksagliptin is a selective reversible competitive inhibitor of DPP-4. In type 2 DM, the activity of the DPP-4 enzyme is inhibited for 24 hours. After oral glucose loading, this inhibition of DPP-4 leads to a threefold increase in circulating active incretin hormones, including GLP-1 and HIP, a decrease in glucagon concentration and an increase in the glucose-dependent β-cell response, which increases insulin and C-peptide concentrations. The release of insulin by β-cells of the pancreas and a decrease in the release of glucagon from pancreatic α-cells is associated with a decrease in fasting glucose and a decrease in glucose after glucose exercise or food intake. The drug improves glycemic control, reduces the concentration of fasting glucose and glycemia after a meal in patients with type 2 diabetes.

Linagliptin is an inhibitor of DPP-4, which is involved in the inactivation of hormones of incretins - glucagon-like peptide type 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (HIP). Linagliptin is actively associated with the enzyme DPP-4 (the connection is reversible), which causes a steady increase in the concentration of incretins and the long-term maintenance of their activity; increases glucose-dependent insulin secretion and decreases glucagon secretion, which leads to the normalization of blood glucose levels. Linagliptin binds selectively to the DPP-4 enzyme and has a 10,000-fold greater selectivity with respect to DPP-4 compared with the enzymes of dipetilpeptidase-8 or dipeptilpeptidase-9 in vitro.

However, it is not always possible to control the blood glucose level with oral preparations without causing complications. There are a number of indications for the appointment of such patients insulin. Insulin is usually prescribed with the ineffectiveness of the diet and receiving the maximum dose of PSP, HbA1c> 7.5%, fasting glucose> 8 mmol / l, with BMI <25 kg / m2, ketoacidosis. With surgical intervention possible temporary transfer to insulin therapy. It is not a secret for anyone that the majority of patients cannot limit themselves only to making adjustments to their lifestyle; therefore, weight gain is often observed, disease progression or the influence of other factors are noted. Therefore, today the question of the use of insulin in the treatment of type 2 diabetes is very relevant.

However, despite this variety of drugs for the treatment of type 2 diabetes, the problem of adequate control over both the disease itself and its complications remains a rather serious and urgent task of modern health care. Early detection of this pathology and creation of new drugs will allow in the future to optimize the treatment of patients with type 2 diabetes.