Type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a common global disease closely associated with the obesity epidemic. People with T2DM are at high risk of both microvascular complications (including retinopathy, nephropathy, and neuropathy) and macrovascular complications (such as cardiovascular disease) due to hyperglycemia and individual components of the insulin resistance syndrome (metabolic syndrome). The main factors contributing to the development of T2DM include both environmental (e.g., obesity, unhealthy diet, and physical inactivity) and genetic factors that influence multiple pathophysiological abnormalities responsible for the impaired glucose homeostasis in T2DM.

Insulin resistance and impaired insulin secretion remain the major defects in T2DM, but at least six other pathophysiological abnormalities contribute to dysregulated glucose metabolism. The multiple pathogenic abnormalities in T2DM dictate the need for combinations of antidiabetic agents to maintain normoglycemia. Treatment must not only be effective and safe, but also improve quality of life. Several new drugs are in development, but the greatest need is for agents that improve insulin sensitivity, halt the progressive pancreatic β-cell failure that characterizes T2DM, and prevent or reverse microvascular complications ( DeFronzo et al., 2015 ).

T2DM is characterized as a heterogeneous disease caused by the combination of two main factors: defective insulin secretion by the pancreas and the inability of insulin-sensitive tissues to adequately respond to insulin. Since insulin production and activity are key processes for glucose homeostasis, the molecular mechanisms involved in insulin synthesis, release, and detection are tightly regulated. Defects in any of the mechanisms involved in these processes can lead to metabolic imbalances responsible for the development of the disease ( Galicia-Garcia et al., 2020 ).

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Causes type 2 diabetes

1. Insulin resistance: One of the main causes of type 2 diabetes. The body's cells become less sensitive to insulin, which helps cells convert glucose into energy. As a result, glucose accumulates in the blood instead of being used by the cells.
2. Insufficient insulin production by the pancreas: Over time, the pancreas may not produce enough insulin to maintain normal blood sugar levels, especially if you have insulin resistance.
3. Overweight and obesity: Particularly the accumulation of fat in the abdominal area increases insulin resistance and is associated with an increased risk of developing type 2 diabetes.
4. Physical inactivity: Lack of exercise contributes to weight gain and increases insulin resistance.
5. Diet: A diet high in high-calorie foods, simple carbohydrates, and saturated fats can contribute to insulin resistance and excess weight.
6. Age: The risk of developing type 2 diabetes increases with age, especially after age 45, although the disease has been increasingly diagnosed in younger people in recent years.
7. Genetic predisposition: Having close relatives with type 2 diabetes increases the risk of developing it.
8. Ethnicity: Certain ethnic groups, such as African Americans, Hispanics, Asians, and Native Americans, have a higher risk of developing type 2 diabetes.
9. Gestational diabetes and polycystic ovary syndrome: Women who have had gestational diabetes or polycystic ovary syndrome are also at increased risk.

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Alcohol

Drinking alcohol with type 2 diabetes requires caution and moderation, as alcohol can have significant effects on blood sugar levels and overall health.

The effect of alcohol on type 2 diabetes:

1. Hypoglycemia: Alcohol can enhance the effects of insulin and oral hypoglycemic drugs, increasing the risk of hypoglycemia, especially if consumed on an empty stomach or in excess. This effect may not be apparent for several hours after consumption.
2. Hyperglycemia: On the other hand, some alcoholic drinks, especially sweet wines and cocktails with sugar or syrups, can raise blood sugar levels.
3. Effect on weight: Alcohol contains a lot of calories, which can contribute to weight gain, increase insulin resistance, and make it harder to control diabetes.
4. Effects on the liver: Excessive alcohol consumption can impair liver function, which plays a key role in regulating blood sugar levels.

Recommendations:

• Moderation: Unless your doctor advises against drinking alcohol, you should drink in moderation—no more than one standard alcoholic drink per day for women and no more than two for men. One standard alcoholic drink is equivalent to 14 grams of pure alcohol (about 150 ml of wine, 350 ml of beer, or 45 ml of spirits).
• Precautions: Always drink alcohol with or after meals to reduce the risk of hypoglycemia.
• Blood Sugar Monitoring: Monitor your blood glucose levels regularly, especially before drinking alcohol and for several hours after drinking it.
• Education: It is important to educate family and friends about the risk of hypoglycemia and how to provide assistance if it occurs.

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Pathogenesis

The pathogenesis of type 2 diabetes mellitus (T2DM) involves a complex relationship between genetic predispositions, metabolic disturbances, and external lifestyle factors that together lead to the development and progression of the disease. Key aspects of T2DM pathogenesis include:

Insulin resistance

One of the main mechanisms by which T2DM develops is insulin resistance, a condition in which the body's cells (especially in muscle, fat, and liver) become less sensitive to the effects of insulin. This forces the pancreas to produce more insulin to maintain normal blood glucose levels. Over time, excess insulin production can cause the β cells to become fatigued and less able to produce insulin.

Impaired insulin secretion

In addition to insulin resistance, the second major pathogenetic factor of T2DM is impaired insulin secretion by the pancreas. This may begin with a failure of the first phase of insulin release in response to increased blood glucose levels. Over time, pancreatic β-cells lose the ability to adequately respond to increased glucose, leading to hyperglycemia.

Increased glucose production by the liver

The liver plays a key role in maintaining blood glucose levels by producing glucose and releasing it into the bloodstream. People with T2DM experience increased gluconeogenesis (the formation of glucose from non-carbohydrate sources), which contributes to hyperglycemia.

Adipose tissue and adipocytokines

Adipose tissue, particularly visceral fat, produces various substances called adipocytokines, which may contribute to the development of insulin resistance and inflammation, important components in the pathogenesis of T2DM.

Inflammation

Chronic low-grade inflammation plays a key role in the development of insulin resistance and T2DM. Inflammatory cytokines produced by adipose tissue and other cells can impair insulin action and contribute to poor glucose control.

Genetic factors

Having a family history of T2DM suggests that genetic factors are important. Research has identified many genetic variations that increase the risk of developing the disease.

Studying genetic factors helps to understand the mechanisms of T2DM development and may contribute to the development of new approaches to prevention and treatment.

Genes associated with type 2 diabetes:

1. TCF7L2 (transcription factor 7-like 2): Most strongly associated with the risk of developing T2DM. Mutations in this gene can affect insulin production and action.
2. PPARG (Peroxisome Proliferator-Activated Receptor Gamma): Involved in the regulation of glucose and lipid metabolism. Mutations can lead to insulin resistance.
3. KCNJ11 (potassium channel, subfamily J, member 11): Mutations in this gene can impair pancreatic β-cell function.
4. SLC30A8 (zinc transporter 8): Involved in the storage and release of insulin from β-cells. Mutations can disrupt these processes.
5. IRS1 (insulin receptor substrate 1): Plays a key role in the insulin signaling pathway. Mutations can lead to impaired insulin action.
6. CDKAL1 (CDK5 regulatory subunit associated protein 1): Mutations can affect β-cell function and insulin secretion.
7. HNF1B (hepatocyte nuclear factor 1β): Mutations can affect pancreatic development and β-cell function.

Loci:

Genome-wide association studies (GWAS) have identified multiple loci in the genome that are associated with T2DM. These loci contain genes or genetic variants that may influence various aspects of metabolism, including insulin secretion and action, glucose metabolism, and lipid metabolism. For example, loci identified in GWAS studies include, but are not limited to, 9p21, 11p12-p11.2, and many others.

Environment and Lifestyle

Lifestyle factors such as poor diet, physical inactivity, and obesity significantly increase the risk of developing T2DM. These factors can increase insulin resistance and impaired insulin secretion.

Symptoms type 2 diabetes

Type 2 diabetes often progresses slowly and may not show symptoms in the early stages, making it difficult to diagnose early. However, as blood glucose control worsens, the following symptoms may appear:

1. Increased thirst and frequent urination: Excess sugar in the blood causes your kidneys to work harder to filter and absorb the excess sugar. If your kidneys can't keep up, the excess glucose is excreted in urine, taking fluids from your tissues with it, which can cause dehydration and thirst.
2. Increased appetite: Your body's inability to digest glucose can lead to increased feelings of hunger.
3. Weight loss for no apparent reason: Despite an increase in appetite, you may be losing weight. Without insulin's ability to move sugar into your cells, muscle tissue and fat stores simply shrink as energy is obtained from other sources.
4. Fatigue: Not enough sugar in your cells can make you unusually tired.
5. Blurred vision: Changes in the fluid levels in your body can cause the lenses of your eyes to swell. This change in shape can lead to blurred vision.
6. Slow wound healing and frequent infections: Diabetes affects your ability to heal wounds and fight infections.
7. Tingling in the hands and feet: Excess sugar in the blood can damage nerves, which can cause a tingling or numb sensation in your hands and feet.

These symptoms may develop gradually and do not always clearly indicate type 2 diabetes, making regular medical examinations important for early detection and treatment of the disease.

Stages

Although the classic divisions into severity and stages may not be as strictly defined for T2DM as for some other diseases, certain phases in the development and progression of the disease can be identified that aid in understanding and treating the condition.

Phases of type 2 diabetes:

1. Prediabetes:

   • Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are often precursors to the development of T2DM.
   • At this stage, glucose levels are higher than normal, but not yet high enough to be classified as diabetes.

2. Early T2DM:

   • In the early stages of T2DM, blood glucose levels are higher than normal, but symptoms may be minimal or absent.
   • At this stage, it is still possible to effectively manage the disease through lifestyle changes and, if necessary, medication.

3. Steady-state T2DM:

   • Blood glucose levels remain elevated most of the time.
   • Symptoms such as increased fatigue, frequent urination, and thirst may occur.
   • Medication is needed to control glucose levels.

4. T2DM with complications:

   • Long-term high blood glucose levels can lead to complications including vascular disease, nerve damage (neuropathy), kidney problems (nephropathy) and eye problems (retinopathy).
   • Complications require additional treatment and can have a significant impact on quality of life.

Severity levels:

• Light:
  • Mild cases can be controlled primarily through diet and exercise.
• Moderate:
  • Moderate severity may require oral hypoglycemic agents.
• Heavy:
  • Severe cases often require combination therapy, including insulin and blood glucose monitoring.

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Complications and consequences

The vascular system is most susceptible to complications of diabetes mellitus type 2. In addition to vascular pathology, a number of other symptoms may develop: hair loss, dry skin, deterioration of the nails, anemia and thrombocytopenia.

Among the severe complications of diabetes, the following should be highlighted:

• progressive atherosclerosis, causing disruption of coronary blood supply, as well as of the limbs and brain tissue;
• stroke;
• renal dysfunction;
• retinal damage;
• degenerative processes in nerve fibers and tissue;
• erosive and ulcerative lesions of the lower extremities;
• infectious diseases (bacterial and fungal infections that are difficult to treat);
• hypoglycemic or hyperglycemic coma.

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Consequences

Since therapeutic measures for diabetes mellitus are usually aimed at preventing the state of decompensation and maintaining the state of compensation, in order to assess the consequences, let us become familiar with these important concepts.

If the patient's blood sugar level is slightly higher than normal, but there is no tendency towards complications, then this condition is considered compensated, that is, the body can still cope with the carbohydrate metabolism disorder on its own.

If the sugar level significantly exceeds the permissible values, and there is a clear tendency towards the development of complications, then this condition is referred to as decompensated: the body will no longer cope without drug support.

There is also a third, intermediate variant of the course: the state of subcompensation. For a more precise division of these concepts, we will use the following scheme.

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Compensation for diabetes mellitus type 2

• sugar on an empty stomach – up to 6.7 mmol/l;
• sugar within 2 hours after eating – up to 8.9 mmol/l;
• cholesterol – up to 5.2 mmol/l;
• amount of sugar in urine – 0%;
• body weight – within normal limits (if calculated using the formula “height minus 100”);
• blood pressure readings – no higher than 140/90 mm Hg.

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Subcompensation of type 2 diabetes mellitus

• sugar level on an empty stomach – up to 7.8 mmol/l;
• sugar level for 2 hours after eating – up to 10.0 mmol/l;
• cholesterol levels – up to 6.5 mmol/l;
• the amount of sugar in urine is less than 0.5%;
• body weight – increased by 10-20%;
• blood pressure readings – no more than 160/95 mm Hg.

Decompensation of diabetes mellitus type 2

• sugar level on an empty stomach – more than 7.8 mmol/l;
• sugar level after meals – more than 10.0 mmol/l;
• cholesterol levels – more than 6.5 mmol/l;
• the amount of sugar in the urine is more than 0.5%;
• body weight – more than 20% of the norm;
• blood pressure readings – 160/95 and above.

In order to prevent the transition from a compensated state to a decompensated one, it is important to use control methods and schemes correctly. This includes regular tests, both at home and in the laboratory.

The ideal option is to check your sugar level several times a day: in the morning on an empty stomach, after breakfast, lunch and dinner, and shortly before bed. The minimum number of checks is in the morning before breakfast and immediately before going to bed.

It is recommended to check the presence of sugar and acetone in urine analysis at least once every 4 weeks. In decompensated conditions – more often.

It is possible to prevent the consequences of type 2 diabetes if you strictly follow your doctor's instructions.

You can live a full life with diabetes if you follow special rules for nutrition and lifestyle, as well as take the medications prescribed by your doctor, strictly following the treatment regimen.

Monitor your condition closely, regularly check your blood sugar levels and blood pressure, and watch your weight.

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Diagnostics type 2 diabetes

Clinical signs of pathology may already suggest that a person has type 2 diabetes. However, this is not enough to confirm the diagnosis; laboratory diagnostic procedures must also be carried out.

The main objective of this type of diagnostics is to detect dysfunction of β-cells: this is an increase in sugar levels before and after meals, the presence of acetone in the urine, etc. Sometimes laboratory test results can be positive even in the absence of clinical signs of the disease: in such cases, they speak of early detection of diabetes mellitus.

The level of sugar in the serum can be determined using autoanalyzers, test strips or a glucometer. By the way, according to the criteria of the World Health Organization, if the blood sugar levels are more than 7.8 mmol/liter twice on different days, the diagnosis of diabetes can be considered confirmed. American specialists have slightly different standards: here the diagnosis is established at levels more than 7 mmol/liter.

The 2-hour oral glucose tolerance test is used when there is doubt about the accuracy of the diagnosis. How is this procedure performed:

• For three days before the examination, the patient receives about 200 g of carbohydrate food per day, and can drink liquids (without sugar) without restrictions;
• testing is carried out on an empty stomach, and at least ten hours must have passed since the last meal;
• blood can be taken from either a vein or a finger;
• the patient is offered to take a glucose solution (75 g per glass of water);
• Blood is taken 5 times: first, before consuming glucose, and then half an hour, an hour, an hour and a half, and 2 hours after consuming the solution.

Sometimes the duration of such a study is shortened by taking blood on an empty stomach and 2 hours after consuming glucose, that is, only twice.

Urine sugar analysis for diabetes diagnosis is used less frequently, since the amount of sugar in urine may not always correspond to the amount of glucose in the blood serum. In addition, sugar in urine may appear for other reasons.

Testing urine for ketone bodies may play some role.

What should a sick person do without fail, in addition to monitoring blood sugar? Monitor blood pressure and periodically take a blood cholesterol test. All indicators taken together can indicate the presence or absence of the disease, as well as the quality of compensation for the pathological condition.

Tests for type 2 diabetes can be performed along with additional diagnostics, which provide the opportunity to identify the development of complications. For this purpose, the patient is recommended to take an ECG, excretory urography, and an examination of the fundus.

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Treatment type 2 diabetes

At the initial stage of the disease, it is sometimes enough to follow the rules of nutrition and do special physical exercises, without using medications. It is important to normalize your body weight, this will help restore carbohydrate metabolism and stabilize sugar levels.

Treatment of subsequent stages of the pathology requires the prescription of medications.

Preparations

Patients with type 2 diabetes are most often prescribed antidiabetic drugs for internal use. Such medications are taken at least once a day. Depending on the severity of the condition, the doctor may use not one drug, but a combination of drugs.

The most common antidiabetic drugs are:

• tolbutamide (pramidex) – can affect the pancreas, activating insulin secretion. Most suitable for elderly patients with compensatory and subcompensatory type 2 diabetes. Possible side effects include allergic reactions and transient jaundice;
• glipizide - use with caution in the treatment of elderly, weakened and debilitated patients with insufficient adrenal and pituitary function;
• Maninil - increases the sensitivity of receptors that perceive insulin. Increases the production of the pancreas's own insulin. The drug should be taken starting with one tablet, gently increasing the dosage if necessary;
• Metformin – does not affect the level of insulin in the body, but can change pharmacodynamics by reducing the ratio of bound insulin to free insulin. Most often prescribed to patients with overweight and obesity. Not used in the treatment of patients with impaired renal function;
• acarbose - inhibits the processes of digestion and absorption of carbohydrates in the small intestine and, in this regard, reduces the increase in blood sugar concentration after eating carbohydrate foods. The drug should not be prescribed for chronic bowel diseases, as well as during pregnancy;
• Magnesium preparations – stimulate the production of insulin by the pancreas, regulate sugar levels in the body.

The use of combinations of drugs is also permitted, for example:

• use of metformin with glipizide;
• use of metformin with insulin;
• combination of metformin with a thiazolidinedione or nateglinide.

Unfortunately, for most people with type 2 diabetes, the above medications gradually lose their effectiveness. In such situations, it is necessary to switch to insulin medications.

Insulin

Insulin for type 2 diabetes can be prescribed temporarily (for certain painful conditions) or permanently when previous therapy with tablets is ineffective.

Of course, insulin therapy should be started only when prescribed by a doctor. He will select the necessary dosage and plan a treatment plan.

Insulin may be prescribed to facilitate blood sugar compensation as much as possible to prevent complications of the disease. In what cases may a doctor switch drug therapy to insulin therapy:

• in case of unmotivated rapid weight loss;
• in the development of complicated manifestations of the disease;
• in case of insufficient compensation of pathology with the usual use of hypoglycemic medications.

The insulin preparation is determined by the attending physician. It may be rapid, intermediate or prolonged action insulin, which is administered by subcutaneous injection in accordance with the treatment regimen proposed by the specialist.

Exercises

The purpose of exercises for type 2 diabetes is to influence the stabilization of blood sugar levels, activate the action of insulin, improve the functionality of the cardiovascular and respiratory systems, and stimulate performance. In addition, physical exercise is an excellent prevention of vascular pathologies.

Exercises can be prescribed for all forms of diabetes. When ischemic heart disease or heart attack develops against the background of diabetes, gymnastic exercises are modified, taking into account these diseases.

Contraindications to physical exercise may include:

• high blood sugar (more than 16.5 mmol/liter);
• acetone in urine;
• pre-comatose state.

Physical exercises for patients who are on bed rest but not in the decompensation stage are performed in a lying position. Other patients perform exercises standing or sitting.

Classes begin with standard exercises for the muscles of the upper and lower extremities and the trunk without weights. Then classes are connected using resistance and weights, using an expander, dumbbells (up to 2 kg) or a fitness ball.

A good effect is observed from breathing exercises. Also welcome are dosed walking, cycling, rowing, swimming pool exercises, skiing.

It is very important that a patient who exercises independently pays attention to his condition. If a feeling of hunger, sudden weakness, trembling in the limbs develops, physical exercises should be stopped and it is necessary to eat. After the condition has normalized, the following day, it is allowed to resume exercises, however, slightly reducing the load.

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Diet

Despite taking medications that regulate blood sugar levels, the diet for diabetes is extremely important. Sometimes mild forms of the disease can be controlled only by diet, without even resorting to medication. Among the well-known therapeutic tables, the diet for type 2 diabetes is defined as diet No. 9. The prescriptions of this diet are aimed at restoring the disrupted metabolic processes in the body.

Nutrition for type 2 diabetes should be balanced and take into account the caloric content of the food consumed. The optimal daily calorie intake depends on body weight:

• normal weight – from 1600 to 2500 kcal;
• excess weight – from 1300 to 1500 kcal;
• obesity grade II-III – from 1000 to 1200 kcal;
• obesity stage IV – from 600 to 900 kcal.

But you can't always limit yourself in calories. For example, in case of kidney diseases, severe arrhythmia, mental disorders, gout, severe liver diseases, food should be nutritious.

It is recommended to avoid fast carbohydrates and limit the consumption of fat and salt.

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Prevention

The basis of type 2 diabetes prevention is adherence to the principles of healthy eating. Eating the "right" food serves as a preventive measure not only for diabetes, but also for other various diseases. After all, it is difficult to imagine the diet of many modern people without fast food, semi-finished products, products with a lot of preservatives, coloring and other chemicals and fast sugars. Preventive measures should be aimed at reducing, or better yet, eliminating all kinds of harmful food from our diet.

In addition to nutrition, you should pay attention to the level of physical activity. If fitness or gymnastics are not for you, try to choose other activities: walking and cycling, swimming, tennis, morning jogging, dancing, etc. It is useful to walk to work, rather than take public transport. It is useful to climb the stairs on your own, without using the elevator. In short, overcome your laziness and move, be active and cheerful.

By the way, an active life position and a stable emotional state are also good methods of preventing type 2 diabetes. It has long been known that chronic stress, anxiety, and depressive states can lead to metabolic disorders, obesity, and, ultimately, the development of diabetes. Our emotions and our state are always closely related. Take care of your nervous system, strengthen your stress resistance, do not react to minor reasons that make you angry: all this will help you be healthy and happy.

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Forecast

Unfortunately, diabetes mellitus type 2 is still considered an incurable chronic disease. According to statistics, this pathology affects more than 500 thousand people worldwide every month. Almost 100 thousand patients undergo limb amputation every month to prolong their lives and stop vascular complications. Let's not mention how many people lose their sight or develop other complications due to diabetes every year. Unfortunately, a disease such as diabetes causes as many deaths as HIV or hepatitis.

That is why it is so important to adhere to basic prevention methods, regularly monitor blood sugar levels, not overeat and not overload the pancreas, not get carried away with sweets, watch your weight and lead an active lifestyle. Preventive measures must be followed by everyone: both healthy people and those who already have this disease. This will prevent the development of complications and will not allow diabetes to move to the next, more severe stage.

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Disability

Whether or not to assign disability for type 2 diabetes is decided by the medical and social expert organization to which the patient is referred by his or her attending physician. That is, you can wait until the doctor decides that you need to apply for disability, but you can insist on it yourself, and the doctor has no right to refuse you.

The mere fact that you have diabetes does not give you the opportunity to receive disability. Such status is granted only in case of violation of some functions of the body, which can limit the full life activity of the patient. Let's consider the criteria for assigning disability:

• Group III is provided for mild and moderate cases of the disease with moderate disorders that prevent full mobility or the ability to work. If diabetes is in the compensation stage and you do not take insulin, disability is not provided in this case;
• Group II is provided to patients with relatively severe disorders (retinopathy grades II-III, renal failure, neuropathy grade II, encephalopathy, etc.);
• Group I can be provided to seriously ill patients with complete blindness, paralysis, severe mental disorders, severe cardiac insufficiency, and amputated limbs. Such patients cannot manage in everyday life without outside help.

A disability group is assigned after the patient has been examined by expert specialists (the so-called commission), who decide whether to assign the group, for how long, and also discuss options for necessary rehabilitation measures.

A standard application to an expert commission regarding disability should include:

• the result of a general urine and blood test;
• the result of the analysis of sugar content in the blood serum before and after meals;
• urine test results for the presence of acetone and sugar;
• renal and hepatic biochemistry;
• ECG;
• conclusion of an ophthalmologist, neurologist, therapist, surgeon.

From the general documentation you may need:

• a written statement made on behalf of the patient;
• passport;
• a referral issued by a doctor;
• a medical card containing the entire history of your illness;
• certificate of completion of education;
• a photocopy of the work book;
• description of working conditions.

If you are applying for a repeat granting of disability, you will also need a certificate stating that you are disabled, as well as the rehabilitation program previously assigned to you.

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Benefits

Regardless of whether you have been assigned a disability or not, you may be eligible for free insulin medications and other benefits for type 2 diabetes.

What else are you entitled to:

• receiving free syringes and sugar-lowering drugs;
• preferential order of glucotests and blood sugar measuring devices;
• participation in social rehabilitation (easing working conditions, training in another profession, retraining);
• spa treatment.

If you are disabled, you will receive a cash benefit (pension).

They say that diabetes is not a disease, but a way of life. Therefore, patients have to adapt to the pathology, pay close attention to nutrition, control their body weight, regularly monitor their condition and take tests. Well, type 2 diabetes is a really complex disease, and only your caring attitude towards yourself can help you live a full and active life as long as possible.