Modern Principles of Treatment of Type 2 Diabetes

The term "diabetes" refers to metabolic disorders of different etiology, characterized by the development of chronic hyperglycemia, accompanied by changes in carbohydrate, fat and protein metabolism that is the result of a defect in insulin action and secretion. Diabetes leads to defeat, dysfunction and the development of failure of various organs and systems, especially the eyes, kidneys, nerves, heart and blood vessels.

Type 2 diabetes - the most widespread form of the disease, which is characterized by impaired insulin action (insulin resistance) and insulin secretion. Type 2 diabetes can develop at any age but most often after age 40. Start gradually, often against a background of excess body weight. Symptoms of diabetes are absent or weakly expressed. This may be due to slow disease progression and as a result of adaptation of patients to long-existing hyperglycemia. Determined sufficient level of C-peptide, autoantibodies to b-cells producing insulin are lacking. Morphologically in the debut of type 2 diabetes revealed normal dimensions of the pancreas, can be marked hypertrophy of the b-cells. b-cells contain a large number of secretory granules. In contrast, type I diabetes is an autoimmune disease where there is an absolute insulin deficiency due to destruction of b-cells. Leave a comment

Figure 1. Pathogenesis of type 2 diabetes

According to modern concepts in the pathogenesis of type 2 diabetes plays a key role in insulin secretion violation of b-cells. Revealed signs of peripheral glucose utilization. Schematically, the pathogenesis of type 2 diabetes is presented in Fig. 1. Leave a comment

Violation of insulin synthesis may occur out of sequence of amino acids in the molecule of insulin and proinsulin conversion to insulin. In both cases, the hormone produced will have low biological activity, leading to the development of hyperglycemia. Insulin secretion may be impaired due to diseases of b-cells with inadequate prenatal and postnatal nutrition, and long existing glyukozotoksichnosti, which supports the secretory defect in insulin secretion, as well as a result of genetic defects in the mechanism of secretion. Leave a comment

Peripheral insulin resistance appears a violation of glucose uptake in peripheral tissues, primarily the liver tissue, muscle and adipose tissue. Most important in her development are defective insulin receptors (decrease in the number and affinity or affinity to insulin) and glucose transporter pathology. Leave a comment

The number of insulin receptors is reduced in obesity, type 2 diabetes mellitus, acromegaly, disease ItsenkoKushinga, glucocorticoid, taking birth control pills. Leave a comment

For the penetration of glucose into the cell is a necessary condition normal functioning of glucose transporters. Fig. Figure 2 shows glucose transport in adipocyte under the influence of insulin. Insulin binds to a-subunit of the receptor on the cell membrane, which leads to autophosphorylation b-subunit. As a result of momentum transfer within the cell system is activated kinase and glucose transporter translocation occurs GLUT-4 in the cell membrane. This ensures the penetration of glucose into the cell. Glucose moves along the concentration gradient by diffusion, which requires no additional energy. In the kidney inflow of glucose occurs against a concentration gradient and requires energy. It is now known glucose transporter 8. The main isoform of the family are shown in Table 1. Leave a comment

Fig. 2. Insulin action on glucose transport in adipocyte

In recent years, there is enough experimental and clinical evidence that the defects in insulin secretion and the development of peripheral insulin resistance is largely due to violations of genetic control. These data are summarized in Table 2. Leave a comment

Non-drug therapies

The most important goals in the treatment of diabetes are: elimination of symptoms, optimal metabolic control, prevention of acute and chronic complications, achieving the highest possible quality of life and accessibility for patients.

Goals are achieved with the basic principles of treatment are crucial for patients with diabetes of both types: diabetic diet, dosed exercise, training and self-control.

If in type 2 diabetes as monotherapy diet is ineffective, requires the appointment of saharoponizhayuschih oral medications. In diabetes type 1 is always assigned to insulin.

Diet therapy for type 2 diabetes must meet the following requirements: the exclusion of refined carbohydrates (sugar, honey, jam, etc.), low intake of saturated fats and total fat content should not exceed 30-35% of daily energy needs; carbohydrates should provide 50-60% protein to 15% calorie daily diet, we recommend the preemptive use of complex carbohydrates and foods rich in soluble fiber, to produce menus use special tables, in which all foods are divided into groups: food,


that can not be limited, the products that must be considered, and products that should be deleted; meals preferably distributed evenly throughout the day, allowed to use beskaloriynyh sweeteners, if not contraindicated, is recommended not to restrict fluid intake, to limit or eliminate alcohol intake.

Very relevant is the question of compensation criteria for type 2 diabetes. According to the recommendations of the European Group Policy diabetes [2], the risk of complications is estimated, as shown in Table 3.

In addition to the state of carbohydrate metabolism, one must also consider the degree of lipid metabolism and blood pressure levels, because hyperglycemia after these factors are essential in the development of cardiovascular complications of diabetes. Leave a comment

Tableted products saharoponizhayuschie

Treatment of type 2 diabetes always begin with the appointment of diet and dosed physical load. It should also explain to the patient the need to conduct self-monitoring and teach it at home using test strips (glucose in the blood and urine). In those cases where it proves to be ineffective, prescribe tablets saharoponi distorting drugs. Use three groups of drugs: inhibitors of a-glucosidase sulfonilamidy and biguanides. Leave a comment

Inhibitors of a-glucosidases (acarbose) reduce glucose absorption in the intestine and are effective in the early stages of the disease. Leave a comment

More commonly used sulfonylureas, which are divided into samples for 1 st and 2 nd generation. Samples for 1 st generation are less effective and is now in our country are not used. Drugs 2 nd generation is active sekretogeny their saharoponizhayuschy effect appears at a daily dose of 50,100 times smaller than that of drugs a second generation. The most commonly used now are gliclazide, glibenclamide, glipizide, glikvidon.

Sulfonylureas stimulate insulin secretion b-cells in the pancreas. Initially, the drug is binding to receptors on the surface of b-cells is closely associated with the ATP-dependent K + channels. Then, the closing of these channels and depolymerization of the membrane. The discovery followed by calcium channel provides a flow of calcium ions inside the b-cells and stimulation of insulin secretion. It should be borne in mind that the appointment of a number of drugs can be marked as a strengthening and weakening of the sulfonylureas. Drugs to lower their operation are as follows: thiazide diuretics, b-blockers, corticosteroids, indomethacin, isoniazid, niacin, calcium antagonists.

Potentiate the action of these drugs: salicylates, sulfonamides, pyrazolone derivatives,

clofibrate, monoamine oxidase inhibitors, anticoagulants, alcohol. Leave a comment

Treatment of derivatives of sulfonylurea is contraindicated in: type 1 diabetes or secondary (pancreatic) diabetes mellitus, pregnancy and lactation (because of teratogenicity), surgery (larger operations), severe infections, trauma, allergy to sulfonylurea drugs or similar drugs history, there is a risk of severe hypoglycemia. Leave a comment

Group tablets saharoponizhayuschih biguanide drugs are now presented with metformin. In contrast to the above-mentioned drugs biguanides do not increase insulin secretion. Saharoponizhayuschee biguanide effect is seen only in the event that the blood has enough insulin. Biguanides enhance its action on peripheral tissues, reducing insulin resistance. Biguanides increase glucose uptake by muscles and adipose tissue by increasing insulin binding to receptors and increase the activity of GLUT-4. They reduce production of glucose by the liver, glucose absorption in the intestine, increase its utilization, reduce appetite. Their purpose is contraindicated in: renal impairment, hypoxic conditions of any cause (cardiovascular disease, lung disease, anemia, infectious disease), acute complications of diabetes, alcohol abuse, laktatatsidoze history.

Insulinotherapy

In patients with a prolonged course of disease often develop secondary resistance to peroral saharoponizhayuschim drugs. At the onset of type 2 diabetes require insulin 2-3% of patients, and 10-15 years from the onset of the disease in half of patients previous treatment is ineffective and there are indications for insulin therapy. On average, 10-15% of patients with type 2 diabetes each year go on insulin therapy.

Indications for use of insulin in type 2 diabetes are: a temporary increase in insulin requirements, a sharp decrease in insulin secretion, cases of hyperglycemia does not respond to other forms of therapy. Insulin therapy in type 2 diabetes may be temporary or lifelong. Temporary insulin therapy is indicated for: stress, acute illness, the need for surgery, acute infections, stroke, myocardial infarction, pregnancy and lactation. Lifelong insulin therapy is indicated for diabetes mellitus with late autoimmune origin and secondary resistance to saharoponizhayuschim tableted drugs. Leave a comment

Secondary resistance to the tableted product is the result of reducing the weight of b-cells and / or increase insulin resistance. Side effects of insulin therapy in type 2 diabetes are: weight gain, frequent hunger, fluid retention and sodium, the risk of hypoglycemia. In this case, may use different modes of insulin therapy: long-acting insulin at bedtime in combination with diet and daily intake of tablets of drugs; twofold insulin short-and long-acting before breakfast and dinner; tablet combination therapy drugs and insulin, intensive insulin therapy in the basal-bolus regime for Persons younger.

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Intensive insulin therapy involves the introduction of long-acting insulin twice a day (usually before breakfast and before bedtime) and short-acting insulin before each meal. To maintain the compensation of the disease at the level of normoglycemia and glycosuria should be learning and self-control patient. Leave a comment

To facilitate injections use a semi-automatic injectors, syringe pens, which use heat-stable insulin. Have ready a mixture of insulin in which insulin short-and long-acting mixed in factory conditions, which is convenient for patients and reduces the error rate when mixed insulin by the patient. Leave a comment

The most difficult question remains about when to start insulin therapy in type 2 diabetes. It should be addressed individually in each case by analyzing the indications, contraindications, the goals of therapy. Achieving and maintaining a stable compensation of the disease is essential for the prevention and timely treatment of chronic complications of diabetes.

In addition to traditional drugs in recent years in clinical practice is being introduced more and more effective new drugs, many of which have unique properties. Thus, the use of new drugs sulfonylureas daily glimepiride and glipizide steps you can take 1 every day. Proposed and a short-acting drug that restores insulin secretion after a meal, repaglinide. Studied drugs that affect peripheral insulin resistance (group glitazones).

Development of diabetology ensures a high metabolic control of patients with type 2 diabetes, because Doctors have in the arsenal of modern tablet preparations and preparations of insulin, the means of their introduction, the means of self-control training system patients. All of this in clinical practice makes it possible to provide a high quality of life and delay the development of chronic complications of the disease.

Educating Patients with Diabetes Mellitus

In diabetes mellitus (especially type 1 diabetes), the patient must spend life rather complicated treatment, right to expect the necessary amount of insulin which is necessary to introduce to balance effect of food (which is evaluated using a system of "bread units), taking into account the level of blood glucose before meal, the effect of physical activity, comorbidities, etc.

In order to successfully manage their own blood glucose levels, the patient must undergo a special training program "Diabetes School". Usually it is held in the form of group sessions, total duration of at least 20-25 hours of study in type 1 diabetes and at least 15-20 hours of type 2 diabetes.

Such training has been called a structured and fundamentally different from simple conversations with patients (or read them lectures) for those or other topics related to diabetes. For structured learning characteristically follow a specially prepared program, divided into topics and learning steps within these themes. Teaching the next block of the material begins only after the group had learned the previous one. The level of knowledge of patients is monitored by means of questionnaire at the beginning and end of the course. Sufficient attention should be given the practical activity of patients: problem solving ("how to act in a particular case"), development of skills of self-control blood glucose, insulin injection techniques, etc.).

Not every endocrinologist (capable of competently treat patients with diabetes) is capable of without the proper training to conduct group training. In this regard, there are special methods of preparation "educator" (which may include doctors (mostly in Russia) or nurses (often overseas)).

When type 2 diabetes, such training is no less important than in type 1 diabetes. Courses for patients with type 2 diabetes not receiving insulin and receiving, are distinct. Education in these categories should always be carried out separately. For patients without insulin emphasis is on nutrition, weight loss. The program also includes a self-blood glucose, proper docking of hypoglycaemia, prevention of complications of diabetes. The result of well-conducted study is to reduce weight, the actual inclusion of glucose-lowering effect of dieting, which reduces the dosage of OSSP. It is shown that the frequency of self-control is correlated with the quality of diabet.

When type 2 diabetes on insulin therapy, in addition to the above, training is needed to the rules of insulin, as well as the fact that the carbohydrate content in foods should be distinguished from the caloric content. The degree of self-correction of insulin varies depending on the abilities and motivation of the patient: the increase / decrease the dose of ICDs for 2-4 units with a high / low blood sugar before eating (this patient is recommended to maintain approximately the same carbohydrate content in meals each day) to intensive diabetes management c calculated required dose of insulin before a meal on the "bread units" as in type 1 diabetes.

The problem, which often takes place in Russia lies in the fact that education in the School of diabetes, "runs the majority of patients, but very often it is formal in nature, conducted in violation of principles of group patient education. As a result, many patients retain the state of decompensation of diabetes and can not really control your blood sugar in spite of the training.

The most frequent errors in training:

Combining the classroom in patients with type 2 diabetes receiving and not receiving insulin (and even more so - with type 1 and type 2) Education in too large groups (more than 8-10 patients), which makes it impossible to work individually with each of them, control the assimilation of material and adjust therapy during the course.

Continuous reading of a series of lectures at the hospital in which hospitalized patients begin studying from 1 st class, but with what is currently Insufficient duration of the course. Lack of proper training and certification of "educator" (eg, conducting classes alternately all doctors belonging to the staff offices).

Lack of interactive learning and its integration with the treatment process. Complete the School of diabetes - is not just a series of lectures (and even more so - not videokurs demonstrated by patients), but detailed answers to questions from the audience, evaluation and self-correction therapy for each participant group. This provides not only the transfer of educational material, but also the creation of the listeners of motivation to adopt the new behaviors required for successful management of diabetes.

In the "Patients" were surveyed site visitors on how quality education they occurred.

Drug-Free Treatment for Type 2 Diabetes

Drug-free treatment - an important part of the patient with diabetes, especially when it comes to treatment and prevention of type 2 diabetes mellitus.

 Key measures of non-drug treatment of diabetes can be characterized as "healthy way of life" - the normalization and maintenance of normal body weight, nutritional therapy (individual meal plan), not smoking and excessive alcohol consumption and regular exercise.

    Treatment of food (nutritional therapy) occupies an important place on the stage of prevention, treatment of diabetes, as well as prevention / slowing the progression of diabetic complications.

    Goal of nutritional therapy - to achieve and maintain target blood glucose, cholesterol, blood pressure, normal body weight with regard to the specifics needs and preferences of individual patients. All dietary restrictions should be based on scientific evidence.

    Clinical studies of the effectiveness of nutritional therapy have shown that adequate nutrition leads to a reduction in HbA1c by 1% in patients with type 1 diabetes and 1.2% in patients with type 2 diabetes, and the effectiveness of individual food plan depends on the length of diabetes - the earlier intervention started, so it efficiently. Meta-analysis of studies of NT in people without diabetes, indicating a decrease in LDL cholesterol by 15-25 mg / dl.

Meta-analysis of clinical trials and expert opinion also confirmed the important role of lifestyle changes in the treatment of hypertension.

Is very important to support physician or other, so our advice on lifestyle changes and / or food should be specific and consistent, and support - regular.

• Patients who are overweight (particularly in patients with type 2 diabetes) to assist in lifestyle modifications - reducing daily caloric intake, primarily - at the expense of fat (no more than 30% of daily calories), the development plan for regular physical activity. Goal - a persistent reduction in body weight by 5-7%. Additional possible gives medical therapy of obesity, while a BMI over 35 kg/m2 is recommended the use of bariatric surgery, which also has a positive effect on diabetes control. Available data do not allow us to recommend a diet for patients with severely restricting carbohydrates, starvation or drastic reduction of daily calories (less than 800 kcal / day).

• As a foundation food (50-60% of daily calories) in patients with diabetes are recommended to complex carbohydrates with plenty of fiber (vegetables, fruits, legumes, whole grains, dairy products low in fat). The key point in achieving normoglycemia, especially in patients treated with insulin injections, is the allowance of carbohydrates in the diet (perhaps use different systems of counting). Restriction of foods with a high glycemic index may bring additional benefits compared with simple light carbohydrate, but not necessarily demand it. If the patient uses the simple carbohydrates, this should be taken into account in treatment. Instead of table sugar and may safely use nekaloriynyh sweeteners, but is not recommended to use fructose in large amounts.

• We recommend limiting consumption of saturated fats (less than 7% of daily calories), particularly in patients with dyslipidemia, and the introduction of the diet of fish dishes (2 or more times per week).

• In the absence of proteinuria, the recommended protein content in food - 15-20% of daily calories.

• If a patient with diabetes, drinking alcohol, it is considered safe moderate drinking (no more than 15 g in terms of pure alcohol per day for women and no more than 30 grams - for men).

• Patients are often asked to advise the "vegetable" for the treatment of diabetes, many of our patients take a variety of dietary supplements and surcharges. Patients should be informed that the scientific evidence on the usefulness of certain herbs and nutritional supplements in people with diabetes do not exist. In addition, their possible side effects and interactions with other drugs are not known.

• A mandatory moment is training in proper behavior during hypoglycemia, as well as measures to prevent it (if you exercise, concomitant diseases, changes in the usual mode of day, etc.).

• Physical activity is especially important for overweight and obesity. It should be regular, with a gradual increase of the intensity of the load and taking into account patient preference and existing comorbidities.

Insulin Therapy in Diabetes Mellitus Type 1

   Basic principles:

    • Intensified insulin therapy (mode "basal bolus"). Such a mode of insulin administration most closely matches the daily profile of insulin in humans without diabetes. Short-acting insulin (ICD) is inserted before each meal, insulin is longer-acting (SDI) introduced 1 or 2 times a day, creating a background concentration of insulin between meals (including at night).

    • The patient can and should be independently change the dose of insulin (in the first place, ICD), depending on blood glucose before meals and the amount of carbohydrates eaten (counting on the "bread units (XE), as well as taking into account physical activity, comorbidities, etc.

    • To successfully manage diabetes, the patient must undergo special training (usually a group) on a structured program "Diabetes School" (at least 20-25 hours of training, with the program, divided into training steps, with sufficient attention to the practical activity of patients, etc.).

    • Diet for type 1 diabetes is a "liberalized". Almost any dish can be estimated action with the help of bread units and balance it correctly calculated the short-acting insulin dose. Saved only minor limitations: (1) not more than 7-10 XE for eating, (2) avoid much carbohydrates (fruit juices, lemonade), because increase blood glucose after taking "ahead of" the action of insulin, (3) avoid foods in which it is difficult to calculate the XE and determine the rate of assimilation.

    • Role of the endocrinologist: monitoring the success of diabetes management (blood glucose measurement results, the patient recorded in the diary of self-control, glycated hemoglobin), assistance in making the right decisions on the calculation of doses of insulin (discussion blog), regular screening for early detection or exclusion of diabetic complications (assessment of the "target organs" DM).
    Means of insulin

    • Insulin syringes (with graduation not in ml, and in units of insulin, and a short (6-13 mm) needle for subcutaneous injection)

    • Syringe-pen (automatic syringe with a cartridge of insulin for several days). Injections and the addition of antimicrobial agents in the insulin eliminates the risk of inflammation and infection at the injection site, even if its holding through a thin layer of clothing. Treatment of skin with alcohol when insulin injections are required.

    • Bezigolny injector for insulin (sold in Russia, but has no great advantages over the syringe-pen)

    • dosing of insulin (insulin pump): portable and small device on his belt, which continuously delivers insulin short-acting subcutaneously injected through the catheter. Background (basal) of insulin similar to longer-acting insulin, and served during the meal boluses - short-acting drug. Dose of insulin (as in the background flow, and during the meal) is determined by the patient on the basis of the doctor's recommendations and the results of self-control (ie, pump does not regulate blood sugar automatically, on the basis of feedback). The pump is not removed at night, but can be switched off for a short time (up to 1-2 hours - on the shower, swimming, etc.).

The advantages of the pump before injection with a pen or a syringe - insulin in the lung at any number of carbohydrates taken even in small "bite" (the usual treatment of ICD is introduced, usually 2-4 times a day) and the ability to fine tune the speed of the background flow insulin at different times of day (important when the phenomenon of "dawn"). Disadvantages - the need for a permanent location on the pump body (even during sleep) and the high cost of equipment and consumables. Insulin pump to fully disclose its advantages in well-trained patients are able to successfully manage their glucose levels with conventional insulin. In this case, the transition to pump therapy treatment leads to some improvement in the diabet (reduction of glycated hemoglobin HbA1c by an average of 1%). 

Technology insulin

The correctness of insulin (both patients and medical staff) is very important, because if not properly introduce undesirable effect of insulin is attenuated or amplified, as is often unpredictable, ie, the strength of insulin action may not completely match the number of input units. If unexpectedly weak effect of insulin or "chaotic behavior" of glycemia during the day checking equipment injections - the first and necessary step in finding the causes of decompensation. This can be done with a special leaflet