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.