Do you need to eat long insulin before bed? Which prolonged insulin is better - Lantus or Levemir? Comparison of the rules for calculating the morning and evening dose

For a person with an absolute deficiency of the hormone insulin, the goal of treatment is to repeat as closely as possible the natural secretion, both basic and stimulated. This article will tell you about the correct selection of the dose of basal insulin.

Among diabetics, the expression "keep an even background" is popular, for this an adequate dose of long-acting insulin is needed.

Long-acting insulin

Long-acting insulin is used to mimic basal secretion. In the diabetic slang of diabetics there are phrases:

• "long insulin"
• "Basic Insulin"
• "basal",
• "extended insulin"
• long insulin.

All of these terms mean long-acting insulin. There are two types of long-acting insulins in use today.

Intermediate-lasting insulin - its action lasts up to 16 hours:

1. Biosulin N.
2. Insuman Bazal.
3. Protafan NM.
4. Humulin NPH.

Ultra-long acting insulin - works for more than 16 hours:

• Levemir.
• Lantus.

Levemir and Lantus differ from other insulins not only in their different duration of action, but also in their external absolute transparency, while the preparations of the first group have a white cloudy color, and before administration they need to be rolled in the palms, then the solution becomes evenly cloudy.

This difference is due to different ways of producing insulin preparations, but more on that later. Intermediate-acting drugs are considered peak, that is, in the mechanism of their action, a not too pronounced path is visible, like short-acting insulins, but still there is a peak.

Insulins of ultra-long action are considered to be peak-free. When choosing a dose of a basal preparation, this feature must be taken into account. However, the general plan rules for all insulins remain the same.

Important! The dose of long-acting insulin should be adjusted in such a way as to keep the concentration of glucose in the blood between meals normal. Small fluctuations within 1-1.5 mmol / l are allowed.

In other words, with the correct dosage, glucose in the bloodstream should not decrease or, conversely, increase. The indicator should be stable during the day.

It should be clarified that the injection of long-acting insulin is done in the thigh or buttock, but not in the stomach and not in the arm. This is the only way to ensure smooth suction. Short-acting insulin is injected into the arm or abdomen to achieve a maximum peak, which should coincide with the period of absorption of food.

Insulin long - dose at night

It is recommended to start the choice of a dose of long-acting insulin with a dose at night. A patient with diabetes should monitor the behavior of glucose in the blood at night. To do this, every 3 hours it is necessary to measure the level of sugar, starting from 21 o'clock and ending at 6 o'clock in the morning of the next day.

If in one of the intervals there are significant fluctuations in the concentration of glucose towards an increase or, conversely, towards a decrease, this indicates that the dose of the drug was chosen incorrectly.

In such a situation, this section of time needs to be reviewed in more detail. For example, the patient goes to rest with glucose 6 mmol / l. At 24:00, the figure rises to 6.5 mmol / l, and at 03:00 it suddenly rises to 8.5 mmol / l. A person meets the morning with a high concentration of sugar.

The situation indicates that the nightly amount of insulin was not enough and the dose should be gradually increased. But there is one "but"!

With the existence of such an increase (and higher) at night, it may not always mean a lack of insulin. Sometimes hypoglycemia is hidden under these manifestations, which makes a kind of “rollback”, manifested by an increase in the level of glucose in the bloodstream.

• To understand the mechanism of the increase in sugar at night, the interval between level measurements must be reduced to 1 hour, that is, measured every hour between 24:00 and 03:00 hh.
• If a decrease in glucose concentration is observed in this place, it is quite possible that this was a disguised “hypovka” with a rollback. In this case, the dose of basic insulin should not be increased, but reduced.
• In addition, the effectiveness of the action of basic insulin is also affected by the food eaten per day.
• Therefore, in order to properly assess the effect of basal insulin, the blood should not have glucose and short-acting insulin from food.
• To do this, the dinner preceding the assessment should be skipped or rescheduled to an earlier time.

Only then the meal and the short insulin introduced at the same time will not affect the clarity of the picture. For the same reason, it is recommended to eat only carbohydrate foods for dinner, but exclude fats and proteins.

These elements are absorbed much more slowly and subsequently can increase the level of sugar, which is highly undesirable for a correct assessment of the action of basal night insulin.

Insulin long - dose per day

Checking basal insulin during the day is also quite simple, for this you just have to starve a little, and do sugar measurements every hour. This method will help to determine in which period there is an increase, and in which - a decrease.

If this is not possible (for example, in young children), the work of basic insulin should be reviewed in periods. For example, you should first skip breakfast and measure every hour from the moment you wake up or from the moment you enter your baseline daily insulin (if one is prescribed) until lunch. A few days later, the pattern is repeated with lunch, and even later - with dinner.

Most long-acting insulins have to be administered 2 times a day (the exception is Lantus, which is injected only once).

Note! All of the insulin preparations listed above, except for Levemir and Lantus, have a secretion peak, which, as a rule, occurs 6-8 hours after the injection.

Therefore, during this period, a decrease in glucose levels may be observed, to maintain which a small dose of a “bread unit” is required.

When changing the dose of basal insulin, all these actions are recommended to be repeated several times. Most likely, 3 days will be enough to make sure the dynamics in one direction or another. Further steps are taken according to the result.

When evaluating basal daily insulin, at least 4 hours should elapse between meals, ideally 5. For those using short insulins rather than ultrashort, this interval should be much longer (6-8 hours). This is due to the specific action of these insulins.

If the long insulin is selected correctly, you can proceed to the selection of short insulin.

Insulin (from lat. insula- islet) is a protein-peptide hormone produced by β-cells of the islets of Langerhans of the pancreas. Under physiological conditions, insulin is formed in β-cells from preproinsulin, a single-chain precursor protein consisting of 110 amino acid residues. After transfer through the membrane of the rough endoplasmic reticulum, a signal peptide of 24 amino acids is cleaved from preproinsulin and proinsulin is formed. The long chain of proinsulin is packed into granules in the Golgi apparatus, where four basic amino acid residues are cleaved off as a result of hydrolysis to form insulin and a C-terminal peptide (the physiological function of the C-peptide is unknown).

The insulin molecule consists of two polypeptide chains. One of them contains 21 amino acid residues (chain A), the second - 30 amino acid residues (chain B). The chains are connected by two disulfide bridges. The third disulfide bridge is formed within chain A. The total molecular weight of the insulin molecule is about 5700. The amino acid sequence of insulin is considered to be conservative. Most species have one insulin gene encoding one protein. The exceptions are rats and mice (they have two insulin genes), they form two insulins that differ in two amino acid residues of the B chain.

The primary structure of insulin in different biological species, incl. and in different mammals, is somewhat different. The closest to the structure of human insulin is porcine insulin, which differs from human insulin by one amino acid (it has an alanine residue in the B chain instead of the threonine amino acid residue). Bovine insulin differs from human insulin in three amino acid residues.

History reference. In 1921, Frederick G. Banting and Charles G. Best, working in the laboratory of John J. R. McLeod at the University of Toronto, isolated an extract from the pancreas (later found to contain amorphous insulin) that lowered blood glucose levels in dogs. with experimental diabetes. In 1922, pancreatic extract was administered to the first patient, 14-year-old Leonard Thompson, who had diabetes, and thus saved his life. In 1923, James B. Collip developed a technique for purifying the extract from the pancreas, which subsequently made it possible to obtain active extracts from the pancreas of pigs and cattle, giving reproducible results. In 1923, Banting and MacLeod were awarded the Nobel Prize in Physiology or Medicine for their discovery of insulin. In 1926, J. Abel and V. Du Vigno received crystalline insulin. In 1939, insulin was first approved by the FDA (Food and Drug Administration). Frederick Sanger completely deciphered the amino acid sequence of insulin (1949-1954) In 1958, Sanger was awarded the Nobel Prize for his work on deciphering the structure of proteins, especially insulin. In 1963 artificial insulin was synthesized. The first recombinant human insulin was approved by the FDA in 1982. An ultra-rapid insulin analog (insulin lispro) was approved by the FDA in 1996.

Mechanism of action. In the implementation of the effects of insulin, the leading role is played by its interaction with specific receptors localized on the plasma membrane of the cell and the formation of the insulin-receptor complex. In combination with the insulin receptor, insulin enters the cell, where it affects the processes of phosphorylation of cellular proteins and triggers numerous intracellular reactions.

In mammals, insulin receptors are found on almost all cells, both on classical insulin target cells (hepatocytes, myocytes, and lipocytes) and on blood, brain, and gonadal cells. The number of receptors on different cells ranges from 40 (erythrocytes) to 300 thousand (hepatocytes and lipocytes). The insulin receptor is constantly synthesized and degraded, its half-life is 7-12 hours.

The insulin receptor is a large transmembrane glycoprotein consisting of two 135 kDa α-subunits (each containing 719 or 731 amino acid residues depending on mRNA splicing) and two 95 kDa β-subunits (620 amino acid residues each). The subunits are interconnected by disulfide bonds and form a heterotetrameric structure β-α-α-β. The alpha subunits are located extracellularly and contain insulin binding sites, being the recognition part of the receptor. Beta subunits form a transmembrane domain, have tyrosine kinase activity, and perform a signal transduction function. Binding of insulin to α-subunits of the insulin receptor leads to stimulation of the tyrosine kinase activity of β-subunits by autophosphorylation of their tyrosine residues, aggregation of α,β-heterodimers and rapid internalization of hormone-receptor complexes occur. An activated insulin receptor triggers a cascade of biochemical reactions, incl. phosphorylation of other proteins within the cell. The first of these reactions is the phosphorylation of four proteins called insulin receptor substrates, IRS-1, IRS-2, IRS-3, and IRS-4.

Pharmacological effects of insulin. Insulin affects almost all organs and tissues. However, its main targets are the liver, muscle and adipose tissue.

Endogenous insulin is the most important regulator of carbohydrate metabolism, while exogenous insulin is a specific sugar-lowering agent. The effect of insulin on carbohydrate metabolism is due to the fact that it enhances the transport of glucose through the cell membrane and its utilization by tissues, promotes the conversion of glucose into glycogen in the liver. Insulin also inhibits endogenous glucose production by inhibiting glycogenolysis (the breakdown of glycogen to glucose) and gluconeogenesis (the synthesis of glucose from non-carbohydrate sources, such as amino acids, fatty acids). In addition to hypoglycemic effects, insulin has a number of other effects.

The effect of insulin on fat metabolism is manifested in the inhibition of lipolysis, which leads to a decrease in the flow of free fatty acids into the bloodstream. Insulin prevents the formation of ketone bodies in the body. Insulin enhances the synthesis of fatty acids and their subsequent esterification.

Insulin is involved in protein metabolism: it increases the transport of amino acids across the cell membrane, stimulates the synthesis of peptides, reduces protein consumption by tissues, and inhibits the conversion of amino acids into keto acids.

The action of insulin is accompanied by the activation or inhibition of a number of enzymes: glycogen synthetase, pyruvate dehydrogenase, hexokinase are stimulated, lipases are inhibited (both hydrolyzing adipose tissue lipids and lipoprotein lipase, which reduces the "turbidity" of blood serum after eating fat-rich foods).

In the physiological regulation of the biosynthesis and secretion of insulin by the pancreas, the main role is played by the concentration of glucose in the blood: with an increase in its content, insulin secretion increases, with a decrease, it slows down. Insulin secretion, in addition to glucose, is influenced by electrolytes (especially Ca 2+ ions), amino acids (including leucine and arginine), glucagon, somatostatin.

Pharmacokinetics. Insulin preparations are administered s.c., i.m. or i.v. You can not enter into / in the suspension of insulin. The temperature of the injected insulin should correspond to room temperature, because. cold insulin is absorbed more slowly. The most optimal way for continuous insulin therapy in clinical practice is subcutaneous administration.

The completeness of absorption and the beginning of the effect of insulin depend on the injection site (usually insulin is injected into the abdomen, thighs, buttocks, upper arms), dose (volume of injected insulin), concentration of insulin in the preparation, etc.

The rate of insulin absorption into the blood from the s / c injection site depends on a number of factors - the type of insulin, the injection site, the local blood flow rate, local muscle activity, the amount of insulin injected (it is recommended to inject no more than 12-16 IU of the drug in one place). Insulin enters the blood faster from the subcutaneous tissue of the anterior abdominal wall, more slowly from the shoulder area, anterior thigh, and even more slowly from the subscapular region and buttocks. This is due to the degree of vascularization of the subcutaneous adipose tissue of these areas. The action profile of insulin is subject to significant fluctuations both in different people and in the same person.

In the blood, insulin binds to alpha and beta globulins, normally 5-25%, but binding may increase during treatment due to the appearance of serum antibodies (the production of antibodies to exogenous insulin leads to insulin resistance; with modern highly purified drugs, insulin resistance rarely occurs ). T 1/2 from the blood is less than 10 minutes. Most of the insulin that enters the bloodstream undergoes proteolytic breakdown in the liver and kidneys. Rapidly excreted from the body by the kidneys (60%) and liver (40%); less than 1.5% is excreted in the urine unchanged.

Insulin preparations currently used differ in a number of ways, incl. according to the source of origin, duration of action, pH of the solution (acidic and neutral), the presence of preservatives (phenol, cresol, phenol-cresol, methylparaben), insulin concentration - 40, 80, 100, 200, 500 IU / ml.

Classification. Insulins are usually classified by origin (bovine, porcine, human, and human insulin analogues) and duration of action.

Depending on the sources of production, there are insulins of animal origin (mainly porcine insulin preparations), semi-synthetic human insulin preparations (obtained from porcine insulin by enzymatic transformation), genetically engineered human insulin preparations (DNA-recombinant, obtained by genetic engineering).

For medical use, insulin was previously obtained mainly from bovine pancreas, then from porcine pancreas, given that porcine insulin is closer to human insulin. Since bovine insulin, which differs from human in three amino acids, often causes allergic reactions, today it is practically not used. Pork insulin, which differs from human insulin by one amino acid, is less likely to cause allergic reactions. Impurities (proinsulin, glucagon, somatostatin, proteins, polypeptides) that can cause various side reactions may be present in insulin medicines if they are not sufficiently purified. Modern technologies make it possible to obtain purified (monopic - chromatographically purified with the release of the "peak" of insulin), highly purified (monocomponent) and crystallized insulin preparations. Of the insulin preparations of animal origin, preference is given to monopeak insulin obtained from the pancreas of pigs. Genetically engineered insulin fully corresponds to the amino acid composition of human insulin.

Insulin activity is determined by a biological method (by the ability to lower blood glucose in rabbits) or by a physicochemical method (by electrophoresis on paper or by chromatography on paper). For one unit of action, or international unit, take the activity of 0.04082 mg of crystalline insulin. The human pancreas contains up to 8 mg of insulin (approximately 200 IU).

Insulin preparations according to the duration of action are divided into preparations of short and ultrashort action - imitate the normal physiological secretion of insulin by the pancreas in response to stimulation, medium-duration and long-acting preparations - imitate basal (background) secretion of insulin, as well as combined preparations (combine both actions) .

The following groups are distinguished:

(the hypoglycemic effect develops 10-20 minutes after s / c injection, the peak of action is achieved on average after 1-3 hours, the duration of action is 3-5 hours):

Insulin lispro (Humalog);

Insulin aspart (NovoRapid Penfill, NovoRapid FlexPen);

Insulin glulisin (Apidra).

Short acting insulins(onset of action usually after 30-60 minutes; maximum action after 2-4 hours; duration of action up to 6-8 hours):

Soluble insulin [human genetically engineered] (Actrapid HM, Gensulin R, Rinsulin R, Humulin Regular);

Soluble insulin [human semi-synthetic] (Biogulin R, Humodar R);

Soluble insulin [pork monocomponent] (Actrapid MS, Monodar, Monosuinsulin MK).

Long-acting insulin preparations- Includes intermediate-acting and long-acting drugs.

(onset after 1.5-2 hours; peak after 3-12 hours; duration 8-12 hours):

Insulin Isophane [human genetically engineered] (Biosulin N, Gansulin N, Gensulin N, Insuman Basal GT, Insuran NPH, Protafan NM, Rinsulin NPH, Humulin NPH);

Insulin isophane [human semi-synthetic] (Biogulin N, Humodar B);

Insulin isophane [pork monocomponent] (Monodar B, Protafan MS);

Composite insulin-zinc suspension (Monotard MS).

Long acting insulins(onset after 4-8 hours; peak after 8-18 hours; total duration 20-30 hours):

insulin glargine (Lantus);

Insulin detemir (Levemir Penfill, Levemir FlexPen).

Combination insulin preparations(biphasic drugs) (hypoglycemic effect begins 30 minutes after s / c injection, reaches a maximum after 2-8 hours and lasts up to 18-20 hours):

Biphasic insulin [human semi-synthetic] (Biogulin 70/30, Humodar K25);

Biphasic insulin [human genetically engineered] (Gansulin 30R, Gensulin M 30, Insuman Comb 25 GT, Mixtard 30 NM, Humulin M3);

Biphasic insulin aspart (NovoMix 30 Penfill, NovoMix 30 FlexPen).

Ultrashort-acting insulins human insulin analogues. It is known that endogenous insulin in pancreatic β-cells, as well as hormone molecules in short-acting insulin solutions produced, are polymerized and are hexamers. With s / c administration, hexameric forms are absorbed slowly and a peak in the concentration of the hormone in the blood, similar to that in a healthy person after a meal, cannot be created. The first short-acting insulin analogue that is absorbed from the subcutaneous tissue 3 times faster than human insulin was insulin lispro. Insulin lispro is a derivative of human insulin obtained by rearranging two amino acid residues in the insulin molecule (lysine and proline at positions 28 and 29 of the B chain). Modification of the insulin molecule disrupts the formation of hexamers and ensures the rapid entry of the drug into the blood. Almost immediately after subcutaneous administration, insulin lispro molecules in the form of hexamers quickly dissociate into monomers in the tissues and enter the bloodstream. Another insulin analogue, insulin aspart, was created by replacing the proline at position B28 with the negatively charged aspartic acid. Like insulin lispro, after subcutaneous administration, it also quickly decomposes into monomers. In insulin glulisine, the replacement of the human insulin asparagine amino acid at position B3 with lysine and the lysine at position B29 with glutamic acid also promotes faster absorption. Rapid-acting insulin analogs can be administered immediately before meals or after meals.

Short acting insulins(also called soluble) are buffered solutions with neutral pH values ​​(6.6-8.0). They are intended for subcutaneous, less often - intramuscular injection. If necessary, they are also administered intravenously. They have a rapid and relatively short hypoglycemic effect. The effect after subcutaneous injection occurs after 15-20 minutes, reaches a maximum after 2 hours; the total duration of action is approximately 6 hours. They are used mainly in the hospital during the establishment of the dose of insulin necessary for the patient, and also when a quick (urgent) effect is required - in diabetic coma and precoma. With intravenous administration, T 1/2 is 5 minutes, therefore, in diabetic ketoacidotic coma, insulin is administered intravenously. Short-acting insulin preparations are also used as anabolic agents and are prescribed, as a rule, in small doses (4-8 IU 1-2 times a day).

Intermediate-acting insulins less soluble, more slowly absorbed from the subcutaneous tissue, resulting in a longer effect. The long-term effect of these drugs is achieved by the presence of a special prolongator - protamine (isophane, protaphan, basal) or zinc. The slowing down of insulin absorption in preparations containing insulin-zinc composite suspension is due to the presence of zinc crystals. NPH-insulin (Hagedorn neutral protamine, or isophane) is a suspension consisting of insulin and protamine (protamine is a protein isolated from fish milk) in a stoichiometric ratio.

For long-acting insulins Insulin glargine, an analogue of human insulin obtained by DNA recombinant technology, is the first insulin preparation that does not have a pronounced peak of action. Insulin glargine is produced by two modifications in the insulin molecule: by replacing position 21 of the A chain (asparagine) with glycine and by adding two arginine residues to the C-terminus of the B chain. The drug is a clear solution with a pH of 4. The acidic pH stabilizes the insulin hexamers and ensures long-term and predictable absorption of the drug from the subcutaneous tissue. However, due to the acidic pH, insulin glargine cannot be combined with short-acting insulins that have a neutral pH. A single dose of insulin glargine provides 24-hour peak-free glycemic control. Most insulin preparations have a so-called. "peak" action, marked when the concentration of insulin in the blood reaches a maximum. Insulin glargine does not have a pronounced peak because it is released into the bloodstream at a relatively constant rate.

Long-acting insulin preparations are available in various dosage forms that have a hypoglycemic effect of different duration (from 10 to 36 hours). The prolonged effect allows to reduce the number of daily injections. They are usually produced in the form of suspensions, administered only subcutaneously or intramuscularly. In diabetic coma and precomatous conditions, prolonged preparations are not used.

Combined insulin preparations are suspensions consisting of neutral soluble short-acting insulin and insulin-isophane (medium-long-acting) in certain ratios. This combination of insulins of different duration of action in one preparation allows the patient to save the patient from two injections when the preparations are used separately.

Indications. The main indication for the use of insulin is type 1 diabetes mellitus, however, under certain conditions, it is also prescribed for type 2 diabetes, incl. with resistance to oral hypoglycemic agents, with severe concomitant diseases, in preparation for surgery, diabetic coma, and diabetes in pregnant women. Short-acting insulins are used not only for diabetes mellitus, but also for some other pathological processes, for example, with general exhaustion (as an anabolic agent), furunculosis, thyrotoxicosis, stomach diseases (atony, gastroptosis), chronic hepatitis, initial forms of liver cirrhosis , as well as with some mental illnesses (the introduction of large doses of insulin - the so-called hypoglycemic coma); it is sometimes used as a component of "polarizing" solutions used to treat acute heart failure.

Insulin is the main specific treatment for diabetes mellitus. Treatment of diabetes mellitus is carried out according to specially designed schemes using insulin preparations of different duration of action. The choice of the drug depends on the severity and characteristics of the course of the disease, the general condition of the patient and the speed of onset and duration of the hypoglycemic effect of the drug.

All insulin preparations are used subject to the obligatory observance of the dietary regimen with the restriction of the energy value of food (from 1700 to 3000 kcal).

When determining the dose of insulin, they are guided by the level of glycemia on an empty stomach and during the day, as well as the level of glycosuria during the day. The final selection of the dose is carried out under the control of reducing hyperglycemia, glucosuria, as well as the general condition of the patient.

Contraindications. Insulin is contraindicated in diseases and conditions that occur with hypoglycemia (for example, insulinoma), in acute diseases of the liver, pancreas, kidneys, gastric and duodenal ulcers, decompensated heart disease, in acute coronary insufficiency and some other diseases.

Application during pregnancy. The main drug treatment for diabetes during pregnancy is insulin therapy, which is carried out under close supervision. In type 1 diabetes mellitus, insulin treatment is continued. In type 2 diabetes, oral hypoglycemic agents are canceled and diet therapy is carried out.

Gestational diabetes mellitus (diabetes in pregnancy) is a carbohydrate metabolism disorder that first occurs during pregnancy. Gestational diabetes mellitus is associated with an increased risk of perinatal mortality, the incidence of congenital malformations, as well as the risk of progression of diabetes 5-10 years after birth. Treatment of gestational diabetes begins with diet therapy. In case of failure of diet therapy, insulin is used.

For patients with pre-existing or gestational diabetes mellitus, it is important to maintain adequate regulation of metabolic processes throughout pregnancy. The need for insulin may decrease in the first trimester of pregnancy and increase in the II-III trimesters. During childbirth and immediately after them, the need for insulin can drop sharply (the risk of developing hypoglycemia increases). Under these conditions, careful monitoring of blood glucose levels is essential.

Insulin does not cross the placental barrier. However, maternal IgG antibodies to insulin pass through the placenta and are likely to cause hyperglycemia in the fetus by neutralizing its secreted insulin. On the other hand, unwanted dissociation of insulin-antibody complexes can lead to hyperinsulinemia and hypoglycemia in the fetus or newborn. It has been shown that the transition from bovine/porcine insulin preparations to monocomponent preparations is accompanied by a decrease in antibody titer. In this regard, during pregnancy, it is recommended to use only human insulin preparations.

Insulin analogs (as well as other recently developed agents) are used with caution during pregnancy, although there are no reliable data on adverse effects. In accordance with the generally accepted recommendations of the FDA (Food and Drug Administration), which determine the possibility of using drugs during pregnancy, insulin preparations for the effect on the fetus belong to category B (the study of reproduction in animals did not reveal an adverse effect on the fetus, and adequate and strictly controlled studies in pregnant women women have not been conducted), or category C (animal reproduction studies have shown adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not been conducted, but the potential benefit associated with the use of drugs in pregnant women may justify its use, despite possible risk). For example, insulin lispro belongs to class B, while insulin aspart and insulin glargine belong to class C.

Complications of insulin therapy. Hypoglycemia. The introduction of too high doses, as well as a lack of carbohydrate intake with food, can cause an undesirable hypoglycemic state, a hypoglycemic coma may develop with loss of consciousness, convulsions and cardiac depression. Hypoglycemia may also develop due to the action of additional factors that increase insulin sensitivity (eg, adrenal insufficiency, hypopituitarism) or increase glucose uptake by tissues (exercise).

Early symptoms of hypoglycemia that are largely associated with activation of the sympathetic nervous system (adrenergic symptoms) include tachycardia, cold sweats, tremors, with activation of the parasympathetic system - severe hunger, nausea, and a tingling sensation in the lips and tongue. At the first signs of hypoglycemia, urgent measures are necessary: ​​the patient should drink sweet tea or eat a few pieces of sugar. In case of hypoglycemic coma, a 40% glucose solution is injected into the vein in an amount of 20-40 ml or more until the patient wakes up from a coma (usually no more than 100 ml). Hypoglycemia can also be relieved by intramuscular or subcutaneous administration of glucagon.

Weight gain with insulin therapy is associated with the elimination of glucosuria, an increase in the real calorie content of food, an increase in appetite and stimulation of lipogenesis under the action of insulin. If you follow the principles of rational nutrition, this side effect can be avoided.

The use of modern highly purified hormone preparations (especially genetically engineered human insulin preparations) relatively rarely leads to the development insulin resistance and phenomena allergies, however, such cases are not excluded. The development of an acute allergic reaction requires immediate desensitizing therapy and drug replacement. If a reaction develops to bovine/porcine insulin preparations, they should be replaced with human insulin preparations. Local and systemic reactions (itching, local or systemic rash, formation of subcutaneous nodules at the injection site) are associated with insufficient purification of insulin from impurities or with the use of bovine or porcine insulin that differs in amino acid sequence from human insulin.

The most common allergic reactions are skin reactions mediated by IgE antibodies. Rarely, systemic allergic reactions are observed, as well as insulin resistance mediated by IgG antibodies.

Violation of vision. Transient refractive errors of the eye occur at the very beginning of insulin therapy and disappear on their own after 2-3 weeks.

Edema. In the first weeks of therapy, transient swelling of the legs also occurs due to fluid retention in the body, the so-called. insulin edema.

Local reactions include lipodystrophy at the site of repeated injections (rare complication). There are lipoatrophy (disappearance of subcutaneous fat deposits) and lipohypertrophy (increased subcutaneous fat deposits). These two states are of a different nature. Lipoatrophy, an immunological reaction mainly due to the administration of poorly purified animal-derived insulin preparations, is now virtually non-existent. Lipohypertrophy also develops with the use of highly purified human insulin preparations and can occur if the injection technique is violated (cold preparation, alcohol getting under the skin), as well as due to the anabolic local action of the drug itself. Lipohypertrophy creates a cosmetic defect, which is a problem for patients. In addition, due to this defect, the absorption of the drug is impaired. To prevent the development of lipohypertrophy, it is recommended to constantly change injection sites within the same area, leaving a distance of at least 1 cm between two punctures.

There may be local reactions such as pain at the injection site.

Interaction. Insulin preparations can be combined with each other. Many drugs can cause hypo- or hyperglycemia, or change the response of a diabetic patient to treatment. It is necessary to take into account the interaction possible with the simultaneous use of insulin with other drugs. Alpha-blockers and beta-agonists increase the secretion of endogenous insulin and enhance the effect of the drug. The hypoglycemic effect of insulin is enhanced by oral hypoglycemic agents, salicylates, MAO inhibitors (including furazolidone, procarbazine, selegiline), ACE inhibitors, bromocriptine, octreotide, sulfonamides, anabolic steroids (especially oxandrolone, methandienone) and androgens (increase tissue sensitivity to insulin and increase tissue resistance to glucagon, which leads to hypoglycemia, especially in case of insulin resistance; insulin dose reduction may be necessary), somatostatin analogues, guanethidine, disopyramide, clofibrate, ketoconazole, lithium preparations, mebendazole, pentamidine, pyridoxine, propoxyphene, phenylbutazone, fluoxetine, theophylline, fenfluramine , lithium preparations, calcium preparations, tetracyclines. Chloroquine, quinidine, quinine reduce the degradation of insulin and may increase the concentration of insulin in the blood and increase the risk of hypoglycemia.

Carbonic anhydrase inhibitors (especially acetazolamide), by stimulating pancreatic β-cells, promote the release of insulin and increase the sensitivity of receptors and tissues to insulin; although the simultaneous use of these drugs with insulin may increase the hypoglycemic effect, the effect may be unpredictable.

A number of drugs cause hyperglycemia in healthy people and exacerbate the course of the disease in patients with diabetes mellitus. The hypoglycemic effect of insulin is weakened by: antiretroviral drugs, asparaginase, oral hormonal contraceptives, glucocorticoids, diuretics (thiazide, ethacrynic acid), heparin, H 2 receptor antagonists, sulfinpyrazone, tricyclic antidepressants, dobutamine, isoniazid, calcitonin, niacin, sympathomimetics, danazol, clonidine , CCA, diazoxide, morphine, phenytoin, somatotropin, thyroid hormones, phenothiazine derivatives, nicotine, ethanol.

Glucocorticoids and epinephrine have an effect on peripheral tissues that is opposite to that of insulin. Thus, long-term use of systemic glucocorticoids can cause hyperglycemia, up to diabetes mellitus (steroid mellitus), which can occur in about 14% of patients taking systemic corticosteroids for several weeks or with prolonged use of topical corticosteroids. Some drugs inhibit insulin secretion directly (phenytoin, clonidine, diltiazem) or by reducing potassium stores (diuretics). Thyroid hormones speed up the metabolism of insulin.

The most significant and often affect the action of insulin beta-blockers, oral hypoglycemic agents, glucocorticoids, ethanol, salicylates.

Ethanol inhibits gluconeogenesis in the liver. This effect is observed in all people. In this regard, it should be borne in mind that the abuse of alcoholic beverages against the background of insulin therapy can lead to the development of a severe hypoglycemic state. Small amounts of alcohol taken with food usually do not cause problems.

Beta-blockers can inhibit insulin secretion, alter carbohydrate metabolism, and increase peripheral insulin resistance, leading to hyperglycemia. However, they can also inhibit the action of catecholamines on gluconeogenesis and glycogenolysis, which is associated with a risk of severe hypoglycemic reactions in patients with diabetes mellitus. Moreover, any of the beta-blockers can mask adrenergic symptoms caused by a decrease in blood glucose levels (including tremor, palpitations), thereby disrupting the patient's timely recognition of hypoglycemia. Selective beta 1 -blockers (including acebutolol, atenolol, betaxolol, bisoprolol, metoprolol) exhibit these effects to a lesser extent.

NSAIDs and salicylates in high doses inhibit the synthesis of prostaglandin E (which inhibits the secretion of endogenous insulin) and thus enhance basal insulin secretion, increase the sensitivity of pancreatic β-cells to glucose; hypoglycemic effect with simultaneous use may require dose adjustment of NSAIDs or salicylates and / or insulin, especially with prolonged joint use.

Currently, a significant number of insulin preparations are being produced, incl. obtained from the pancreas of animals and synthesized by genetic engineering. The drugs of choice for insulin therapy are genetically engineered highly purified human insulins with minimal antigenicity (immunogenic activity), as well as analogues of human insulin.

Insulin preparations are produced in glass bottles, hermetically sealed with rubber stoppers with aluminum rim, in special so-called. insulin syringes or syringe pens. When using syringe pens, the drugs are in special cartridge bottles (penfills).

Intranasal forms of insulin and oral insulin preparations are being developed. When insulin is combined with a detergent and administered as an aerosol to the nasal mucosa, effective plasma levels are reached as quickly as with intravenous bolus administration. Insulin preparations for intranasal and oral administration are under development or undergoing clinical trials.

Preparations

Preparations - 712 ; Trade names - 126 ; Active ingredients - 22

Insulin is one of the important hormones in the human body. Insulin is produced in the pancreas and has a multifaceted effect on metabolic processes in body tissues. The main task of this bioactive compound is to reduce the concentration of sugars in the body.

When insulin production is impaired, a person develops a disease called diabetes mellitus. As a result of the development of this disease, there is a violation of the processes of carbohydrate metabolism.

People with diabetes are faced with the fact that the level of insulin in the body should be maintained artificially. The amount of insulin injected into the body depends on the size of the difference between the insulin produced by the body and the amount of insulin that the body needs for normal functioning. Existing insulin preparations are divided into several varieties, depending on the speed of achieving the effect and the duration of the drug's action in the body. One type is long-acting insulin.

Extended insulin has a prolonged action due to this property, this type of preparation is called prolonged insulin. This type of artificial hormone acts as the main basic hormone that creates the required insulin background in the patient's body.

Preparations of this type are able to accumulate insulin in the body throughout the day. During the day, it is enough to carry out 1-2 injections to normalize the content of the hormone in the blood. Gradually, from the use of long-acting insulin, the hormonal background in the body normalizes. The effect is achieved on the second or third day, it should be noted that the maximum effect is achieved after 2-3 days, and the drug begins to act after a few hours.

The most common long-acting insulin preparations are as follows:

• Insulin Monodar Long;
• Insulin Ultralong;
• Insulin Lantus.

Among long-acting drugs, the so-called faceless insulin preparations stand apart. This type of insulin, when administered to the body, does not have a pronounced peak of action. The effect of these drugs on the body is smooth and softer. The most famous drugs in this group are Levemir and Lantus.

All types of insulin are given subcutaneously and the injection site should be changed each time. Insulin preparations must not be mixed and diluted.

Choice of long-acting insulin

Before choosing long-acting insulins, you should study information about what this type of insulin is. Additionally, you should study the information specified in the instructions for use and consult with an endocrinologist.

To date, two types of extended-acting insulins are used to treat the disease:

• Insulins with a duration of action up to 16 hours;
• Insulins that have an ultra-long action that lasts more than 16 hours.

The group of first insulins includes:

1. Gensulin N.
2. Biosulin N.
3. Isuman NM.
4. Insuman Bazal.
5. Protafan NM.
6. Humulin NPH.

The group of ultra-long-acting insulins includes:

• Tresiba NEW.
• Levemir.
• Lantus.

Ultralong insulins are peakless. When calculating the dose for an injection with an ultra-long-acting drug, this feature must be taken into account. The remaining selection rules are common to all types of insulin.

When calculating the dose of a single dose in the body, the indicator should be such that the concentration of glucose throughout the entire time between injections remains at the same level within the normal range. Permissible fluctuations should not exceed 1-1.5 mmol / l during this time.

With the correct choice of the dose of insulin, the concentration of glucose in the blood is stable.

It is forbidden to use medicines containing insulin, the shelf life of which is overdue. In the process of storing drugs, it is required to comply with the storage conditions and the shelf life of medical devices. The use of expired insulin in the treatment can provoke increased sweating, weakness, tremors, convulsions, and in some cases even a coma in the patient's body.

Modern long-acting insulin preparations can be taken not only by injection, but also by oral administration of the drug in the process of eating.

Oral administration of the drug is a promising development, which is designed to make life easier for a person with diabetes mellitus.

The action of insulin, indications for use and method of administration

Sugar level

Subcutaneous administration of the drug allows the hormone to be in fatty tissue for some time, which makes it possible to slow down its absorption into the bloodstream.

Indications for the use of long-acting insulin are:

1. The patient has type 1 diabetes.
2. The patient has type 2 diabetes.
3. The presence of the patient's immunity to oral drugs intended to reduce the content of sugars in the blood plasma.
4. Use as a component of complex therapy.
5. Carrying out surgical interventions.
6. Presence of gestational diabetes in pregnancy.

The volume of the hormone used is determined by the endocrinologist on an individual basis and taking into account all the individual characteristics of the patient's body. The endocrinologist will be able to calculate the dose only after receiving the results of a comprehensive examination of the patient and obtaining laboratory tests.

Do not shake the vial of insulin before injecting. Before administering the drug, you only need to scroll the vial of insulin in the palm of your hand, this will allow a homogeneous composition to form and at the same time allow you to warm up the medication before the injection.

When a patient switches from animal insulin to human insulin, the dose should be recalculated.

In the case of a transfer of a patient from one type of drug to another, it is also necessary to adjust the dose of insulin received.

Characteristics of the most common types of extended-acting insulin

One of the common insulin preparations with a prolonged action is Digludec. This drug has a super long-term effect. It is an analogue of human insulin. The manufacturer of this drug is the Danish company Novo Nordisk.

The action of this drug is based on enhancing the utilization of glucose from blood plasma by fat cells and muscle tissue cells.

This process is activated by attaching the hormone to cell receptors. The second effect of the drug is to block the production of glucose by liver cells, which reduces the amount of glucose in the patient's body.

The duration of action of this drug is more than 42 hours. The maximum concentration of insulin in the body is reached 24-36 hours after the administration of the drug.

Insulin glargine is produced by the French company Sanori-Aventis. The composition of the drug includes insulin-glargine, m-cresol, zinc chloride, glycerol, sodium hydroxide, water for injection are used as auxiliary compounds in the composition of the drug.

This form of the drug is an analogue of human insulin.

With the introduction of the drug once a day, a stable concentration of the compound in the patient's body is observed for 2 to 4 days after the administration procedure.

Having a long duration of action of the drug, it allows you to use it during the day only once. After the injection, the effect of the drug begins one hour after the injection.

The drug is allowed to be used only by subcutaneous injection. The drug is injected into the subcutaneous fatty tissue in the abdomen, shoulder or thigh.

Side effects of the use of this remedy are the development of lipodystrophy and a delay in the absorption of insulin.

Contraindication to use is the presence of hypersensitivity to insulin glargine or any of the components of the medication. Additionally, this drug should not be used in children under 6 years of age.

The drug Humulin L is a medical device produced by the American company Eli-Lilli. The tool is a sterile suspension of crystalline human insulin. The drug has a long-term effect.

In the video in this article, the doctor will continue to cover the topic of extended insulin.

Sugar level

Recent discussions.

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There is no absolute cure for diabetes in the world. But the use of prolonged preparations can reduce the number of necessary injections and significantly improve the quality of life.

What is the importance of long-acting insulin in the human body? Medium and long-acting drugs are administered by a diabetic 1-2 times a day (morning and evening) and are basic. The peak of effectiveness of long insulin occurs after 8-10 hours, but the decrease in sugar is noticeable after 3-4 hours.

How to choose a dose of insulin sufficient for a person: small volumes (no more than 10 units) are effective for about 12 hours, a larger amount of the drug - up to a day. If prolonged insulin is prescribed at a dosage exceeding 0.6 units per 1 kg of body weight, then the injection is made in several stages in different places (shoulder, thigh, abdomen).

What gives such treatment?

Long-acting insulin is needed to maintain fasting glucose levels. Only a specialist, based on the patient's self-monitoring, can determine whether the patient needs injections of a short-acting drug before each meal and of medium and long-term action.

The insulin regimen is based on weekly self-checking blood sugar data. In addition, it must be taken into account how the short and long hormones affect the body.

The most effective long-acting insulins are Lantus, Levemir. They are used in both types of diabetes and are administered 1-2 times a day.

Long-acting insulin is prescribed even if the patient is already injecting and short type (before meals). This combination allows you to maintain the state of the body and prevent numerous complications.

Important. Long-acting insulin is a complete replacement for the basal hormone secreted by the pancreas. It also slows down the death of beta cells.

Misapplication

1. Long-term preparations are not used to stabilize glucose after meals. They will not be able to quickly block hyperglycemia. This is explained by a rather slow approach to the peak of efficiency, which differs from short-term funds.
2. Injections not on schedule can greatly affect a person's health:

• sugar level constantly "jumps";
• feeling tired;
• complications of diabetes develop.

Action at night and morning hours

People diagnosed with type 2 diabetes almost always have high blood sugar in the morning. This means that at night the body does not have enough long insulin. But before requiring an extended hormone, the doctor needs to check when the person last eats. If eating occurs five hours or less before bedtime, then long-acting background drugs will not help stabilize sugar.

Poorly explained by experts and the phenomenon of "morning dawn". Shortly before awakening, the liver rapidly neutralizes hormones, which leads to hyperglycemia. And even if you adjust the dose, this phenomenon still makes itself felt.

The effect on the body of this phenomenon determines the injection regimen: the injection is given eight hours or less before the approximate moment of awakening. Already after 9-10 hours, prolonged insulin acts much weaker.

The long-acting drug cannot maintain the sugar level in the morning. If this happens, then the doctor has prescribed an excessive amount of the hormone. Excess drug is fraught with hypoglycemia. In a dream, by the way, it can manifest itself in the form of restlessness and nightmares.

To avoid this condition, you can do this check: four hours after the injection, you need to wake up and measure your glucose level. If the indicator is less than 3.5 mmol / l, then it is advisable to inject prolonged insulin in two stages - immediately before bedtime and after another 4 hours.

Using this regimen allows you to reduce the dose to 10-15%, control the “dawn” phenomenon and wake up with ideal blood sugar.

Common long-acting drugs

Among the long-acting hormones, the following names appear most often (according to RLS):

• ultratape;
• humulin;
• insumanbasal;
• glargine;
• detemir.

The last two samples are characterized as having the most even effect on glucose. Such prolonged insulin is injected only once a day and does not provoke the development of hypoglycemia at night. It is considered promising in the field of insulin therapy.

The long-term effect of insulin Lantus (glargine formulation) can be explained by the very slow absorption when administered subcutaneously. True, to maintain this effect, each time you need to choose a new injection site.

The dose of insulin Lantus is prescribed for long-term stabilization of glucose in the body (up to a day). The product is available in cartridges and syringe pens with a volume of 3 ml and vials with 10 ml of the drug. The duration of action is from 24 to 29 hours. True, the effect throughout the day largely depends on the physiological characteristics of a person.

In the first type of diabetes, long-acting insulin Lantus is prescribed as the main one, in the second type it can be combined with a number of other sugar-lowering drugs.

When switching from short and medium samples to prolonged insulin, the dosage and injection schedule are adjusted in the first days. By the way, in recent years there has been a certain trend in which patients are trying to transfer to ultra-long drugs to reduce the number of injections and improve the quality of life.

Ultra long effect

The long-acting insulins described above are the most effective. They are also distinguished by absolute transparency: they do not need to be shaken, rolled in hands to ensure even distribution of sediment. Along with Lantus, Levemir is the most stable drug, its characteristics are similar for diabetics with both types of the disease.

It should be noted that long forms still have a slight peak of their activity. In turn, these drugs do not have it. And the peculiarity must be taken into account in the process of adjusting the dose.

The basal preparation is calculated based on the ability to maintain a constant, stable blood sugar level. Permissible fluctuations - no more than 1.5 mmol / l. However, during the day after the injection, this should not happen, in principle. As a rule, the prolonged drug is injected into the thigh or buttock. Here, the fatty layer slows down the absorption of the hormone into the blood.

Often, inexperienced diabetics try to replace short insulin with long insulin, which cannot be done. After all, each type of hormone is necessary to perform a strictly defined function. Therefore, the task of the patient is to strictly comply with the prescribed insulin therapy.

Only if long-acting insulin is used correctly, is it possible to achieve a permanently normal reading on the glucometer.

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