Insulin therapy

Insulin is a hormone consisting of amino acids. Pancreatic cells produce proinsulin, which is inactive. As a result of the action of enzymes, an active insulin is formed. It enters the bloodstream and enters the liver. In the liver, half of the insulin supplied binds to the receptors. The rest of the hormone enters the general bloodstream, and then into the muscles and fatty tissue. The major part of the hormone, about 80%, is processed in the liver and kidneys. The rest is processed in muscle and adipose tissue. Isolation of insulin by the pancreas is divided into basal and food. Basal secretion provides optimal glucose in the blood in breaks between meals. Food release of insulin occurs after a meal, as a result of which the level of glucose in the blood rises. During the day, there is also a fluctuation in the release of insulin. The greatest amount is produced in the early morning hours, the smallest - in the evening. For the treatment of diabetes, the best drug is human insulin, obtained semi-synthetic or biosynthetic method. The semi-synthetic method consists in replacing one amino acid with another in porcine insulin. The biosynthetic method is that a genetic material of an intestinal bacterium or a yeast culture is embedded in a section of the human genetic material that is responsible for the formation of insulin. As a result of this manipulation, microorganisms begin to isolate human insulin.

Insulin preparations are divided into preparations of short and prolonged action. Short-acting drugs undergo rapid absorption, which provides a large concentration of insulin in the blood. Short-acting insulins have several routes of administration: subcutaneous, intramuscular, intravenous. Insulins of prolonged action are divided into 2 groups: medium action and long-acting. Drugs of medium duration of action are slowly absorbed, which ensures the onset of their action approximately 1-1.5 h after administration. Long-acting drugs consist of large crystals, which provides an even slower absorption. Preparations of this group begin to act 4-5 hours after administration. The duration of their action is 28-36 hours. The maximum action is reached after 8-14 hours after administration. Despite such a long-lasting effect of drugs of this group, one injection per day is usually not enough. This is explained by the inability to provide these drugs with sufficient levels of insulin in the blood during the day.

There are a number of indications for insulinotherapy .These include: type I diabetes mellitus, removal of the pancreas, the inability to achieve the restoration of metabolic processes by diet in diabetes mellitus during pregnancy, and a number of conditions arising during the course of diabetes mellitus type II.Such conditions include: coma, precomatosis, progressive weight loss, ketoacidosis, fasting blood glucose over 15 mmol / l, inability to achieve normal metabolism against the prescription of tableted hypoglycemic drugs at the maximum daily dose, the appearance and rapid progression of latecomplications of diabetes, various surgical interventions.

There are several principles of treatment with insulin preparations. The first principle is that the necessary amount of insulin during the day is provided by double administration of insulin preparations - in the morning and in the evening. The second principle is that the replacement of insulin production with the pancreas occurs due to the introduction of short-acting preparations before each meal. The dose of the drug is calculated based on the estimated amount of carbohydrates that a person plans to take. In addition, the existing glucose level in the blood before taking food is taken into account. This level of blood sugar is determined by yourself using an individual glucose meter.

People with type II diabetes usually do not need to take insulin preparations. Nevertheless, in some cases, it is necessary to take such drugs. Such people are divided into two groups. The first group includes young people( 28-40 years old) who are not obese. The second group includes people with type II diabetes who for a long time used to treat sulfanylurea preparations, against which they developed resistance to this group of drugs.

There are several tactics of treatment with insulin. Sometimes insulin treatment is temporary and can last from a few weeks to several months. This tactic is used in the absence of a true deficiency of insulin. The abolition of insulin administration in this case occurs gradually.

Another tactic of treatment is the appointment of insulin in combination with tableted sugar reducing drugs from the very beginning. The dosage of insulin is made by taking into account the following data: blood glucose, time of day, the number of bread units to be consumed, and the intensity of exercise before and after eating. The time interval between the introduction of insulin and the intake of food is selected individually. In most cases, this interval is from 15 to 30 minutes. One of the goals of treating insulin is to normalize the blood sugar level on an empty stomach. Evening dose of insulin is introduced at about 22-23 h, as its effect occurs after 8-9 h.

When large amounts of insulin are administered at night, at 2-3 h, hypoglycemia develops( excessive reduction of blood sugar level).This can be manifested by sleep disorders with nightmarish dreams, some unconscious actions may begin, in the morning one can note the appearance of a headache and a state of weakness. The development of the state of hypoglycemia at night causes the release of the hormone glucagon into the bloodstream, which causes the blood sugar level to increase excessively by the morning time. This phenomenon is called Somogy phenomenon. Closer by the morning, the action of insulin is reduced and may stop at all, which also causes an increase in blood glucose levels. This phenomenon is called the phenomenon of "morning dawn."

For diabetes, subcutaneous insulin is used. Intramuscular and intravenous administration is used in emergency situations. The onset of the effect after the administration of short-acting insulin depends on the site of injection. The fastest action is observed when administered under the skin of the abdomen. The effect is observed after 15-30 minutes, reaching a maximum after 45-60 minutes. The slowest action is observed when administered under the skin of the thigh. The onset of the effect is observed after 1 to 1.5 hours, with only 75% of all insulin injected absorbed. Intermediate position is occupied by injections into the shoulder area. It is recommended to introduce short-acting insulin under the skin of the abdomen, and under the skin of the shoulder or hips - insulin of medium duration. The rate of absorption of insulin increases when the injection site is warmed up. The site of the drug should be constantly changed. Distances between injections should be at least 12 cm.

The introduction of insulin is now widespread with the help of syringes. Insulin therapy is accompanied by a number of complications. The most common state of hypoglycemia( excessive reduction in blood sugar) and hypoglycemic coma. The latter is the most dangerous complication. In addition, there may be allergic reactions, which can be both local and common. Local allergic reactions are located at the site of insulin administration and can be manifested by itching, redness, or condensation. Common allergic reactions are manifested by hives, Quinck's edema or anaphylactic shock. The latter are extremely rare.

Types of insulin

Currently, pig insulin and human insulin are used.

Insulin also varies in duration of action.

Short insulin starts to act after 15-20 minutes. The maximum effect occurs after 1 -1.5 hours and ends in 3-4 hours.

Insulin of medium duration begins its effect after 1.5-2 hours, with a maximum effect after 4-5 hours and ends after 6-8h

Long-acting insulins begin to function in 3-4 hours. Achieve maximum effect after 6 hours. Duration of their action is 12-14 h.

In addition, there are also insulin of super long-acting action. They start their action in 6-8 hours. They reach the maximum effect in 10-16 hours and finish in 24-26 hours.

There are also so-called multi-peak insulin, when in a single vial short-term and long-acting insulins are mixed in certain proportions.

Usually breakfast requires 2 units of insulin, for lunch - 1.5 units, and for dinner 1 unit. But these figures are strictly individual and can be determined only by constantly monitoring the sugar in the blood. This is the so-called intensified insulin therapy( closest to the normal operation of the pancreas and allows to lead a lifestyle that differs little from that of people without diabetes mellitus).There is also a so-called traditional insulin therapy, when the patient makes two( less often one) injections. Insulin injections of short and long-acting are done twice a day: before breakfast and before dinner. This kind of insulin therapy has a significant drawback: lunch should be eaten at a strictly certain time( during the peak of the action of prolonged insulin, which is introduced in the morning) and should contain a certain number of grain units.

Under the rules of storage, insulin should be stored in the refrigerator on the lower shelf. The vial can be stored at room temperature. In no case should you allow the freezing of insulin. Before the injection, the insulin flask should be warmed by lowering it for several seconds into hot water.

To correctly dial the dose, it is necessary: ​​to get into the syringe air for as many divisions as necessary to introduce insulin long-acting, and to introduce air into the vial with this insulin. Do not remove the syringe, dial the necessary amount of insulin prolonged action. You should also do with a bottle containing insulin of short action, letting out air bubbles from the syringe. Introduce insulin under the skin. Injections can be done in the abdomen, thigh, buttocks, under the shoulder blade or in the arm.

Insulin is the most tested drug used for diabetes mellitus by all type I patients and for certain indications - for type II diabetes mellitus. Patients with type I diabetes require constant insulin replacement therapy, the hormone should be administered daily, because only in this case the body can absorb glucose.

Insulin is a protein compound, therefore, getting into the gastrointestinal tract, it under the influence of gastric juice is digested and loses its healing properties. Therefore, it is injected for direct admission into the blood.

For the introduction of insulin, special syringes and syringes are used, which make it possible to produce injections practically painlessly, in any situation, without preliminary sterilization.

To ensure that blood sugar levels are close to normal during the day, injections should maximally simulate the secretion of insulin in a healthy person, that is, ensure its constant level and increase in quantity after the increase in blood sugar concentration due to food. The peaks of the therapeutic action of insulin should, if possible, coincide with the peaks of the rise in blood sugar( which occurs after eating), which is checked by the level of sugar in the blood at 1 and 2 hours after breakfast or lunch.

Currently, there are many types of insulin, differing in time of action, so the doctor has the opportunity to select an individual treatment regimen for each patient. Determination of the optimal types of insulin and the patterns of their use are determined by the endocrinologist, taking into account the severity of diabetes mellitus, complications, concomitant diseases.

Insulin therapy is usually prescribed to patients with type I diabetes, but with ketoacidosis, diabetic precoma and coma, with infectious complications and surgical interventions insulin is one of the most important remedies.

Insulin in serum

Reference values ​​of serum insulin concentration in adults are 3-17 μED / ml( 21.5-122 pmol / L).

Insulin is a polypeptide whose monomeric form consists of two chains: A( of 21 amino acids) and B( of 30 amino acids).Insulin is formed as a product of proteolytic cleavage of the insulin precursor, called proinsulin. Actually, insulin is formed after exiting the cell. Cleavage of the C-chain( C-peptide) from proinsulin occurs at the level of the cytoplasmic membrane, in which the corresponding proteases are enclosed.

Insulin is necessary for cells to transport glucose, potassium and amino acids to the cytoplasm. It has an inhibitory effect on glycogenolysis and gluconeogenesis. In adipose tissue insulin enhances glucose transport and intensifies glycolysis, increases the rate of synthesis of fatty acids and their esterification and inhibits lipolysis. With prolonged action, insulin increases the synthesis of enzymes and the synthesis of DNA, activates growth.

In the blood, insulin reduces the concentration of glucose and fatty acids, as well as( albeit insignificantly) amino acids. Insulin comparatively rapidly breaks down in the liver under the action of the enzyme glutathioneisulin trans-hydrogenase. The half-life of insulin, administered intravenously, is 5-10 minutes.

The cause of diabetes is insufficiency( absolute or relative) of insulin. Determination of the concentration of insulin in the blood is necessary for differentiation of various forms of diabetes mellitus, the choice of a therapeutic drug, the selection of optimal therapy, and the establishment of the degree of p-cell insufficiency. In healthy people, when carrying out PTTG, the concentration of insulin in the blood reaches a maximum one hour after taking glucose and decreases after 2 hours.

The violation of glucose tolerance is characterized by a slowing of the rise in the insulin concentration in the blood relative to the rise in glycemia during PTTG.The maximum increase in insulin levels in these patients is observed 1.5-2 hours after taking glucose. The content in the blood of proinsulin, C-peptide, glucagon in the normal range.

Diabetes mellitus type 1. Basal insulin concentration in the blood is normal or decreased, observe a smaller rise in insulin in all periods of PTGT.The content of proinsulin and C-peptide is reduced, the glucagon level is either within normal limits, or slightly elevated.

Diabetes mellitus type 2. With a mild form, the concentration of insulin in the blood on an empty stomach is slightly increased. In the course of PTGT, it also exceeds the normal values ​​during all periods of the study. The blood content of proinsulin, C-peptide and glucagon has not been changed. In the form of moderate severity, an increase in the concentration of insulin in the blood on an empty stomach is revealed. In the process of PTGT, the maximum insulin release is observed at the 60th minute, after which a very slow decrease in its concentration in the blood occurs, therefore, a high insulin content is observed after 60, 120 and even 180 minutes after loading with glucose. The content of proinsulin, C-peptide in the blood is reduced, glucagon - increased.

Hyperinsulinism. Insulinoma is a tumor( adenoma) consisting of pancreatic islet pancreatic islets. A tumor can develop in people of any age, it is usually single, benign, but can be multiple, combined with an ademotosis, and in rare cases - malignant. In the organic form of hyperinsulinism( insulinoma or nezidioblastoma) there is a sudden and inadequate production of insulin, which causes the development of hypoglycemia, usually paroxysmal. Hyperproduction of insulin does not depend on glycemia( usually above 144 pmol / l).The ratio of insulin / glucose is more than 1: 4.5.Often there is an excess of proinsulin and C-peptide on the background of hypoglycemia. The diagnosis is not in doubt, if the level of insulin in the plasma is higher than 72 pmol / l against a background of hypoglycemia( blood glucose concentration less than 1.7 mmol / l).As a diagnostic sample, loads of tolbutamide or leucine are used: in patients with insulin-producing tumors, there is often a high rise in insulin concentration in the blood and a more marked decrease in glucose levels compared to healthy ones. However, the normal nature of these samples does not exclude the diagnosis of a tumor.

Many types of malignant tumors( carcinomas, especially hepatocellular, sarcomas) lead to the development of hypoglycemia. Most often hypoglycemia accompanies tumors of mesoderm origin, resembling fibrosarcomas and localized primarily in the retroperitoneal space.

Functional hyperinsulinism often develops in various diseases with impaired carbohydrate metabolism. It is characterized by hypoglycemia, which can occur against the background of unchanged or even elevated insulin concentrations in the blood, and hypersensitivity to the insulin administered. The samples with tolbutamide and leucine are negative.

Insulin-like growth factor I in serum

The main factor determining the concentration of IGFR I ​​in serum is the age. The concentration of IGFR I ​​in the blood increases from very low values ​​(20-60 ng / ml) at birth and reaches peak values ​​(600-1100 ng / ml) during puberty. Already in the second decade of a person's life, the level of IGFR I ​​begins to decline rapidly, reaching average values ​​(350 ng / ml) at the age of 20 years, and then decreases more slowly with each decade. At 60 years, the concentration of IGFR I ​​in the blood is not more than 50% of that at the age of 20 years. Daily fluctuations in the concentration of IGFR I ​​in the blood were not detected.

The concentration of IGFR I ​​in the blood depends on the STG, as well as on the T4.A low level of IGFR I ​​is detected in patients with severe T4 deficiency. Carrying out substitution therapy with preparations of levothyroxine sodium leads to a normalization of the concentration of IGFR I ​​in the blood serum.

Another factor determining the concentration of IGFR I ​​in the blood is the nutritional status. Adequate protein-energy supply of the body is the most important condition for maintaining the normal concentration of IGFR I ​​in the blood both in children and adults. In children with severe energy and protein deficiency, the concentration of IGFR I ​​in the blood is reduced, but it is easily amenable to correction during normalization of nutrition. Other catabolic disorders, such as hepatic insufficiency, inflammatory bowel disease, or renal failure, are also associated with a low content of IGFR I ​​in the blood.

In clinical practice, the study of IGFR I ​​is important for assessing the somatotropic function of the pituitary gland.

In acromegaly, the concentration of IGFR I ​​in the blood is constantly increased and therefore is considered a more reliable criterion for acromegaly than the content of STH.The average concentration of IAPF I in the blood serum in patients with acromegaly is approximately 7 times higher than the normal age. The sensitivity and specificity of the IGFR I ​​study for the diagnosis of acromegaly in patients over 20 years old exceeds 97%.The degree of increase in the concentration of IGFR I ​​in the serum correlates with the activity of the disease and the growth of soft tissues. The determination of the serum level of IGFR I ​​is used to monitor the effectiveness of treatment, as it correlates well with the residual secretion of the STH.

The following laboratory parameters are considered as criteria for the cure of acromegaly:

the concentration of hypertensive glucose in the blood on an empty stomach is below 5 ng / ml;

concentration of blood glucose in the blood below 2 ng / ml for PTTG;

is the concentration of IGFR I ​​in the blood within normal limits.

Antibodies to serum insulin

ELISA is used to detect autoantibodies of IgG class to insulin in serum. Long-term insulin therapy usually causes an increase in the number of circulating antibodies to the insulin injectable in patients with type 1 diabetes. The insulin resistance of insulin in the blood of patients is the cause of insulin resistance, the extent of which depends on their concentration. In most patients, a high level of AT to the hormone has a significant effect on the pharmacokinetics of the insulin administered. The level of insulin detected in the blood of AT is an important diagnostic parameter that allows the attending physician to correct insulin therapy and targeted immunosuppressive treatment.

At the same time, there is not always a direct correlation between the concentration of AT and the degree of insulin resistance. Most often, the phenomenon of insulin resistance occurs when insufficiently purified bovine insulin preparations containing proinsulin, glucagon, somatostatin and other impurities are introduced. To prevent the development of insulin resistance, highly purified insulins( mainly porcine) are used, which do not cause the formation of AT.AT to insulin can be detected in the blood of patients treated not only with insulin, but also with oral hypoglycemic drugs from the sulfonylurea group.

The titer of AT to insulin can be increased in 35-40% of patients with newly diagnosed diabetes mellitus( that is, not treated with insulin) and almost in 100% of children within 5 years from the onset of type 1 diabetes. This is due to hyperinsulinemia havinga place in the initial stage of the disease, and the reaction of the immune system. Therefore, the definition of AT for insulin can be used to diagnose the initial stages of diabetes mellitus, its debut, erased and atypical forms( sensitivity - 40-95%, specificity - 99%).After 15 years from the onset of the disease, only 20% of patients are diagnosed with insulin.

Serum proinsulin

Reference values ​​for the concentration of proinsulin in the serum in adults are 2-2.6 pmol / l.

One of the reasons for the development of diabetes mellitus may be a violation of the secretion of insulin from the p-cells into the blood. For the diagnosis of impaired secretion of insulin in the blood, the definition of proinsulin and C-peptide is used.

Insulin plays a very important role in the body, which consists not only in the regulation of carbohydrate metabolism. First of all, insulin is the only hormone that helps the sugar circulating in the blood to pass into muscle, fat, liver cells. If insulin is not enough, then glucose is not fully used, does not burn, sugar accumulates in the blood and blocks the work of the body. There is a famine amidst abundance. When the blood sugar level increases( more than 9-10 mmol / l), it begins to be excreted through the kidneys, and the person begins to lose weight even with abundant nutrition. Together with sugar from the body goes and water - there are thirst and increased urination. In the end, the body begins to use other types of fuel, including fats and proteins. But for their cleavage, insulin is also needed, and since it is very small, fats do not burn up to the end, with the formation of so-called ketone bodies, which leads to poisoning of the body and can provoke a severe complication - to whom the death of the patient.