Hello everyone! The girls who were in similar situations, respond! On the 27th of May the first screening took place. By the way, everything was in order. They wrote down the phone just in case, but I didn’t expect that they could call back, and now a week later a call - come for a referral to the cpsir, you have a high risk. I don’t remember myself, I arrived in tears, on wadded legs, took all the papers. Risk 1:53. The next day, I went for an examination. The uzist looked at the abdomen and vaginally for a very long time, turned on the doppler several times, and everything seemed to be fine, but he did not like DOPLEROMETRY OF THE TRISCUPITAL VALVE: REGURGITATION. I entered the data of the new ultrasound into the program and the results of screening a week ago, the computer issued a risk of DM 1:6. Sent to a geneticist. After looking at the report, she explained to me that this regurgitation may simply be a feature of the fetus, but coupled with a low PAPP-A value of 0.232 MoM, this is a marker of chromosomal abnormalities. Everything else is within the normal range. They suggested a chorionic villus biopsy. I have so far refused, the nurse almost fell off her chair, like the risk is so high and XA is not treated, and in my place she would not even think for a minute. I asked the geneticist about the Panorama analysis (terribly expensive maternal blood test), she answered me that of course you can do it, but it excludes only 5 main CAs and a few very rare ones, it cannot completely eliminate anomalies, and in my case it is recommended invasion. I have already read a ton of articles, questions and everything like that on this topic, and I just don’t understand what they found so terrible in my analyzes? Regurgitation, as it turned out, is physiological at this time and disappears by 18-20 weeks (if it does not go away, this indicates a risk of heart defects, many go away after childbirth, and some live with it and do not affect anything. Especially since my husband has prolapse mitral valve, which was inherited from my mother, maybe this is somehow interconnected). Hormones in general may not be indicative, because. I’ve been taking it since the beginning of pregnancy, I ate 2 hours before the analysis (it turns out you can’t eat 4 hours before, they didn’t tell me about it), I drank coffee, I was nervous and worried about ultrasound and I’m afraid to donate blood, and in Lately chronic fatigue, with the older child I get tired. And all this affects the results. The geneticist didn’t ask anything like that, he wasn’t interested, they generally have some kind of assembly line there, and it was as if for statistics they shoved me there. But they planted a bit of doubt in me, I burst into tears, I was worried for a year ahead. The husband asks for a biopsy. I am terribly afraid of the consequences, I am afraid of losing or harming the child, especially if he is healthy. On the one hand, if everything is fine, I will breathe a sigh of relief and send all the doctors away. On the other hand, if everything is bad, what to do? Will I be able to terminate the pregnancy, allow my child to be dismembered inside me, especially now when I think I am starting to feel it. But another option is whether I can raise such a child who needs a special approach and a lot of attention, when sometimes you want to run away from a completely healthy daughter ... Damn, all these thoughts are eating me up. I don’t know what to do ... Just in case, I will give the screening data:
B-ty term: 13 weeks
Heart rate 161 bpm
Venous duct PI 1.160
Chorion/Planceta low on the anterior wall
Umbilical cord 3 vessels
Anatomy of the fetus: everything is determined, everything is normal
b-hCG 1.091 MoM
PAPP-A 0.232 MoM
Uterine artery PI 1,240 MoM
Trisomy 21 1:6
Trisomy 18 1:311
Trisomy 13 1:205
Preeclampsia up to 34 weeks b-ti 1:529
Pre-eclampsia up to 37 weeks b-ti 1:524
In the prevention of multifactorial diseases with a hereditary predisposition, which include IDDM, a necessary link ismedical genetic counseling. The main task of a medical genetic consultation is to determine the genetic risk of a disease and explain its meaning in an accessible form. With diabetes, spouses most often turn to medical genetic counseling to assess the risk of the disease in future children due to the presence of this disease in previous children, or in the spouses themselves and / or their relatives. Population genetic studies have made it possible to calculate that the contribution of genetic factors to the development of DM withputs 60-80%. In this regard, medical genetic counseling of relatives of patients with diabetes acquires exceptional relevance and perspective.
The main questions that doctors usually have to deal with relate to the risk of developing diabetes. with existing children or siblingssick, the possibility of classifying it, and forecast regardingfuture (planned) family members.
Counseling families of patients with type 1 diabetes consists of several generally accepted stages, which have their own characteristics for this contingent.
11.1. Stages of counseling
First stage of counseling -clarification of the diagnosis of the disease.
Usually the diagnosis of type 1 diabetes in childhood and adolescence is not difficult. However, if other family members have diabetes, it is necessary to verify their type of diabetes, which in some cases can be a difficult task and will require the doctor to carefully collect an anamnesis of a sick relative. Differential diagnosis between the two main types of DM (1 and 2) is carried out according to generally accepted criteria.
The genetic heterogeneity of the two main types of DM, proven in population genetic studies, indicates their nosological independence and independence of inheritance. This means that the cases of type 2 diabetes in the pedigree of individual patients are random and should not be taken into account when assessing family risk.
When conducting medical genetic counseling, it is also necessary to exclude genetic syndromes, which include diabetes mellitus, since they are characterized by monogenic inheritance.
The second stage of counseling – determination of the risk of developing the disease in relation to existing family members and planned offspring.
Empirically, average estimates of the risk of developing diabetes for family members with relatives with type 1 diabetes were obtained. Relatives of the 1st degree of kinship (children, parents, siblings) have the maximum risk - on average from 2.5-3% to 5-6%. It has been found that the incidence of diabetes in children from fathers with type 1 diabetes are 1-2% higher than from mothers with type 1 diabetes.
In each particular family, the risk of developing the disease depends on many factors: the number of sick and healthy relatives, the age of manifestation of diabetes in family members, the age of the counselor, etc.
Table 8
Empirical risk for relatives of patients with type 1 diabetes
Calculate according to a special method development risk tablesSD 1 type depending on the number of sick and healthy relatives and the age of the consulted for families of various types. Family types, parental status, and number of affected siblings are presented in Table 9.
7.1. CLASSIFICATION OF DIABETES MELLITUS
Diabetes(DM) - a group of metabolic diseases characterized by hyperglycemia due to impaired secretion and/or effectiveness of insulin action. Chronic hyperglycemia that develops in diabetes is accompanied by the development of complications from many organs and systems, primarily from the heart, blood vessels, eyes, kidneys and nerves. DM in total affects 5-6% of the population. In economically developed countries of the world every 10-15 years the number of patients with diabetes increases by 2 times. Life expectancy in DM is reduced by 10-15%.
The causes of DM vary widely. In the vast majority of cases, diabetes develops either as a result of an absolute deficiency of insulin. (type 1 diabetes) CD-1), or due to a decrease in the sensitivity of peripheral tissues to insulin in combination with secretory dysfunction of pancreatic β-cells (diabetes mellitus type 2 - SD-2). In some cases, it is difficult to assign a patient to DM-1 or DM-2, however, in practice, compensation for DM is more significant, rather than an accurate determination of its type. The etiological classification distinguishes four main clinical classes of diabetes (Table 7.1).
The most common DM-1 (section 7.5), DM-2 (section 7.6) and gestational DM (section 7.9) are discussed in separate chapters. On the other specific types accounts for only about 1% of cases of DM. The etiology and pathogenesis of these types of DM seems to be more studied compared to DM-1 and especially DM-2. A number of variants of DM are due to monogenically inherited genetic defects in functionβ -cells. This includes various variants of the autosomal dominantly inherited MODY syndrome (Eng. onset diabetes of the young- diabetes of the adult type in young), which are characterized by a violation, but not the absence of insulin secretion with normal sensitivity of peripheral tissues to it.
Tab. 7.1. Classification diabetes
Incidentally rare genetic defects in insulin action, associated with mutation of the insulin receptor (leprechaunism, Rabson-Mandehall syndrome). DM naturally develops with diseases of the exocrine pancreas, leading to the destruction of β-cells (pancreatitis, pancreatectomy, cystic fibrosis, hemochromatosis), as well as in a number of endocrine diseases, in which there is an excessive production of contra-insular hormones (acromegaly, Cushing's syndrome). Medicines and chemicals(vacor, pentamidine, a nicotinic acid, diazoxide, etc.) are rarely the cause of DM, but can contribute to the manifestation and decompensation of the disease in people with insulin resistance. Row infectious diseases(rubella, cytomegaly, coxsackie- and adenovirus infection) may be accompanied by destruction of β-cells, while in most patients immunogenetic markers of CD-1 are determined. TO rare forms immune-mediated diabetes include diabetes that develops in patients with "stiff-rnan" syndrome (an autoimmune neurological disease), as well as diabetes due to exposure to autoantibodies to insulin receptors. Various options DM occurs at an increased frequency in
many genetic syndromes, in particular, with Down syndrome, Klinefelter, Turner, Wolfram, Prader-Willi and a number of others.
7.2. CLINICAL ASPECTS OF THE PHYSIOLOGY OF CARBOHYDRATE METABOLISM
Insulin synthesized and secreted by β-cells of the islets of Langerhans of the pancreas (PZhZh). In addition, the islets of Langerhans secrete glucagon (α-cells), somatostatin (δ-cells), and pancreatic polypeptide (PP-cells). Hormones islet cells interact with each other: glucagon normally stimulates the secretion of insulin, and somatostatin suppresses the secretion of insulin and glucagon. The insulin molecule consists of two polypeptide chains (A-chain - 21 amino acids; B-chain - 30 amino acids) (Fig. 7.1). Insulin synthesis begins with the formation of preproinsulin, which is cleaved by a protease to form proinsulin. In the secretory granules of the Golgi apparatus, proinsulin is broken down into insulin and C-peptide, which are released into the blood during exocytosis (Fig. 7.2).
The main stimulator of insulin secretion is glucose. Insulin is released in response to an increase in blood glucose two-phase(Fig. 7.3). The first, or acute, phase lasts a few minutes, and it is associated with the release of accumulated
Rice. 7.1. Scheme primary structure insulin molecules
Rice. 7.2. Scheme of insulin biosynthesis
β-cell insulin in the period between meals. The second phase continues until the level of glycemia reaches normal fasting (3.3-5.5 mmol / l). The β-cell is similarly affected by sulfonylurea drugs.
Through the portal system, insulin reaches liver- its main target organ. Hepatic receptors bind half of the secreted hormone. The other half, getting into systemic circulation reaches the muscles and adipose tissue. Most of the insulin (80%) undergoes proteolytic breakdown in the liver, the rest - in the kidneys, and only a small amount is metabolized directly by muscle and fat cells. Normal PZhZh
Rice. 7.3. Biphasic release of insulin under the influence of glucose
an adult secretes 35-50 units of insulin per day, which is 0.6-1.2 units per 1 kg of body weight. This secretion is divided into food and basal. food secretion insulin corresponds to the postprandial rise in glucose levels, i.e. due to it, the neutralization of the hyperglycemic effect of food is ensured. The amount of dietary insulin approximately corresponds to the amount of carbohydrates taken - about 1-2.5 units
per 10-12 g of carbohydrates (1 bread unit - XE). Basal insulin secretion provides an optimal level of glycemia and anabolism in the intervals between meals and during sleep. Basal insulin is secreted at a rate of approximately 1 U / h, with prolonged physical exertion or prolonged fasting, it decreases significantly. Food insulin accounts for at least 50-70% of daily insulin production (Fig. 7.4).
Insulin secretion is subject not only to dietary, but also daily-
Rice. 7 .4.
Diagram of daily insulin production is normal
fluctuations: the need for insulin rises in the early morning hours, and then gradually falls during the day. So, for breakfast, 2.0-2.5 U of insulin is secreted for 1 XE, for lunch - 1.0-1.5 U, and for dinner - 1.0 U. One of the reasons for this change in insulin sensitivity is the high level of a number of contrainsular hormones (primarily cortisol) in the morning, which gradually drops to a minimum at the beginning of the night.
Main physiological effects insulin are the stimulation of glucose transfer through the cell membranes of insulin-dependent tissues. The main target organs of insulin are the liver, adipose tissue and muscles. Insulin-independent tissues, the supply of glucose to which does not depend on the effects of insulin, primarily include the central and peripheral tissues. nervous system, vascular endothelium, blood cells, etc. Insulin stimulates the synthesis of glycogen in the liver and muscles, the synthesis of fats in the liver and adipose tissue, the synthesis of proteins in the liver, muscles and other organs. All these changes are aimed at the utilization of glucose, which leads to a decrease in its level in the blood. The physiological antagonist of insulin is glucagon, which stimulates the mobilization of glycogen and fats from the depot; Normally, glucagon levels change reciprocally with insulin production.
The biological effects of insulin are mediated by its receptors located on target cells. The insulin receptor is a glycoprotein composed of four subunits. With a high level of insulin in the blood, the number of its receptors decreases according to the principle of down regulation, which is accompanied by a decrease in the sensitivity of the cell to insulin. After insulin binds to the cellular receptor, the resulting complex enters the cell. Further inside the muscle and fat cells, insulin causes the mobilization of intracellular vesicles that contain glucose transporter GLUT-4. As a result, the vesicles move to the cell surface, where GLUT-4 acts as an inlet for glucose. Similar action GLUT-4 is affected by exercise.
7.3. LABORATORY DIAGNOSTICS AND COMPENSATION CRITERIA FOR DIABETES MELLITUS
Laboratory diagnosis of diabetes is based on the determination of blood glucose levels, while the diagnostic criteria are the same for all
types and variants of SD (Table 7.2). Data from other laboratory studies (glucosuria level, determination of the level of glycated hemoglobin) should not be used to verify the diagnosis of diabetes. The diagnosis of DM can be established on the basis of two detections of one of the three criteria:
1. At obvious symptoms DM (polyuria, polydipsia) and glucose level in whole capillary blood more than 11.1 mmol/l, regardless of the time of day and previous meal.
2. When the level of glucose in whole capillary blood on an empty stomach is more than 6.1 mmol / l.
3. When the glucose level in capillary whole blood 2 hours after ingestion of 75 grams of glucose (oral glucose tolerance test) is more than 11.1 mmol / l.
Tab. 7.2. Criteria for diagnosing diabetes
The most important and meaningful test in the diagnosis of diabetes is to determine the level of glycemia on an empty stomach (at least 8 hours of fasting). In the Russian Federation, the level of glycemia, as a rule, is estimated in whole blood. Glucose testing is widely used in many countries
in blood plasma. Oral glucose tolerance test(OGTT; determination of glucose level 2 hours after ingestion of 75 grams of glucose dissolved in water) is given less importance in this regard. However, based on OGTT, it is diagnosed impaired glucose tolerance(NTG). NTG is diagnosed if the level of glycemia of capillary whole blood on an empty stomach does not exceed 6.1 mmol/l, and 2 hours after the glucose load is above 7.8 mmol/l, but below 11.1 mmol/l. Another variant of carbohydrate metabolism disorder is disturbed fasting glycemia(NGNT). The latter is set if the level of glycemia of whole capillary blood on an empty stomach is in the range of 5.6-6.0 mmol/l, and 2 hours after the glucose load is less than 7.8 mmol/l). NTG and NGNT are currently combined by the term prediabetes, since both categories of patients have a high risk of manifestation of diabetes and the development of diabetic macroangiopathy.
For the diagnosis of diabetes, the level of glycemia should be determined by standard laboratory methods. When interpreting glycemic values, it should be borne in mind that fasting glucose levels in the whole venous blood corresponds to its level in the whole capillary. After a meal or OGTT, its level in venous blood is about 1.1 mmol/l lower than in capillary blood. Plasma glucose is approximately 0.84 mmol/l higher than that of whole blood. In order to assess compensation and the adequacy of diabetes therapy, the level of glycemia is assessed in capillary blood using portable glucometers patients themselves, their relatives or medical personnel.
With any type of DM, as well as with a significant load of glucose, glucosuria, which is a consequence of exceeding the threshold of glucose reabsorption from primary urine. The threshold for glucose reabsorption varies significantly individually (≈ 9-10 mmol/l). As a single indicator, glycosuria should not be used to make a diagnosis of DM. Normally, with the exception of cases of a significant dietary load of refined carbohydrates, glucosuria does not occur.
Products ketone bodies(acetone, acetoacetate, β-hydroxybutyrate) is significantly intensified with absolute insulin deficiency. With decompensation of SD-1, a pronounced ketonuria(examined using test strips that fall into the urine). Mild (trace) ketonuria can be determined in healthy people with starvation and a carbohydrate-free diet.
Important laboratory indicator, which is used for differential diagnosis of types of DM, as well as for detecting the formation of insulin deficiency in patients with DM-2, is the level C-peptide. The level of C-peptide in the blood can indirectly judge the insulin-secreting ability of pancreas β-cells. The latter produce proinsulin, from which the C-peptide is cleaved before secretion, which enters the blood in equal amounts with insulin. Insulin is 50% bound in the liver and has a half-life in peripheral blood of about 4 minutes. The C-peptide is not removed from the bloodstream by the liver and has a blood half-life of about 30 minutes. In addition, it does not bind to cellular receptors in the periphery. Therefore, the determination of the C-peptide level is a more reliable test for assessing the function of the insular apparatus. The level of C-peptide is most informative to investigate against the background of stimulation tests (after a meal or administration of glucagon). The test is not informative if it is carried out against the background of severe decompensation of diabetes, since severe hyperglycemia has toxic effect on β-cells (glucose toxicity). Insulin therapy during the previous few days will not affect the test results in any way.
Basic goal of treatment of any type of DM is the prevention of its late complications, which can be achieved against the background of its stable compensation for a number of parameters (Table 7.3). The main criterion for the quality of carbohydrate metabolism compensation in DM is the level glycated (glycosylated) hemoglobin (HbA1c). The latter is hemoglobin non-covalently bound to glucose. Glucose enters erythrocytes independently of insulin, and hemoglobin glycosylation is an irreversible process, and its degree is directly proportional to the concentration of glucose with which it has been in contact for 120 days of its existence. A small part of hemoglobin is glycosylated and is normal; with DM, it can be significantly increased. The level of HbA1c, in contrast to the level of glucose, which is constantly changing, integrally reflects glycemia over the past 3-4 months. It is with this interval that it is recommended to determine the level of HbA1c in order to assess compensation for diabetes.
Chronic hyperglycemia is far from the only risk factor for the development and progression of late complications of DM. Concerning evaluation of DM compensation based on the complex
laboratory and instrumental research methods (Table 7.3). In addition to indicators characterizing the state of carbohydrate metabolism, the level of blood pressure and lipid profile of the blood.
Tab. 7.3. Compensation criteria for diabetes mellitus
In addition to the above compensation criteria, when planning goals for the treatment of diabetes, it is necessary to individual approach. The likelihood of development and progression of late complications of DM (especially microangiopathy) increases with the duration of the disease. Thus, if in children and young patients, whose diabetes experience can reach several decades in the future, it is necessary to achieve optimal glycemic indices, then in patients in whom DM manifested in the elderly and senile age, rigid euglycemic compensation, which significantly increases the risk of hypoglycemia, not always appropriate.
7.4. INSULIN AND INSULIN THERAPY
Insulin preparations are vital for patients with type 1 diabetes; in addition, up to 40% of patients with type 2 diabetes receive them. To general indications for the appointment of insulin therapy in diabetes, many of which actually overlap with one another include:
1. Type 1 diabetes
2. Pancreatectomy
3. Ketoacidotic and hyperosmolar coma
4. For type 2 diabetes:
Overt signs of insulin deficiency such as progressive weight loss and ketosis, severe hyperglycemia;
Major surgical interventions;
Acute macrovascular complications (stroke, myocardial infarction, gangrene, etc.) and severe infectious diseases accompanied by decompensation of carbohydrate metabolism;
The level of glycemia on an empty stomach is more than 15-18 mmol / l;
Lack of stable compensation, despite the appointment of the maximum daily doses of various tableted hypoglycemic drugs;
Late stages of late complications of diabetes (severe polyneuropathy and retinopathy, chronic renal failure).
5. Inability to achieve compensation for gestational diabetes with the help of diet therapy.
Origin Insulin preparations can be classified into three groups:
Animal insulins (pork);
Human insulins (semi-synthetic, genetically engineered);
Insulin analogues (lispro, aspart, glargine, detemir).
Advances in technology for the production of human insulin have led to the fact that the use of porcine insulin(differs from human by one amino acid) has recently decreased significantly. Pork insulin can be used to make human insulin semi-synthetic method, which involves the replacement of one different amino acid in its molecule. Most high quality different genetic engineering human insulins. To obtain them, the region of the human genome responsible for the synthesis of insulin is associated with the genome E.coli or yeast culture, as a result of which the latter begin to produce human insulin. Creation insulin analogues with the help of permutations of various amino acids, the goal was to obtain drugs with a given and most favorable pharmacokinetics. So, insulin lispro (Humalog) is an analogue
insulin ultra short action, while its hypoglycemic effect develops already 15 minutes after the injection. In contrast, the insulin analog glargine (Lantus) is characterized by a long-term effect that lasts throughout the day, while the kinetics of the drug is characterized by the absence of pronounced peaks in plasma concentration. Most of the currently used insulin preparations and its analogues are produced in concentration 100 U/ml. By duration of action insulins are divided into 4 main groups (Table 7.4):
Tab. 7.4. Pharmacokinetics of drugs and insulin analogues
1.
Ultrashort-acting (lispro, aspart).
2. Short-acting (simple human insulin).
3. Average duration of action (insulins on neutral protamine Hagedorn).
4. Long-acting (glargine, detemir).
5. Mixtures of insulins of various duration of action (Novomix-30, Humulin-MZ, Humalog-Mix-25).
Preparations ultra short action[lispro (Humalog), aspart (Novorapid)] are insulin analogs. Their advantages are fast development hypoglycemic effect after injection (after 15 minutes), which allows injection immediately before meals or even immediately after meals, as well as a short duration of action (less than 3 hours), which reduces the risk of hypoglycemia. Preparations short action(simple insulin, regular insulin) are a solution containing insulin at a concentration of 100 U / ml. A simple insulin injection is given 30 minutes before a meal; duration of action is about 4-6 hours. Ultrashort and short acting preparations can be administered subcutaneously, intramuscularly and intravenously.
Among the drugs medium duration actions the most commonly used preparations on the neutral protamine Hagedorn (NPH). NPH is a protein that non-covalently adsorbs insulin, slowing down its absorption from the subcutaneous depot. The effective duration of action of NPH insulins is usually about 12 hours; they are administered subcutaneously only. NPH insulin is a suspension, and therefore, unlike regular insulin, it is cloudy in the vial, and a suspension is formed during prolonged standing, which must be thoroughly mixed before injection. NPH insulins, unlike other long-acting drugs, can be mixed in any ratio with short-acting insulin (simple insulin), while the pharmacokinetics of the components of the mixture will not change, since NPH will not bind additional amounts of simple insulin (Fig. 7.5). In addition, protamine is used to prepare standard mixtures of insulin analogues (Novomix-30, Humalog-Mix-25).
Among the drugs long-acting Insulin analogs are now widely used glargine(Lantus) and detemir(Levemir). A favorable feature of the pharmacokinetics of these drugs is that, unlike NPH insulins, they provide a more uniform and prolonged intake of the drug from the subcutaneous depot. In this regard, glargine can be administered only once a day, and almost regardless of the time of day.
Rice. 7.5. Pharmacokinetics various drugs insulin:
a) monocomponent; b) standard mixtures of insulins
In addition to monocomponent insulin preparations, in clinical practice widely used standard mixtures. Usually, we are talking about mixtures of short or ultra-short insulin with intermediate-acting insulin. For example, the drug "Humulin-MZ" contains in one vial 30% of simple insulin and 70% of NPH insulin; Novomix-30 contains 30% insulin aspart and 70% crystalline protamine suspension of insulin aspart; Humalog-Mix-25 contains 25% insulin lispro and 75% insulin lispro protamine suspension. advantage
standard mixtures of insulins is the replacement of two injections with one and a somewhat greater accuracy of dosage of the components of the mixture; the disadvantage is the impossibility of individual dosing of the individual components of the mixture. This determines the preference for using standard insulin mixtures for the treatment of DM-2 or with the so-called traditional insulin therapy(prescribing fixed doses of insulin), while for intensive insulin therapy(flexible dose selection depending on glycemic indicators and the amount of carbohydrates in food), the use of monocomponent preparations is preferable.
The key to successful insulin therapy is strict adherence to injection techniques. There are several ways to administer insulin. The simplest and at the same time reliable method is injections using insulin syringe. More convenient way insulin injections are injections using syringe pens, which is a combined device containing an insulin reservoir (cartridge), a dosing system and a needle with an injector.
For maintenance therapy (when we are not talking about severe decompensation of diabetes or critical conditions), insulin is administered subcutaneously. It is recommended to inject short-acting insulin into the subcutaneous adipose tissue of the abdomen, long-acting insulin - into the tissue of the thigh or shoulder (Fig. 7.6 a). Injections are made deep into the subcutaneous tissue through widely compressed skin at an angle of 45 ° (Fig. 7.6 b). The patient should be advised to change daily insulin injection sites within the same area in order to prevent the development of lipodystrophy.
TO factors affecting the rate of insulin absorption from the subcutaneous depot, the dose of insulin should be attributed (increasing the dose increases the duration of absorption), the injection site (absorption is faster from the abdominal tissue), temperature environment(warming and massaging the injection site speeds up absorption).
A more complex method of administration, which, nevertheless, in many patients allows to achieve good results treatment is the use insulin dispenser, or systems for continuous subcutaneous administration of insulin. The dispenser is a portable device consisting of a computer that sets the insulin delivery mode, as well as an insulin delivery system through a catheter and a miniature hypodermic needle.
Rice. 7.6. Insulin injections: a) typical injection sites; b) the position of the needle of the insulin syringe during injection
fatty tissue. With the help of a dispenser, continuous basal administration of short-acting or ultra-short-acting insulin is carried out (speed of the order of 0.5-1 U / hour), and before eating, depending on the content of carbohydrates in it and the level of glycemia, the patient injects the necessary bolus dose of the same short-acting insulin. The advantage of insulin therapy with a dispenser is the introduction of only short-acting (or even ultra-short) insulin, which in itself is somewhat more physiological, since the absorption of prolonged insulin preparations is subject to large fluctuations; in this regard, the continuous administration of short-acting insulin is more manageable. The disadvantage of insulin therapy with a dispenser is the need to constantly wear the device, as well as long stay injection needle into subcutaneous tissue requiring periodic monitoring of the process of insulin supply. Insulin therapy using a dispenser is primarily indicated for patients with type 1 diabetes who are ready to master the technique of its administration. Especially in this regard, attention should be paid to patients with a pronounced “dawn” phenomenon, as well as to pregnant and planning pregnancy patients with DM-1 and patients
Ents with a disordered lifestyle (the possibility of a more flexible diet).
7.5. TYPE 1 DIABETES
CD-1 - organ-specific autoimmune a disease leading to the destruction of insulin-producing β-cells of the islets of the pancreas, manifested by an absolute deficiency of insulin. In some cases, patients with overt DM-1 do not have markers of autoimmune damage to β-cells. (idiopathic CD-1).
Etiology
CD-1 is a disease with a hereditary predisposition, but its contribution to the development of the disease is small (determines its development by about 1/3). Concordance in identical twins for CD-1 is only 36%. The probability of developing DM-1 in a child with a sick mother is 1-2%, father - 3-6%, brother or sister - 6%. One or more humoral markers of autoimmune β-cell damage, which include antibodies to pancreatic islets, antibodies to glutamate decarboxylase (GAD65), and antibodies to tyrosine phosphatase (IA-2 and ΙΑ-2β), are found in 85-90% of patients . Nevertheless, the factors of cellular immunity are of primary importance in the destruction of β-cells. CD-1 is associated with such HLA haplotypes as DQA and DQB, while some alleles HLA-DR/DQ may be predisposing to the development of the disease, while others are protective. With an increased frequency, CD-1 is combined with other autoimmune endocrine (autoimmune thyroiditis, Addison's disease) and non-endocrine diseases, such as alopecia, vitiligo, Crohn's disease, rheumatic diseases (Table 7.5).
Pathogenesis
CD-1 manifests when 80-90% of β-cells are destroyed by the autoimmune process. The speed and intensity of this process can vary significantly. Most often when typical course diseases in children and young people, this process proceeds quite quickly, followed by a rapid manifestation of the disease, in which only a few weeks can pass from the appearance of the first clinical symptoms to the development of ketoacidosis (up to ketoacidotic coma).
Tab. 7.5. Type 1 diabetes
Continuation of the table. 7.5
In others, much more rare cases usually in adults older than 40 years, the disease may be latent (latent autoimmune diabetes in adults - LADA), at the same time, at the onset of the disease, such patients are often diagnosed with DM-2, and for several years, compensation for DM can be achieved by prescribing sulfonylurea drugs. But in the future, usually after 3 years, there are signs of absolute insulin deficiency (weight loss, ketonuria, severe hyperglycemia, despite taking hypoglycemic tablets).
At the heart of the pathogenesis of DM-1, as mentioned, is the absolute deficiency of insulin. The inability to supply glucose to insulin-dependent tissues (fat and muscle) leads to energy insufficiency, as a result of which lipolysis and proteolysis are intensified, which are associated with weight loss. An increase in the level of glycemia causes hyperosmolarity, which is accompanied by osmotic diuresis and severe dehydration. Under conditions of insulin deficiency and energy deficiency, the production of contrainsular hormones (glucagon, cortisol, growth hormone) is inhibited, which, despite increasing glycemia, causes stimulation of gluconeogenesis. Increased lipolysis in adipose tissue leads to a significant increase in the concentration of free fatty acids. With insulin deficiency, the liposynthetic ability of the liver is suppressed, and free
nye fatty acids begin to be included in ketogenesis. The accumulation of ketone bodies leads to the development of diabetic ketosis, and later - ketoacidosis. With a progressive increase in dehydration and acidosis, a coma develops (see paragraph 7.7.1), which, in the absence of insulin therapy and rehydration, inevitably ends in death.
Epidemiology
DM-1 accounts for about 1.5-2% of all cases of diabetes, and this relative figure will continue to decrease due to the rapid increase in the incidence of DM-2. The lifetime risk of developing CD-1 in a white race is about 0.4%. The incidence of DM-1 is increasing by 3% per year: by 1.5% due to new cases and by another 1.5% due to an increase in the life expectancy of patients. The prevalence of CD-1 varies depending on the ethnic composition of the population. As of 2000, it was 0.02% in Africa, 0.1% in South Asia and South and Central America, and 0.2% in Europe and North America. The highest incidence of DM-1 is in Finland and Sweden (30-35 cases per 100 thousand population per year), and the lowest in Japan, China and Korea (0.5-2.0 cases, respectively). The age peak of manifestation of CD-1 corresponds to approximately 10-13 years. In the vast majority of cases, CD-1 manifests itself before the age of 40.
Clinical manifestations
V typical cases especially in children and young people, CD-1 debuts with a vivid clinical picture that develops over several months or even weeks. The manifestation of CD-1 can be provoked by infectious and other concomitant diseases. Characteristic symptoms common to all types of diabetes, associated with hyperglycemia: polydipsia, polyuria, pruritus, but with SD-1 they are very pronounced. So, throughout the day, patients can drink and excrete up to 5-10 liters of fluid. specific for DM-1, a symptom that is caused by an absolute deficiency of insulin is weight loss, reaching 10-15 kg over 1-2 months. Characterized by a pronounced general and muscle weakness, decreased performance, drowsiness. At the onset of the disease, some patients may experience an increase in appetite, which is replaced by anorexia as ketoacidosis develops. The latter is characterized by the appearance of the smell of acetone (or fruity smell) from the mouth,
note, vomiting, often abdominal pain (pseudoperitonitis), severe dehydration and ends with the development coma(see clause 7.7.1). In some cases, the first manifestation of CD-1 in children is a progressive impairment of consciousness up to coma on the background of concomitant diseases usually infectious or acute surgical pathology.
In relatively rare cases of the development of CD-1 in persons older than 35-40 years (latent autoimmune diabetes in adults) the disease may not manifest so clearly (moderate polydipsia and polyuria, no weight loss) and even be detected incidentally during routine determination of the level of glycemia. In these cases, the patient is often diagnosed with DM-2 at the beginning and prescribes oral hypoglycemic drugs (TSP), which for some time provide acceptable compensation for DM. However, over the course of several years (often within a year), the patient develops symptoms due to the increasing absolute deficiency of insulin: weight loss, the inability to maintain normal glycemia against the background of TSP, ketosis, ketoacidosis.
Diagnostics
Considering that CD-1 has a vivid clinical picture, and is also relatively rare disease, screening determination of the level of glycemia for the purpose of diagnosing CD-1 is not shown. The probability of developing the disease in the next of kin of patients is low, which, together with the lack of effective methods primary prevention CD-1 determines the inappropriateness of studying immunogenetic markers of the disease in them. Diagnosis of DM-1 in the vast majority of cases is based on the detection of significant hyperglycemia in patients with severe clinical manifestations of absolute insulin deficiency. OGTT for the purpose of diagnosing DM-1 has to be performed very rarely.
In doubtful cases (detection of moderate hyperglycemia in the absence of obvious clinical manifestations, manifestation at a relatively middle age), as well as for the purpose of differential diagnosis with other types of DM, the determination of the level C-peptide(basal and 2 hours after a meal). Indirect diagnostic value in doubtful cases may have a definition immunological markers CD-1 - antibodies to islets
PZhZh, to glutamate decarboxylase (GAD65) and tyrosine phosphatase (IA-2 and IA-2β). Differential diagnosis of CD-1 and CD-2 is presented in Table. 7.6.
Tab. 7.6. Differential diagnosis and differences between CD-1 and CD-2
Treatment
Treatment of any type of DM is based on three main principles: hypoglycemic therapy (in DM-1 - insulin therapy), diet and patient education. insulin therapy with SD-1 wears substitution and its goal is to maximally imitate the physiological production of the hormone in order to achieve the accepted compensation criteria (Table 7.3). Closest to physiological insulin secretion intensive insulin therapy. The need for insulin corresponding to its basal secretion, provided with two injections of intermediate-acting insulin (morning and evening) or one injection of long-acting insulin (glargine). The total dose of basal insulin
line should not exceed half of the total daily requirement for the drug. Meal or bolus secretion of insulin is replaced by injections of short or ultra-rapid insulin before each meal, while its dose is calculated based on the amount of carbohydrates that are expected to be taken during the upcoming meal and the existing level of glycemia, determined by the patient using a glucometer before each injection of insulin (Fig. 7.7 ).
Estimated intensive insulin regimen, which will change almost every day, can be represented as follows. Based on the fact that daily requirement in insulin is about 0.5-0.7 U per 1 kg of body weight (for a patient weighing 70 kg, about 35-50 U). About 1 / s - 1 / 2 of this dose will be long-acting insulin (20-25 U), 1 / 2 - 2 / s short-acting or ultra-short-acting insulin. The dose of NPH insulin is divided into 2 injections: in the morning 2 / s of its dose (12 U), in the evening - 1 / s (8-10 U).
aim first stage selection of insulin therapy is the normalization of fasting glucose levels. The evening dose of NPH insulin is usually given at 10-11 pm, followed by a morning dose of short-acting insulin before breakfast. When choosing an evening dose of NPH insulin, it is necessary to keep in mind the possibility of developing a number of
Rice. 7.7. Scheme of intensive insulin therapy
quite typical phenomena. The cause of morning hyperglycemia may be an insufficient dose of long-acting insulin, since by morning the need for insulin increases significantly (the "dawn" phenomenon). In addition to insufficiency of the dose, its excess can lead to morning hyperglycemia - Somoji phenomenon(Somogyi), posthypoglycemic hyperglycemia. This phenomenon is explained by the fact that the maximum sensitivity of tissues to insulin occurs between 2 and 4 am. It is at this time that the level of the main contra-insular hormones (cortisol, growth hormone, etc.) is normally the lowest. If the evening dose of long-acting insulin is excessive, then at this time develops hypoglycemia. Clinically, it can manifest as poor sleep with nightmares, unconscious sleep activities, morning headaches, and fatigue. The development of hypoglycemia at this time causes a significant compensatory release of glucagon and other contrainsular hormones, followed by hyperglycemia in the morning. If in this situation the dose of long-acting insulin administered in the evening is not reduced, but increased, nocturnal hypoglycemia and morning hyperglycemia will worsen, which may eventually lead to chronic insulin overdose syndrome (Somogyi syndrome), which is a combination of obesity with chronic decompensation of diabetes, frequent hypoglycemia and progressive late complications. To diagnose the Somogyi phenomenon, it is necessary to study the level of glycemia at about 3 am, which is an integral component of the selection of insulin therapy. If a decrease in the evening dose of NPH to a safe nocturnal hypoglycemia is accompanied by hyperglycemia in the morning (dawn phenomenon), the patient should be advised to wake up earlier (6-7 am), while insulin administered at night still continues to maintain normal glycemic levels.
A second injection of NPH insulin is usually given before breakfast, along with a short-acting (ultra-short)-acting insulin injection in the morning. In this case, the dose is selected mainly based on the indicators of the level of glycemia before the main daily meals (lunch, dinner); in addition, it may be limited by the development of hypoglycemia between meals, for example at noon, between breakfast and lunch.
whole dose of insulin prolonged action(glargine) is administered once a day, it does not matter at what time. Kinetics
insulins glargine and detemir are more favorable in terms of the risk of developing hypoglycemia, including nocturnal ones.
The dose of short-acting or ultra-short-acting insulin, even on the first day of insulin administration for the patient, will depend on the amount of carbohydrates consumed ( bread units) and pre-injection glycemic levels. Conventionally, based on the daily rhythm of insulin secretion in the norm, about 1/4 dose of short-acting insulin (6-8 IU) is taken for dinner, the remaining dose is approximately equally divided into breakfast and lunch (10-12 IU). The higher the initial level of glycemia, the less it will decrease per unit of insulin administered. Short-acting insulin is given 30 minutes before meals, ultra-short-acting insulin is given just before a meal, or even immediately after a meal. The adequacy of the dose of short-acting insulin is assessed by glycemia indicators 2 hours after a meal and before the next meal.
To calculate the dose of insulin during intensive insulin therapy, it is sufficient to calculate the number of XE, based only on the carbohydrate component. At the same time, not all carbohydrate-containing products are taken into account, but only the so-called countable ones. The latter include potatoes, grain products, fruits, liquid dairy and sugary foods. Products containing non-digestible carbohydrates (most vegetables) are not taken into account. Special exchange tables have been developed, with the help of which, by expressing the amount of carbohydrates in XE, it is possible to calculate the required dose of insulin. One XE corresponds to 10-12 g of carbohydrates (Table 10.7).
After a meal containing 1 XE, the level of glycemia increases by 1.6-2.2 mmol / l, i.e. about as much as the level of glucose decreases with the introduction of 1 unit of insulin. In other words, for each XU contained in the food that is planned to be eaten, it is necessary to pre-administer (depending on the time of day) about 1 unit of insulin. In addition, it is necessary to take into account the results of self-monitoring of the level of glycemia, which is performed before each injection, and the time of day (about 2 IU of insulin per 1 XE in the morning and at lunch, 1 IU per 1 XE for dinner). So, if hyperglycemia is detected, the dose of insulin, calculated in accordance with the upcoming meal (according to the number of XE), must be increased, and vice versa, if hypoglycemia is detected, less insulin is administered.
Tab. 7.7. Equivalent substitution of products that make up 1 XE
For example, if a patient has a glycemic level of 7 mmol/l 30 minutes before the planned dinner containing 5 XE, he needs to inject 1 unit of insulin in order for the glycemia to decrease to normal level: from 7 mmol/l to about 5 mmol/l. In addition, 5 units of insulin must be administered to cover 5 XE. Thus, the patient in this case will inject 6 units of short-acting or ultra-rapid insulin.
After the manifestation of CD-1 and the start of insulin therapy for a sufficiently long time, the need for insulin may be small and be less than 0.3-0.4 U / kg. This period is referred to as the remission phase, or "Honeymoon". After a period of hyperglycemia and ketoacidosis, which suppress the secretion of insulin by 10-15% of the remaining β-cells, compensation for hormonal and metabolic disorders by the administration of insulin restores the function of these cells, which then take over providing the body with insulin at a minimum level. This period can last from several weeks to several years, but eventually, due to autoimmune destruction of the remaining β-cells, the “honeymoon” ends.
Diet with DM-1 in trained patients who have the skills of self-control and selection of the dose of insulin, it can be liberalized, i.e. approaching free. If the patient is not overweight or underweight, the diet should be
isocaloric. The main component of food in DM-1 is carbohydrates, which should account for about 65% of daily calories. Preference should be given to foods containing complex, slowly absorbed carbohydrates, as well as foods rich in dietary fiber. Foods containing easily digestible carbohydrates (flour, sweet) should be avoided. The proportion of proteins should be reduced to 10-35%, which helps to reduce the risk of developing microangiopathy, and the proportion of fats to 25-35%, while limiting fats should account for up to 7% of calories, which reduces the risk of atherosclerosis. In addition, you should avoid taking alcoholic beverages especially strong ones.
An integral component of work with a patient with DM-1 and the key to its effective compensation is patient education. Throughout life, the patient must independently change the dose of insulin daily, depending on numerous factors. Obviously, this requires the possession of certain skills that the patient needs to be taught. The "School of the patient with SD-1" is organized in endocrinological hospitals or on an outpatient basis and consists of 5-7 structured sessions, in which a doctor or a specially trained nurse in an interactive mode, using various visual aids, teaches patients the principles self-control.
Forecast
In the absence of insulin therapy, a patient with DM-1 inevitably dies from ketoacidotic coma. With inadequate insulin therapy, against which the criteria for compensating for diabetes are not achieved and the patient is in a state of chronic hyperglycemia (Table 7.3), late complications begin to develop and progress (Section 7.8). With SD-1, the greatest clinical significance in this regard, they have manifestations of diabetic microangiopathy (nephropathy and retinopathy) and neuropathy (diabetic foot syndrome). Macroangiopathy in DM-1 comes to the fore relatively rarely.
7.6. DIABETES MELLITUS TYPE 2
Type 2 diabetes- chronic illness, manifested by a violation of carbohydrate metabolism with the development of hyperglycemia due to insulin resistance and secretory dysfunction of β-cells,
as well as lipid metabolism with the development of atherosclerosis. Since the main cause of death and disability of patients are complications of systemic atherosclerosis, CD-2 is sometimes called a cardiovascular disease.
Tab. 7.8. Type 2 diabetes
Etiology
CD-2 is a multifactorial disease with a hereditary predisposition. Concordance for CD-2 in identical twins reaches 80% or more. Most patients with CD-2 indicate the presence of CD-2 in the next of kin; in the presence of CD-2 in one of the parents, the probability of its development in the offspring throughout life is 40%. No one gene, the polymorphism of which determines the predisposition to CD-2, has been found. Great importance in the implementation of hereditary predisposition to CD-2, environmental factors play, first of all, lifestyle features. Risk factors for the development of CD-2 are:
Obesity, especially visceral (see section 11.2);
Ethnicity (especially when changing the traditional way of life to the Western one);
Sedentary lifestyle;
Diet specifics (high intake of refined carbohydrates and low maintenance fiber);
Arterial hypertension.
Pathogenesis
Pathogenetically, CD-2 is a heterogeneous group of metabolic disorders, and this is precisely what determines its significant clinical heterogeneity. Its pathogenesis is based on insulin resistance (a decrease in insulin-mediated utilization of glucose by tissues), which is realized against the background of secretory dysfunction of β-cells. Thus, there is an imbalance between insulin sensitivity and insulin secretion. Secretory dysfunctionβ -cells It consists in slowing down the "early" secretory release of insulin in response to an increase in blood glucose levels. At the same time, the 1st (fast) phase of secretion, which consists in emptying the vesicles with accumulated insulin, is virtually absent; The 2nd (slow) phase of secretion is carried out in response to stabilizing hyperglycemia constantly, in a tonic mode, and, despite excessive secretion of insulin, the level of glycemia against the background of insulin resistance does not normalize (Fig. 7.8).
The consequence of hyperinsulinemia is a decrease in the sensitivity and number of insulin receptors, as well as suppression
post-receptor mechanisms mediating the effects of insulin (insulin resistance). The content of the main glucose transporter in muscle and fat cells (GLUT-4) is reduced by 40% in individuals with visceral obesity and by 80% in individuals with DM-2. Due to insulin resistance of hepatocytes and portal hyperinsulinemia, hyperproduction of glucose by the liver, and fasting hyperglycemia develops, which is detected in most patients with DM-2, including in the early stages of the disease.
By itself, hyperglycemia adversely affects the nature and level of secretory activity of β-cells (glucose toxicity). Long-term, over many years and decades, existing hyperglycemia eventually leads to the depletion of insulin production by β-cells and the patient may develop some symptoms. insulin deficiency- weight loss, ketosis with concomitant infectious diseases. However, residual insulin production, which is sufficient to prevent ketoacidosis, is almost always preserved in DM-2.
Epidemiology
CD-2 determines the epidemiology of diabetes in general, since it accounts for about 98% of cases of this disease. The prevalence of CD-2 varies in different countries and ethnic groups. In European
Rice. 7.8. Secretory dysfunction of β-cells in type 2 diabetes mellitus (prolapse of the 1st fast phase secretion of insulin)
countries, USA and Russian Federation it makes up about 5-6% of the population. With age, the incidence of DM-2 increases: among adults, the prevalence of DM-2 is 10%, among people over 65 it reaches 20%. The incidence of CD-2 is 2.5 times higher among the native inhabitants of America and Hawaiian Islands; among the Indians of the Pima tribe (Arizona), it reaches 50%. Among rural population India, China, Chile and African countries that lead a traditional lifestyle, the prevalence of CD-2 is very low (less than 1%). On the other hand, among the migrants to the Western industrial countries, it reaches a significant level. So, among immigrants from India and China, living in the USA and Great Britain, the prevalence of CD-2 reaches 12-15%.
WHO predicts an increase in the number of people with diabetes in the world by 122% over the next 20 years (from 135 to 300 million). This is due both to the progressive aging of the population and to the spread and aggravation of the urbanized lifestyle. V last years there is a significant "rejuvenation" of CD-2 and an increase in its incidence among children.
Clinical manifestations
In most cases, pronounced clinical manifestations absent, and the diagnosis is established by routine glycemic testing. The disease usually manifests over the age of 40 years, while the vast majority of patients have obesity and other components. metabolic syndrome(see clause 11.2). Patients do not complain about a decrease in performance, if there are no other reasons for this. Complaints of thirst and polyuria rarely reach significant severity. Quite often, patients are concerned about skin and vaginal itching, and therefore they turn to dermatologists and gynecologists. Since many years often pass from the actual manifestation of CD-2 to the diagnosis (on average, about 7 years), in many patients at the time of detection of the disease, the clinical picture is dominated by symptoms and manifestations of late complications of diabetes. Moreover, the first visit of a patient with CD-2 for medical care very often occurs due to late complications. Thus, patients may be hospitalized in surgical hospitals With ulcerative lesion legs (diabetic foot syndrome) contact an ophthalmologist in connection with a progressive decrease in vision (diabetic retinopathy), be hospitalized with heart attacks, strokes
with obliterating lesion of the vessels of the legs in institutions where hyperglycemia is first detected in them.
Diagnostics
Diagnostic criteria, common for all types of diabetes, are presented in paragraph 7.3. The diagnosis of DM-2 in the vast majority of cases is based on the detection of hyperglycemia in individuals with typical clinical signs CD-2 (obesity, age over 40-45 years, positive family history of CD-2, other components of the metabolic syndrome), in the absence of clinical and laboratory signs of absolute insulin deficiency (pronounced weight loss, ketosis). The combination of the high prevalence of type 2 diabetes, its inherent long asymptomatic course, and the possibility of preventing it severe complications provided early diagnosis predetermine the need screening, those. conducting a survey to exclude CD-2 among people without any symptoms of the disease. The main test, as mentioned, is the determination fasting glycemic levels. It is shown in the following situations:
1. In all people over the age of 45, especially with excess body weight (BMI over 25 kg / m 2) with an interval of once every 3 years.
2. At a younger age, in the presence of excess body weight (BMI over 25 kg / m 2) and additional risk factors, which include:
Sedentary lifestyle;
CD-2 in the next of kin;
Belonging to nationalities at high risk of developing CD-2 (African Americans, Hispanics, Native Americans, etc.);
Women who have given birth to a child weighing more than 4 kg and / or with a history of gestational diabetes;
Arterial hypertension (≥ 140/90 mm Hg);
HDL > 0.9 mmol/l and/or triglycerides > 2.8 mmol/l;
polycystic ovary syndrome;
NTG and NGNT;
Cardiovascular diseases.
A significant increase in the incidence of DM-2 among children dictates the need for screening determination of the level of glycemia among children and teenagers(starting at age 10 with an interval of 2 years or with the onset
puberty, if it occurred more than early age), belonging to high-risk groups, which include children overweight(BMI and/or weight > 85 percentile for age, or weight greater than 120% of ideal weight) and any two of the following additional risk factors:
CD-2 among relatives of the first or second line of kinship;
Belonging to high-risk nationalities;
Clinical manifestations associated with insulin resistance (acanthosis nigricans, arterial hypertension, dyslipidemia);
Diabetes, including gestational, in the mother.
Differential Diagnosis
The greatest clinical significance is the differential diagnosis of CD-2 and CD-1, the principles of which are described in paragraph 7.5 (Table 7.6). As mentioned, in most cases it is based on data clinical picture. In cases where the establishment of the type of SD is difficult, or there is a suspicion of some rare variant Diabetes, including within hereditary syndromes, the most important practical question to be answered is whether the patient needs insulin therapy.
Treatment
The main components of the treatment of DM-2 are: diet therapy, increased physical activity, hypoglycemic therapy, prevention and treatment of late complications of DM. Since the majority of patients with DM-2 are obese, the diet should be aimed at weight loss (hypocaloric) and the prevention of late complications, primarily macroangiopathy (atherosclerosis). hypocaloric diet necessary for all patients with excess body weight (BMI 25-29 kg / m 2) or obesity (BMI> 30 kg / m 2). In most cases, it should be recommended to reduce the daily caloric intake of food to 1000-1200 kcal for women and to 1200-1600 kcal for men. The recommended ratio of the main food components in DM-2 is similar to that in DM-1 (carbohydrates - 65%, proteins 10-35%, fats up to 25-35%). Use alcohol should be limited due to the fact that it is a significant source of additional calories, in addition, alcohol intake against the background of therapy
PII with sulfonylurea drugs and insulin can provoke the development of hypoglycemia (see section 7.7.3).
Recommendations for expansion physical activity must be individualized. At the beginning, aerobic exercise (walking, swimming) of moderate intensity is recommended for 30-45 minutes 3-5 times a day (about 150 minutes a week). In the future, a gradual increase physical activity, which significantly contributes to the reduction and normalization of body weight. In addition, physical activity helps to reduce insulin resistance and has a hypoglycemic effect. The combination of diet therapy and the expansion of physical activity without the appointment of hypoglycemic drugs allows you to maintain compensation for diabetes in accordance with the established goals (Table 7.3) in approximately 5% of patients with type 2 diabetes.
Preparations for hypoglycemic therapy with CD-2 can be divided into four main groups.
I. Drugs that help reduce insulin resistance (sensitizers). This group includes metformin and thiazolidinediones. Metformin is the only currently used drug from the group biguanides. The main components of its mechanism of action are:
1. Suppression of hepatic gluconeogenesis (decrease in hepatic glucose production), which leads to a decrease in fasting glycemia.
2. Decreased insulin resistance (increased utilization of glucose by peripheral tissues, primarily muscles).
3. Activation of anaerobic glycolysis and reduction of glucose absorption in the small intestine.
Metformin is the drug of first choice for hypoglycemic therapy in patients with type 2 diabetes, obesity and fasting hyperglycemia. The starting dose is 500 mg at night or during dinner. In the future, the dose gradually increases to 2-3 grams for 2-3 doses. Among the side effects, dyspeptic symptoms (diarrhea) are relatively common, which are usually transient and disappear on their own after 1-2 weeks of taking the drug. Since metformin does not have a stimulating effect on insulin production, hypoglycemia does not occur during monotherapy with this drug.
develop (its action will be designated as antihyperglycemic, and not as hypoglycemic). Contraindications to the appointment of metformin are pregnancy, severe cardiac, hepatic, renal and other organ failure, as well as hypoxic conditions of another origin. An extremely rare complication that occurs when prescribing metformin without taking into account the above contraindications is lactic acidosis, which is a consequence of hyperactivation of anaerobic glycolysis.
Thiazolidinediones(pioglitazone, rosiglitazone) are peroxisome proliferator-activated receptor agonists (PPAR-γ). Thiazolidinediones activate the metabolism of glucose and lipids in muscle and adipose tissues, which leads to an increase in the activity of endogenous insulin, i.e. To eliminate insulin resistance (insulin sensitizers). The daily dose of pioglitazone is 15-30 mg / day, rosiglitazone - 4-8 mg (for 1-2 doses). The combination of thiazolidinediones with metformin is very effective. A contraindication to the appointment of thiazolidinediones is an increase (by 2.5 times or more) in the level of hepatic transaminases. In addition to hepatotoxicity, side effects of thiazolidinediones include fluid retention and edema, which are more common when combined with insulin.
II. Drugs that act onβ cell and enhance insulin secretion. This group includes sulfonylurea drugs and glinides (prandial glycemic regulators), which are used primarily to normalize glycemic levels after meals. main target sulfonylurea drugs(PSM) are the β-cells of the pancreatic islets. PSMs bind to specific receptors on the β-cell membrane. This leads to the closure of ATP-dependent potassium channels and depolarization of the cell membrane, which in turn contributes to the opening calcium channels. The entry of calcium into β-cells leads to their degranulation and the release of insulin into the blood. In clinical practice, a lot of PSM are used, which differ in the duration and severity of the hypoglycemic effect (Table 7.9).
Tab. 7.9. Sulfonylureas
The main and fairly common side effect PSM is hypoglycemia (see section 7.7.3). It can occur with an overdose of the drug, its cumulation (renal failure),
non-compliance with the diet (skipping meals, drinking alcohol) or regimen (significant physical activity, before which the dose of PSM is not reduced or carbohydrates are not taken).
To the group glinides(prandial glycemic regulators) are repaglinide(derivative of benzoic acid; daily dose 0.5-16 mg/day) and nateglinide(D-phenylalanine derivative; daily dose 180-540 mg/day). After administration, the drugs interact rapidly and reversibly with the sulfonylurea receptor on the β-cell, resulting in a short rise in insulin levels that mimics the first phase of its secretion normally. The drugs are taken 10-20 minutes before the main meals, usually 3 times a day.
III. Drugs that reduce the absorption of glucose in the intestine.
This group includes acarbose and guar gum. The mechanism of action of acarbose is the reversible blockade of α-glycosidases small intestine, as a result of which the processes of sequential fermentation and absorption of carbohydrates slow down, the rate of resorption and entry of glucose into the liver decreases, and the level of postprandial glycemia decreases. The initial dose of acarbose is 50 mg 3 times a day, in the future the dose can be increased to 100 mg 3 times a day; the drug is taken immediately before meals or during meals. The main side effect of acarbose is intestinal dyspepsia (diarrhea, flatulence), which is associated with the entry of unabsorbed carbohydrates into the colon. The hypoglycemic effect of acarbose is very moderate (Table 7.10).
In clinical practice, tableted hypoglycemic drugs are effectively combined with each other and with insulin preparations, since most patients have both fasting and postprandial hyperglycemia at the same time. There are numerous fixed combinations drugs in one tablet. Most often, metformin is combined with various PSMs in one tablet, as well as metformin with thiazolidinediones.
Tab. 7.10. Mechanism of action and potential efficacy of tableted antidiabetic drugs
IV. Insulins and insulin analogues
At a certain stage, up to 30-40% of patients with type 2 diabetes begin to receive insulin preparations. Indications for insulin therapy in DM-2 are given at the beginning of section 7.4. The most common option for switching patients with type 2 diabetes to insulin therapy is to prescribe a long-acting insulin (NPH insulin, glargine or detemir) in combination with the hypoglycemic tablets taken. In a situation where the level of fasting glycemia cannot be controlled by the appointment of metformin or the latter is contraindicated, the patient is prescribed an evening (at night) injection of insulin. If it is impossible to control both fasting and postprandial glycemia with the help of tablet preparations, the patient is transferred to monoinsulin therapy. Usually, with DM-2, insulin therapy is carried out according to the so-called "traditional" scheme which involves the appointment of fixed doses of long-acting and short-acting insulin. In this plan
convenient standard insulin mixtures containing short-acting (ultra-short) and prolonged-acting insulin in one vial. The choice of traditional insulin therapy is determined by the fact that with DM-2 it is often prescribed to elderly patients, whose training to independently change the dose of insulin is difficult. In addition, intensive insulin therapy, the goal of which is to maintain compensation of carbohydrate metabolism at a level approaching normoglycemia, carries an increased risk of hypoglycemia. While mild hypoglycemia does not pose a serious risk to young patients, it can have very adverse cardiovascular effects in older patients with a reduced hypoglycemia threshold. Young patients with type 2 diabetes, as well as patients promising in terms of the possibility of effective learning, can be prescribed an intensive version of insulin therapy.
Forecast
The main cause of disability and death in patients with DM-2 are late complications (see section 7.8), most often diabetic macroangiopathy. The risk of developing individual late complications is determined by a complex of factors that are discussed in the relevant chapters. A universal risk factor for their development is chronic hyperglycemia. Thus, a 1% decrease in the HbA1c level in patients with type 2 diabetes leads to a decrease in overall mortality by about 20%, by 2% and 3% - by about 40%, respectively.
7.7. ACUTE COMPLICATIONS OF DIABETES MELLITUS
7.7.1. diabetic ketoacidosis
Diabetic ketoacidosis (DKA)- decompensation of DM-1, caused by an absolute deficiency of insulin, in the absence of timely treatment ending in ketoacidotic coma (KK) and death.
Etiology
The cause of DKA is an absolute deficiency of insulin. This or that severity of DKA is determined in most patients at the time of manifestation of DM-1 (10-20% of all cases of DKA).
In a patient with an established diagnosis of type 1 diabetes, DKA can develop when insulin administration is stopped, often by the patient himself (13% of DKA cases), against the background of concomitant diseases, primarily infectious ones, in the absence of an increase in insulin dose
Tab. 7.11. diabetic ketoacidosis
Up to 20% of cases of DKA in young patients with type 1 diabetes are associated with psychological problems and / or disorders eating behavior(fear of weight gain, fear of hypoglycemia, adolescent problems). A fairly common cause of DKA in a number of countries is
cancellation of insulin by the patient himself due to the high cost of drugs for some segments of the population (Table 7.11).
Pathogenesis
The pathogenesis of DKA is based on an absolute deficiency of insulin in combination with an increase in the production of contrainsular hormones, such as glucagon, catecholamines, and cortisol. As a result, there is a significant increase in glucose production by the liver and a violation of its utilization by peripheral tissues, an increase in hyperglycemia and a violation of the osmolarity of the extracellular space. Insulin deficiency in combination with a relative excess of contrainsular hormones in DKA leads to the release of free fatty acids into the circulation (lipolysis) and their unrestrained oxidation in the liver to ketone bodies (β-hydroxybutyrate, acetoacetate, acetone), resulting in hyperketonemia, and further metabolic acidosis. As a result of severe glucosuria, osmotic diuresis, dehydration, loss of sodium, potassium and other electrolytes develop (Fig. 7.9).
Epidemiology
The frequency of new cases of DKA is 5-8 per 1000 patients with DM-1 per year and directly depends on the level of organization medical care patients with SD. Approximately 100,000 hospitalizations for DKA occur in the United States each year, and considering the cost per patient for hospitalization of $13,000, each year hospital treatment DKA spends over $1 billion a year. In the Russian Federation in 2005, DKA was recorded in 4.31% of children, 4.75% of adolescents and 0.33% of adult patients with DM-1.
Clinical manifestations
The development of DKA, depending on the cause that caused it, can take from several weeks to days. In most cases, DKA is preceded by symptoms of decompensated diabetes, but sometimes they may not have time to develop. Clinical symptoms of DKA include polyuria, polydipsia, weight loss, generalized abdominal pain (“diabetic pseudoperitonitis”), dehydration, severe weakness, acetone breath (or fruity odor), and gradual clouding of consciousness. True coma in DKA has recently developed relatively rarely due to early diagnosis. Physical examination reveals signs of dehydration: decreased
Rice. 7.9. The pathogenesis of ketoacidotic coma
skin turgor and density eyeballs, tachycardia, hypotension. In advanced cases, Kussmaul breathing develops. More than 25% of patients with DKA develop vomiting, which can resemble coffee grounds in color.
Diagnostics
Based on clinical picture data, indications of the presence of DM-1 in the patient, as well as data laboratory research. DKA is characterized by hyperglycemia (in some cases insignificant), ketonuria, metabolic acidosis, hyperosmolarity (Table 7.12).
Tab. 7.12. Laboratory diagnosis of acute complications of diabetes mellitus
When examining patients with acute decompensation of diabetes, it is necessary to determine the level of glycemia, creatinine and urea, electrolytes, on the basis of which the effective osmolarity is calculated. In addition, an assessment of the acid-base state is necessary. Effective osmolarity(EO) is calculated using the following formula: 2 *. Normal EO is 285 - 295 mOsm / l.
Most patients with DKA have leukocytosis, the severity of which is proportional to the level of ketone bodies in the blood. Level sodium, as a rule, it is reduced due to the osmotic outflow of fluid from the intracellular spaces to the extracellular ones in response to hyperglycemia. Rarely, sodium levels may be false positive as a result of severe hyperthyroidism.
triglyceridemia. Level potassium Serum may initially be elevated due to its movement from the extracellular spaces.
Differential Diagnosis
Other causes of loss of consciousness in patients with diabetes. Differential diagnosis with hyperosmolar coma, as a rule, does not cause difficulties (it develops in elderly patients with type 2 diabetes) and is not of great clinical importance, because The principles of treatment for both conditions are similar. If it is impossible to quickly find out the cause of the loss of consciousness in a patient with diabetes, he is shown the introduction of glucose, because. hypoglycemic states are much more common, and the rapid positive dynamics against the background of glucose administration in itself makes it possible to find out the cause of the loss of consciousness.
Treatment
Treatment of DKA includes rehydration, correction of hyperglycemia, electrolyte disorders, and treatment of diseases that caused diabetes decompensation. Treatment is most optimally carried out in the intensive care unit of a specialized medical institution. In adult patients without severe concomitant cardiac pathology, already at the prehospital stage, as a primary measure to rehydration it is recommended to administer an isotonic solution (0.9% NaCl) at approximately a liter per hour (about 15-20 ml per kilogram of body weight per hour). Full replacement of fluid deficiency, which in DKA is 100-200 ml per kg of body weight, should be achieved within the first day of treatment. With concomitant cardiac or kidney failure this time period should be extended. For children, the recommended volume of isotonic solution for rehydration therapy is 10-20 ml per kg of body weight per hour, while in the first 4 hours it should not exceed 50 ml per kg of body weight. Full rehydration is recommended to be achieved in about 48 hours. After the level of glycemia decreases to about 14 mmol / l against the background of parallel insulin therapy, they switch to transfusion of a 10% glucose solution, which continues rehydration.
The concept of "small doses" has now been adopted insulin in the treatment of DKA. Only short-acting insulin is used. The most optimal use intravenous administration insu-
line. Intramuscular administration insulin, which is less effective, is possible only with moderate severity of DKA, with stable hemodynamics and with the impossibility of intravenous therapy. In the latter case, injections are made into the rectus abdominis muscle, while on insulin syringe needle is put on intramuscular injections(for reliable intramuscular injection), and insulin is drawn from the vial into the syringe through this needle.
Several options for intravenous insulin administration are possible. Firstly, insulin can be injected into the "gum" of the infusion system, while required amount insulin is drawn into an insulin syringe, after which 1 ml of isotonic solution is drawn into it. Until the level of glycemia reaches 14 mmol / l, the patient is injected hourly with 6-10 units of short-acting insulin; further (in parallel with changing the rehydration solution from isotonic to 10% glucose) depending on hourly determined indicators of glycemia, the dose of insulin is reduced to 4-8 units per hour. The recommended rate of glycemic decline should not exceed 5 mmol/l per hour. Another option for intravenous insulin therapy involves the use of a perfusor. To prepare a solution for a perfusor, the following ratio is taken: 2 ml of a 20% human albumin solution is added to 50 units of short-acting insulin, after which 50 mg of a 0.9% isotonic solution is added. If the intramuscular route of insulin administration is chosen, initially 20 units of short-acting insulin are administered, then 6 units every hour, and after reaching a glycemia level of 14 mmol / l, the dose is reduced to 4 units per hour. After complete stabilization of hemodynamics and compensation of acid-base disorders, the patient is transferred to subcutaneous insulin injections.
As noted, despite significant potassium deficiency in the body (total loss of 3-6 mmol / kg), with DKA, its level before the start of insulin therapy may be slightly increased. However, the initiation of a potassium chloride solution transfusion is recommended at the same time as the initiation of insulin therapy if the plasma potassium level is less than 5.5 mmol/L. Successful correction of potassium deficiency occurs only against the background of pH normalization. At low pH, the intake of potassium into the cell is significantly reduced, in connection with this, if possible, it is desirable to adapt the dose of transfused potassium chloride to a specific pH indicator (Table 7.13).
Tab. 7.13. Potassium deficiency correction scheme
* The following data is used for the calculation:
1 g KCl = 13.4 mmol; 1 mmol KCl \u003d 0.075 g. In a 4% solution of KC1: in 100 ml - 4 g of KC1, in 25 ml - 1 g of KC1, in 10 ml 0.4 g of KC1.
The cause of diabetes decompensation is often infectious diseases(pyelonephritis, infected ulcer in diabetic foot syndrome, pneumonia, sinusitis, etc.). There is a rule according to which, in DKA, antibiotic therapy is prescribed for almost all patients with low-grade fever or fever, even in the absence of a visible focus of infection, since an increase in body temperature is not typical for DKA itself.
Forecast
Mortality in DKA is 0.5-5%, with most cases due to late and unskilled medical care. Mortality is highest (up to 50%) among elderly patients.
7.7.2. Hyperosmolar coma
Hyperosmolar coma(GOK) - rare acute complication SD-2, which develops as a result of severe dehydration and hyperglycemia against the background of the absence of absolute insulin deficiency, is accompanied by high mortality (Table 7.14).
Etiology
GOK, as a rule, develops in elderly patients with type 2 diabetes. Such patients are most often lonely, live without care, neglect their condition and self-control, and do not take enough fluids. Infections often lead to decompensation (diabetic foot syndrome, pneumonia, acute pyelonephritis), disorders of the brain
circulatory and other conditions, as a result of which patients move poorly, do not take hypoglycemic drugs and fluids.
Tab. 7.14. Hyperosmolar coma (GOC)
Pathogenesis
Increasing hyperglycemia and osmotic diuresis cause severe dehydration, which, for the above reasons, is not replenished from the outside. The result of hyperglycemia and dehydration is plasma hyperosmolarity. An integral component of the pathogenesis of GOK is a relative deficiency of insulin and an excess of contra-insular hormones, however, residual insulin secretion remaining in DM-2 is sufficient to suppress lipolysis and ketogenesis, as a result of which ketoacidosis does not develop.
In some cases, moderate acidosis can be determined as a result of hyperlactatemia against the background of tissue hypoperfusion. In severe hyperglycemia, to maintain the osmotic balance in the cerebrospinal fluid, the content of sodium coming from the cells increases. brain where potassium is exchanged. The transmembrane potential of nerve cells is disturbed. A progressive stupefaction of consciousness develops in combination with convulsive syndrome(Fig. 7.10).
Epidemiology
GOC accounts for 10-30% of acute hyperglycemic conditions in adult and elderly patients with type 2 diabetes. Approximately 2/3 of cases of GOK develop in individuals with previously undiagnosed diabetes.
Clinical manifestations
Features of the clinical picture hyperosmolar coma are:
A complex of signs and complications of dehydration and hypoperfusion: thirst, dry mucous membranes, tachycardia, arterial hypotension, nausea, weakness, shock;
Focal and generalized seizures;
Fever, nausea and vomiting (40-65% of cases);
Of the concomitant diseases and complications, deep vein thrombosis, pneumonia, cerebrovascular accidents, and gastroparesis are common.
Diagnostics
It is based on the data of the clinical picture, the age of the patient and the anamnesis of CD-2, severe hyperglycemia in the absence of ketonuria and ketoacidosis. Typical laboratory signs GOK are presented in table. 7.12.
Rice. 7 .10.
The pathogenesis of hyperosmolar coma
Differential Diagnosis
Other acute conditions that develop in patients with diabetes, most often with comorbidities, which led to severe decompensation of DM.
Treatment
Treatment and monitoring for GOC, with the exception of some features, do not differ from those described for ketoacidotic diabetic coma (section 7.7.1):
Larger volume of initial rehydration 1.5-2 liters per 1 hour; 1 l - for the 2nd and 3rd hour, then 500 ml / h of isotonic sodium chloride solution;
The need for the introduction of potassium-containing solutions, as a rule, is greater than with ketoacidotic coma;
Insulin therapy is similar to that for QC, but the need for insulin is less and the level of glycemia must be reduced no faster than 5 mmol / l per hour to avoid the development of cerebral edema;
Introductions hypotonic solution(NaCl 0.45%) best avoided (only in severe hypernatremia: > 155 mmol/l and/or effective osmolarity > 320 mOsm/l);
There is no need to administer bicarbonate (only in specialized intensive care units for acidosis with pH< 7,1).
Forecast
Mortality in GOK is high and amounts to 15-60%. The worst prognosis is in elderly patients with severe comorbidity, which is often the cause of DM decompensation and the development of GOC.
7.7.3. hypoglycemia
hypoglycemia- Decreased blood glucose levels<2,2- 2,8 ммоль/л), сопровождающее клинический синдром, характеризующийся признаками активации симпатической нервной системы и/или дисфункцией центральной нервной системы. Гипогликемия как лабораторный феномен не тождественен понятию «гипогликемическая симптоматика», поскольку лабораторные данные и клиническая картина не всегда совпадают.
Etiology
Overdose of insulin preparations and its analogues, as well as sulfonylurea preparations;
Insufficient food intake against the background of unchanged hypoglycemic therapy;
Reception of alcoholic beverages;
Physical activity against the background of unchanged hypoglycemic therapy and / or without additional intake of carbohydrates;
The development of late complications of diabetes (autonomic neuropathy with gastroparesis, renal failure) and a number of other diseases (adrenal insufficiency, hypothyroidism, liver failure, malignant tumors) with unchanged hypoglycemic therapy (continuation and accumulation of TSP against the background of renal failure, maintaining the same dose of insulin);
Violation of the technique of insulin administration (intramuscular injection instead of subcutaneous);
Artifical hypoglycemia (conscious overdose of hypoglycemic drugs by the patient);
Organic hyperinsulinism - insulinoma (see section 10.3).
Pathogenesis
The pathogenesis of hypoglycemia consists in an imbalance between the entry of glucose into the blood, its utilization, the level of insulin and contrainsular hormones. Normally, at the level of glycemia in the range of 4.2-4.7 mmol/l, the production and release of insulin from β-cells is suppressed. A decrease in the level of glycemia less than 3.9 mmol / l is accompanied by stimulation of the production of contrainsular hormones (glucagon, cortisol, growth hormone, adrenaline). Neuroglycopenic symptoms develop with a decrease in the level of glycemia less than 2.5-2.8 mmol / l. Overdose insulin and/or drugs sulfonylurea hypoglycemia develops due to the direct hypoglycemic action of an exogenous or endogenous hormone. In case of an overdose of sulfonylurea drugs, hypoglycemic symptoms can recur many times after the attack has been relieved due to the fact that the duration of action of a number of drugs can reach a day or more. TSPs that do not have a stimulating effect on insulin production (metformin, thiazolidinediones) by themselves cannot cause hypoglycemia, but when they are added to sulfonylurea drugs or insulin, taking the latter at the same dose can cause hypoglycemia due to the cumulation of the hypoglycemic effect of combination therapy (Table .7.15).
Tab. 7.15. hypoglycemia
The end of the table. 7.15
When you receive alcohol there is a suppression of gluconeogenesis in the liver, which is the most important factor counteracting hypoglycemia. Physical exercise contribute to insulin-independent glucose utilization, due to which, against the background of unchanged hypoglycemic therapy and / or in the absence of additional intake of carbohydrates, they can cause hypoglycemia.
Epidemiology
Mild, rapidly reversing hypoglycaemia in patients with type 1 diabetes receiving intensive insulin therapy may develop several times a week and is relatively harmless. For one patient on intensive insulin therapy, there is 1 case of severe hypoglycemia per year. In most cases, hypoglycemia develops at night. In T2DM, 20% of patients receiving insulin and 6% of patients receiving sulfonylurea drugs develop at least one episode of severe hypoglycemia over 10 years.
Clinical manifestations
There are two main groups of symptoms: adrenergic, associated with the activation of the sympathetic nervous system and the release of adrenaline by the adrenal glands, and neuroglycopenic, associated with impaired functioning of the central nervous system against the background of a deficiency of its main energy substrate. TO adrenergic symptoms include: tachycardia, mydriasis; anxiety, aggressiveness; shivering, cold sweat, paresthesia; nausea, severe hunger, hypersalivation; diarrhea, excessive urination. TO neuroglycopenic symptoms include asthenia,
decreased concentration, headache, fear, confusion, disorientation, hallucinations; speech, visual, behavioral disorders, amnesia, impaired consciousness, convulsions, transient paralysis, to whom. There may not be a clear relationship between the severity and sequence of symptoms as hypoglycemia worsens. Only adrenergic or only neuroglycopenic symptoms may occur. In some cases, despite the restoration of normoglycemia and ongoing therapy, patients may remain in a stuporous or even comatose state for several hours or even days. Prolonged hypoglycemia or its frequent episodes can lead to irreversible changes in the central nervous system (primarily in the cerebral cortex), the manifestations of which vary significantly from delirious and hallucinatory-paranoid episodes to typical epileptic seizures, the inevitable outcome of which is persistent dementia.
Hyperglycemia is subjectively tolerated by patients more easily than episodes of even mild hypoglycemia. Therefore, many patients, because of the fear of hypoglycemia, consider it necessary to maintain glycemia at a relatively high level, which actually corresponds to the decompensation of the disease. Overcoming this stereotype sometimes requires considerable efforts of doctors and teaching staff.
Diagnostics
The clinical picture of hypoglycemia in a patient with diabetes in combination with laboratory (usually using a glucometer) detection of low blood glucose levels.
Differential Diagnosis
Other causes leading to loss of consciousness. If the cause of the loss of consciousness of a patient with diabetes is unknown and it is impossible to conduct an express analysis of the level of glycemia, he is shown the introduction of glucose. Often there is a need to find out the cause of the development of frequent hypoglycemia in patients with diabetes. Most often they are the result of inadequate hypoglycemic therapy and the patient's low level of knowledge about his disease. It should be remembered that a number of diseases (adrenal insufficiency, hypothyroidism, renal and hepatic insufficiency), including malignant tumors, can lead to a decrease in the need for hypoglycemic therapy up to its complete cancellation (“disappeared diabetes”).
Treatment
For the treatment of mild hypoglycemia, in which the patient is conscious and can help himself, it is usually sufficient to take food or liquid containing carbohydrates in the amount of 1-2 bread units (10-20 g of glucose). This amount is contained, for example, in 200 ml of sweet fruit juice. Drinks are more effective in stopping hypoglycemia, since glucose is absorbed much faster in liquid form. If symptoms continue to worsen despite continued carbohydrate intake, intravenous glucose or intramuscular glucagon is needed. Severe hypoglycemia with loss of consciousness is treated similarly. In this case, the patient is injected with about 50 ml 40% glucose solution intravenously. The introduction of glucose must be continued until the attack is relieved and glycemia normalizes, although a larger dose - up to 100 ml or more, as a rule, is not required. Glucagon administered (usually by a factory-prepared, filled syringe) intramuscularly or subcutaneously. After a few minutes, the level of glycemia due to the induction of glycogenolysis by glucagon returns to normal. However, this does not always happen: with a high level of insulin in the blood, glucagon is ineffective. The half-life of glucagon is shorter than that of insulin. With alcoholism and liver disease, glycogen synthesis is impaired, and the administration of glucagon may be ineffective. A side effect of glucagon administration may be vomiting, which creates an aspiration hazard. It is desirable for relatives of the patient to master the technique of injecting glucagon.
Forecast
Mild hypoglycemia in trained patients with good disease compensation is safe. Frequent hypoglycemia is a sign of poor DM compensation; in most cases, such patients have more or less pronounced hyperglycemia and a high level of glycated hemoglobin in the rest of the day. In elderly patients with late complications of diabetes, hypoglycemia can provoke such vascular complications as myocardial infarction, stroke, retinal hemorrhage. Hypoglycemic coma lasting up to 30 minutes with adequate treatment and a rapid return of consciousness, as a rule, does not have any complications and consequences.
7.8. LATE COMPLICATIONS OF DIABETES MELLITUS
Late complications develop in both types of DM. Five main late complications of DM are clinically distinguished: macroangiopathy, nephropathy, retinopathy, neuropathy, and diabetic foot syndrome. The nonspecificity of late complications for certain types of DM is determined by the fact that their main pathogenetic link is chronic hyperglycemia. In this regard, at the time of manifestation of DM-1, late complications in patients almost never occur, developing over years and decades, depending on the effectiveness of the therapy. The greatest clinical significance in DM-1, as a rule, acquires diabetic microangiopathy(nephropathy, retinopathy) and neuropathy (diabetic foot syndrome). In DM-2, on the contrary, late complications are often detected already at the time of diagnosis. Firstly, this is due to the fact that CD-2 manifests itself long before the diagnosis is made. Secondly, atherosclerosis, clinically manifested by macroangiopathy, has many links of pathogenesis in common with DM. In DM-2, the greatest clinical significance, as a rule, acquires diabetic macroangiopathy, which at the time of diagnosis is detected in the vast majority of patients. In each case, the set and severity of individual late complications vary from their paradoxical complete absence, despite the significant duration of the disease, up to a combination of all possible options in a severe form.
Late Complications are main cause of death patients with diabetes, and taking into account its prevalence - the most important medical and social health problem in most countries. Concerning main goal of treatment and monitoring of patients with diabetes is the prevention (primary, secondary, tertiary) of its late complications.
7.8.1. Diabetic macroangiopathy
Diabetic macroangiopathy- a collective concept that unites atherosclerotic lesions of large arteries in diabetes,
clinically manifested by coronary heart disease (CHD), obliterating atherosclerosis of cerebral vessels, lower extremities, internal organs and arterial hypertension (Table 7.16).
Tab. 7.16. Diabetic macroangiopathy
Etiology and pathogenesis
Probably similar to the etiology and pathogenesis of atherosclerosis in individuals without DM. Atherosclerotic plaques do not differ in microscopic structure in individuals with and without DM. However, in DM, additional risk factors may come to the fore, or DM exacerbates known non-specific factors. Those with SD should include:
1. Hyperglycemia. It is a risk factor for the development of atherosclerosis. An increase in the level of HbA1c by 1% in patients with DM-2 increases
There is a 15% risk of developing myocardial infarction. The mechanism of the atherogenic effect of hyperglycemia is not entirely clear; it may be associated with glycosylation of the end products of LDL metabolism and vascular wall collagen.
2. Arterial hypertension(AG). In pathogenesis, great importance is attached to the renal component (diabetic nephropathy). Hypertension in DM-2 is no less significant risk factor for heart attack and stroke than hyperglycemia.
3. Dyslipidemia. Hyperinsulinemia, which is an integral component of insulin resistance in T2DM, causes a decrease in HDL levels, an increase in triglycerides and a decrease in density, i.e. increased atherogenicity of LDL.
4. Obesity, which affects the majority of patients with CD-2, is an independent risk factor for atherosclerosis, myocardial infarction and stroke (see section 11.2).
5. insulin resistance. Hyperinsulinemia and high levels of insulin-proinsulin-like molecules increase the risk of atherosclerosis, possibly associated with endothelial dysfunction.
6. Violation of blood coagulation. In diabetes, an increase in the level of fibrinogen, platelet inhibitor activator and von Willebrand factor is determined, resulting in the formation of a prothrombotic state of the blood coagulation system.
7. endothelial dysfunction, characterized by increased expression of the plasminogen inhibitor activator and cell adhesion molecules.
8. oxidative stress, leading to an increase in the concentration of oxidized LDL and F2-isoprostane.
9. systemic inflammation, at which there is an increase in the expression of fibrinogen and C-reactive protein.
The most significant risk factors for the development of coronary artery disease in DM-2 are elevated LDL, low HDL, arterial hypertension, hyperglycemia and smoking. One of the differences between the atherosclerotic process in DM is the more common and distal nature of the occlusive lesion, those. Relatively smaller arteries are often involved in the process, which complicates surgical treatment and worsens the prognosis.
Epidemiology
The risk of developing coronary artery disease in people with type 2 diabetes is 6 times higher than in people without diabetes, while it is the same for men and women. Arterial hypertension is detected in 20% of patients with DM-1 and in 75% with DM-2. In general, it occurs twice as often in patients with DM than in those without it. Obliterating atherosclerosis of peripheral vessels develops in 10% of patients with DM. Thromboembolism of cerebral vessels develops in 8% of patients with diabetes (2-4 times more often than in people without diabetes).
Clinical manifestations
Basically do not differ from those in individuals without DM. In the clinical picture of DM-2, macrovascular complications (myocardial infarction, stroke, occlusive lesion of the vessels of the legs) often come to the fore, and it is during their development that hyperglycemia is often first detected in a patient. Perhaps due to concomitant autonomic neuropathy, up to 30% of myocardial infarctions in people with diabetes occur without a typical anginal attack (painless infarction).
Diagnostics
The principles of diagnosing complications of atherosclerosis (IHD, cerebrovascular accident, occlusive lesions of the arteries of the legs) do not differ from those for persons without DM. Measurement blood pressure(BP) should be carried out at each visit of a patient with diabetes to a doctor, and the determination of indicators lipid spectrum blood (total cholesterol, triglycerides, LDL, HDL) in diabetes should be carried out at least once a year.
Differential Diagnosis
Other cardiovascular diseases, symptomatic arterial hypertension, secondary dyslipidemia.
Treatment
♦ Blood pressure control. The proper level of systolic blood pressure in diabetes is less than 130 mmHg, and diastolic 80 mmHg (Table 7.3). Most patients will need multiple antihypertensive drugs to achieve this goal. The drugs of choice for antihypertensive therapy in diabetes are ACE inhibitors and angiotensin receptor blockers, which, if necessary, are supplemented with thiazide diuretics. The drugs of choice for patients with diabetes who have had myocardial infarction are β-blockers.
♦ Correction of dyslipidemia. Target levels of lipid spectrum indicators are presented in table. 7.3. The drugs of choice for lipid-lowering therapy are inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase (statins).
♦ antiplatelet therapy. Therapy with aspirin (75-100 mg/day) is indicated for patients with diabetes older than 40 years with an increased risk of developing cardiovascular disease (complicated family history, arterial hypertension, smoking, dyslipidemia, microalbuminuria), as well as for all patients with clinical manifestations of atherosclerosis as secondary prevention.
♦ Screening and treatment of coronary artery disease. Stress tests to exclude coronary artery disease are indicated for patients with symptoms of cardiovascular disease, as well as in the detection of pathology in the ECG.
Forecast
75% of patients with DM-2 and 35% of patients with DM-1 die from cardiovascular diseases. Approximately 50% of patients with type 2 diabetes die from complications of coronary artery disease, 15% from cerebral thromboembolism. Mortality from myocardial infarction in people with diabetes exceeds 50%.
7.8.2. diabetic retinopathy
diabetic retinopathy(DR) - microangiopathy of the retinal vessels, characterized by the development of microaneurysms, hemorrhages, exudative changes and proliferation of newly formed vessels, leading to partial or complete loss of vision (Table 7.17).
Etiology
The main etiological factor in the development of DR is chronic hyperglycemia. Other factors (arterial hypertension, dyslipidemia, smoking, pregnancy, etc.) are less important.
Pathogenesis
The main links in the pathogenesis of DR are:
Microangiopathy of the retinal vessels, leading to narrowing of the lumen of the vessels with the development of hypoperfusion;
Degeneration of vessels with the formation of microaneurysms;
Progressive hypoxia, stimulating vascular proliferation and leading to fatty degeneration and deposition of calcium salts in the retina;
Tab. 7.17. diabetic retinopathy
microinfarcts with exudation, leading to the formation of soft "cotton spots";
Deposition of lipids with the formation of dense exudates;
Growth in the retina of proliferating vessels with the formation of shunts and aneurysms, leading to dilatation of the veins and aggravation of retinal hypoperfusion;
The phenomenon of stealing with further progression of ischemia, which is the cause of the formation of infiltrates and scars;
Detachment of the retina as a result of its ischemic disintegration and the formation of vitreoretinal tractions;
Hemorrhages in the vitreous body as a result of hemorrhagic infarcts, massive vascular invasion and rupture of aneurysms;
Proliferation of the vessels of the iris (diabetic rubeosis), leading to the development of secondary glaucoma;
Maculopathy with retinal edema.
Epidemiology
DR is the most common cause of blindness among the working-age population in developed countries, and the risk of developing blindness in patients with DM is 10-20 times higher than in the general population. At the time of diagnosing DM-1, DR is not detected in almost any of the patients; after 5 years, the disease is detected in 8% of patients, and with a thirty-year history of diabetes, in 98% of patients. At the time of diagnosis of CD-2, DR is detected in 20-40% of patients, and among patients with a fifteen-year experience of CD-2 - in 85%. With SD-1, proliferative retinopathy is relatively more common, and with SD-2, maculopathy (75% of cases of maculopathy).
Clinical manifestations
According to the generally accepted classification, there are 3 stages of DR
(Table 7.18).
Diagnostics
A complete ophthalmological examination, including direct ophthalmoscopy with retinal photography, is indicated for patients with DM-1 3-5 years after the onset of the disease, and for patients with DM-2 immediately after its detection. In the future, such studies should be repeated annually.
Tab. 7.18. Classification of diabetic retinopathy
Differential Diagnosis
Other eye diseases in patients with diabetes.
Treatment
The basic principle of the treatment of diabetic retinopathy, as well as other late complications, is the optimal compensation for DM. The most effective treatment for diabetic retinopathy and prevention of blindness is laser photocoagulation. aim
Rice. 7.11. Diabetic retinopathy:
a) non-proliferative; b) preproliferative; c) proliferative
laser photocoagulation is the cessation of the functioning of newly formed vessels, which pose the main threat to the development of such severe complications as hemophthalmia, traction retinal detachment, iris rubeosis and secondary glaucoma.
Forecast
Blindness is recorded in 2% of patients with DM (3-4% of patients with DM-1 and 1.5-2% of patients with DM-2). The approximate rate of new cases of blindness associated with DR is 3.3 cases per 100,000 population per year. With DM-1, a decrease in HbA1c to 7.0% leads to a decrease in the risk of developing DR by 75% and a decrease in the risk of progression of DR by 60%. With DM-2, a 1% decrease in HbA1c leads to a 20% decrease in the risk of developing DR.
7.8.3. diabetic nephropathy
diabetic nephropathy(DNF) is defined as albuminuria (more than 300 mg of albumin per day or proteinuria of more than 0.5 g of protein per day) and / or a decrease in the filtration function of the kidneys in people with diabetes in the absence of urinary infections, heart failure or other kidney diseases. Microalbuminuria is defined as albumin excretion of 30–300 mg/day or 20–200 mcg/min.
Etiology and pathogenesis
The main risk factors for DNF are the duration of diabetes, chronic hyperglycemia, arterial hypertension, dyslipidemia, and kidney disease in parents. In DNF, it is primarily affected glomerular apparatus kidneys.
1. One of the possible mechanisms by which hyperglycemia contributes to the development of glomerular lesions, is the accumulation of sorbitol due to the activation of the polyol pathway of glucose metabolism, as well as a number of advanced glycation end products.
2. Hemodynamic disturbances, namely intraglomerular arterial hypertension(increased blood pressure inside the glomeruli of the kidney) is an essential component of the pathogenesis
The cause of intraglomerular hypertension is a violation of the tone of arterioles: expansion of the afferent and narrowing of the efferent.
Tab. 7.19. diabetic nephropathy
This, in turn, occurs under the influence of a number of humoral factors, such as angiotensin-2 and endothelin, as well as due to a violation of the electrolyte properties of the glomerular basement membrane. In addition, systemic hypertension contributes to intraglomerular hypertension, which is present in most patients with DNF. Due to intraglomerular hypertension, basement membranes and filtration pores are damaged,
through which traces begin to penetrate (microalbuminuria), followed by significant amounts of albumin (proteinuria). Thickening of the basement membranes causes a change in their electrolyte properties, which in itself leads to more albumin entering the ultrafiltrate even in the absence of a change in the size of the filtration pores.
3. Genetic predisposition. In relatives of patients with DNF, arterial hypertension occurs with an increased frequency. There is evidence of a relationship between DNP and ACE gene polymorphism. Microscopically, DNF reveals thickening of the basement membranes of the glomeruli, expansion of the mesangium, as well as fibrotic changes in the afferent and efferent arterioles. At the final stage, which clinically corresponds to chronic renal failure (CRF), focal (Kimmelstiel-Wilson) and then diffuse glomerulosclerosis is determined.
Epidemiology
Microalbuminuria is determined in 6-60% of patients with DM-1 5-15 years after its manifestation. DNF is determined in 35% of those with DM-1, more often in men and in individuals who developed DM-1 at the age of less than 15 years. With DM-2, DNF develops in 25% of the representatives of the European race and in 50% of the Asian race. The overall prevalence of DNF in T2DM is 4-30%.
Clinical manifestations
A relatively early clinical manifestation that is indirectly associated with DNF is arterial hypertension. Other clinically obvious manifestations are late. These include manifestations of nephrotic syndrome and chronic renal failure.
Diagnostics
Screening for DNF in people with DM involves annual testing for microalbuminuria with DM-1 5 years after the manifestation of the disease, and with DM-2 - immediately after its detection. In addition, at least an annual determination of the level of creatinine is required to calculate glomerular filtration rate (GFR). GFR can be calculated using various formulas, such as the Cockcroft-Gault formula:
For men: a = 1.23 (GFR norm 100 - 150 ml/min) For women: a = 1.05 (GFR norm 85 - 130 ml/min)
In the initial stages of DNF, an increase in GFR can be detected, which gradually falls as CRF progresses. Microalbuminuria begins to be determined 5-15 years after the manifestation of CD-1; in DM-2 in 8-10% of cases, it is detected immediately after its detection, probably due to the long asymptomatic course of the disease before diagnosis. The peak of overt proteinuria or albuminuria in T1DM occurs between 15 and 20 years after onset. Proteinuria is indicative of irreversibility DNF, which sooner or later will lead to CRF. Uremia develops on average 7-10 years after the onset of overt proteinuria. It should be noted that GFR does not correlate with proteinuria.
Differential Diagnosis
Other causes of proteinuria and renal failure in people with diabetes. In most cases, DNF is associated with arterial hypertension, diabetic retinopathy or neuropathy, in the absence of which the differential diagnosis should be especially careful. In 10% of cases with DM-1 and in 30% of cases with DM-2, proteinuria is not associated with DNF.
Treatment
♦ Basic conditions for primary and secondary prevention
DNF are compensation for diabetes and maintenance of normal systemic arterial pressure. In addition, primary prevention of DNF implies a reduction in protein intake - less than 35% of daily calories.
♦ At stages microalbuminuria and proteinuria patients are shown the appointment of ACE inhibitors or angiotensin receptor blockers. With concomitant arterial hypertension, they are prescribed in antihypertensive doses, if necessary in combination with other antihypertensive drugs. With normal blood pressure, these drugs are prescribed in doses that do not lead to the development of hypotension. Both ACE inhibitors (in DM-1 and DM-2) and angiotensin receptor blockers (in DM-2) help prevent the transition of microalbuminuria to proteinuria. In some cases, microalbuminuria is eliminated against the background of this therapy in combination with diabetes compensation according to other parameters. In addition, starting from the stage of microalbuminuria, it is necessary
reducing protein intake to less than 10% of daily calories (or less than 0.8 grams per kg of weight) and salt to less than 3 grams per day.
♦ On stage CKD, as a rule, correction of hypoglycemic therapy is required. Most patients with type 2 diabetes need to be switched to insulin therapy, since the accumulation of TSP carries the risk of developing severe hypoglycemia. In most patients with type 1 diabetes, there is a decrease in the need for insulin, since the kidney is one of the main sites of its metabolism. With an increase in serum creatinine to 500 µmol/l or more, it is necessary to raise the issue of preparing the patient for extracorporeal (hemodialysis, peritoneal dialysis) or surgical (kidney transplantation) method of treatment. Kidney transplantation is indicated at creatinine levels up to 600-700 µmol/l and a decrease in glomerular filtration rate less than 25 ml/min, hemodialysis - 1000-1200 µmol/l and less than 10 ml/min, respectively.
Forecast
In 50% of patients with type 1 diabetes and 10% with type 2 diabetes who have proteinuria, CKD develops over the next 10 years. 15% of all deaths in patients with type 1 diabetes under 50 years of age are associated with CRF due to DNF.
7.8.4. Diabetic neuropathy
Diabetic neuropathy(DNE) is a combination of syndromes of damage to the nervous system, which can be classified depending on the predominant involvement in the process of its various departments (sensory-motor, autonomic), as well as the prevalence and severity of the lesion (Table 7.20).
I. Sensorimotor neuropathy:
symmetrical;
Focal (mononeuropathy) or polyfocal (cranial, proximal motor, limb and trunk mononeuropathy).
II. Autonomic (vegetative) neuropathy:
Cardiovascular (orthostatic hypotension, cardiac denervation syndrome);
Gastrointestinal (gastric atony, biliary dyskinesia, diabetic enteropathy);
Urogenital (with dysfunction of the bladder and sexual function);
Impairment of the patient's ability to recognize hypoglycemia;
Impaired pupil function;
Violation of the functions of the sweat glands (distal anhidrosis, hyperhidrosis when eating).
Tab. 7.20. Diabetic neuropathy
Etiology and pathogenesis
The main cause of DNE is hyperglycemia. Several mechanisms of its pathogenesis are proposed:
Activation of the polyol pathway of glucose metabolism, resulting in the accumulation of sorbitol and fructose in nerve cells and a decrease in the content of myoinositol and glutathione. This, in turn, leads to the activation of free radical processes and a decrease in the level of nitric oxide;
Non-enzymatic glycosylation of membrane and cytoplasmic proteins of nerve cells;
Microangiopathy vasa nervorum, which leads to slowing of capillary blood flow and nerve hypoxia.
Epidemiology
The prevalence of DNE in both types of DM is about 30%. With DM-1, after 5 years from the onset of the disease, it begins to be detected in 10% of patients. The frequency of new cases of DNE in DM-2 is about 6% of patients per year. The most common variant is the distal symmetrical sensorimotor NNE.
Clinical manifestations
Sensorimotor DNE manifested by a complex of motor and sensory disorders. A common symptom of the distal form of DNE is paresthesia, which are manifested by a feeling of "crawling", numbness. Patients often complain of coldness of the legs, although they remain warm to the touch, which is a sign that distinguishes polyneuropathy from ischemic changes when the legs are cold to the touch. Vibration sensitivity is an early manifestation of sensory neuropathy. Characteristic is the syndrome of "restless legs", which is a combination of nocturnal paresthesia and hypersensitivity. Pain in the legs more often disturbed at night, while sometimes the patient cannot bear the touch of a blanket. In a typical case, the pain, in contrast to that of obliterating diseases of the arteries, may be relieved by walking. Years later, the pain may spontaneously stop due to the death of small nerve fibers responsible for pain sensitivity. Hypoesthesia manifested by loss of sensitivity of the type of "stocking" and "gloves". Violation of deep, proprioceptive sensitivity leads to impaired coordination and difficulty in movement (sensory ataxia). The patient complains of "someone else's legs", a feeling of "standing on cotton wool". Violation of trophic innervation leads to degenerative changes in the skin, bones and tendons. Violation of pain sensitivity leads to frequent, unnoticed by the patient microtraumas of the feet, which are easily infected. Violation of coordination and walking leads to a non-physiological redistribution of the load on the joints of the foot. As a result, the anatomical relationships in the musculoskeletal system of the leg are disturbed.
The arch of the foot is deformed, swelling, fractures, chronic purulent processes develop (see paragraph 7.8.5).
There are several forms of autonomous DNE. Cause cardiovascular form- violation of the innervation of the cardio-pulmonary complex and large vessels. The vagus nerve is the longest nerve, and therefore it is affected earlier than others. As a result of the predominance of sympathetic influences develops resting tachycardia. Inadequate response to orthostasis manifests itself orthostatic hypotension and syncope. Autonomic denervation of the pulmonary-cardiac complex leads to the absence of heart rate variability. An increased prevalence of painless myocardial infarction among diabetic patients is associated with autonomic neuropathy.
Symptoms gastrointestinal form DNEs are gastroparesis with delayed or, conversely, rapid emptying of the stomach, which can create difficulties in the selection of insulin therapy, since the time and volume of absorption of carbohydrates vary indefinitely; atony of the esophagus, reflux esophagitis, dysphagia; watery diarrhea. For urogenital form DNE is characterized by atony of the ureters and bladder, leading to a tendency to urinary infections; erectile dysfunction (about 50% of patients with diabetes); retrograde ejaculation.
Other possible manifestations of autonomic DNE are impaired ability to recognize hypoglycemia, impaired pupillary function, impaired sweat gland function (anhidrosis), and diabetic amyotrophy.
Diagnostics
Neurological examination of patients with DM should be carried out annually. At a minimum, it involves testing to detect distal sensorimotor neuropathy. For this, vibration sensitivity is assessed using a graduated tuning fork, tactile sensitivity using a monofilament, as well as temperature and pain sensitivity. According to the indications, the state of the autonomic nervous system is studied: a number of functional tests are used to diagnose insufficiency of the parasympathetic innervation of the heart, such as measuring heart rate during deep breathing with an assessment of variability
heart rate and Valsalva test; an orthostatic test is used to diagnose insufficiency of the sympathetic innervation of the heart.
Differential Diagnosis
Neuropathy of another origin (alcoholic, uremic, with B 12 deficiency anemia, etc.). The diagnosis of dysfunction of one or another organ as a result of autonomic neuropathy is established only after the exclusion of organ pathology.
Treatment
1. Optimization of hypoglycemic therapy.
2. Foot care (see paragraph 7.8.5).
3. The effectiveness of neurotropic drugs (α-lipoic acid) is not confirmed in all studies.
4. Symptomatic therapy (pain relief, sildenafil for erectile dysfunction, fludrocortisone for orthostatic hypotension, etc.).
Forecast
In the initial stages, DNE may be reversible against the background of stable compensation for DM. DNE is determined in 80% of patients with ulcers and is the main risk factor for leg amputation.
7.8.5. diabetic foot syndrome
diabetic foot syndrome(SDS) - a pathological condition of the foot in DM that occurs against the background of damage to peripheral nerves, skin and soft tissues, bones and joints and manifests itself in acute and chronic ulcers, osteoarticular lesions and purulent necrotic processes (Table 7.21).
Etiology and pathogenesis
The pathogenesis of DFS is multicomponent and is represented by a combination of neuropathic and perfusion disorders with a pronounced tendency to infection. Based on the predominance in the pathogenesis of one or another of the listed factors, there are 3 main forms
Tab. 7.21. diabetic foot syndrome
I. Neuropathic form(60-70 %):
Without osteoarthropathy;
with diabetic osteoarthropathy.
II. Neuroischemic (mixed) form(15-20 %).
III. Ischemic form(3-7 %).
neuropathic form of SDS. In diabetic neuropathy, the distal parts of the longest nerves are primarily affected. Prolonged deficiency of trophic impulses leads to hypotrophy of the skin, bones, ligaments, tendons and muscles. The result of hypotrophy of the connective structures is the deformity of the foot with a non-physiological redistribution of the support load and its excessive increase in certain areas. In these places, for example, in the projection of the heads of the metatarsal bones, thickening of the skin and the formation of hyperkeratosis are noted. Constant pressure on these areas leads to inflammatory autolysis of the underlying soft tissues, which creates the preconditions for the formation of an ulcer. As a result of atrophy and impaired perspiration, the skin becomes dry and easily cracked. Due to the decrease in pain sensitivity, the patient often does not pay attention to the ongoing changes. He cannot timely detect the inconvenience of shoes, which leads to the formation of scuffs and calluses, does not notice the introduction of foreign bodies, small wounds in places of cracking. The situation is exacerbated by a violation of deep sensitivity, manifested in a violation of gait, incorrect installation of the foot. Most often, a peptic ulcer is infected with staphylococci, streptococci, bacteria of the intestinal group; anaerobic flora often joins. Neuropathic osteoarthropathy is the result of pronounced dystrophic changes in the osteoarticular apparatus of the foot (osteoporosis, osteolysis, hyperostosis).
Ischemic form of SDS is a consequence of atherosclerosis of the arteries of the lower extremities, leading to a violation of the main blood flow, i.e. is one of the variants of diabetic macroangiopathy.
Epidemiology
SDS is observed in 10-25%, and according to some data, in one form or another in 30-80% of patients with diabetes. In the United States, the annual cost of treating diabetic patients with DFS is $1 billion.
Clinical manifestations
At neuropathic form SDS distinguishes the two most common types of lesions: neuropathic ulcer and osteoarthropathy (with the development
Rice. 7.12. Neuropathic ulcer in diabetic foot syndrome
Rice. 7.13. Charcot joint in diabetic foot syndrome
Charcot joint). neuropathic ulcers, as a rule, they are localized in the area of the sole and interdigital spaces, i.e. on the areas of the foot that experience the greatest pressure (Fig. 7.12).
Destructive changes in the bone and ligamentous apparatus of the foot can progress over many months and lead to severe bone deformity - diabetic osteoarthropathy and formation charcot joint, at the same time, the foot is figuratively compared with a “bag of bones”
At ischemic form of SDS
the skin on the feet is cold, pale or cyanotic; rarely has a pinkish-red tint due to the expansion of superficial capillaries in response to ischemia. Ulcerative defects occur as acral necrosis - on the tips of the fingers, the marginal surface of the heels (Fig. 7.14).
The pulse on the arteries of the foot, popliteal and femoral arteries is weakened or not palpable.
In typical cases, patients complain of "intermittent claudication". The severity of ischemic damage to the limb is determined by three main factors: the severity of stenosis, the development of collateral blood flow, the state of the blood coagulation system.
Diagnostics
Examination of the legs of a patient with diabetes should be performed every time during a visit to the doctor, at least once every six months. Diagnosis of SDS includes:
Rice. 7.14. Acral necrosis in ischemic form of diabetic foot syndrome
Examination of the legs;
Assessment of the neurological status - various types of sensitivity, tendon reflexes, electromyography;
Assessment of the state of arterial blood flow - angiography, dopplerography, dopplerography;
X-ray of the feet and ankles;
Bacteriological examination of the wound discharge.
Differential Diagnosis
It is carried out with wound processes on the feet of a different origin, as well as other occlusive diseases of the vessels of the lower extremities and pathology of the joints of the foot. In addition, it is necessary to differentiate the clinical forms of SDS (Table 7.22).
Treatment
Treatment neuropathically infected VTS forms include a set of the following activities:
Optimization of DM compensation, as a rule, an increase in the dose of insulin, and in case of DM-2 - transfer to it;
Systemic antibiotic therapy;
Complete unloading of the foot (this can lead to healing of ulcers that have existed for years within a few weeks);
Local treatment of the wound with the removal of areas of hyperkeratosis;
Foot care, proper selection and wearing of special shoes. Timely conservative therapy allows
avoid surgery in 95% of cases.
Tab. 7.22. Differential diagnosis of clinical forms of SDS
Treatment ischemic VTS forms include:
Optimization of DM compensation, as a rule, an increase in the dose of insulin, and in case of DM-2 - transfer to it;
In the absence of ulcerative-necrotic lesions, occupational therapy (1-2-hour walking per day, which contributes to the development of collateral blood flow);
Revascularization operations on the affected vessels;
Conservative therapy: anticoagulants, aspirin (up to 100 mg / day), if necessary - fibrinolytics, prostaglandin E1 and prostacyclin preparations.
With the development of an extensive purulent-necrotic lesion in all variants of SDS, the question of amputation is raised.
Forecast
From 50 to 70% of the total number of leg amputations performed are in patients with DM. Leg amputations are 20 to 40 times more common in diabetic patients than in non-diabetic patients.
7.9. DIABETES AND PREGNANCY
Gestational diabetes mellitus(GDM) is a glucose intolerance first identified during pregnancy (Table 7.23). This definition does not exclude the possibility that the pathology of carbohydrate metabolism could precede the onset of pregnancy. GDM should be distinguished from situations where a woman with previously diagnosed diabetes (because of age, more often type 1 diabetes) becomes pregnant.
Etiology and pathogenesis
With GDM, they are similar to those with SD-2. High levels of ovarian and placental steroids, as well as an increase in the production of cortisol by the adrenal cortex, lead to the development of physiological insulin resistance during pregnancy. The development of GDM is associated with the fact that insulin resistance, which naturally develops during pregnancy, and, consequently, an increased need for insulin in predisposed individuals, exceeds the functional capacity of pancreatic β-cells. After childbirth, with the return of hormonal and metabolic relationships to the initial level, it usually disappears.
Tab. 7.23. Gestational diabetes mellitus
GDM usually develops in the middle of the 2nd trimester, between 4 and 8 months of pregnancy. The vast majority of patients have an excess of body weight and a burdened history of CD-2. Risk factors for the development of GDM, as well as groups of women with a low risk of developing GDM, are given in Table. 7.24.
Tab. 7.24. Risk Factors for Gestational Diabetes Mellitus
Maternal hyperglycemia leads to hyperglycemia in the baby's circulatory system. Glucose easily crosses the placenta and continuously passes to the fetus from the mother's blood. Active transport of amino acids and transfer of ketone bodies to the fetus also occur. In contrast, insulin, glucagon, and free fatty acids from the mother do not enter the blood of the fetus. In the first 9-12 weeks of pregnancy, the pancreas of the fetus does not yet produce its own insulin. This time corresponds to the phase of fetal organogenesis when, with constant hyperglycemia, various malformations (heart, spine, spinal cord, gastrointestinal tract) can form in the mother. From the 12th week of pregnancy, the fetal pancreas begins to synthesize insulin, and in response to hyperglycemia, reactive hypertrophy and hyperplasia of β-cells of the fetal pancreas develop. Due to hyperinsulinemia, fetal macrosomia develops, as well as inhibition of lecithin synthesis, which explains the high incidence of respiratory distress syndrome in newborns. As a result of β-cell hyperplasia and hyperinsulinemia, there is a tendency to severe and prolonged hypoglycemia.
Epidemiology
DM affects 0.3% of all women of reproductive age, 0.2-0.3% of pregnant women already initially have DM, and 1-14% of pregnancies develop GDM or manifest true DM. The prevalence of GDM varies in different populations, for example, in the United States it is detected in approximately 4% of pregnant women (135 thousand cases per year).
Clinical manifestations
Not present in GSD. There may be non-specific symptoms of decompensated diabetes.
Diagnostics
Fasting blood glucose levels are indicated for all pregnant women as part of a biochemical blood test. Women who belong to the risk group (Table 7.24) are shown to have oral glucose tolerance test(OGTT). Many variants of its implementation in pregnant women are described. The simplest of them implies the following rules:
3 days before the examination, the woman is on a normal diet and adheres to her usual physical activity;
The test is carried out in the morning on an empty stomach, after an overnight fast of at least 8 hours;
After taking a blood sample on an empty stomach, a woman drinks a solution for 5 minutes, consisting of 75 grams of dry glucose dissolved in 250-300 ml of water; repeated determination of the level of glycemia is carried out after 2 hours.
The diagnosis of GDM is based on the following criteria:
Glucose of whole blood (venous, capillary) on an empty stomach> 6.1 mmol/l or
Venous plasma glucose ≥ 7 mmol/l or
Glucose in capillary whole blood or venous plasma 2 hours after a load of 75 g of glucose ≥ 7.8 mmol / l.
If the results of the study are normal for a woman who belongs to the risk group, the test is repeated at 24-28 weeks of pregnancy.
Differential Diagnosis
GSD and true SD; glycosuria in pregnancy.
Treatment
The risk for the mother and fetus, as well as approaches to the treatment of diabetes and the features of its control in GDM and in true diabetes are the same. Late complications of diabetes during pregnancy can progress significantly, however, with high-quality compensation for diabetes, there are no indications for termination of pregnancy. A woman with diabetes (usually DM-1) should plan pregnancy at a young age, when the risk of complications is lowest. If pregnancy is planned, it is recommended to cancel con-
reception a few months after reaching optimal compensation. Contraindications to pregnancy planning are severe nephropathy with progressive renal failure, severe ischemic heart disease, severe proliferative retinopathy that cannot be corrected, ketoacidosis in early pregnancy (ketone bodies are teratogenic factors).
The goal of treatment GDM and true diabetes during pregnancy is the achievement of the following laboratory parameters:
fasting glucose< 5-5,8 ммоль/л;
Glycemia 1 hour after eating< 7,8 ммоль/л;
Glycemia 2 hours after eating< 6,7 ммоль/л;
Mean Daily Glycemic Profile< 5,5 ммоль/л;
The level of HbA1c at monthly control, as in healthy people (4-6%).
With DM-1, as well as outside pregnancy, a woman should receive intensive insulin therapy, however, the level of glycemia during pregnancy is recommended to be assessed 7-8 times a day. If it is impossible to achieve normoglycemic compensation against the background of conventional injections, it is necessary to consider transferring the patient to insulin therapy using an insulin dispenser.
At the first stage treatment of GDM diet therapy is prescribed, which consists in limiting the daily calorie intake to about 25 kcal / kg of actual weight, primarily due to easily digestible carbohydrates and fats of animal origin, as well as expanding physical activity. If on the background of diet therapy it is not possible to achieve the goals of treatment, the patient should be prescribed intensive insulin therapy. Any tableted antidiabetic drugs (TSP) during pregnancy contraindicated. About 15% of women need to be transferred to insulin therapy.
Forecast
With unsatisfactory compensation of GDM and DM during pregnancy, the likelihood of developing various pathologies in the fetus is 30% (risk 12 times higher than in the general population). More than 50% of women who develop GDM during pregnancy develop CD-2 over the next 15 years.
Diabetes mellitus is complex disease which is difficult to treat. With its development in the body, there is a violation of carbohydrate metabolism and a decrease in the synthesis of insulin by the pancreas, as a result of which glucose ceases to be absorbed by cells and settles in the blood in the form of microcrystalline elements. The exact reasons why it begins to develop this disease, scientists have not yet been able to establish. But they have identified risk factors for diabetes that can trigger the onset of this disease in both the elderly and young people.
A few words about pathology
Before considering the risk factors for developing diabetes, it must be said that this disease has two types, and each of them has its own characteristics. Type 1 diabetes is characterized by systemic changes in the body, in which not only carbohydrate metabolism but also the functionality of the pancreas. For some reason, her cells stop producing insulin in the right amount, as a result of which sugar, which enters the body with food, does not undergo cleavage processes and, accordingly, cannot be absorbed by cells.
Type 2 diabetes is a disease in which the functionality of the pancreas is preserved, but due to impaired metabolism, body cells lose sensitivity to insulin. Against this background, glucose simply ceases to be transported into the cells and settles in the blood.
But no matter what processes occur in diabetes mellitus, the result of this disease is the same - a high level of glucose in the blood, which leads to serious problems with health.
The most common complications of this disease are the following conditions:
- hyperglycemia - an increase in blood sugar levels beyond the normal range (over 7 mmol / l);
- hypoglycemia - a decrease in blood glucose levels beyond the normal range (below 3.3 mmol / l);
- hyperglycemic coma - an increase in blood sugar levels over 30 mmol / l;
- hypoglycemic coma - a decrease in blood glucose below 2.1 mmol / l;
- diabetic foot - decreased sensitivity of the lower extremities and their deformation;
- - decreased visual acuity;
- thrombophlebitis - the formation of plaques in the walls of blood vessels;
- hypertension - increased blood pressure;
- gangrene - necrosis of the tissues of the lower extremities with the subsequent development of an abscess;
- stroke and myocardial infarction.
Common complications of diabetes
These are far from all the complications that the development of diabetes mellitus is fraught with for a person at any age. And in order to prevent this disease, it is necessary to know exactly what factors can provoke the onset of diabetes and what measures are included in the prevention of its development.
Type 1 diabetes and its risk factors
Type 1 diabetes mellitus (DM1) is most commonly diagnosed in children and young people aged 20-30 years. It is believed that the main factors of its development are:
- viral diseases;
- intoxication of the body;
- malnutrition;
- frequent stress.
In the occurrence of DM1 leading role plays a hereditary predisposition. If one of the family members suffers from this disease, then the risks of its development in the next generation are approximately 10-20%.
It should be noted, however, that in this case we are not talking about established fact but about predisposition. That is, if a mother or father has type 1 diabetes, this does not mean at all that their children will also be diagnosed with this disease. Predisposition says that if a person does not conduct preventive actions and leads an unhealthy lifestyle, then he has a high risk of becoming diabetic within a few years.
When diagnosing diabetes in both parents at once, the risks of developing the disease in their children increase several times.
However, in this case, it must be borne in mind that if both parents suffer from diabetes at once, then the likelihood of their child developing it is significantly increased. And it is often in such situations that this disease is diagnosed in children as early as school age although they do not yet have bad habits and lead active image life.
It is believed that diabetes mellitus is most often “transmitted” through male line. But if only the mother has diabetes, then the risks of having a baby with this disease are very low (no more than 10%).
Viral diseases
Viral diseases are another reason why type 1 diabetes can develop. Especially dangerous in this case are diseases such as parotitis and rubella. Scientists have long been proven that these diseases adversely affect the work of the pancreas and lead to damage to its cells, thus reducing the level of insulin in the blood.
It should be noted that this applies not only to children already born, but also to those who are still in the womb. Any viral diseases that a pregnant woman suffers can trigger the development of type 1 diabetes in her child.
Body intoxication
Many people work in factories and enterprises where chemical substances, the action of which negatively affects the work of the whole organism, including the functionality of the pancreas.
Chemotherapy, which is carried out to treat various oncological diseases, also have a toxic effect on the cells of the body, so their implementation also several times increases the likelihood of developing type 1 diabetes in humans.
Improper nutrition
Malnutrition is one of the most common causes of T1DM. Daily diet modern man contains a huge amount of fats and carbohydrates, which puts a heavy burden on digestive system, including the pancreas. Over time, its cells are damaged and insulin synthesis is disrupted.
Improper nutrition is dangerous not only for the development of obesity, but also for the violation of the pancreas
It should also be noted that due to malnutrition, DM1 can also develop in children aged 1-2 years. And the reason for this is the early introduction into the diet of the baby cow's milk and cereal crops.
Frequent stress
Stress is a trigger various diseases, including CD1. If a person is stressed, a lot of adrenaline is produced in his body, which contributes to the rapid processing of sugar in the blood, resulting in hypoglycemia. This condition is temporary, but if it occurs systematically, the risks of T1DM increase several times.
Type 2 diabetes and its risk factors
As mentioned above, type 2 diabetes mellitus (DM2) develops as a result of a decrease in cell sensitivity to insulin. This can also happen for several reasons:
- hereditary predisposition;
- age-related changes in organism;
- obesity;
- gestational diabetes.
hereditary predisposition
In the development of DM2, hereditary predisposition plays an even greater role than in DM1. As statistics show, the risks of this disease in the offspring in this case are 50% if DM2 was diagnosed only in the mother, and 80% if this disease was detected in both parents at once.
When DM2 is detected in parents, the probability of having a sick child is significantly higher than in DM1
Age-related changes in the body
Doctors consider DM2 a disease of the elderly, since it is in them that it is detected most often. The reason for this is age-related changes in the body. Unfortunately, with age, under the influence of internal and external factors internal organs"wear out" and their functionality is impaired. In addition, with age, many people develop hypertension, which further increases the risk of developing type 2 diabetes.
Important! In view of all this, doctors highly recommend to all people over 50 years old, regardless of general well-being and gender, regularly take tests to determine the level of sugar in the blood. And in case of detection of any deviations, immediately begin treatment.
Obesity is the leading cause of T2DM in both older and younger people. The reason for this is the excessive accumulation of fat in the cells of the body, as a result of which they begin to draw energy from it, and sugar becomes unnecessary for them. Therefore, with obesity, the cells stop absorbing glucose, and it settles in the blood. And if a person in the presence overweight The body also leads a passive lifestyle, which further increases the likelihood of developing DM2 at any age.
Obesity provokes the appearance of not only type 2 diabetes, but also other health problems
Gestational diabetes
Gestational diabetes is also referred to as gestational diabetes because it develops during pregnancy. Its occurrence is due hormonal disorders in the body and excessive activity of the pancreas (she has to work for "two"). Because of increased loads it wears out and stops producing insulin in the right quantities.
After childbirth, this disease disappears, but leaves a serious mark on the health of the child. Due to the fact that the mother's pancreas stops producing insulin in the right amount, the baby's pancreas begins to work in an accelerated mode, which leads to damage to its cells. In addition, with the development of gestational diabetes, the risk of obesity in the fetus increases, which also increases the risk of developing type 2 diabetes.
Prevention
Diabetes mellitus is a disease that can be easily prevented. To do this, it is enough to constantly carry out its prevention, which includes the following activities:
- Proper nutrition. Human nutrition should include many vitamins, minerals and proteins. Fats and carbohydrates should also be present in the diet, because without them the body cannot function normally, but in moderation. You should especially beware of easily digestible carbohydrates and trans fats, since they are the main cause of overweight and the further development of diabetes. As for babies, parents should make sure that the introduced complementary foods are as beneficial as possible for their body. And what and in which month you can give the baby, you can find out from the pediatrician.
- Active lifestyle. If you neglect sports and lead a passive lifestyle, you can also easily "earn" SD. Human activity contributes to the rapid burning of fats and energy consumption, resulting in an increased need for cells to glucose. At passive people the metabolism slows down, as a result of which the risks of developing diabetes increase.
- Regularly monitor blood sugar levels. This rule is especially true for those who have a hereditary predisposition to this disease, and people who have "knocked" 50 years. To monitor blood sugar levels, it is not at all necessary to constantly go to the clinic and take tests. It is enough just to purchase a glucometer and conduct blood tests yourself at home.
It should be understood that diabetes is a disease that cannot be cured. As it develops, it is necessary to constantly take medications and inject insulin. Therefore, if you do not want to always be in fear for your health, lead healthy lifestyle of life and promptly treat the diseases that arise in you. This is the only way to prevent the occurrence of diabetes and maintain your health for many years!
Down syndrome is not a disease, it is a pathology that cannot be prevented and cured. A fetus with Down syndrome has a third extra chromosome in the 21st pair of chromosomes, as a result, their number is not 46, but 47. Down syndrome occurs in one in 600-1000 newborns from women over the age of 35. The reason why this happens , has not been fully elucidated. The English physician John Langdon Down first described the syndrome in 1866, and in 1959 the French professor Lejeune proved that it was due to genetic changes.
It is known that children receive half of the chromosomes from the mother, and half from the father. Since there is none effective method treatment of Down syndrome, the disease is considered incurable, you can take measures and, if you wish to give birth to a healthy child, contact a medical genetic consultation, where, based on the chromosomal analysis of the parents, it will be determined whether the child will be born healthy or with Down syndrome.
Recently, such children are born more often, they associate this with late marriage, with pregnancy planning at the age of 40. It is also believed that if a grandmother gave birth to her daughter after 35, then grandchildren may be born with Down syndrome. Although prenatal diagnosis is difficult process examination, its conduct is very necessary in order to be able to terminate the pregnancy.
What is Down Syndrome. It can usually be accompanied by a delay in motor development. Such children have birth defects heart, pathology of organ development gastrointestinal tract. 8% of patients with Down syndrome have leukemia. Medical treatment can stimulate mental activity, normalize hormonal imbalance. With the help of physiotherapy procedures, massage, therapeutic gymnastics You can help your child acquire the skills necessary for self-care. Down syndrome is associated with genetic disorder, but this does not always lead to a violation of the physical and mental development child. Such children, and in the future adults, can participate in all spheres of life, some of them become actors, athletes and can be involved in public affairs. How a person with this diagnosis will develop depends largely on the environment in which he grows up. Good conditions, love and care contribute to the full development.
Down syndrome risk table, by age
The likelihood of Down syndrome depends on the age of the mother, but it can be detected by a genetic test for early stages pregnancy, and in some cases by ultrasound. The chance of a baby having Down's syndrome at birth is lower than at earlier stages of pregnancy. some fetuses with Down syndrome do not survive.
What risk is considered low and what is considered high?
In Israel, the risk of Down syndrome is considered high if it is higher than 1:380 (0.26%). Anyone in this risk group should have their amniotic fluid tested. This risk equates to that of women who become pregnant at age 35 or older.
Risk lower than 1:380 is considered low.
But keep in mind that these borders can be floating! So, for example, in England, high level risk is considered to be risk above 1:200 (0.5%). This is due to the fact that some women consider the risk of 1 in 1000 as high, and others 1 in 100 as low, since with such a risk they have a chance of giving birth healthy child is equal to 99%.
Risk factors for Down syndrome, Edwards, Patau
The main risk factors are age (particularly significant for Down syndrome), as well as exposure to radiation, some heavy metals. It should be borne in mind that even without risk factors, the fetus may have a pathology.
As can be seen from the graph, the dependence of the risk value on age is most significant for Down syndrome, and less significant for the other two trisomies:
Down Syndrome Risk Screening
To date, all pregnant women, in addition to relying tests, are recommended to undergo a screening test to identify the degree of risk of Down syndrome for childbirth and congenital malformations of the fetus. The most productive examination occurs at week 11 + 1 day or at week 13 + 6 days with the coccyx-parietal size of the embryo from 45 mm to 84 mm. A pregnant woman can be examined, and use a specific ultrasound for this.
More accurate diagnosis is done using a biopsy of the chorionic villi and examination of the amniotic fluid, which is taken with a special needle directly from amniotic sac. But every woman should know that such methods are associated with the risk of pregnancy complications such as miscarriage, infection of the fetus, the development of hearing loss in the child, and much more.
Full combined screening of the I - II trimester of pregnancy allows you to identify congenital malformations in the fetus. What does it include given test? First, it is necessary ultrasonography at 10-13 weeks of gestation. The risk is calculated by determining the presence of the nasal bone, by the width of the cervical fold of the fetus, where subcutaneous fluid accumulates in the first trimester of pregnancy.
In the second, a blood test is taken for chorionic gonadotropin at 10-13 weeks and for alpha-feto-protein at 16-18 weeks. Combination screening data is processed in a special way. computer program. Scientists have proposed new technique screening - combining the evaluation of the results obtained during the studies in the first and second trimesters. This allows for a unified assessment of the risk of Down syndrome during pregnancy.
For the first trimester, the results of determining PAPP-A and measuring the thickness of the collar space are used, and for the second trimester, combinations of AFP, unconjugated estriol, hCG and inhibin-A are used. Application integral assessment for screening examination allows, after invasive interventions, to reduce the frequency of abortion for fetuses with a normal karyotype according to the results of cytogenetic diagnostics.
Integral and biochemical testing for screening for Down syndrome allows additional detection of more cases of chromosomal abnormalities. This helps to prevent unwanted abortions resulting from amniocentesis or chorionic villus sampling.
Expert editor: Mochalov Pavel Alexandrovich| MD general practitioner
Education: Moscow medical institute them. I. M. Sechenov, specialty - "Medicine" in 1991, in 1993 "Occupational diseases", in 1996 "Therapy".
