Etiology and pathogenesis of diabetes mellitus

Associate Professor of the Department of Internal Medicine № 2
with a course in Krasnodar State Medical University, N.B.

Diabetes mellitus is one of the most common diseases; it is characterized by a long (life-long) course, the development of complications and the damage of various organs and systems leading to early disability and a shortened life expectancy of the patient. Early diagnosis and timely treatment of diabetes mellitus largely determine the nature of its course, the primary and secondary prevention of diabetic angiopathy and other changes, contribute to the preservation of disability.

Diabetes - A group of metabolic diseases that are united by a common symptom - chronic hyperglycemia, which is the result of defects in insulin secretion, the action of insulin, or both.

Classification

Etiological classification of glycemia disorders (WHO, 1999)

Type 1 diabetes mellitus (caused by the destruction of beta cells, usually leads to absolute insulin deficiency): autoimmune, idiopathic.

Type 2 diabetes mellitus (can range from the prevalence of insulin resistance with a relative insulin deficiency to the prevalence of insulin secretion defects with or without insulin resistance).

Gestational diabetes.

Other specific types:

- genetic defects causing dysfunction of beta cells,

- genetic defects causing violations of the action of insulin,

- diseases of the exocrine pancreas,

- induced by pharmacological and chemical agents,

- rare forms of immune mediated diabetes,

- other genetic syndromes, sometimes combined with diabetes

Genetic defects of beta-cell function:

MODY- (chromosome 12, HNF-1a),

MODY-2 (chromosome 7, glucokinase gene),

MODY-1 (chromosome 20, gene HNF-4a),

Mitochondrial DNA mutation,

Genetic defects that cause violations of the action of insulin:

Type A insulin resistance,

Rabson syndrome - Mendeholla,

Diseases of the exocrine pancreas:

Diabetes mellitus induced by pharmacological and chemical agents:

Other genetic syndromes sometimes associated with diabetes:

Lawrence-Moun-Beadle Syndrome

Pradera syndrome - Ville,

Unusual forms of immune-mediated diabetes

"Stiff-man" - a syndrome (immobility syndrome),

Insulin receptor autoantibodies,

Type 1 diabetes stage

Type 1 diabetes reflects the process beta cell destruction, which always leads to the development of diabetes mellitus, in which insulin is required for survival, to prevent the development of ketoacidosis, coma and death. Type one is usually characterized by the presence of antibodies to GAD (glutamate decarboxylase), a beta cell (ICA) or insulin, which confirm the presence of an autoimmune process.

Stages of development of diabetes mellitus of the first type (EisenbarthG.S, 1989)

Stage 1genetic predispositionwhich is implemented in less than half of genetically identical twins and 2-5% siblings. Of great importance is the presence of HLA antibodies, especially the second class - DR, DR4 and DQ. At the same time, the risk of developing diabetes of the first type increases many times. In the general population - 40%, in patients with diabetes - up to 90%.

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Stage 2 - hypothetical starting moment - viral infection, stress, nutrition, chemicals, i.e. Trigger factors: infectious (enterovirus, retroviral, congenital rubella, parasites, bacteria, fungi), non-infectious: dietary components: gluten, soy, other plants, cow's milk, heavy metals, nitrites, nitrates, beta cell toxins (drugs) , psychoassociation factors, UV irradiation.

Stage 3stage of immunological disorders - normal insulin secretion is maintained. Immunological markers of diabetes mellitus of the first type are determined - antibodies to antigens of beta - cells, insulin, GAD (GAD is determined for 10 years).

Stage 4stage of pronounced autoimmune disorders characterized by a progressive decrease in insulin secretion due to the development of insulitis. Glycemia is maintained normal. There is a decrease in the early phase of insulin secretion.

Stage 5stage of clinical manifestation develops with the death of 80 - 90% of the mass of beta cells. At the same time, residual secretion of C-peptide is maintained.

Type 2 diabetes, etiology, pathogenesis

Type 2 diabetes - a heterogeneous disease characterized by a complex of metabolic disorders, which are based on insulin resistance and varying degrees of severity dysfunction of beta cells.

Etiologytype 2 diabetes . Most forms of type 2 diabetes are polygenic, i.e. certain combination of genes, which determines the susceptibility to the disease, and its development and clinic are determined by such non-genetic factors as obesity, overeating, sedentary lifestyle, stressas well as insufficient nutrition in the uterine state and on first year of life.

Pathogenesis of diabetes of the second type. According to modern concepts, in the pathogenesis of type 2 diabetes mellitus, two mechanisms play a key role:

  1. insulin secretion disorder beta cells
  2. increased peripheral resistance to insulin action (decreased peripheral glucose uptake by the liver or increased glucose production). Most often, insulin resistance develops in abdominal obesity.

Symptoms of diabetes mellitus type 1 and 2

Differential diagnosis type 1 and 2

Clinical symptoms Type 1 diabetes there are acute, often in young people (between 15 and 24 years), there are seasonal outbreaks after infection. Manifestations of diabetic syndrome are pronounced, there is a tendency to ketoacidosis, often 25-0% come in pre- and comatose state. With a long course of the disease in conditions of unsatisfactory compensation, the clinical picture will be determined by late complications, mainly microangiopathies.

Type 2 diabetes. Due to the lack of absolute insulin deficiency, the disease manifests more gently. Diagnosis is often made randomly with the routine determination of glycemia. Characterized by overweight, manifestation after 40 years, a positive family history, no signs of absolute insulin deficiency. Very often, at the time of diagnosis, late complications are identified, primarily macroangiopathy (atherosclerosis), which determine the clinical picture of the disease, as well as latently current infections (pyelonephritis, fungal infection).

For the differential diagnosis of type 1 and type 2, as well as the diagnosis of insulin requirements in type 2 diabetes, the level of C-peptide is examined in tests with glucagon and food stimulation. (5 XE). A fasting C-peptide concentration above 0.6 nmol / l and above 1.1 nmol / l after food stimulation or the administration of 1 mg of glucagon indicates a sufficient production of insulin by b-cells. The level of stimulated C-peptide of 0.6 nmol / l and less indicates the need for exogenous insulin.

Diagnostics

Diagnostic criteria for overt diabetes mellitus (WHO, 1999)

1. Clinical symptoms of diabetes mellitus (polyuria, polydipsia, unexplained loss of body weight) in combination with the level of glucose in capillary blood at any time (regardless of meal times), greater or equal 11.1 mlmol / l.

2. Fasting glucose level in capillary blood (fasting for at least 8 hours) is greater than or equal to 6.1 mlmol / l.

. Capillary blood glucose In 2 hours after loading glucose (75g), large or equal 11.1 mlmol / l.

In order to identify latent diabetes mellitus (impaired glucose tolerance) in individuals with an increased risk of developing diabetes mellitus, a glucose tolerance test (TSH) is conducted.

OralTSH(Report of WHO Consultation, 1999)

The oral glucose tolerance test should be carried out in the morning against the background of at least one-day unlimited nutrition (more than 150 g of carbohydrates per day) and normal physical activity. Factors that could influence the test results (for example, medication, low physical activity, presence of infection) should be recorded. The test should be preceded by night fasting for 8-14 hours (you can drink water). The last evening meal should contain 0-50 g of carbohydrates. After taking a blood sample on an empty stomach, the subject should drink no more than 5 minutes to drink 75 g of anhydrous glucose or 82.5 glucose monohydrate dissolved in 250-00 ml of water. For children, the load is 1.75 g of glucose per kg of body weight, but not more than 75 g. Smoking is not allowed during the test. After 2 hours, repeated blood collection is performed. For epidemiological or screening purposes, a single fasting glucose level or 2-hour glucose level during TSH is sufficient. For clinical diagnostic purposes, diabetes mellitus should always be confirmed by repeated testing on the following day, with the exception of cases of undoubted hyperglycemia with acute metabolic decompensation or obvious symptoms.

Etiology of type 1 diabetes

More often, the aggregate of a group of factors lies at the basis of the etiology of DM 1.

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  • Genetic addiction.
  • Viruses: Coxsackie enterovirus, measles, chicken pox, cytomegalovirus.
  • Chemicals: nitrates, nitrites.
  • Medications: corticosteroids, strong antibiotics.
  • Diseases of the pancreas.
  • Large consumption of carbohydrates and fats of animal origin.
  • Stress.

The etiology of type 1 diabetes mellitus is not specifically established. Type 1 diabetes refers to multifactorial diseases, since doctors cannot name the exact etiological factor among the above. Diabetes 1 is very attached to heredity. In most patients, the genes for the HLA system are found, the presence of which is genetically transmitted. It is also important that this type of diabetes manifests itself in childhood and mostly up to 30 years.

The starting point in diabetes mellitus pathogenesis schemes is insulin deficiency - a deficiency of 80–90% in type 1 against the background of non-fulfillment of its functions by pancreatic beta cells. This leads to disruption of all types of metabolism. But first of all, glucose penetration into insulin-dependent tissues and its use are reduced. Glucose is the main energy component and its deficiency leads to starvation of cells. Undigested glucose accumulates in the blood, which is indicated by the development of hyperglycemia. The inability of the kidneys to filter sugar is manifested by the appearance of glucose in the urine. Glycemia has the ability of an osmotic diuretic, which is manifested in the form of symptoms such as polyuria (pathologically frequent urination), polydipsia (unnaturally strong thirst), hypotension (reduced pressure).

The lack of insulin upsets the balance between lipolysis and lipogenesis with the predominance of the first. The result of this is the accumulation of large amounts of fatty acids in the liver, which leads to the development of its fatty degeneration. Oxidation of these acids is accompanied by the synthesis of ketone bodies, which cause symptoms such as the smell of acetone from the mouth, vomiting, and anorexia. The scheme of all these factors adversely affects the water and electrolyte balance, which is manifested in the violation of the heart activity, a drop in blood pressure and the possibility of a collapse.

Causes of type 2 diabetes

The etiological factors of type 2 diabetes are similar to those of type 1 diabetes. But above all, the wrong diet comes to the fore, namely a large amount of carbohydrates and fats that overload the pancreas and lead to loss of insulin sensitivity of the tissues. Type 2 diabetes mainly affects people with obesity. Sedentary lifestyle, sedentary work, diabetes in the immediate family, unhealthy diet, or gestational diabetes during pregnancy - the etiology of type 2 diabetes. The pathogenesis of diabetes mellitus 2 is based on the disruption of pancreatic cells and an increase in insulin perception resistance, which is hepatic and peripheral. Distinctive signs - the patient is overweight, high blood pressure and the slow development of diabetes.

For diabetes 1 and 2 types

For 1 type lightning. In just a few days, a person’s condition deteriorates greatly: severe thirst, itchy skin, dry mouth, discharge of more than 5 liters of urine per day. Often, type 1 makes itself felt with the development of diabetic coma. Therefore, only substitution therapy is used for treatment - injection of insulin, since 10% of the hormone of the required amount is not able to perform all the necessary functions.

The course of diabetes 1 and 2 is different. If type 1 develops with lightning speed and is characterized by severe symptoms, then in type 2 patients often for a long time are unaware of the presence of violations.

Type 2 diabetes begins slowly and imperceptibly to humans. Against the background of obesity, muscle weakness, frequent dermatitis, purulent processes, itching, pain in the legs, slight thirst appear. If you turn to an endocrinologist in time, compensation can be achieved only with the help of diet and exercise. But most often, patients try not to notice deterioration and the disease progresses. Overweight people need to be attentive to themselves and with a minimum change in condition, consult a doctor.

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Types of sugar disease

The etiology of diabetes is well understood and in general terms it can be described as follows. When problems of a pathological nature arise with the endocrine system, as a result of which the pancreas ceases to synthesize insulin, which is responsible for the utilization of carbohydrates or, conversely, the tissue does not respond to “help” from its organ, the doctors state the occurrence of this serious disease.

As a result of these changes, sugar begins to accumulate in the blood, increasing its “sugar content”. Immediately without slowing down, another negative factor is turned on - dehydration. Tissues are not able to hold water in the cells and the kidneys excrete sugar syrup in the form of urine. Sorry for such a free interpretation of the process - this is just for a better understanding.

By the way, it was for this feature that ancient China was diagnosed with this disease, allowing ants to go to the urine.

An unintelligent reader may have a natural question: why is it a sugar disease, they say, well, the blood has become sweeter, so what?

First of all, diabetes is dangerous complications that it provokes. Affection of the eyes, kidneys, bones and joints, brain, death of the tissues of the upper and lower extremities occurs.

In a word, this is the worst enemy of not only man, but also of humanity, if we again return to statistics.

Medicine divides the diabetes into two types (type):

  1. Insulin-dependent - type 1. Its peculiarity lies in pancreatic dysfunction, which, due to its illness, is not able to produce insulin in sufficient quantity for the body.
  2. Insulin independent - type 2. Here the reverse process is characteristic - the hormone (insulin) is produced in sufficient volume, however, due to certain pathological circumstances, the tissues are unable to adequately respond to it.

It should be noted that the second type occurs in 75% of patients. They are most often sick of older and elderly people. The first type, on the contrary, does not spare children and young people.

Causes of type 1 diabetes

This type of diabetes, which is also called juvenile, is the worst enemy of the young, because it most often appears before the age of 30. The etiology and pathogenesis of type 1 diabetes are continuously studied. Some medical scientists are inclined to believe that the cause of this disease lies in the viruses that provoke the occurrence of measles, rubella, chicken pox, mumps, hepatitis, and the intestinal Coxsackie virus.

What happens in these cases in the body?

The above sores are able to hit the pancreas and its components - β-cells. The latter cease to produce insulin in the quantity necessary for metabolic processes.

Scientists identify the most important etiological factors of diabetes in children:

  • prolonged temperature stresses of the body: overheating and hypothermia,
  • excessive intake of proteins
  • genetic predisposition.

The sugar killer doesn’t show his “nasty” essence immediately, but after the majority dies - 80% of the cells that produce insulin synthesis.

Diagram of diabetes pathogenesis or scenario (algorithm) of disease development is typical for most patients and affects common cause-and-effect relationships:

  1. Genetic motivation for the development of the disease.
  2. Emotional impact. Moreover, people with increased excitability due to the daily adverse psychological situation can become hostage to the disease.
  3. Insulitis is an inflammatory process of pancreatic areas and mutation of β-cells.
  4. The emergence of cytotoxic (killer) antibodies that inhibit and then block the body’s natural immune response, disrupting the overall metabolic process.
  5. Necrosis (death) of β-cells and the manifestation of obvious signs of diabetes.

Video from Dr. Komarovsky:

Risk factors for developing type 2 diabetes

The reasons for the development of type 2 diabetes, in contrast to the first, are in the reduction or lack of perception of insulin produced by the pancreas.

Simply put: for the breakdown of blood sugar, β-cells produce a sufficient amount of this hormone, however, the organs involved in the metabolic process, due to various reasons, do not “see” it and do not “feel” it.

This condition is called insulin resistance or decreased tissue sensitivity.

The following negative factors are attributed to risk factors by medicine:

  1. Genetic. Statistics "insists" that 10% of people with a type 2 diabetics are at risk of joining the ranks of patients.
  2. Obesity. This is perhaps the decisive reason to help get this ailment at an accelerated pace. What is there to convince? Everything is extremely simple - because of the thick layer of fat, the tissues no longer take insulin, moreover, they don’t "see" it at all!
  3. Power failure. This factor "umbilical cord" is associated with the previous one. Irrepressible zhor, flavored with a fair amount of flour, sweet, spicy and smoked delicacies not only contributes to weight gain, but also mercilessly torments the pancreas.
  4. Cardiovascular diseases. Contribute to the non-perception of insulin at the cellular level such diseases as atherosclerosis, arterial hypertension, coronary heart disease.
  5. Stress and constant peak nerve loads. During this period, there is a powerful release of catecholamines in the form of adrenaline and noradrenaline, which, in turn, increase blood sugar.
  6. Hypocorticism. This is a chronic dysfunction of the adrenal cortex.

The pathogenesis of type 2 diabetes can be described as a sequence of heterogeneous (heterogeneous) disorders manifested during the metabolic (metabolic) process in the body. The basis, as previously emphasized, is insulin resistance, that is, not the perception of insulin by tissues, which is intended for glucose utilization.

As a result, there is a powerful imbalance between the secretion (production) of insulin and its perception (sensitivity) of the tissues.

In a simple example, using unscientific terms, what happens can be explained as follows. In a healthy process, the pancreas, “seeing” that there has been an increase in the sugar content in the blood, together with β-cells, generates insulin and injects it into the blood. This happens during the so-called first (fast) phase.

This phase is absent in pathology, since iron "does not see" the need for insulin generation, they say, why, it is already present. But the problem with this is that the back reaction does not occur, the sugar level does not decrease, since the tissues do not connect its splitting process.

Slow or 2nd phase of secretion occurs already as a reaction to hyperglycemia. In the tonic (constant) mode, insulin production occurs, however, despite the excess hormone, the decrease in sugar for a known reason does not occur. It repeats endlessly.

Video from Dr. Malysheva:

Exchange violations

Consideration of the etiopathogenesis of diabetes mellitus type 1 and 2, its causal relationships, will certainly lead to the analysis of such phenomena as a violation of metabolic processes that enhance the course of the disease.

It should immediately be noted that the violations themselves are not treated with pills alone. They will require a change in the whole way of life: nutrition, physical and emotional stress.

Fat exchange

Contrary to the well-established opinion about the dangers of fat, it is worth noting that it is fats that are sources of energy for striated muscles, kidneys and liver.

Speaking of harmony and preaching the axiom - everything should be in moderation, it is necessary to emphasize that the deviation from the norm of the amount of fat, in one direction or another, is equally harmful to the body.

Characteristic disorders of fat metabolism:

  1. Obesity. The rate of accumulated fat in the tissues: for men - 20%, for women - up to 30%. All that is higher is pathology. Obesity is an open gate for the development of coronary heart disease, hypertension, diabetes, atherosclerosis.
  2. Cachexia (exhaustion). This is a condition in which the fat mass present in the body is below normal. The causes of exhaustion can be different: from a long-term intake of low-calorie foods to hormonal pathology, such as a deficiency of glucocorticoids, insulin, somatostatin.
  3. Dyslipoproteinemia. The disease is caused by an imbalance in the normal proportion between the various fats present in the plasma. Dyslipoproteinemia is a concomitant component of diseases such as ischemic heart disease, pancreas inflammation, atherosclerosis.

Basic and energy exchange

Proteins, fats, carbohydrates are a kind of fuel for the energy engine of the whole organism. When the body is intoxicated with decay products due to various pathologies, including diseases of the adrenal glands, pancreas and thyroid gland, a breakdown of energy metabolism occurs in the body.

How to determine and how to express the optimal amount of energy costs necessary for a person’s life support?

Scientists have introduced such a thing as basic metabolism, in practice, meaning the amount of energy required for the normal functioning of the body with minimal metabolic processes.

With simple and intelligible words, this can be explained as follows: science claims that a healthy person of normal build weighing 70 kg on an empty stomach, in a supine position, with an absolute relaxed state of muscles and an indoor temperature of 18 ° C, 1700 kcal / day is necessary to maintain all vital functions .

If the main exchange is carried out with a deviation of ± 15%, then it is considered to be within the normal range, otherwise pathology is ascertained.

Pathology, provoking an increase in basal metabolism:

  • hyperthyroidism, chronic thyroid disease,
  • hyperactivity of the sympathetic nerves
  • increased production of norepinephrine and adrenaline,
  • enhancing the functions of the sex glands.

Reduction in basal metabolic rate may be the result of prolonged starvation, which can provoke dysfunction of the thyroid and pancreas.

Water exchange

Water is the most important component of a living organism. Its role and importance as an ideal “vehicle” of organic and inorganic substances, as well as an optimal dissolution medium and various reactions in metabolic processes, cannot be overestimated.

But here, speaking of balance and harmony, it is worth emphasizing that both its excess and deficiency are equally harmful to the body.

In diabetes, possible violations of water exchange processes in one way or the other:

  1. Dehydration occurs as a result of prolonged fasting and with increased fluid loss due to kidney activity in diabetes.
  2. In another case, when the kidneys fail to cope with the tasks entrusted to them, there is an excessive accumulation of water in the intercellular space and in the body cavities. This condition is called hyperosmolar overhydratation.

To restore the acid-base balance, stimulate metabolic processes and restore the optimal aquatic environment, doctors recommend drinking mineral water.

The best water from natural mineral sources:

  • Borjomi,
  • Essentuki,
  • Mirgorod,
  • Pyatigorsk,
  • Istisu
  • Berezovskiy mineralized waters.

Carbohydrate exchange

The most common types of metabolic disorders are hypoglycemia and hyperglycemia.

Consonant names have differences of principle:

  1. Hypoglycemia. This is a condition in which the level of glucose in the blood is significantly below normal. The cause of hypoglycemia may be digestion, due to the violations in the mechanism of splitting and absorption of carbohydrates. But not only this reason can be. The pathology of the liver, kidneys, thyroid gland, adrenal glands, as well as a diet low in carbohydrates can cause a decrease in sugar to a critical level.
  2. Hyperglycemia. This state is the complete opposite of the above, when the sugar level significantly exceeds the norm. Etiology of hyperglycemia: diet, stress, adrenal cortex tumors, adrenal medulla tumor (pheochromocytoma), abnormal thyroid gland enlargement (hyperthyroidism), liver failure.

Symptomatic disorders of carbohydrate processes in diabetes

Reduced amount of carbohydrates:

  • apathy, depression,
  • unhealthy weight loss
  • weakness, dizziness, drowsiness,
  • ketoacidosis, a condition in which cells need glucose, but do not get it for some reason.

Increased amount of carbohydrates:

  • high pressure,
  • hyperactivity,
  • problems with the cardiovascular system,
  • body tremor - rapid, rhythmic trembling of the body, associated with imbalance of the nervous system.

Diseases arising from the violation of carbohydrate metabolism:

EtiologyDiseaseSymptomatology
Excess CarbohydrateObesityIntermittent heavy breathing, shortness of breath
Unsupervised weight gain
Hypertension
Irrepressible appetite
Fatty dystrophy of internal organs as a result of their disease
DiabetesPainful weight fluctuations (set, decrease)
Itching of the skin
Fatigue, weakness, drowsiness
Increased urination
Healing wounds
Lack of carbohydratesHypoglycemiaDrowsiness
Sweating
Dizziness
Nausea
Hunger
Gyrke disease or glycogenosis is a hereditary disease caused by defects in enzymes that are involved in the production or breakdown of glycogen.Hyperthermia
Skin xanthoma - a violation of the lipid (fat) metabolism of the skin
Delayed puberty and growth
Violation of the respiratory rhythm, shortness of breath

Official medicine claims that type 1 and type 2 diabetes cannot be completely cured. But thanks to the constant monitoring of the state of his health, as well as the use of drug therapy, the disease will slow down in its development so that it will allow the patient not to feel a certain limitation in the perception of everyday joys and heal a full life.

Watch the video: Diabetes. Clinical Presentation (February 2020).