Diabetes mellitus: etiology, pathogenesis, criteria for diagnosis

The human pancreas, namely the beta cells of the islets of Langerhans, produce insulin. If these particular cells are destroyed, then we are talking about type 1 diabetes.

For this organ-specific malady, absolute hormone insulin is characteristic.

In some cases, diabetics will have no markers of autoimmune lesions (idiopathic type 1 diabetes).

Etiology of the disease

Type 1 diabetes is a hereditary disease, but a genetic predisposition determines its development by only a third. The probability of pathology in a child with a diabetic mother is no more than 1-2%, a sick father is from 3 to 6%, and a brother or sister is about 6%.

One or several humoral markers of the pancreas, which include antibodies to the islets of Langerhans, can be detected in 85-90% of patients:

  • antibodies to glutamate decarboxylase (GAD);
  • antibodies to tyrosine phosphatase (IA-2 and IA-2beta).

At the same time, the main importance in the destruction of beta cells is given to factors of cellular immunity. Type 1 diabetes is commonly associated with HLA haplotypes, like DQA and DQB.

Often this type of pathology is combined with other autoimmune endocrine disorders, for example, Addison's disease, autoimmune thyroiditis. Also, the non-endocrine etiology plays a significant role:

  • vitiligo;
  • rheumatic diseases;
  • alopecia;
  • Crohn's disease.

Pathogenesis of diabetes

Type 1 diabetes makes itself felt when the autoimmune process is destroyed from 80 to 90% of the pancreatic beta cells. Moreover, the intensity and speed of this pathological process always varies. Most often, in the classical course of the disease in children and young people, the cells are destroyed quite quickly, and diabetes manifests violently.

From the onset of the disease and its first clinical symptoms to the development of ketoacidosis or ketoacidotic coma can pass no more than a few weeks.

In other, quite rare cases, in patients older than 40 years, the disease may be hidden (latent autoimmune diabetes mellitus Lada).

Moreover, in such a situation, doctors diagnosed type 2 diabetes and recommended to their patients how to compensate for insulin deficiency with sulfonylureas.

However, over time, symptoms of an absolute lack of a hormone begin to show:

  1. ketonuria;
  2. weight loss;
  3. obvious hyperglycemia on the background of regular use of pills to reduce blood sugar.

The pathogenesis of type 1 diabetes is based on an absolute hormone deficiency. Due to the impossibility of sugar intake in insulin-dependent tissues (muscle and fat), energy deficiency develops and, as a result, lipolysis and proteolysis become more intense. Such a process becomes the cause of weight loss.

With increasing blood glucose levels, hyperosmolarity occurs, accompanied by osmotic diuresis and dehydration. With a lack of energy and the hormone insulin, the secretion of glucagon, cortisol and somatotropin is inhibited.

Despite the growing glycemia, gluconeogenesis is stimulated. Acceleration of lipolysis in fat tissues causes a significant increase in fatty acids.

If there is a deficiency of insulin, then the liposynthetic ability of the liver is suppressed, and free fatty acids are actively involved in ketogenesis. The accumulation of ketones causes the development of diabetic ketosis and its consequences - diabetic ketoacidosis.

Against the background of a progressive increase in dehydration and acidosis, a coma may develop.

It, if there is no treatment (adequate insulin therapy and rehydration), in almost 100% of cases will be the cause of death.

Symptoms of type 1 diabetes

This type of pathology is quite rare - no more than 1.5-2% of all cases of the disease. The risk of a lifetime is 0.4%. Often a person reveals such diabetes at the age of 10 to 13 years. In the bulk of the manifestation of the pathology occurs up to 40 years.

If the case is typical, especially in children and young people, then the disease will manifest itself as a bright symptom. It can develop in a few months or weeks. Infectious and other concomitant diseases can provoke the manifestation of diabetes.

Symptoms typical for all types of diabetes will be:

  • polyuria;
  • itching of the skin;
  • polydipsia.

These signs are especially pronounced with type 1 disease. During the day, the patient can drink and release at least 5-10 liters of fluid.

Specific for this type of disease will be a dramatic weight loss, which in 1-2 months can reach 15 kg. In addition, the patient will suffer from:

  • muscle weakness;
  • sleepiness;
  • decrease in working capacity.

At the very beginning, he may be disturbed by an unjustified increase in appetite, alternating with anorexia as ketoacidosis increases. The patient will feel the characteristic smell of acetone from the oral cavity (maybe a fruity odor), nausea and pseudoperitonitis - abdominal pain, severe dehydration, which can cause a comatose state.

In some cases, the first sign of type 1 diabetes in pediatric patients will be a progressive impairment of consciousness. It can be so pronounced that against the background of comorbidities (surgical or infectious) the child may fall into a coma.

Rarely, when a patient over 35 years of age (with latent autoimmune diabetes) suffers from diabetes, the disease may not be so vividly, and it is diagnosed completely by chance during a routine blood test for blood sugar.

A person will not lose weight, he will have moderate polyuria and polydipsia.

First, the doctor can diagnose type 2 diabetes and start treatment with drugs to reduce the sugar in the tablets. This will allow some time later to guarantee acceptable compensation for the disease. However, after a few years, usually after 1 year, the patient will show signs caused by an increase in total insulin deficiency:

  1. drastic weight loss;
  2. ketosis;
  3. ketoacidosis;
  4. the inability to maintain the level of sugar at the desired level.

Criteria for diagnosing diabetes

If we take into account that type 1 disease is characterized by bright symptoms and is a rare pathology, a screening study is not performed to diagnose blood sugar levels. The likelihood of type 1 diabetes in close relatives is minimal, which, together with the lack of effective methods for the initial diagnosis of the disease, determines the inappropriateness of a thorough study of their immunogenetic markers of pathology.

The detection of the disease in the majority of cases will be based on the designation of a significant excess of the level of glucose in the blood of those patients who have symptoms of absolute insulin deficiency.

Oral testing to identify the disease is extremely rare.

Not the last place is occupied by differential diagnostics. It is necessary to confirm the diagnosis in doubtful cases, namely, to identify moderate glycemia in the absence of clear and vivid signs of type 1 diabetes, especially when manifesting in middle-aged people.

The purpose of such a diagnosis may be the differentiation of the disease with other types of diabetes. To do this, use the method of determining the level of basal C-peptide and 2 hours after a meal.

Criteria for indirect diagnostic value in ambiguous cases are the definition of immunological markers of type 1 diabetes:

  • antibodies to pancreatic islet complexes;
  • glutamate decarboxylase (GAD65);
  • tyrosine phosphatase (IA-2 and IA-2P).

Treatment regimen

Treatment of any type of diabetes will be based on 3 basic principles:

  1. decrease in blood sugar (in our case, insulin therapy);
  2. diet food;
  3. patient education.

Treatment with insulin in pathology type 1 is of a replacement nature. Her goal is to maximize imitation of natural insulin secretion in order to get accepted compensation criteria. Intensive insulin therapy will be closest to the physiological production of the hormone.

The daily need for a hormone will correspond to the level of its basal secretion. To provide the body with insulin will be able to 2 injections of the drug of average duration of exposure or 1 injection of long insulin Glargin.

The total volume of basal hormone should not exceed half the daily need for the drug.

The bolus (food) secretion of insulin will be replaced by pricks of a human hormone of a short or ultrashort exposure time taken before a meal. The dosage is calculated based on the following criteria:

  • the amount of carbohydrates to be consumed during the meal;
  • available blood sugar level determined before each injection of insulin (measured using a glucometer).

Immediately after the manifestation of type 1 diabetes mellitus and as soon as its treatment began for quite a long time, the need for insulin preparations may be small and will be less than 0.3-0.4 U / kg. This period has the name "honeymoon" or the phase of stable remission.

After the phase of hyperglycemia and ketoacidosis, in which insulin production is inhibited by remaining beta cells, compensation for hormonal and metabolic disruptions is provided by insulin injections. The drugs restore the work of the cells of the pancreas, which, after taking on a minimal insulin secretion.

This period can last from a couple of weeks to several years. However, ultimately, as a result of autoimmune destruction of residues of beta cells, the remission phase ends and serious treatment is required.

Insulin-independent diabetes mellitus (type 2)

This type of pathology develops when the tissues of the body cannot adequately absorb sugar or do it in incomplete amounts. This problem has another name - extra pancreatic insufficiency. The etiology of this phenomenon may be different:

  • changes in the structure of insulin in the development of obesity, overeating, sedentary lifestyle, arterial hypertension, in old age and in the presence of destructive habits;
  • failure of the functions of insulin receptors due to a violation of their size or structure;
  • inadequate sugar production by the liver;
  • intracellular pathology, in which impulse transmission to the cell organelles from the insulin receptor is hampered;
  • change in insulin secretion in the pancreas.

Disease classification

Depending on the severity of type 2 diabetes, it will be divided into:

  1. mild degree. It is characterized by the ability to compensate for the lack of insulin, subject to the use of drugs and diet, allowing in a short time to reduce blood sugar;
  2. medium degree. You can compensate for metabolic changes, provided you use at least 2-3 drugs to reduce glucose. At this stage, a failure in metabolism will be combined with angiopathy;
  3. severe stage. To normalize the condition requires the use of several means of reducing glucose and insulin injections. A patient at this stage often suffers from complications.

How is type 2 diabetes?

The classic clinical picture of diabetes mellitus will consist of 2 stages:

  • fast phase. Instant emptying of accumulated insulin in response to glucose;
  • slow phase. Insulin secretion to reduce residual high blood sugar levels is slow. Starts to work immediately after the fast phase, but under the condition of insufficient stabilization of carbohydrates.

If there is a pathology of beta cells that become insensitive to the effects of pancreatic hormone, an imbalance of carbohydrates in the blood gradually develops. In type 2 diabetes mellitus, the fast phase is simply absent, and the slow phase prevails. Insulin production is insignificant and for this reason it is not possible to stabilize the process.

When there is a lack of insulin receptor function or post-receptor mechanisms, hyperinsulinemia develops. With a high level of insulin in the blood, the body triggers its compensation mechanism, which is aimed at stabilizing the hormonal balance. This characteristic symptom can be observed even at the very beginning of the disease.

A clear pattern of pathology develops after persistent hyperglycemia over several years. Excessive blood sugar has a negative effect on beta cells. This causes their exhaustion and wear, causing a decrease in insulin production.

Clinically, insulin deficiency will manifest itself by a change in weight and the formation of ketoacidosis. In addition, the symptoms of this type of diabetes will be:

  • polydipsia and polyuria. Metabolic syndrome develops due to hyperglycemia, provoking an increase in osmotic blood pressure. To normalize the process, the body begins an active excretion of water and electrolytes;
  • itching of the skin. The skin itches because of a sharp increase in urea and blood ketones;
  • overweight.

Insulin resistance will cause many complications, both primary and secondary. So, the first group of doctors include: hyperglycemia, slowing down the production of glycogen, glucosuria, inhibition of body reactions.

The second group of complications should include: stimulation of the release of lipids and protein to transform them into carbohydrates, inhibiting the production of fatty acids and proteins, reducing tolerance to carbohydrates consumed, impaired rapid secretion of the pancreatic hormone.

Type 2 diabetes is quite common. By and large, the true prevalence rates of the disease can exceed the official at least 2-3 times.

Moreover, patients seek medical help only after the onset of serious and dangerous complications. For this reason, endocrinologists insist that it is important not to forget about regular medical examinations. They will help to identify the problem as soon as possible and quickly begin treatment.

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