What kind of disease: diabetes mellitus

Atlas company blog, Geektimes

Everyone has their own ideas about diabetes. Someone thinks that it starts if you eat thirty chocolates in a row, although this is not the case. For someone, diabetes mellitus is a "harmless" chronic disease. But according to statistics from the World Health Organization, 1.5 million people die from diabetes a year – this is more than from the human immunodeficiency virus.

Today, Atlas talks about what diabetes mellitus is, why it occurs, and how to manage the risks of developing the disease.

To understand the mechanism of development of diabetes mellitus, you need to know the principles of carbohydrate metabolism. This is a complex metabolic process, as a result of which the body receives and consumes energy.

Glucose is a source of energy in the body

For normal functioning, cells need energy, the main source of which is carbohydrates. They are found in most foods that a person eats.

In the intestine, carbohydrates are broken down to simple compounds (monosaccharides), absorbed into the mucosa and enter the blood. The body is always ready to respond to a deviation in glucose levels. In this he is helped by some receptors and signaling molecules–peptides that the stomach secretes. In a healthy body, this reaction occurs very quickly.

Glucose cannot enter the cells on its own: in order to avoid uncontrolled movement of glucose, the cell closes its doors with a lock. The receptors of the GLUT family act as a locking device – proteins on the surface of the cell membrane. Some of them open automatically, but most need a key – a special hormone insulin.

The exception is brain cells: this is too important an organ to outsource its energy supply. Therefore, the "locks"–GLUT receptors in brain cells open automatically, without the participation of insulin. The concentration of glucose in the blood is equated with the concentration in neurons. That is why, when we are hungry, we want to eat something sweet and immediately provide energy to brain cells.

Insulin triggers glucose into the cell

Insulin is produced by beta cells of the pancreas located in the islets of Langerhans. From the name of these cells Insulae pancreaticae comes the name of insulin. Beta cells react to an increase in blood glucose levels, as well as to the signaling peptides of the APUD system, which are released when food enters the stomach, long before glucose increases.

In response to these signals, beta cells of the islets of Langerhans activate insulin production. The hormone enters the bloodstream, bypasses the cells of the body, opens the locks – and the cells receive the necessary energy.

But the story doesn't end there. What if the body has received more energy than its cells need? And what to do after eating when the glucose level drops? Evolution has a simple answer to these questions: food does not happen every day, and everything that can be postponed must be postponed.

Glycogen and triglycerides – glucose storage

There are several energy stores in the body: for example, a refrigerator where you can leave food for a couple of days, and a cellar where food is stored for the winter.

The refrigerator, or the nearest storage, is glycogen reserves. While glucose bypasses the cells, its excess is packed into glycogen in the liver. This process is called glycogenogenesis. Packaging requires energy, but unpacking does not. Therefore, glycogen is convenient to use to maintain energy when the level of glucose in the blood decreases. This happens a few hours after eating.

The hormone glucagon is released in the absence of insulin and helps to unpack glycogens and decompose to the state of simple glucose. This process is called glycogenolysis, it occurs in the liver and in the muscles. Glucose is transported from the liver to the blood and can then be used in different tissues. In the muscles, unpacked glucose is consumed immediately and is not transported anywhere.

The "refrigerator" is not rubber, and when glycogen reserves are created, and glucose is still circulating in the blood, the body stores unspent glucose in the form of fat. In the liver, carbohydrates are transformed into fatty acids. Then glycerol is added to them, the molecules are converted into triglycerides and sent for storage in adipose tissue.

Triglycerides and fatty acids can enter the body with food, as part of fatty foods. Some of them are transported to the liver and then into the blood; the other part is sent directly to the adipose tissue through the lymphatic system. Cells can use fatty acids as an energy source or send them for storage in adipose tissues.

To transform fat molecules into glucose, the body expends a lot of energy. Therefore, he resorts to such measures only after all other energy sources have been used up – both glucose and glycogen. The process of glucose recovery from non-carbohydrate elements is called gluconeogenesis.

Metabolic processes in the body allow you to regulate glucose levels and maintain energy supply at the right level not only during meals, but also on an empty stomach. As is often the case with complex cascade reactions, a failure in the operation of one element leads to an imbalance of the entire system.

Type 1 diabetes mellitus – lack of insulin

Type 1 diabetes mellitus (DM1) accounts for 10% of all cases of diabetes mellitus. It is also called "children's". Despite the fact that a quarter of the cases are adults, this variant of diabetes is more often manifested in childhood and adolescence.

Type 1 diabetes mellitus is a chronic disease that often occurs due to autoimmune disorders. For reasons not fully understood, the body begins to attack the beta cells of the islets of Langerhans. Any external stressful event can become a trigger: beta cells have an imperfect complex of antigens, and the immune system can consider them a tumor and launch an attack.

Destroyed beta cells stop producing insulin. Now there is no one to open the "locks" of cells, they do not receive energy, and tissue starvation begins. The body "unpacks" fat reserves at a rate that metabolic processes are not designed for. Too many toxic ketone bodies enter the bloodstream, which acidify the blood and cause ketoacidosis. This is a metabolic disease in which the acid balance in the body shifts. Ketoacidosis is the main reason why patients with type 1 diabetes end up in the hospital.

Among the possible factors affecting the risk of DM1 are genetic predisposition and infections. This is a rare disease, and even the presence of a genetic predisposition does not significantly affect its risk. Among the infectious diseases associated with DM1, Coxsackie virus, Epstein-Barr virus, cytomegalovirus are noted. These viruses can destroy beta cells of the islets of Langerhans or provoke an autoimmune attack on them. There is no connection between vaccinations and the risk of DM1.

Symptoms of type 1 diabetes mellitus: loss of appetite and weight, excessive thirst and urination, constant fatigue. SD1 develops quite quickly. The onset of the disease may coincide with stressful situations – infections, surgical operations. Often, the patient learns about the disease already in the emergency room, after losing consciousness as a result of ketoacidosis. Therefore, it is important for parents to remember that severe thirst and frequent urination in a child is a reason to consult a doctor without delay.

No treatment for type 1 diabetes has been found yet, but there are tools to control glucose levels. To do this, patients constantly measure blood glucose levels and inject insulin. There have been attempts to transplant the pancreas, but such operations have not shown sufficient effectiveness.

Automated tools are being developed that will maintain normal glucose levels. Last year, the FDA approved an artificial pancreas. This is an external wearable device that consists of an insulin pump and a sensor. The algorithm calculates the dose and automatically injects the right amount of insulin.

There are also no effective methods of preventing DM1 – and this is its difference with diabetes mellitus 2 types.

Type 2 diabetes mellitus – helplessness of insulin

Type 2 diabetes mellitus (DM2) is a multifactorial disease in the development of which both genetic factors and lifestyle play a role. It accounts for 90% of cases of diabetes mellitus.

DM2 develops due to low sensitivity of cells to insulin, against which the normal amount of insulin becomes insufficient. If type 1 diabetes mellitus begins after the death of beta cells, then in type 2 diabetes mellitus, the cells of the islets of Largeness continue to function (at least at the time of manifestation). They continue to produce insulin, which also goes to the cells, in front of which crowds of glucose have accumulated – but the trouble is, the lock was sealed with some kind of muck. The key receptor does not work, and glucose cannot enter the cell.

The causes of DM2 are a genetic predisposition multiplied by overweight and a low–activity lifestyle. At the same time, obesity does not trigger the disease by itself, but only when negative hereditary factors are superimposed. In the absence of a genetic predisposition, excess weight may not lead to type 2 diabetes mellitus (which does not exclude cardiovascular complications). But among overweight people, only 6.8–36.6% have no metabolic disorders and a tendency to insulin resistance.

The classic symptoms of type 2 diabetes are similar to DM1 – the same chronic fatigue, excessive thirst and urination, weight loss while maintaining a lifestyle. Diagnosis at the stage when the disease has already manifested itself in the form of symptoms is considered late. There are earlier symptoms: a problem with gums and teeth, pustular rashes, frequent diseases of the urinary tract. If there are similar manifestations, you need to take an analysis for glycated hemoglobin.

At the stage of timely diagnosis, type 2 diabetes mellitus has no symptoms. DM2 can develop for years and go unnoticed. In order to detect signs of diabetes as early as possible, you need to fill out special questionnaires, and after 40 years – to undergo an annual screening examination.

Preventive check is recommended for people who are overweight combined with one of the following factors:

• The diagnosis of type 2 diabetes mellitus in a relative;
• Cardiovascular diseases in the medical history;
• Elevated cholesterol levels in the blood;
• High blood pressure;
• Sedentary lifestyle;
• Childbirth of a large child (more than 3600 g).

Unlike type 1 diabetes, the risk of DM2 can be managed. Proper nutrition, normal weight and at least 150 minutes of exercise per week (cardio and aerobic exercise) reduce the risk of type 2 diabetes, even with genetic prerequisites. Strength training and weightlifting do not affect the risk of DM2, although such exercises are especially well given to people with a predisposition to diabetes.

Type 2 diabetes cannot be completely cured, you can only slow down its development and control complications. In the early stages, it is enough to change your lifestyle and take pills. They increase insulin sensitivity and compensate for genetic prerequisites.

If you lose weight to normal BMI values, the sensitivity of tissues to insulin can be restored, and blood glucose will be maintained at a normal level. In this case, patients are still recommended to take pills to help their own insulin maintain its effectiveness.

Diabetes mellitus leads to severe complications

Diabetes mellitus types 1 and 2 have three types of complications. Neuropathic disorders occur due to sudden changes in sugar levels. Microvascular complications include kidney and retina damage due to consistently high sugar levels. Macrovascular diseases are affected by cholesterol levels and the very fact of diabetes.

Diabetes mellitus is associated with a high risk of atherosclerosis. Constantly elevated blood sugar levels cause systemic inflammation, which leads to the deposition of cholesterol in the walls of blood vessels and their narrowing. With the growth of plaques, a blood clot can form and block the blood flow.

Type 2 diabetes mellitus is accompanied by an increase in blood pressure, as insulin stimulates the reabsorption of sodium in the kidneys. This causes water retention and an increase in blood volume. This is the most significant risk factor for strokes and heart attacks. We will talk about how to properly control blood pressure in another article.

Another complication of diabetes mellitus is diabetic foot syndrome. It occurs for two reasons: due to peripheral nerve damage or vascular blockage in atherosclerosis. In the first case, the sensitivity and nutrition of the skin of the feet decreases, ulcers occur. As a rule, they do not hurt and can remain unnoticed for a long time. In such a situation, unloading the foot and treating the wound helps.

When blood vessels are blocked, the blood supply to the foot is disrupted – this is a potentially more dangerous case. Delay in treatment can lead to tissue necrosis and, in severe cases, to leg amputation. Therefore, if there is a violation of the blood supply and the appearance of pain, you should immediately consult a doctor and restore blood flow. If this is not done within 24 hours, the leg will not be saved.

To avoid such consequences, you need to carefully follow the rules of prevention and respond to changes in time.

Genetics affect the risk of developing type 2 diabetes

The risk of developing diabetes mellitus is affected by a complex of about one hundred genes. They are at different levels related to the work of insulin, from synthesis to transportation and the structure of receptors. Here we will tell only about some of them.

Insulin receptors encode genes of the GLUT family. Different types of receptors are found in different cells: GLUT1 delivers glucose to red blood cells, GLUT2 – to the liver and pancreas, GLUT3 – to nerve tissue and placenta, GLUT4 – to adipose and muscle tissue and to myocardial cells (heart muscles). Mutations in these genes lead to insulin resistance.

The TCF7L2 gene determines the work of signaling pathways, the synthesis and secretion of insulin and proglucagon, the precursor protein of glucagon, depends on it. Mutations in the gene lead to a decrease in insulin production in the body. The GCGR gene encodes a glucagon receptor protein, a hormone that, together with insulin, helps regulate blood glucose levels.

Since obesity increases the risk of DM2, genes that influence eating behavior are associated with the disease. For Example, the FTO – Fat Mass And Obesity Associated gene. His work is associated with a sense of satiety. In people with a certain variant of the FTO gene, the feeling of satiety occurs 10-15 minutes late. During this time, you can have time to eat too much. Therefore, people with this gene variant have a potentially higher risk of obesity and type 2 diabetes.

In type 2 diabetes, the composition of the microbiota changes

Obesity, type 2 diabetes, insulin resistance – all these diseases are associated with chronic inflammation. Some of these processes take place in the intestine and depend on the composition of the community of intestinal bacteria.

Different types of bacteria live in the intestine, all together they are called microbiota. Each type of bacteria has its own tasks. Some bacteria, mainly from the clostridium class, produce butyric acid. It is a useful substance that nourishes the intestinal walls and protects against inflammation. For the synthesis of butyric acid, bacteria need fiber. In patients with type 2 diabetes mellitus, the level of butyric acid–producing bacteria decreases, and inflammation begins in the intestine.

With DM2, the microbiota lacks another bacterium – Akkermansia muciniphila. The presence of this type of bacteria in the intestine is an indicator of a healthy metabolism. Ackermancy of mucinifil is often found in people with normal weight, but with obesity its number decreases sharply.

According to the composition of the microbiota, you can see in advance the changes in the intestinal bacterial community characteristic of inflammation and begin prevention: first of all, change the diet. You need to add more high-fiber foods to your diet to support the gut bacteria that protect against inflammation.

The risks of type 2 diabetes can be managed

Type 1 diabetes mellitus is rare, and, unfortunately, its development cannot be prevented. But the risk of developing type 2 diabetes can be managed. To do this, you need to monitor your weight, especially with a genetic predisposition, maintain an active lifestyle, choose the right diet.

It is not enough to count the number of calories received and consumed per day. It is necessary to monitor the balance of nutrients in food and give preference to complex carbohydrates and fiber.

Hereditary risks of type 2 diabetes will help determine the genetic test "Atlas". The role of intestinal bacteria and their contribution to protecting the body from the disease will be evaluated by the Microbiota Genetics test. If you have a predisposition to diabetes mellitus, or a relative with such a disease, contact an endocrinologist to make an individual prevention plan.

Portal "Eternal youth" http://vechnayamolodost.ru 24.04.2017