Insulin resistance is an impaired biological response of body tissues to the action of insulin. And it does not matter where the insulin comes from, from the own pancreas (endogenous) or from injections (exogenous).
Insulin resistance not only increases the likelihood of type 2 diabetes, but also atherosclerosis, a heart attack, and sudden death due to a blockage of the vessel with a blood clot.
The effect of insulin is in the regulation of metabolism (not only carbohydrates, but also fats and proteins), as well as mitogenic processes - this is growth, cell multiplication, DNA synthesis, gene transcription.
The modern concept of insulin resistance is not limited only to impaired carbohydrate metabolism and an increased risk of type 2 diabetes. It also includes changes in the metabolism of fats, proteins, gene expression. In particular, insulin resistance leads to problems with endothelial cells that cover the inside of the walls of blood vessels. Because of this, the lumen of blood vessels narrows, and atherosclerosis progresses.
Symptoms of insulin resistance and diagnosis
You may be suspicious of insulin resistance if symptoms and / or tests show that you have metabolic syndrome. It includes:
- obesity at the waist (abdominal);
- hypertension (high blood pressure);
- poor blood tests for cholesterol and triglycerides;
- detection of protein in the urine.
Abdominal obesity is the main symptom. In second place is arterial hypertension (high blood pressure). It rarely happens that a person does not have obesity and hypertension, but blood tests for cholesterol and fats are already bad.
Diagnosing insulin resistance with the help of analyzes is problematic. Because the concentration of insulin in the blood plasma can vary greatly, and this is normal. In the analysis of insulin in fasting blood plasma, the norm ranges from 3 to 28 μED / ml. If insulin in the blood on an empty stomach turns out to be above the norm, then the patient has hyperinsulinism.
An increased concentration of insulin in the blood occurs when the pancreas produces an excess amount of it to compensate for tissue insulin resistance. This result indicates that the patient has a significant risk of type 2 diabetes and / or cardiovascular disease.
The exact laboratory method for determining insulin resistance is called hyperinsulinemic insulin clamp. It involves continuous intravenous administration of insulin and glucose for 4-6 hours. This is a time-consuming method, and therefore it is rarely used in practice. Limited to fasting blood analysis for plasma insulin
Studies have shown that insulin resistance occurs:
- 10% of all people without metabolic disorders;
- 58% of patients with hypertension (blood pressure above 160/95 mm Hg. Art.);
- 63% of persons with hyperuricemia (serum uric acid is greater than 416 μmol / l in men and above 387 μmol / l in women);
- 84% of people with elevated levels of blood fats (triglycerides greater than 2.85 mmol / l);
- 88% of people with low “good” cholesterol (below 0.9 mmol / l in men and below 1.0 mmol / l in women);
- 84% of patients with type 2 diabetes;
- 66% of individuals with impaired glucose tolerance.
When you donate a blood test for cholesterol - check not total cholesterol, but separately “good” and “bad”.
How insulin regulates metabolism
Normally, an insulin molecule binds to its receptor on the surface of muscle cells, adipose tissue, or liver tissue. After this, insulin receptor autophosphorylation takes place with the participation of tyrosine kinase and its subsequent connection with the substrate of insulin receptor 1 or 2 (IRS-1 and 2).
In turn, the molecules of IRS activate phosphatidylinositol-3-kinase, which stimulates the translocation of GLUT-4. It is a carrier of glucose into the cell through the membrane. This mechanism provides the activation of metabolic (glucose transport, glycogen synthesis) and mitogenic (DNA synthesis) insulin effects.
- Glucose uptake by muscle, liver and adipose tissue cells;
- Synthesis of glycogen in the liver (storage of “fast” glucose in reserve);
- Capture cells of amino acids;
- DNA synthesis;
- Protein synthesis;
- Fatty acid synthesis;
- Ion transport.
- Lipolysis (the breakdown of adipose tissue with the intake of fatty acids in the blood);
- Gluconeogenesis (transformation of glycogen in the liver and the flow of glucose into the blood);
- Apoptosis (cell self-destruction).
Note that insulin blocks the breakdown of adipose tissue. That is why, if the level of insulin in the blood is elevated (hyperinsulinism is a frequent occurrence with insulin resistance), then it is very difficult, almost impossible to lose weight.
Genetic causes of insulin resistance
Insulin resistance is the problem of a huge percentage of all people. It is believed that it is caused by genes that have become predominant in the course of evolution. In 1962, they hypothesized that this is a survival mechanism during a long famine. Because it enhances the accumulation of fat reserves in the body during periods of abundant nutrition.
Scientists subjected mice to starvation for a long time. The longest survived were those individuals in whom genetically mediated insulin resistance was found. Unfortunately, in modern people, the same mechanism “works” for the development of obesity, hypertension and type 2 diabetes.
Studies have shown that patients with type 2 diabetes have genetic defects in signal transmission after insulin is connected to its receptor. This is called postreceptor defects. First of all, translocation of the glucose transporter GLUT-4 is impaired.
In patients with type 2 diabetes, impaired expression of other genes that metabolize glucose and lipids (fats) has also been found. These are the genes for glucose-6-phosphate dehydrogenase, glucokinase, lipoprotein lipase, fatty acid synthase, and others.
If a person has a genetic predisposition to develop type 2 diabetes, then it may or may not result in metabolic syndrome and diabetes. It depends on the lifestyle. The main risk factors are excessive nutrition, especially the consumption of refined carbohydrates (sugar and flour), as well as low physical activity.
What is insulin sensitivity in various tissues of the body?
For the treatment of diseases, insulin sensitivity of muscle and adipose tissue, as well as liver cells, is of the greatest importance. But is the insulin resistance of these tissues the same? In 1999, experiments showed no.
Normally, to suppress lipolysis (fat breakdown) in adipose tissue by 50%, insulin concentrations in the blood are sufficient to be no higher than 10 μED / ml For 50% suppression of glucose release into the blood by the liver, about 30 μU / ml of insulin in the blood is required. And in order for glucose uptake by muscle tissue to increase by 50%, an insulin concentration in the blood of 100 μED / ml and higher is needed.
We remind you that lipolysis is the breakdown of adipose tissue. The action of insulin inhibits it, as does glucose production by the liver. And the seizure of glucose by muscles under the influence of insulin increases. Note that in type 2 diabetes mellitus, the indicated values of the required concentration of insulin in the blood are shifted to the right, i.e., towards an increase in insulin resistance. This process begins long before diabetes manifests itself.
The sensitivity of body tissues to insulin is reduced due to genetic predisposition, and most importantly - because of an unhealthy lifestyle. In the end, after many years, the pancreas ceases to cope with increased stress. Then they diagnose “real” type 2 diabetes. The patient is greatly benefited if the treatment of the metabolic syndrome is started as early as possible.
What is the difference between insulin resistance and metabolic syndrome
You should know that insulin resistance occurs in people and other health problems that are not included in the concept of “metabolic syndrome”. It:
- polycystic ovaries in women;
- chronic renal failure;
- infectious diseases;
- glucocorticoid therapy.
Insulin resistance sometimes develops during pregnancy, and after childbirth - passes. It also usually rises with age. And it depends on what kind of lifestyle an elderly person leads to, whether it will cause type 2 diabetes and / or cardiovascular problems. In the article “Diabetes in the elderly” you will find a lot of useful information.
The cause of type 2 diabetes
In type 2 diabetes mellitus, insulin resistance of muscle cells, liver and adipose tissue is of the greatest clinical significance. Due to the loss of insulin sensitivity, less glucose enters and “burns out” in muscle cells. In the liver, for the same reason, the process of glycogen decomposition to glucose (glycogenolysis) is activated, as well as the synthesis of glucose from amino acids and other “raw materials” (gluconeogenesis).
Insulin resistance of adipose tissue is manifested in the fact that the anti-lipolytic effect of insulin weakens. At first, this is offset by increased insulin production by the pancreas. In the later stages of the disease, more fat breaks down into glycerol and free fatty acids. But during this period, losing weight does not bring much joy.
Glycerol and free fatty acids enter the liver, where very low density lipoproteins are formed from them. These are harmful particles that are deposited on the walls of blood vessels, and atherosclerosis progresses. Also from the liver in the bloodstream enters an excess amount of glucose, which appears as a result of glycogenolysis and gluconeogenesis.
Symptoms of metabolic syndrome in humans precede the development of diabetes. Because insulin resistance has been compensated for many years by excessive insulin production by beta cells of the pancreas. In this situation, there is an increased concentration of insulin in the blood - hyperinsulinemia.
Hyperinsulinemia with a normal level of glucose in the blood is a marker of insulin resistance and a precursor of the development of type 2 diabetes. Over time, the beta cells of the pancreas no longer cope with the load, which is several times higher than normal. They produce less insulin, the patient's sugar level in the blood rises and diabetes is manifested.
First of all, the 1st phase of insulin secretion suffers, i.e. the rapid release of insulin into the blood in response to the food load. And the basal (background) insulin secretion remains excessive. When the blood sugar level rises, it further enhances the insulin resistance of tissues and inhibits the function of beta cells by insulin secretion. This mechanism of diabetes is called “glucose toxicity.”
It is known that in patients with type 2 diabetes, cardiovascular mortality increases by 3-4 times, compared with people without metabolic disorders. Now more and more scientists and medical practitioners are convinced that insulin resistance and, along with it, hyperinsulinemia is a serious risk factor for heart attack and stroke. Moreover, this risk does not depend on whether the patient has developed diabetes or not.
Since the 1980s, studies have shown that insulin has a direct atherogenic effect on the walls of blood vessels. This means that atherosclerotic plaques and the narrowing of the vascular lumen are progressing under the action of insulin in the blood that flows through them.
Insulin causes the proliferation and migration of smooth muscle cells, the synthesis of lipids in them, the proliferation of fibroblasts, activation of the blood coagulation system, a decrease in the activity of fibrinolysis. Thus, hyperinsulinemia (increased concentration of insulin in the blood due to insulin resistance) is an important cause of atherosclerosis. This happens long before the onset of type 2 diabetes in a patient.
Studies show a clear direct relationship between excess insulin and risk factors for cardiovascular diseases. Insulin resistance leads to the fact that:
- increased abdominal obesity;
- the blood cholesterol profile is deteriorating, and plaque from “bad” cholesterol is formed on the walls of blood vessels;
- increases the likelihood of blood clots in the vessels;
- the wall of the carotid artery becomes thicker (the lumen of the artery narrows).
This stable relationship has been proven both in patients with type 2 diabetes and in those without it.
Treatment of insulin resistance
An effective method of treating insulin resistance in the early stages of type 2 diabetes, and even better before it develops, is a diet with restriction of carbohydrates in the diet. To be precise, this is not a way of treatment, but only of control, restoring balance with impaired metabolism. Low-carbohydrate diet with insulin resistance - it must be followed for life.
After 3-4 days of switching to a new diet, most people notice an improvement in their state of health. After 6-8 weeks, tests show that the “good” cholesterol in the blood rises and the “bad” drops. The level of triglycerides in the blood drops to normal. Moreover, this happens after 3-4 days, and cholesterol tests improve later. Thus, the risk of atherosclerosis is reduced several times.
There are currently no methods for real treatment of insulin resistance. Experts in the field of genetics and biology are working on this. You can control this problem well by eating a low-carb diet. First of all, you need to stop eating refined carbohydrates, that is, sugar, sweets and white flour products.
Metformin gives good results (siofor, glucofage). Use it in addition to the diet, and not instead of it, and first consult your doctor about taking pills. Every day we follow the news in the treatment of insulin resistance. Modern genetics and microbiology work wonders. And there is hope that in the coming years they will be able to finally solve this problem. Want to find out first - subscribe to our newsletter, it's free.
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