Hyperinsulinism is a clinical syndrome, which is expressed by an increase in insulin concentrations and a decrease in glucose values ​​in the bloodstream.

The consequence of this decrease in the supply of glucose to the blood is hypoglycemia, which leads to weakness. general, increased hunger, dizziness, psychomotor agitation and tremor.

When pancreatic formations are detected, surgical tactics of treatment are used, and in the case of extra-pancreatic variants, the underlying disease is treated and a specific diet food.

Hypoglycemic disease, otherwise - hyperinsulinism - a disorder of a congenital or acquired nature, which is characterized by the occurrence of relative or absolute hyperinsulinemia of the endogenous type.

The manifestations of the disease were highlighted at the beginning of the 20th century by the physician Harris and the surgeon Oppel.

For reference!

The congenital type of hyperinsulinism occurs occasionally, no more than 1 child out of 50,000. The acquired type occurs at 35-50 years of age and is mainly diagnosed in women.

Clinical endocrinology often uses the classification of hyperinsulinism in accordance with the causes that provoked the pathology, and divides the disease into primary and secondary types.

The primary option is divided into the following types:

Primary type of hyperinsulinism- a consequence of neoplasm or hyperplasia of beta cells of the insular part of the pancreas.

An overestimation of insulin values ​​​​by 90% can occur due to benign tumors, specifically insulinomas, and occasionally due to carcinomas, malignant tumor processes.

The organic type is characterized by a severe course with vivid clinical manifestations and regular bouts of hypoglycemia.

The secondary form of hyperinsulinism is divided into the following types:

It is associated with a lack of contra-insular physiologically active compounds, and may also be a consequence of impaired functioning of the liver and nervous system.

Exacerbations occur rarely and in fact have no relationship with meals.

For reference!

Daily fasting in the secondary type of the disease does not lead to an exacerbation of symptoms and a significant drop in glucose.

Doctors distinguish 3 degrees of hyperinsulinism:

1. Light characterized by the absence of obvious symptoms in the interictal period, and there is also no organic disturbance of the GM cortex.

Exacerbations occur no more than 1 time / month and are easy to eliminate.

1. Medium characterized by a greater frequency of attacks than the mild stage. There is a possibility of loss of consciousness and coma.

The interictal period is described by small behavioral disturbances.

1. heavy arises in the case of irreversible processes in the GM crust. Seizures are frequent, ending in loss of consciousness.

In the interictal period, a person is disoriented, suffers from memory impairment, tremors and emotional instability are observed.

The main causative factors that can provoke the development of a congenital type of hyperinsulinism are the following:

• intrauterine developmental disorders;
• intrauterine growth retardation;
• genome mutations.

The acquired pancreatic form is a consequence of malignant and benign formations of the pancreas and hyperplasia of its beta cells.

The acquired non-pancreatic form of pathology develops due to such reasons:

• violations of eating habits;
• various disorders of the functioning of the liver;
• abuse of sugar-lowering drugs in diabetes;
• endocrinopathies leading to a decrease in ACTH, cortisol.

There is a possibility that hyperinsulinism was triggered by a lack of certain enzymes involved in glucose metabolism.

Mechanisms of development and clinical picture of hyperinsulinism

Glucose is a key nutrient for the CNS and is required for the proper functioning of the GM.

Elevated concentrations of insulin, the accumulation of glycogen in the liver structures and the slowness of glycogenolysis leads to a decrease in glucose values ​​in the bloodstream.

Hypoglycemia leads to slow energy and metabolic processes in the cellular structures of the brain.

At this time, the function of the sympathoadrenal system is activated, the synthesis of ketacholamines is enhanced and the hyperinsulin attack progresses.

A prolonged lack of glucose leads to a breakdown of all metabolic processes, an increase in blood supply to the GM and spasm of peripheral vessels can become the basis for the development of a heart attack.

If the middle, medulla oblongata, as well as the pons varolii, were involved in the process, convulsions progress, heart activity malfunctions and respiratory system.

The symptomatic picture of hyperinsulinism is caused by a drop in glucose levels in the bloodstream. The initial symptoms of the condition are as follows:

• increased feeling of hunger;
• enhanced functioning of the sweat glands;
• general weakness;
• tachycardia.

In the future, the patient feels such negative manifestations of hyperinsulinism:

• feeling of unreasonable fear;
• anxiety states;
• tremor;
• excessive exuberance.

With the progression of the attack, there is a feeling of disorientation in space, paresthesia, convulsions are likely. In case of absence medical care hypoglycemic coma develops.

In the interictal period, the patient experiences the following:

• weakening the ability to remember;
• emotional weakness;
• apathetic states;
• numbness of the body, in particular - the limbs.

Due to frequent meals with fast carbohydrates, weight is rapidly growing and obesity develops.

If the condition is ignored, such health disorders may occur, which can be conditionally divided into late and early ones.

Early consequences occur a few hours after the attack and are expressed by stroke and heart attack due to the rapid drop in the intensity of metabolic processes of the GM and the heart.

Late ones are able to make themselves felt after months and even years after an attack, they are expressed in the following states:

• memory disorders;
• speech disorders;
• encephalopathy;
• parkinsonism.

With untimely diagnosis and the absence of adequate therapy, the endocrine capabilities of the pancreas are depleted and the metabolic syndrome occurs.

Diagnosis of pathology

Diagnosis is based on symptomatic manifestations, information about the history of the disease.

The doctor determines the possible presence of genetic and other pathological processes, and then hardware and laboratory tests are performed:

• Determination of blood glucose values. Otherwise, the glycemic profile of the patient.
• With deviations in the glycemic profile, a fasting test is prescribed.
• Susceptibility tests for leucine and tolbutamide are being performed.
• Based on the results of the susceptibility test, an ultrasound examination of the peritoneum is prescribed, and specifically, MRI GM, MRI of the pancreas, pancreatic scintigraphy.

Differentiation is required in relation to Zollinger-Ellison syndrome, type 2 diabetes, neurological pathologies and mental disorders.

Therapeutic measures

Therapeutic measures depend on the underlying cause of hyperinsulinemia.

In the case of organic origin, surgical intervention is required, expressed by partial resection of the pancreas or total pancreatectomy, enucleation of the formation.

The severity of surgical intervention is selected in accordance with the volume and localization of the tumor process.

After the intervention, it is often detected that needs correction medications and dietary nutrition with low carbohydrate concentrations.

The values ​​return to normal approximately one month after the operation.

In the case of inoperable formations, palliative treatment is performed, which is purposeful to prevent hypoglycemia.

In malignant processes, chemotherapy acts as an auxiliary measure.

Therapy of severe variants of hyperinsulinism, subject to the patient's condition, is performed in an intensive care hospital with detoxification infusion treatment - intravenous adrenaline and glucocorticoids are administered.

Forecast and preventive measures

The prognosis in the case of hyperinsulinism depends on the stage of the pathology and the underlying causes. Excision of benign formations in 9 out of 10 cases leads to recovery.

In case of malignant or inoperable neoplasms that lead to irreversible changes in the neurological plan, constant monitoring of the patient's parameters is required.

Therapy of the primary pathology in the functional type of hyperinsulinism leads to a regression of symptoms and a cure.

Preventive measures imply the normalization of nutrition and the revision of the patient's eating habits - meals should have a frequency of 2-3 hours, and it is also necessary to comply with the drinking regimen.

• restriction of consumption;
• smoking cessation;
• monitoring blood sugar levels.

To maintain and correct, regularly engaged in moderate physical activity.

Many diseases that occur in a chronic form often precede the onset of diabetes mellitus.

For example, hyperinsulinemia in children and adults is detected in rare cases, but indicates excessive production of a hormone that can provoke a decrease in sugar levels, oxygen starvation and dysfunction of all internal systems. Absence medical measures, aimed at suppressing the production of insulin, can lead to the development of uncontrolled diabetes.

Causes of pathology

Hyperinsulinism in medical terminology is considered clinical syndrome, the occurrence of which occurs against the background of an excessive increase in insulin levels.

In this state, a drop in the value of glucose contained in the blood is observed in the body. A lack of sugar can provoke oxygen starvation of the brain, which can result in impaired functioning of the parts of the nervous system.

Hyperinsulism in some cases proceeds without special clinical manifestations, but most often the disease leads to severe intoxication.

Forms of the disease:

1. Congenital hyperinsulinism. It is based on a genetic predisposition. The disease develops against the background of pathological processes occurring in the pancreas that prevent the normal production of hormones.
2. Secondary hyperinsulinism. This form progresses due to other diseases that have caused excessive secretion of the hormone. Functional hyperinsulinism has manifestations that are combined with disorders in carbohydrate metabolism and are identified with a sudden increase in the concentration of glycemia in the bloodstream.

The main factors that can cause an increase in the level of the hormone:

• production by cells of unusable insulin with a composition that is different from the norm, which is not perceived by the body;
• violation of resistance, resulting in uncontrolled production of the hormone;
• deviations in the transport of glucose through the bloodstream;
• overweight;
• atherosclerosis;
• hereditary predisposition;
• anorexia, which is neurogenic in nature and associated with obsessive thought about excess body weight;
• cancer processes in abdominal cavity;
• unbalanced and untimely nutrition;
• abuse of sweets, leading to an increase in glycemia, and, consequently, increased secretion of the hormone;
• liver pathology;
• uncontrolled insulin therapy or excessive use of drugs to lower the concentration of glucose, which leads to the appearance of medication;
• endocrine pathologies;
• insufficient amount of enzyme substances involved in metabolic processes.

The causes of hyperinsulinism may not manifest themselves for a long time, but at the same time they have a detrimental effect on the work of the whole organism.

At-risk groups

The following groups of people most often develop hyperinsulinemia:

• women who have polycystic ovaries;
• people who have a genetic inheritance for this disease;
• patients with disorders in the functioning of the nervous system;
• women who are on the eve of menopause;
• aged people;
• patients leading an inactive lifestyle;
• women and men receiving hormone therapy or drugs from the beta-blocker group.

Symptoms of hyperinsulinism

The disease contributes to a sharp weight gain, so most diets are ineffective. Fat deposits in women are formed in the waist area, as well as the abdominal cavity. This is caused by a large depot of insulin stored in the form of a specific fat (triglyceride).

Manifestations of hyperinsulinism are in many ways similar to those that develop against the background of hypoglycemia. The onset of an attack is characterized by increased appetite, weakness, sweating, tachycardia, and a feeling of hunger.

Subsequently, a panic state joins, in which the presence of fear, anxiety, trembling in the limbs and irritability is noted. Then there is disorientation in the area, numbness in the limbs, and seizures may occur. Left untreated, it can lead to loss of consciousness and coma.

Disease grades:

1. Light. It is characterized by the absence of any signs in the periods between attacks, but at the same time continues to organically affect the cerebral cortex. The patient notes the deterioration of the condition at least 1 time during the calendar month. To stop the attack, it is enough to use the appropriate medications or eat sweet food.
2. Average. The frequency of occurrence of seizures is several times a month. The person may lose consciousness at this point or fall into a coma.
3. Heavy. This degree of disease is accompanied by irreversible brain damage. Seizures often occur and almost always lead to loss of consciousness.

The manifestations of hyperinsulism are practically the same in children and adults. A feature of the course of the disease in young patients is the development of seizures against the background of lower glycemia, as well as a high frequency of their recurrence. The result of constant exacerbations and regular relief of this condition with drugs is a violation of mental health in children.

Why is the disease dangerous?

Any pathology can lead to complications if no action is taken in a timely manner. Hyperinsulinemia is no exception, therefore it is also accompanied by dangerous consequences. The disease proceeds in acute and chronic forms. Passive flow leads to blunting of brain activity, negatively affects the psychosomatic state.

Main complications:

• violations in the functioning of systems and internal organs;
• development of diabetes;
• obesity;
• coma;
• deviations in work of cardio-vascular system;
• encephalopathy;
• parkinsonism

Hyperinsulinemia due to childhood negatively affects the development of the child.

Diagnostics

It is often difficult to identify the disease due to the lack of specific symptoms.

If a deterioration in well-being is detected, a doctor's consultation is required, who can determine the source of this condition using the following diagnostic tests:

• analysis for hormones produced by the pituitary gland and pancreas;
• MRI of the pituitary gland to exclude oncology;
• abdominal ultrasound;
• pressure measurement;
• checking the level of glycemia.

The diagnosis is made on the basis of an analysis of the results of the examination and the patient's complaints.

Treatment of the disease

Therapy depends on the characteristics of the course of the disease, therefore it differs during periods of exacerbation and remission. To stop the attacks, the use of drugs is required, and the rest of the time it is enough to follow a diet and treat the underlying pathology (diabetes).

Help with exacerbation:

• eat carbohydrate or drink sweet water, tea;
• inject a glucose solution in a jet to stabilize the condition (maximum amount - 100 ml / 1 time);
• when coma occurs, intravenous glucose should be performed;
• in the absence of improvement, an injection of adrenaline or glucagon should be given;
• apply tranquilizers for convulsions.

Patients in serious condition should be taken to a hospital and treated under the supervision of doctors. With organic damage to the gland, resection of the organ and surgical intervention may be required.

The diet for hyperinsulinemia is selected taking into account the severity of the course of the disease. Frequent and difficult to manage seizures require the presence of an increased amount of carbohydrates in the daily diet (up to 450 g). At the same time, the consumption of fats and protein foods should be maintained within the normal range.

In the normal course of the disease, the maximum amount of carbohydrates received with food per day should not exceed 150 g. Sweets, confectionery, alcohol should be excluded from the diet.

Video from an expert:

To reduce the manifestations of hyperinsulinemia, it is important to constantly control the course of diabetes and follow the main recommendations:

• eat fractionally and balanced;
• constantly check the level of glycemia, adjust it if necessary;
• observe the required drinking regimen;
• lead a healthy and active lifestyle.

If the excessive production of insulin was the result of a specific disease, then the main prevention of the development of seizures is reduced to the treatment of the pathology, which acts as the main cause of their occurrence.

Congenital hyperinsulinism

M.A. MELIKYAN Congenital hyperinsulinism

Research Institute of Pediatric Endocrinology, Endocrinological Research Center, Moscow

Congenital hyperinsulinism (CHI) is one of the main causes of persistent hypoglycemic conditions in childhood. Biochemically, CHI is characterized by inadequate hypersecretion of insulin by pancreatic β-cells. CHI is a heterogeneous disease in terms of both clinical manifestations and morphological forms, as well as molecular genetic defects underlying it. This article outlines modern views on the main mechanisms of CHI development, presents the clinical characteristics of the disease, and proposes international protocols for the examination and treatment of children suffering from this pathology.

Key words: congenital hyperinsulinism, nesidioblastosis, hypoglycemic syndrome, ATP-dependent potassium channels.

Congenital hyperinsulinism (CHI) is one of the main causes underlying the development of persistent hypoglycemic conditions in children. Biochemically, CHI is characterized by inadequate insulin secretion from pancreatic a-cells. CHI is a heterogeneous pathology in terms of clinical manifestations, morphological features, and molecular-genetic defects contributing to its development. The present paper is focused on the current views of CHI pathogenesis; the clinical characteristic of the disease is given and the internationally accepted protocols for the examination and treatment of children with congenital hyperinsulinism are described.

Key words: congenital hyperinsulinism, nesidioblastosis, hypoglycemic syndrome, ATP-dependent-potassium channels.

Congenital hyperinsulinism (CHI) is a hereditary disease characterized by inadequate hypersecretion of insulin by pancreatic β-cells, which leads to the development of persistent hypoglycemic conditions. The literature describes 8 genes involved in the development of CHI. From 40 to 60% of cases of CHI are associated with defects in the KSH11 and ABCC8 genes encoding proteins that are involved in the ATP-dependent potassium channels of pancreatic β-cells. About 15-20% are associated with activating mutations in the GCK and GLUD1 genes involved in the regulation of intracellular glucose metabolism. The literature also contains single descriptions of CHI cases associated with defects in the HADH, HOT4a, INSR, and CP2 genes. In 30-40% of all cases of CHI, it is not possible to identify molecular genetic defects in these genes.

The prevalence of CHI varies from 1:30,000 to 1:50,000 newborns, and in populations with a high level of consanguineous marriages, it reaches 1:2500 newborns.

CHI was first described as "idiopathic hypoglycemia of childhood" by scientist I. MacQuarrie in 1954. Subsequently, CHI was designated by such terms as, for example, "leucine-sensitive hypoglycemia", "beta-cell dysregulation syndrome", "persistent hypoglycemia". Rinsulinemic hypoglycemia in infancy. Long time to determine WGI

the term "nesidioblastosis" was used. This term was introduced by G. Leidlo back in 1938.

Nesidioblastosis is a total transformation of the ductal epithelium of the pancreas into insulin-producing β-cells. To date, it has been proven that such a morphological picture is normal in infancy and does not cause hyperinsulinism.

Morphologically, CHI is divided into 3 main forms: diffuse, in which all p-cells of the pancreas are affected, focal, if the lesion is limited to a small area of ​​hyperplastic cells containing large nuclei, and atypical.

The true cause of insulin hypersecretion in CHI is most often inadequate functioning of ATP-dependent K-channels of pancreatic β-cells, which is due to molecular genetic defects in the KSH11 and ABCC8 genes.

Etiology and pathogenesis. Normal secretion of insulin by pancreatic β-cells is a consequence of an increase in the level of intracellular ATP. An increase in the ATP/ADP ratio leads to the closure of ATP-dependent K-channels, subsequent depolarization of the membrane, the opening of voltage-dependent calcium channels, and the entry of Ca2+ into the cell, stimulating insulin release. A sufficient rise in ATP is achieved by a sequential cascade of glucose oxidation reactions (Fig. 1).

© M.A. Melikyan, 2010

e-mail: [email protected]

Rice. 1. Mechanism of insulin secretion by the P-cell of the pancreas.

Upon entry into the cell, glucose is phosphorylated to the active metabolite glucose-6-phosphate. This reaction occurs when the enzyme glucokinase is activated. Leucine also serves as one of the main stimulators of insulin secretion. It is a specific activator of the enzyme glutamate dehydrogenase, which catalyzes the conversion of glutamate to a-ketoglutarate. Glucose and leucine activate the intracellular Krebs cycle, which results in the synthesis of ATP. An increase in the ATP/ADP ratio inhibits the work of ATP-dependent potassium channels, which leads to membrane depolarization and the opening of voltage-dependent calcium channels. The entry of interstitial Ca2+ into the cell stimulates the release of insulin.

With a decrease in blood glucose levels, its intracellular metabolism is inhibited, which changes (reduces) the ATP / ADP ratio and leads to the opening of potassium channels and the closure of calcium channels, thereby blocking insulin secretion.

Disturbances in the function of ATP-dependent K-channels, as well as defects in the regulation of intracellular glucose metabolism, can lead to the development of hyperinsulinemic hypoglycemic conditions. The most common cause of CHI is inactivating mutations in the KCNJ11 and ABCC8 genes.

ATP-dependent potassium channels of β-cells are octameric structures, the inner sections of which are represented by 4 subunits of the Kir6.2 protein encoded by the KCNJ11 gene, and the outer sections are represented by 4 subunits of the SUR1 protein encoded by the ABCC8 gene. These channels are able to change the degree of cell membrane polarization. functional activity channels is regulated by the level of intracellular adenine nucleotides. Inactivating mutations in the KCNJ11 and ABCC8 genes lead to the closure of these channels, which leads to excess Ca2+ entry into the cell and insulin hypersecretion.

Both autosomal recessive and autosomal dominant mutations of these genes have been described. To date, more than 150 mutations in the ABCC8 gene and 25 mutations in the KCNJ11 gene have been identified.

CHI associated with recessive mutations in the KCNJ11 and ABCC8 genes is characterized by a severe course, early onset of hypoglycemia, and, as a rule, is not amenable to conservative therapy.

Dominantly inherited forms are milder, manifest later, and in most cases are sensitive to diazoxide therapy.

In addition to disruptions in the functioning of ATP-dependent potassium channels in β-cells, the development of CHI can be caused by disruptions in the functioning of enzymes involved in intracellular glucose metabolism. These include glucokinase, glutamate dehydrogenase, and 3-hydroxyacyl-CoA dehydrogenase.

Glucokinase is one of the important regulatory factors of insulin secretion. This enzyme catalyzes the phosphorylation of glucose to its active metabolite, glucose-6-phosphate. Activating dominant mutations in the GCK gene lead to an increase in the expression of the enzyme, which leads to hypersecretion of insulin. This form of CHI is characterized by the variability of the clinical picture. An asymptomatic course has been described. Some mutations manifest themselves only as hypoglycemic states after eating while maintaining normal level fasting blood glucose. There are also descriptions of severe, therapy-resistant forms.

The mitochondrial enzyme glutamate dehydrogenase (encoded by the GDL1 gene) catalyzes the conversion of glutamine to α-ketoglutarate and ammonium. Mutations in the GnF1 gene weaken the sensitivity of the enzyme to leucine, which is

is its specific inhibitor, which leads to an increase in enzyme activity and excessive production of ATP due to the activating effect of leucine and ammonium on the reactions of the Krebs cycle. There is an increase in the level of ammonia in the blood. This form of HHI is also called hyperammonemia-leucine-sensitive hypoglycemia. Mutations in the GnF1 gene are inherited in an autosomal dominant fashion. Hypoglycemic conditions with defects in glutamate dehydrogenase are stopped by a low-protein diet, respond well to diazoxide therapy.

Another rare cause of recessively inherited CHI is a defect in the NADH gene encoding the enzyme 3-hydroxyacyl-CoA dehydrogenase. This enzyme catalyzes the penultimate reaction in the process of p-oxidation of short chain fatty acids, resulting in the formation of 3-keto-acyl-CoA. Inactivating mutations in the NADH gene lead to hyperproduction of insulin and excessive accumulation of ketogenesis products. The mechanism of hyperinsulinism in these mutations remains unclear. This is the only form of hyperinsulinemic hypoglycemia that occurs with ketosis. An increase in the level of 3-hydroxybutyryl-carnitine in the blood and 3-hydroxyglutarate in the urine is characteristic. As a rule, the course is mild and there is a good therapeutic effect from diazoxide.

Focal forms of CHI are formed in the case of a somatic decrease in the homozygosity of a mutation inherited from the father in the ABCC8 and KSIL1 genes and a specific loss of the maternal allele in the imprinting region by 11p 15. In this case, a change in the expression of imprinting genes in the 11p 15.5 region occurs: the expression of the H19 and P57K1P2 genes, which are tumor growth suppressors, and increased expression of the gene encoding insulin-like growth factor type 2 (IGF2), which is a powerful factor in cell proliferation. This combination of violations

mutations in the KSH11 or ABCC8 genes lead to the development of focal adenomatosis of the pancreatic tissue. These forms of the disease account for about 40% of all cases of CHI. According to its clinical manifestations, focal CHI does not differ from diffuse CHI. With timely molecular genetic diagnosis and visualization of the formation, it is possible surgery in the form of selective resection of the focus, which leads to complete recovery. The main genetic forms of CHI are presented in Table. 1.

clinical picture. CHI, as a rule, manifests itself in the neonatal period, but a later debut is also possible, up to 3 years of age. The earlier the disease appears, the more severe it is. Hypoglycemic conditions in HHI are usually severe and quickly lead to the development of seizures and loss of consciousness. Mild forms are also described, occurring almost asymptomatically, manifested only by hypodynamia and reduced appetite. Due to the excess production of insulin even in the prenatal period, children with CHI are usually born large. At birth, macrosomia, cardiomyopathy, and hepatomegaly are often detected. Mothers may experience excessive weight gain during pregnancy. Children with HHI require extremely high doses of glucose to maintain normoglycemia. The need for intravenous infusion of glucose solution can reach 20 mg / kg / min.

Diagnostics. The main criteria for the diagnosis of CHI is the determination of the level of insulin in plasma (more than 2.0 U/l) at the time of hypoglycemia (blood glucose<2,4 ммоль/л у детей старше 1 года и <2,2 ммоль/л у детей до года) . Кроме того, критериями, подтверждающими диагноз ВГИ, являются гипокетотический характер гипогликемий (отсутствие кетоновых тел в моче, низкий уровень 3-ги-

Table 1. Forms of congenital hyperinsulinism depending on the molecular genetic cause

Gene Chromosomal Protein Type of inheritance Phenotype

localization

KSS11 11p15.1 Jug6.2 Autosomal recessive Severe hypoglycemia resistant to therapy.

ABCC8 SUR1 Autosomal dominant Inheritance of paternal mutation with loss of heterozygosity Debut in the first days of life Hypoglycemia of moderate severity. The effect of conservative therapy is possible. Focal forms. The severity of hypoglycemia can vary

OSK 7p15-13 Glucokinase Autosomal dominant The clinical picture is variable. Isolated postprandial hypoglycemia may occur

oit 10a23.3 Glutamate dehydrogenase Autosomal dominant Mild course. Increased blood ammonia levels. Good effect from conservative therapy and on the background of a low-protein diet

NABI 4e22-26 3-HydroxyacylCoA dehydrogenase Autosomal recessive Mild course. Comes with ketosis. Sensitive to conservative therapy

droxibutyrate in the blood), a pronounced hyperglycemic response to the administration of glucagon (an increase in blood glucose by more than 1.7 mmol / l), high or normal levels of C-peptide against the background of hypoglycemia, the need for high doses of glucose (> 8 mg / l). kg/min), low levels of amino acids (valine, leucine) and normal levels of contrainsular hormones ( growth hormone, cortisol, glucagon) in the blood. It is worth noting that in many patients with HHI there is no pronounced rise in cortisol and glucagon levels in response to hypoglycemia. This circumstance is associated with the immaturity of the hormonal system of counterregulation, as well as its depletion caused by persistent hypoglycemic conditions. Children with a late onset of the disease are shown to undergo ultrasound and multislice computed tomography of the pancreas in order to exclude mass formation (insulinoma). All patients diagnosed with CHI are recommended to undergo a molecular genetic study of the KSH11 and ABCC8 genes. In the presence of gene defects characteristic of focal forms, positron emission tomography with 18-fluorin-l-3,4-dihydroxyphenylalanine (PET with 18-F-dopa) is indicated.

Differential Diagnosis. HHI must be differentiated from other forms of hypoglycemia, such as congenital defects in fatty acid β-oxidation; syndromal forms of hyperinsulinism (Beckwith-Wiedemann syndrome, Sotos syndrome, Usher syndrome, etc.), from congenital glycosylation diseases and insulin-producing pancreatic tumors, deficiency of contra-insular hormones, glycogen liver diseases, defects in ketogenesis and gluconeogenesis. In addition, do not forget about transient forms of neonatal hyperinsulinism associated with diabetic fetopathy, intrauterine growth retardation and perinatal asphyxia. Schemes for the differential diagnosis of the main forms of hypoglycemic syndrome are presented in Table. 2.

Treatment. The main goal of CHI treatment is to maintain stable normoglycemia (3.5-6.0 mmol/l). Even single episodes of hypoglycemic conditions in the first months of life can be fraught with severe neurological complications. Due to the high demand for glucose in patients with CHI, the placement of a central catheter is recommended, which makes it possible to inject large volumes of a concentrated solution.

Table 2. Differential diagnosis of the main forms of hypoglycemic syndrome in children

Hypoglycemic conditions

Disease

ketotic

non-ketotic

Idiopathic ketotic hypoglycemia

Deficiency of contra-insular hormones (congenital hypopituitarism, isolated growth hormone deficiency, primary/secondary adrenal insufficiency) Glycogenosis types 0, I, III, VI, IX

Defects in gluconeogenesis (phospho-enylpyruvate carboxinase deficiency, fructose 1-6-bisphosphatase deficiency) Congenital hyperinsulinism

Insulin-producing tumors

Fatty acid p-oxidation defects

Beckwith-Wiedemann Syndrome

Congenital glycosylation diseases types! a, b

Age over one year, low birth weight, hypoglycemia against the background of prolonged starvation, infections, physical exertion. Decreased alanine in the blood Growth retardation, hypoglycemia on the background of stress, infections, hyperthermia. Low levels of IGF-1/cortisol. Bone age lag

An increase in the size of the liver, an increase in the level of lactate, ALT, AST, the absence of a hyperglycemic reaction to the administration of glucagon

Increased levels of lactate, triglycerides, cholesterol, uric acid. Adequate response to glucagon

Need for high doses of glucose, early age, macrosomia at birth

Age over 8 years, ultrasound/MSCT signs of pancreatic mass

Associated cardiomyopathy. Changes in the ratio of amino acids according to TMS

Transient hypoglycaemia, macrosomia at birth, hemihyperplasia, umbilical hernia, characteristic furrow on the earlobes, fetal tumors, increased

Characteristic stigmas of disembryogenesis (inverted nipples, microcephaly, osteodysplasia), delayed physical development, diarrhea, vomiting, increased levels of ALT, AST, proteinuria_

Note. STH - somatotropic hormone; MSCT - multislice computed tomography; IGF-1 - insulin-like growth factor type 1; ALT - alanine aminotransferase; ASAT - aspartate aminotransferase; TMS - tandem mass spectrometry.

Recommended fractional feeding of carbohydrate-enriched foods. Some patients require a gastric tube for adequate nutrition. The block of ketogenesis caused by insulin hypersecretion deprives children with CHI of alternative energy resources for the brain, which very quickly leads to the development of seizures and, in the absence of adequate treatment, to the formation of autonomous epilepsy. According to the latest international recommendations, patients with CHI are shown to maintain a blood glucose level of at least 3.8-4.0 mmol / l. Among the drugs used to treat hyperinsulinemic hypoglycemic conditions, diazoxide is the drug of choice. Diazoxide is an agonist of ATP-dependent K-channels in pancreatic β-cells. The mechanism of its action is to activate the work of the channels themselves. The effectiveness of therapy varies depending on the molecular genetic defects. Most patients with recessively inherited mutations in the IFN and ABCC8 genes, as well as some mutations in the GCK gene, are resistant to this treatment. To potentiate the action of diazoxide, in some cases it is possible to add chlorthiazide. Nifedipine, being a calcium channel blocker, has a suppressive effect on insulin secretion. Its effectiveness in the treatment of CHI is extremely low, there are only a few reports of its successful monotherapy. Somatostatin, being an analogue of the hormone of the same name, activates specific receptors located in the pancreatic tissue, which suppresses insulin secretion. This drug is effective in combination with a fractional feeding regimen. In rare cases, it is possible to use prolonged

forms when the injection is performed once a month. Glucagon is used in acute situations to relieve hypoglycemia. Its long-term use is possible only in the form of continuous subcutaneous infusion. High doses of glucagon (>20 µg/kg/h) cause the opposite reaction - the release of insulin. In table. Table 3 lists the main drugs for the treatment of CHI.

Surgical treatment of VHI. In case of resistance to these methods of treatment and persistence of the hypoglycemic state, surgical treatment is recommended for patients with CHI. In diffuse forms, subtotal pacreatectomy is performed, when 95-98% of the pancreatic tissue is removed. This operation is extremely invalidating, since in 40-50% of cases it leads to the development of insulin-dependent diabetes mellitus (IDDM). Such surgical intervention is indicated only for severe, resistant to all types conservative treatment VGI forms. With focal forms, selective resection of the focus is performed, the result of which is a complete recovery. For the differential diagnosis of diffuse and focal forms, screening for molecular genetic defects in the IFN and ABCC8 genes is used. In the case of genetic verification of focal CHI, PET with 18^-dopa is used to visualize the formation. The use of other imaging modalities, such as ultrasound, magnetic resonance imaging, multispiral computed tomography, fluoroglucose PET, is not informative in this pathology. Previously, selective calcium-stimulated angiography of the pancreatic vessels was performed to localize the focus, however, given the invasiveness this procedure,

Table 3. Drugs for the treatment of hypoglycemic conditions in congenital hyperinsulinism

Drug Method, frequency of administration Dose Mechanism of action Side effects

Diazoxide Orally 3-4 times a day 5--20 mg / kg / day ATP agonist- Often: hypertrichosis, over-

dependent K-channels fluid retention.

Rare: hyperuricemia, eo-

sinophilia, leukopenia,

hypotension

Chlorthiazide (used Orally 2 times a day 7-10 mg / kg / day Activates the work of Hyponatremia, hypokali-

nyatsya in a combination of ATP-dependent emia

with diazoxide) K-channels. Potenti-

no diazoxide effect

Nifedipine Orally 3 times a day 0.25-2.5 mg/kg/day Calcium blocker Hypotension (rare)

Glucagon By constant subcutaneous method - 1-20 mcg / kg / h Activates glycogen - Nausea, vomiting. Rare: pa-

noy infusion (in pomah) lysis and gluconeogenesis radoxal rise in

Somatostatin Subcutaneously 3-4 times a day. 5-25 mcg/kg/day Receptor activation Anorexia, nausea, vomiting

Permanent subcutaneous infu- to somatostatin 5th grade, flatulence, diarrhea, ho-

zia. type; inhibits polelithiasis, suppression of semen-

Intravenous infusion of Ca2+ into the cell, secretions of STH, TSH, ACTH,

reduces the activity of glucagon, growth retardation,

acetylcholine tachyphylaxis

Note. STH - somatotropic hormone; TSH - thyroid-stimulating hormone; ACTH - adrenocorticotropic hormone.

Rice. 2. Protocol for the treatment and monitoring of patients with CHI.

as well as a high frequency of complications, at the moment, it is practically not used in the world. The international protocol for the management of patients with CHI is presented in fig. 2.

remote observations. In most patients with HHI, the severity and frequency of episodes of hypoglycemia decrease sharply with increasing age. Many cases of spontaneous recovery have been described. In the case of conservative treatment, on average, by 3-4 years of age, the average daily dose of diazoxide is reduced to the minimum therapeutic dose (5 mg/kg/day). There are data in the literature indicating the development of diabetes mellitus with age in non-operated patients with CHI. Among children who underwent subtotal pancreatectomy, about 40% have IDDM, up to 60% do not need insulin therapy, 2-5% require treatment with diazoxide to maintain normoglycemia. According to various authors, psychomotor developmental delay is observed in 30-40% of all patients with CHI. In 15-20% of cases revealed

the formation of autonomous epilepsy, which requires therapy with anticonvulsants. The severity of neurological complications directly depends on the age of disease manifestation, as well as on the timeliness and adequacy of the therapy.

In this review of the literature, the main molecular genetic prerequisites for the development of CHI were considered, and modern views on the existence of relationships between the genotype and phenotype are presented. Based on international experience, modern protocols for the diagnosis, treatment and monitoring of children with CHI have been proposed. Timely diagnosis, choice of adequate treatment and dynamic control can minimize neurological complications of hypoglycemic conditions. Despite a breakthrough in understanding the etiology and pathogenesis of CHI, in 50% of cases the molecular genetic diagnosis remains unclear, which requires further research in this area.

LITERATURE

1. James C., Kapoor R.R., Ismail D. et al. The genetic basis of congenital hyperinsulinism. J Med Genet 2009;46:289-299.

2. Otonkoski T., Ammala C., Huopio H. et al. A point mutation inactivating the sulfonylurea receptor causes the severe form of persistent hyperinsulinemic hypoglycemia of infancy in Finland. Diabetes 1999;48:408-415.

3. DeLeon D.D., Stanley C.A. Mechanisms of disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab 2007;3:57-68.

4. McQuarrie I. Idiopathic spontaneously occurring hypoglycemia in infants: clinical significance of problem and treatment. AMA Am J Dis Child 1954;87:399-428.

5. Rahier J., Guiot Y., Sempoux C. Persistent hyperinsulinaemic hypo-glycaemia of infancy: a heterogeneous syndrome unrelated to nesidioblastosis. Arch Dis Child Fetal Neonatal Ed 2000;82:F108-F112.

6. Kapoor R.R., Flanagan S.E., James C. et al. Hyperinsulinaemic hypoglycaemia. Arch Dis Child 2009;94:450-457.

7. Kapoor R.R., James C., Hussain K. Advances in the diagnosis and management of hyperinsulinemic hypoglycemia. Nat Clin Pract Endocrinol Metab 2009;5:2:101-112.

8. Thomas P., Ye Y., Lightner E. Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy. Hum Mol Genet 1996;5:1809-1812.

9. Thomas P.M., Cote G.J., Wohllk N. et al. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science 1995;268:426-429.

10. Nestorowicz A., Inagaki N., Gonoi T. et al. A nonsense mutation in the inward rectifier potassium channel gene, Kir6.2, is associated with familial hyperinsulinism. Diabetes 1997;46:1743-1748.

11. Dunne M.J., Kane C., Shepherd R.M. et al. Familial persistent hyperinsulinemic hypoglycemia of infancy and mutations in the sulfonylurea receptor. N Engl J Med 1997;336:703-706.

12. Flanagan S.E., Clauin S., Bellanne-Chantelot C. et al. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism. Hum Mutat 2009;30:170-180.

13. Pinney S.E., MacMullen C., Becker S. et al. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J Clin Inv 2008;118:2877-2886.

14. Zelent D., Najafi H., Odili S. et al. Glucokinase and glucose homeostasis: proven concepts and new ideas. Biochem Soc Trans 2005;33:306-310.

15. Christesen H.B., Brusgaard K., Beck Nielsen H., Brock Jacobsen B. Non-insulinoma persistent hyperinsulinaemic hypoglycaemia caused by an activating glucokinase mutation: hypoglycaemia un-awareness and attacks. Clin Endocrinol (Oxford) 2008;68:1011.

16. Fahien L.A., MacDonald M.J., Kmiotek E.H. et al. Regulation of insulin release by factors that also modify glutamate dehydrogenase. J Biol Chem 1980;263:13610-13614.

17. Weinzimer S.A., Stanley C.A., Berry G.T. et al. A syndrome of congenital hyperinsulinism and hyperammonemia. J Pediat 1997;130:661-664.

18. Zammarchi E., Filippi L., Novembre E., Donati M.A. Biochemical evaluation of a patient with a familial form of leucine-sensitive

hypoglycemia and concomitant hyperammonemia. Metabolism 1996;45:957-960.

19. Clayton P. T., Eaton S, Aynsley-Green A. et al. Hyperinsulinism in short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion. J Clin Inv 2001;108:457-465.

20. Hussain K, Clayton P.T., Krywawych S. et al. Hyperinsulinism of infancy associated with a novel splice site mutation in the S CHAD gene. J Pediat 2005;146:706-708.

21. Ryan F., Devaney D, Joyce C. et al. Hyperinsulinism: molecular aetiology of focal disease. Arch Dis Child 1998;79:445-447.

22. Damaj L, le Lorch M, Verkarre V. et al. Chromosome 11p15 Paternal Isodisomy in Focal Forms of Neonatal Hyperinsulinism. J Clin Endocrinol Metab 2008;93:4941-4947.

23. Palladino A.A., Bennett M.J., Stanley C.A. Hyperinsulinism in infancy and childhood: when an insulin level is not always enough. Ann Biol Clin (Paris) 2009;67:3:245-254.

24. Wolfsdorf J.I., Weinstein D.A. Hypoglycemia in Children, Pediatric. 5th edition. Endocrinology 2007;1:291-327.

25. Hussain K., Hindmarsh P., Aynsley-Green A. Neonates with symptomatic hyperinsulinemic hypoglycemia generate inappropriately low serum cortisol counterregulatory hormonal responses. J Clin Endocrinol Metab 2003;88:9:4342-4347.

26. Hussain K, Adzick N.S., Stanley C.A. et al. The diagnosis of ectopic focal hyperinsulinism of infancy with [ 18 F]-dopa positron emission tomography. J Clin Endocrinol Metab 2006;91:2839-2842.

27. Hussain K., Blankenstein O., De Lonlay P., Christesen H.T. Hyper-insulinaemic hypoglycaemia: biochemical basis and the importance of maintaining normoglycaemia during management. Arch Dis Child 2007;92:568-570.

28. Aynsley-Green A., Hussain K, Hall J. et al. Practical management of hyperinsulinism in infancy. Arch Dis Child Fetal Neonatal 2000;82:98-107.

29. Glaser B., Landau H, Smilovici A., Nesher R. Persistent hyperinsulinaemic hypoglycaemia of infancy: long-term treatment with the somatostatin analogue Sandostatin. Clin Endocrinol (Oxford) 1989;31:71-80.

30. Moens K., Berger V., Ahn J.M. et al. Assessment of the role of interstitial glucagon in the acute secretory glucoseory responsiveness of in situ pancreatic beta-cells. Diabetes 2002;51:669-675.

31. Greene S.A., Aynsley-Green A., Soltesz G., Baum J.D. Management of secondary diabetes mellitus after pancreatectomy in infancy. Arch Dis Child 1984;59:356-359.

32. De Vroede M., Bax N.M., Brusgaard K. et al. Laparoscopic diagnosis and cure of hyperinsulinism in two cases of focal adenomatous hyperplasia in infancy. Pediatrics 2004;114:e520-e522.

33 Gussinyer M., Clemente M., Cebrián R. et al. Glucose intolerance and diabetes are observed in the long-term follow-up of nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of infancy due to mutations in the ABCC8 gene. Diabetes Care 2008;31:6:1257-1259.

34. Mercimek-Mahmutoglu S., Rami B., Feucht M. et al. Long-term follow-up of patients with congenital hyperinsulinism in Austria. J Pediatr Endocrinol Metab 2008;21:6:523-532.

35. Mazor-Aronovitch K., Gillis D., LobelD. et al. Long-term neurode-velopmental outcome in conservatively treated congenital hyper-insulinism. Eur J Endocrinol 2007;157:4:491-497.

If left untreated, the disease will progress to uncontrolled diabetes.

Causes

The occurrence of hyperinsulinism indicates the pathological functioning of the body. The reasons may lie deep inside and not make themselves felt for many years. This disease is more common in women, this is due to frequent hormonal changes. The main causes of occurrence:

• The production of unusable insulin by the pancreas, which differs in composition and is not perceived by the body.
• Susceptibility disorder. The receptors do not identify insulin, which leads to uncontrolled production.
• Disruptions in the transport of glucose in the blood.
• genetic propensity.
• Obesity.
• Atherosclerosis.
• Neurogenic anorexia - psychological disorder against the background of obsessive thoughts about being overweight, which entails refusal to eat, and subsequently endocrine disorders, anemia, fluctuations in blood sugar.
• Oncology in the abdominal cavity.

Back to index

At-risk groups

Predisposition to increase insulin levels with the development of hyperinsulinism occurs:

Women with PCOS are more likely to have this condition.

• In people with poor heredity. If among relatives there are those who have been diagnosed with the disease, then the risk increases several times. Scientists have proven that the presence of HLA antigens leads to hyperinsulinism.
• With violations of the functioning of the central nervous system, the brain gives the wrong signal, which leads to an excess of insulin in the body.
• In females on the eve of menopause.
• When leading an inactive lifestyle.
• In old age.
• In patients with polycystic appendages.
• In people taking hormonal drugs, beta-blockers.

Back to index

Symptoms of hyperinsulinism

Functional hyperinsulinism leads to rapid weight gain, and diets are often ineffective. In women, fat is deposited in the waist and abdominal cavity. This is due to a large supply of insulin, which is stored as a specific fat called triglyceride.

It should be noted that hyperinsulinism has many common symptoms with hypoglycemia:

What is dangerous insidious disease?

Each disease in the absence of competent treatment leads to complications. Hyperinsulinism can have not only sharp shape, but also chronic, which is much more difficult to resist. A chronic disease dulls brain activity and affects the psychosomatic state of the patient, and in men potency worsens, which is fraught with infertility. Congenital hyperinsulinism in 30% of cases leads to oxygen starvation of the brain and affects the full development of the child. There is a list of other factors to consider:

• The disease affects the functioning of all organs and systems.
• Hyperinsulinism can cause diabetes.
• There is a constant increase in weight with the ensuing consequences.
• The risk of hypoglycemic coma increases.
• Problems with the cardiovascular system develop.

Back to index

Diagnosis of the disease

Identification of hyperinsulinism is complicated by the absence of specific symptoms, and often by asymptomaticity. If the general condition worsens, you should immediately consult a doctor. You will need an open analysis for hormones with a complete picture of the work of the pancreas and pituitary gland. If suspected, an MRI of the pituitary gland is performed with a marker that will exclude the possibility of oncology. For women, diagnosis is based on ultrasound of the abdominal cavity, reproductive organs, since the disease is associated with the production of hormones. To confirm the result, you should measure your blood pressure and check your blood sugar levels. The patient's complaints are taken into account, which can confirm the presence of the disease.

Treatment of the disease

If hyperinsulinism was detected at the initial stage, there is a high chance of curing the disease. Nutrition plays a paramount role, the compiled diet is observed, clearly following the schedule. Increased physical activity, which allows you to disperse the metabolism, get rid of excess weight. Pregnancy complicates the treatment, and the diet will be different. The doctor will include a vitamin complex that allows the growing body to develop fully. If necessary, add:

• medicines to reduce blood pressure;
• metabolic drugs;
• supplements that suppress appetite.

Back to index

Hyperinsulinism in children: general information

Hypoglycemia in most children with hyperinsulinism usually manifests itself in the first 18 months. life, but sometimes later. Hyperinsulinism is the most common cause persistent hypoglycemia in the first months of life. Children with hyperinsulinism are usually born large, which is associated with the anabolic effect of insulin in utero. However, in such cases, the mother does not have diabetes mellitus. The concentration of insulin on the background of hypoglycemia is disproportionately high. In case of hypoglycemia not associated with hyperinsulinism, the plasma insulin concentration should be less than 5 μU / ml, in any case not higher than 10 μU / ml, but with hyperinsulinism it usually exceeds these figures. Some authors propose more stringent criteria and consider insulin levels above 2 μU/ml against the background of hypoglycemia to be pathological. The ratio of insulin (μU / ml) / glucose (mg%), as a rule, exceeds 0.4; the content of ketone bodies and free fatty acids in plasma is reduced.

Hypoglycemia in children with macrosomia can be observed from the first days of life. However, with a lesser degree of hyperinsulinemia, it manifests itself only after a few weeks or months, when children begin to feed less often, especially at night, and hyperinsulinemia prevents the mobilization of endogenous glucose. Common symptoms are increased appetite requiring more frequent feeding, fasciculations, tremors, and overt convulsions. Hypoglycemia develops already 4-8 hours after feeding, i.e. faster than in other cases (Table 140.1 and Table 140.2). To stop it, one has to administer exogenous glucose in large doses (often more mg/kg/min). There is no ketonemia or acidosis. The content of C-peptide and proinsulin in the blood serum against the background of hypoglycemia is increased, which distinguishes hyperinsulinism from artificial hypoglycemia caused by the administration of exogenous insulin. Trials with tolbutamide or leucine in infants are optional; hypoglycemia inevitably occurs within a few hours after feeding, and in a blood sample taken at this time, it is possible to simultaneously determine the content of glucose, insulin, ketone bodies and free fatty acids. The introduction of glucagon against the background of hypoglycemia significantly increases the level of glucose in the blood (by at least 40 mg%). This indicates that the mechanisms of glycogenolysis are preserved and that it is insulin that prevents the mobilization of glucose (Table 140.3-3, Table 140.4-4).

Diagnosis of hyperinsulinemia is facilitated by determining the concentration of IGF-binding protein-1. Insulin sharply suppresses its secretion, and with hypoglycemia associated with hyperinsulinism, its level is low. With spontaneous hypoglycemia or fasting hypoglycemia (with ketonemia), the level of insulin decreases, the content of this protein is increased.

Endogenous hyperinsulinism should be distinguished from familial hyperinsulinism and non-familial hyperinsulinism. In infants, due to diffuse hyperplasia of beta cells, as well as their focal hyperplasia and beta cell adenomas. Plasma insulin levels alone cannot distinguish between these conditions. They are based on various genetic disorders in the endocrine part of the pancreas, leading to autonomous secretion of insulin. Spontaneous or fasting-induced hypoglycemia in such cases is not accompanied by a decrease in its level (Table 140.3).

Modern clinical, biochemical and molecular genetic approaches make it possible to divide congenital hyperinsulinism (formerly called nesidioblastosis) into separate nosological forms. One of the forms of congenital chronic hyperinsulinemic hypoglycemia is inherited as an autosomal recessive trait and is characterized by a severe course. It is based on mutations that disrupt the function of K + channels in pancreatic beta cells (Fig. 140.1). Normally, glucose enters beta cells via the insulin-independent transporter GLUT-2. Under the action of glucokinase, it is phosphorylated, turning into glucose-6-phosphate, and then oxidized to form ATP. An increase in the ATP/ADP molar ratio closes the ATP-sensitive K+ channels of the cell membrane. These channels consist of two subunits: KlR6.2 (belonging to the family of K + channels of abnormal straightening) and a closely related regulatory component, the sulfonylurea receptor (SUR). Normally, ATP-sensitive K+ channels are open, but with an increase in the intracellular concentration of ATP, they close and potassium accumulates in the cells. The cell membrane depolarizes, voltage-dependent Ca2+ channels open, and calcium entering the cell stimulates exocytosis (secretion) of insulin.

The SUR gene and the KIR6.2 gene are located close to each other on the short arm of chromosome 11 (in the same place where the insulin gene is located). Mutations that inactivate the SUR gene (or, more rarely, the KIR6.2 gene) prevent the opening of K+ channels. When they are closed, the cell membrane remains depolarized, calcium continuously enters the cell, stimulating a constant section of insulin. A milder dominant form of such defects has also been described. An activating mutation of the glucokinase gene also leads to the closure of K + channels (due to excessive production of ATP) and, accordingly, to hyperinsulinism. In contrast, inactivating mutations in this gene cause insufficient insulin secretion and underlie juvenile non-insulin dependent diabetes mellitus (MODY).

Hyperinsulinism: causes, symptoms, treatment

The production of insulin in the human body is regulated by the work of the pancreas, the islets of Langerhans are responsible for the production of this substance. Excessive release of the hormone into the blood indicates the development of a pathology called hyperinsulinism, in which blood sugar levels drop sharply. There is a disease hyperinsulinism in children and adults, it is very difficult to tolerate, it is treated for a long time.

Forms of the disease

According to the nature of the course, the chronic form of the disease and the acute form are distinguished. chronic course pathology often ends with apathy, decreased mental perception, weakness, coma. The work of all organs and systems is disrupted. Based on what caused the pathology, they distinguish:

• pancreatic (primary), organic hyperinsulinism;
• extrapancreatic (secondary), functional hyperinsulinism.

The primary development of the disease is provoked by malfunctions of the pancreas, the development of certain pathologies of this organ. While the secondary occurs as a result of chronic diseases of any organ. The disease can affect a small area of ​​the pancreas, be focal in nature, or cover the entire zone of the islets.

Diagnosing a form of pathology, specialists monitor the patient's condition throughout the day, take blood, urine for analysis, determine glycemia with a sugar load, make tests for adrenaline, insulin. In addition, in the organic form of pathology, the sudden production of insulin is not regulated and is not compensated by hypoglycemic mechanisms. This happens because the work of the neuron is disrupted. endocrine system, there is a lack of glucose.

Any form of the disease is very dangerous, requires the immediate intervention of specialists, soon, proper treatment. It is impossible to make a diagnosis without an experienced doctor and special diagnostics.

Causes

The disease can occur at absolutely any age, even in newborns. This type of pathology is dangerous, pancreatic hyperinsulinism occurs for a number of reasons:

• diseases of the central nervous system;
• damage to the islets of Langerhans by a tumor, malignant and benign origin;
• diffuse hyperplasia (tumor) of the pancreas;
• development of diabetes;
• obesity;
• metabolic disease;
• endocrine diseases.

The secondary form of the disease is provoked by diseases of the liver, digestive system, gallbladder. This happens from a lack of sugar in the blood, which is inherent in some endocrine diseases, impaired metabolism, prolonged starvation, hard physical labor. Along with the fact that all the reasons are more or less clear, doctors emphasize that why oncology develops on the pancreas still remains unclear. It is not clear what leads to a general defeat, to a partial one.

Symptoms

Depending on why hyperinsulinism occurs, the symptoms may vary. In addition to low blood sugar, doctors distinguish:

• headache;
• constant fatigue;
• weakness;
• drowsiness;
• pallor;
• general malaise;
• constant feeling of hunger;
• trembling of the limbs;
• increased irritation;
• fainting;
• convulsions;
• pressure drop;
• increased sweating;
• decrease in body temperature;
• cardiopalmus;
• feeling of fear;
• depressive states;
• a state of disorientation.

Depending on the form of the disease, for example, with functional hyperinsulinism, the symptoms may be more advanced. In each case, some symptoms are superior to others or pass together. Hyperinsulinism in children is not so pronounced, but in any case it is noticeable, it requires diagnosis and treatment, the pathology will gradually increase, provoking more extensive symptoms. So, if you start the disease, then soon the symptoms will be so pronounced that a state of clinical coma is possible.

Congenital hyperinsulinism

Modern medicine is increasingly using the term congenital hyperinsulinism, pathology occurs in newborns and infants. The causes of the pathology remain unexplored, so doctors suggest that poor heredity, a genetic defect, affects here. This form is also called idiopathic hyperinsulinism, its symptoms are also mild.

How to give first aid

Being close to a person who has experienced a sudden discharge a large number insulin into the blood, the main thing is not to panic yourself. To alleviate the patient's condition, relieve the primary symptoms of an attack, you need to give the patient a sweet candy, pour sweet tea. In case of loss of consciousness, immediately inject glucose.

After the condition improves and there are no obvious signs of recurrence, the patient should be immediately taken to the hospital or call specialists at home. Such a phenomenon cannot be left without attention, a person needs treatment, possibly urgent hospitalization, this must be understood.

Treatment

Immediately after establishing the correct diagnosis, the doctor prescribes drug treatment, however, this is with the mildest forms of pathology. Most often, the procedure is surgical intervention, the tumor is removed or along with it a certain part of the pancreas. After that, medications that restore the functionality of the pancreas and other organs are prescribed.

If functional hyperinsulinism is observed, then treatment initially focuses on eliminating provoking pathologies, reducing this symptomatology.

Nutrition

When treating the pathology of the functional form of the disease, the severity of the disease, the possibility of complications in the work of other organs, and the complexity of treatment are taken into account. All this leads to the fact that patients are recommended a special diet, which in no case should be violated. Nutrition for hyperinsulinism should be strictly balanced, saturated with complex carbohydrates. Eating stretches up to 5-6 times a day.

Prevention

Experienced specialists say that to date, measures to prevent the occurrence and growth of tumor cells in the pancreas are unknown. However, it is advised to support your body as a whole, preventing the occurrence of provoking pathologies:

• move actively;
• eat right, do not overeat;
• lead the right way of life;
• avoid mental trauma;
• avoid constant physical and emotional overload;
• do not use drugs that help lower blood sugar, unless advised by a doctor.

If, nevertheless, it is not possible to avoid such a pathology, especially when it comes to newborns, those suffering from this disease should immediately go to the hospital. Follow all the requirements and recommendations of specialists, agreeing to the proposed methods of treatment. Only in this way, the treatment of hyperinsulinism will be effective and henceforth it will be possible to avoid relapses. It must be remembered that, according to statistics, 10% of such patients die due to untimely seeking professional help, neglect of the pathology, and refusals in treatment.

Hyperinsulinemia in children

HYPERINSULINISM (Greek, hyper- + insulin) is a clinical syndrome manifested by symptoms of hypoglycemia of varying severity, due to increased secretion of insulin. With increased resistance to insulin G. can proceed without a wedge, manifestations of hypoglycemia (see).

Etiology

G. observed with insulin-producing tumors emanating from the beta cells of the pancreatic islets of Langerhans (see Insuloma), spontaneous idiopathic hypoglycemia in children, in initial stages diabetes mellitus (including functional reactive hypoglycemia), obesity, dumping syndrome, a number of endocrine diseases(acromegaly, thyrotoxicosis, Itsenko-Cushing's disease) or may occur under the influence of various alimentary stimuli.

Pathogenesis

G. with functional reactive hypoglycemia of neurogenic origin occurs due to an excessive reaction of beta cells of the pancreatic islets to a normal carbohydrate load and develops 1.5 to 4 hours after a meal; an increase in the content of immunoreactive insulin in the blood (hyperinsulinemia) is observed after 0.5-1 hour, i.e., at the same time as in healthy people, but its absolute value is much greater than in healthy people. In the test with a glucose load: the blood sugar level increases within normal values, but after 11/2-4 hours hypoglycemia develops, followed by an independent restoration of normal blood sugar levels.

G. in the initial stages of diabetes mellitus (see Diabetes mellitus) is associated with an increase in insulin secretion during carbohydrate loads. When these patients are tested for glucose tolerance, a late maximum rise in immunoreactive insulin and subsequent longer insulinemia at a higher level compared to healthy ones are noted. The content of sugar in the blood on an empty stomach is normal or slightly increased, but after taking glucose it remains elevated for 2-2.5 hours, and by the third hour it decreases to a hypoglycemic level.

With dumping syndrome in patients who have undergone gastric resection, G.'s development is associated with the rapid absorption of glucose when it enters the intestines and blood. Adequately, insulin secretion increases, and hypoglycemia occurs 1-2 hours after eating.

Pathogenesis

The pathogenesis of G. with increased idiopathic sensitivity to leucine, more often observed in children, is not clear. It is believed that in response to the intake of leucine (with food), insulin begins to be released excessively. G. with spontaneous idiopathic hypoglycemia in children is more often associated with hypertrophy and hyperplasia of beta cells of pancreatic islets, which often accompanies hereditary forms of diabetes mellitus.

Clinical picture

The clinical picture is characterized by hypoglycemic conditions, manifested by weakness, increased appetite and sweating, tachycardia, irritability, in severe cases - the appearance of convulsions, diplopia, mental disorders (inappropriate behavior, incorrect assessment of the environment, etc.), loss of consciousness.

However, with G.'s forms that are not associated with insulinoma, hypoglycemic conditions are not severe and are accompanied by symptoms of increased activity of the sympathetic nervous system.

Diagnosis

If G. is suspected, it is necessary to examine the blood for sugar content. Repeated studies are required on an empty stomach, as well as during an attack of hypoglycemia. Functional reactive hypoglycemia develops mainly during the day, after eating a meal with a high content of carbohydrates. The content of sugar in the blood rarely drops below 50 mg%, patients usually do not lose consciousness. The content of immunoreactive insulin in fasting blood is often increased.

Important in G.'s diagnosis is a functional test with fasting for 18-24 hours, counting from the last evening meal, and a test with the appointment of a low-calorie diet rich in proteins, but with a sharp restriction of carbohydrates and fats, for 72 hours. When conducting such a test, the patient receives 200 g of meat, 200 g of cottage cheese, 30 g of butter, 50 g of bread, 500 g of vegetables (except potatoes and legumes). Blood is tested daily for fasting sugar and throughout the day. In patients with G., the blood sugar content usually decreases to 50 mg% and below.

Tests for tolerance to glucose and insulin in patients with G. can give different results, so they have no diagnostic value.

Carry out tests for sensitivity to tolbutamide and leucine. After intravenous administration of 1 g of tolbutamide or leucine (200 mg per 1 kg of body weight, per os), an increase in immunoreactive insulin and a decrease in sugar are found in the blood of patients with G..

Treatment

Treatment should be aimed at eliminating and preventing hypoglycemia. Frequent meals with a complete protein content in food and an even distribution of carbohydrates throughout the day are recommended.

At G. connected with hypersensitivity to a leucine, it is necessary to limit consumption of the products containing a leucine (dairy products). Patients with spontaneous hypoglycemia are recommended frequent meals, and in severe cases, glucocorticoid preparations, sometimes ACTH, glucagon, adrenaline, are prescribed.

At benign tumors of the pancreas, patients produce an incomplete resection of the gland, with malignant tumors - extended pancreatectomy (see).

Hyperinsulinism in children

Hyperinsulinism in children, as in adults, is manifested by hypoglycemic conditions of varying severity. However, hypoglycemic conditions in children appear at a lower blood glucose level than in adults. With frequent repeated hypoglycemic conditions in children, the psyche is disturbed faster than in adults (true disorders due to severe hypoglycemia with an irreversible course and false ones that disappear under the influence of treatment).

The mechanism of functional G.'s development in children born to women with diabetes mellitus is not clear. It is believed that G. of the fetus is a compensatory response to maternal hyperglycemia; 60-80% of children born to women with diabetes mellitus are found to have G. In such children, hyperplasia of pancreatic cells is noted. After birth, glucose levels drop rapidly, and the newborn may become hypoglycemic within 1–2 hours. Low glucose and free fatty to-t in the blood - a consequence of the inhibitory effect of insulin on lipolysis. These children are overweight, which is associated with the anabolic action of insulin. In women with diabetes mellitus detected during pregnancy, serum insulin activity is increased, in newborns from mothers with diabetes mellitus, the insulin response to glucose administration is more pronounced than in children born to healthy women.

G.'s pathognomonic symptoms are absent in newborns. Seizures, cyanosis, respiratory arrest, and lethargy may occur in children with intracranial trauma, sepsis, pulmonary disease, hypocalcemia, and other metabolic disorders. G.'s diagnosis is established by the content of sugar in the blood (20 mg% or less in a child with normal birth weight).

G., arising under the influence of alimentary irritants, must be differentiated from congenital intolerance to fructose, with a cut hypoglycemia is not associated with G. This rare disease is characteristic of childhood and is manifested by the development of severe hypoglycemic conditions and vomiting after taking products containing fructose. It is due congenital insufficiency fructose-1-phosphate-aldolase, leading to the accumulation of fructose-1-phosphate in the liver. The exclusion from the diet of foods containing fructose eliminates hypoglycemia. At children with a severe form of an erythroblastosis functional G. can also develop; its reason is not clear. G. develops in children with constitutional exogenous obesity. The coefficient of insulin secretion in these patients is increased. The study of immunoreactive insulin can to some extent characterize the functional state of the insular apparatus of a sick child: the more pronounced obesity, the higher the content of immunoreactive insulin in the blood.

In obese children with diabetes, early stages its development, the content of insulin in the blood on an empty stomach is higher than in healthy children and in obese children without diabetes, sometimes more than 3 times.

The coefficient of insulin secretion in these patients is reduced compared to healthy ones, which indicates relative G.

G.'s treatment at children depends on its form. For benign tumors of the pancreas, an incomplete resection is performed, and for malignant tumors, an extended pancreatectomy is performed. With congenital intolerance to fructose - the exclusion from food of foods containing it. With G. in children associated with others diseases, treatment underlying disease.

Bibliography: Nikolaev O. V. and Weinberg E. G. Insuloma, M., 1968, bibliogr.; Guide to endocrinology, ed. B. V. Aleshina et al., M., 1973; Hardy J. D. Islet cell tumors, Amer. J. med. Sc., v. 246, p. 218, 1963; Howard J. M., Moss N. H. a. Rhoads J. E. Collective review, hyperinsulinism and islet cell tumors of pancreas with 398 recorded tumors, Int. Abstr. Surg., v. 90, p. 417, 1950; Koutras P. a. White R. R. Insulin-secreting tumors of the pancreas, Surg. Clin. N. Amer., v. 52, p. 299, 1972; Labhart A. Clinic der inneren Sekretion, B. u. a., 1971; RosenbloomA. L. a. Sherman L. The natural history of idiopathic hypoglycemia of infancy and its relation to diabetes mellitus, New Engl. J. Med., v. 274, p. 815, 1966; Textbook of endocrinology, ed. by R. H. Williams, Philadelphia, 1974.

hyperinsulinism

Hyperinsulinism is a clinical syndrome characterized by an increase in insulin levels and a decrease in blood sugar. Hypoglycemia leads to weakness, dizziness, increased appetite, tremor, psychomotor agitation. In the absence of timely treatment, hypoglycemic coma develops. Diagnosis of the causes of the condition is based on the features of the clinical picture, functional test data, dynamic glucose testing, ultrasound or tomographic scanning of the pancreas. Treatment of pancreatic neoplasms is surgical. With an extrapancreatic variant of the syndrome, the underlying disease is treated, a special diet is prescribed.

hyperinsulinism

Hyperinsulinism (hypoglycemic disease) is a congenital or acquired pathological condition in which absolute or relative endogenous hyperinsulinemia develops. The signs of the disease were first described at the beginning of the twentieth century by the American physician Harris and the domestic surgeon Oppel. Congenital hyperinsulinism is quite rare - 1 case per 50 thousand newborns. The acquired form of the disease develops with age and more often affects females. Hypoglycemic disease occurs with periods of absence of severe symptoms (remission) and with periods of a detailed clinical picture (attacks of hypoglycemia).

Causes of hyperinsulinism

Congenital pathology occurs due to intrauterine developmental anomalies, fetal growth retardation, mutations in the genome. The causes of acquired hypoglycemic disease are divided into pancreatic, leading to the development of absolute hyperinsulinemia, and non-pancreatic, causing a relative increase in insulin levels. The pancreatic form of the disease occurs with malignant or benign neoplasms, as well as hyperplasia of beta-cells of the pancreas. The non-pancreatic form develops under the following conditions:

• Eating disorders. Prolonged fasting, increased loss of fluid and glucose (diarrhea, vomiting, lactation), intense physical activity without the consumption of carbohydrate foods cause a sharp decrease in blood sugar levels. Excessive consumption of refined carbohydrates increases blood sugar levels, which stimulates the active production of insulin.
• Liver damage of various etiologies (cancer, fatty hepatosis, cirrhosis) leads to a decrease in glycogen levels, metabolic disorders and hypoglycemia.
• Uncontrolled intake of hypoglycemic drugs for diabetes mellitus (insulin derivatives, sulfonylurea) causes drug-induced hypoglycemia.
• Endocrine diseases leading to a decrease in the level of counter-insulin hormones (ACTH, cortisol): pituitary dwarfism, myxedema, Addison's disease.
• The lack of enzymes involved in the processes of glucose metabolism (hepatic phosphorylase, renal insulinase, glucose-6-phosphatase) causes relative hyperinsulinism.

Pathogenesis

Glucose is the main nutrient substrate of the central nervous system and is necessary for the normal functioning of the brain. Elevated insulin levels, accumulation of glycogen in the liver and inhibition of glycogenolysis lead to a decrease in blood glucose levels. Hypoglycemia causes inhibition of metabolic and energy processes in brain cells. There is a stimulation of the sympathoadrenal system, the production of catecholamines increases, an attack of hyperinsulinism develops (tachycardia, irritability, a sense of fear). Violation of redox processes in the body leads to a decrease in oxygen consumption by the cells of the cerebral cortex and the development of hypoxia (drowsiness, lethargy, apathy). Further glucose deficiency causes a violation of all metabolic processes in the body, an increase in blood flow to the brain structures and a spasm of peripheral vessels, which can lead to a heart attack. When involved in the pathological process of the ancient structures of the brain (medulla oblongata and midbrain, pons varolii) develop convulsive states, diplopia, as well as impaired respiratory and cardiac activity.

Classification

In clinical endocrinology, the classification of hyperinsulinemia is most often used depending on the causes of the disease:

1. Primary hyperinsulinism (pancreatic, organic, absolute) is the result of a tumor process or hyperplasia of beta cells of the pancreatic islet apparatus. An increase in insulin levels in 90% is facilitated by benign neoplasms (insulinoma), less often by malignant ones (carcinoma). Organic hyperinsulinemia occurs in a severe form with a pronounced clinical picture and frequent bouts of hypoglycemia. A sharp drop in blood sugar occurs in the morning, associated with skipping meals. This form of the disease is characterized by the Whipple triad: symptoms of hypoglycemia, a sharp decrease in blood sugar and relief of attacks by the introduction of glucose.
2. Secondary hyperinsulinism (functional, relative, extrapancreatic) is associated with a deficiency of contra-insular hormones, damage to the nervous system and liver. An attack of hypoglycemia occurs for external reasons: starvation, an overdose of hypoglycemic drugs, intense physical activity, psycho-emotional shock. Exacerbations of the disease occur irregularly, are practically not associated with food intake. Daily fasting does not cause extensive symptoms.

Symptoms of hyperinsulinism

The clinical picture of hypoglycemic disease is due to a decrease in blood glucose levels. The development of an attack begins with an increase in appetite, sweating, weakness, tachycardia and a feeling of hunger. Later, panic states join: a feeling of fear, anxiety, irritability, trembling in the limbs. With the further development of the attack, there is disorientation in space, diplopia, paresthesia (numbness, tingling) in the limbs, up to the occurrence of convulsions. If left untreated, loss of consciousness and hypoglycemic coma occur. The interictal period is manifested by a decrease in memory, emotional lability, apathy, impaired sensitivity and numbness in the extremities. Frequent intake of food rich in easily digestible carbohydrates provokes an increase in body weight and the development of obesity.

In modern practice, there are 3 degrees of hyperinsulinism depending on the severity of the course of the disease: mild, moderate and severe. Light degree manifested by the absence of symptoms of the interictal period and organic lesions of the cerebral cortex. Exacerbations of the disease appear less than 1 time per month and are quickly stopped by medications or sweet foods. With moderate severity, attacks occur more often than once a month, loss of consciousness and the development of a coma are possible. The interictal period is characterized by mild behavioral disorders (forgetfulness, decreased thinking). A severe degree develops with irreversible changes in the cerebral cortex. In this case, seizures occur frequently and end in loss of consciousness. In the interictal period, the patient is disoriented, memory is sharply reduced, there is a tremor of the limbs, a sharp change in mood and increased irritability are characteristic.

Complications of hyperinsulinism

Complications can be conditionally divided into early and late. Early complications that occur in the next few hours after an attack include stroke, myocardial infarction due to a sharp decrease in the metabolism of the heart muscle and brain. In severe situations, hypoglycemic coma develops. Late complications appear several months or years after the onset of the disease and are characterized by impaired memory and speech, parkinsonism, and encephalopathy. The lack of timely diagnosis and treatment of the disease leads to the depletion of the endocrine function of the pancreas and the development of diabetes mellitus, metabolic syndrome, and obesity. Congenital hyperinsulinism in 30% of cases leads to chronic hypoxia of the brain and a decrease in the full mental development of the child.

Diagnosis of hyperinsulinism

Diagnosis is based on the clinical picture (loss of consciousness, tremor, psychomotor agitation), data on the anamnesis of the disease (time of onset of the attack, its connection with food intake). The endocrinologist clarifies the presence of concomitant and hereditary diseases (fatty hepatosis, diabetes mellitus, Itsenko-Cushing's syndrome), after which he prescribes laboratory and instrumental studies. The patient undergoes a daily measurement of blood glucose levels (glycemic profile). If deviations are detected, functional tests are performed. The fasting test is used for the differential diagnosis of primary and secondary hyperinsulinism. During the test, C-peptide, immunoreactive insulin (IRI), and blood glucose are measured. An increase in these indicators indicates the organic nature of the disease.

To confirm the pancreatic etiology of the disease, tests for sensitivity to tolbutamide and leucine are performed. At positive results functional tests are indicated by ultrasound, scintigraphy and MRI of the pancreas. In secondary hyperinsulinism, to exclude neoplasms of other organs, ultrasound of the abdominal cavity, MRI of the brain are performed. Differential diagnosis of hypoglycemic disease is carried out with Zollinger-Ellison syndrome, the onset of type 2 diabetes mellitus, neurological (epilepsy, brain neoplasms) and mental (neurosis-like states, psychosis) diseases.

Treatment of hyperinsulinism

Treatment tactics depend on the cause of hyperinsulinemia. With organic genesis, surgical treatment is indicated: partial resection of the pancreas or total pancreatectomy, enucleation of the neoplasm. Volume surgical intervention determined by the location and size of the tumor. After surgery, transient hyperglycemia is usually noted, requiring medical correction and low carbohydrate diets. Normalization of indicators occurs a month after the intervention. With inoperable tumors, palliative therapy is carried out, aimed at preventing hypoglycemia. In malignant neoplasms, chemotherapy is additionally indicated.

Functional hyperinsulinism primarily requires treatment of the underlying disease that caused increased insulin production. All patients are prescribed a balanced diet with a moderate decrease in carbohydrate intake (g per day). Preference is given to complex carbohydrates (rye bread, durum wheat pasta, whole grains, nuts). Food should be fractional, 5-6 times a day. Due to the fact that periodic attacks cause the development of panic conditions in patients, a consultation with a psychologist is recommended. With the development of a hypoglycemic attack, the use of easily digestible carbohydrates (sweet tea, candy, white bread) is indicated. In the absence of consciousness, intravenous administration of a 40% glucose solution is necessary. With convulsions and severe psychomotor agitation, injections of tranquilizers and sedatives are indicated. Treatment of severe attacks of hyperinsulinism with the development of coma is carried out in the intensive care unit with detoxification infusion therapy, the introduction of glucocorticoids and adrenaline.

Forecast and prevention

Prevention of hypoglycemic disease includes a balanced diet with an interval of 2-3 hours, drinking enough drinking water, giving up bad habits, and controlling glucose levels. To maintain and improve metabolic processes in the body, moderate physical activity is recommended in compliance with the diet. The prognosis for hyperinsulinism depends on the stage of the disease and the causes of insulinemia. Removal of benign neoplasms in 90% of cases provides recovery. Inoperable and malignant tumors cause irreversible neurological changes and require constant monitoring of the patient's condition. Treatment of the underlying disease in the functional nature of hyperinsulinemia leads to regression of symptoms and subsequent recovery.

What is hyperinsulinemia and why is it dangerous?

Many diseases that occur in a chronic form often precede the onset of diabetes mellitus.

For example, hyperinsulinemia in children and adults is detected in rare cases, but indicates excessive production of a hormone that can provoke a decrease in sugar levels, oxygen starvation and dysfunction of all internal systems. The lack of therapeutic measures aimed at suppressing the production of insulin can lead to the development of uncontrolled diabetes.

Causes of pathology

Hyperinsulinism in medical terminology is considered a clinical syndrome, the occurrence of which occurs against the background of an excessive increase in insulin levels.

In this state, a drop in the value of glucose contained in the blood is observed in the body. A lack of sugar can provoke oxygen starvation of the brain, which can result in impaired functioning of the parts of the nervous system.

Hyperinsulism in some cases proceeds without special clinical manifestations, but most often the disease leads to severe intoxication.

1. congenital hyperinsulinism. It is based on a genetic predisposition. The disease develops against the background of pathological processes occurring in the pancreas that prevent the normal production of hormones.
2. Secondary hyperinsulinism. This form progresses due to other diseases that have caused excessive secretion of the hormone. Functional hyperinsulinism has manifestations that are combined with disorders in carbohydrate metabolism and are identified with a sudden increase in the concentration of glycemia in the bloodstream.

The main factors that can cause an increase in the level of the hormone:

• production by cells of the pancreas of unsuitable insulin with a different composition from the norm, which is not perceived by the body;
• violation of resistance, resulting in uncontrolled production of the hormone;
• deviations in the transport of glucose through the bloodstream;
• overweight;
• atherosclerosis;
• hereditary predisposition;
• anorexia, which is neurogenic in nature and associated with an obsessive thought about excess body weight;
• oncological processes in the abdominal cavity;
• unbalanced and untimely nutrition;
• abuse of sweets, leading to an increase in glycemia, and, consequently, increased secretion of the hormone;
• liver pathology;
• uncontrolled insulin therapy or excessive use of drugs to lower the concentration of glucose, which leads to the appearance of drug-induced hypoglycemia;
• endocrine pathologies;
• insufficient amount of enzyme substances involved in metabolic processes.

The causes of hyperinsulinism may not manifest themselves for a long time, but at the same time they have a detrimental effect on the work of the whole organism.

At-risk groups

The following groups of people most often develop hyperinsulinemia:

• women who have polycystic ovaries;
• people who have a genetic inheritance for this disease;
• patients with disorders in the functioning of the nervous system;
• women who are on the eve of menopause;
• aged people;
• patients leading an inactive lifestyle;
• women and men receiving hormone therapy or drugs from the beta-blocker group.

Symptoms of hyperinsulinism

The disease contributes to a sharp weight gain, so most diets are ineffective. Fat deposits in women are formed in the waist area, as well as the abdominal cavity. This is caused by a large depot of insulin stored in the form of a specific fat (triglyceride).

Manifestations of hyperinsulinism are in many ways similar to those that develop against the background of hypoglycemia. The onset of an attack is characterized by increased appetite, weakness, sweating, tachycardia, and a feeling of hunger.

Subsequently, a panic state joins, in which the presence of fear, anxiety, trembling in the limbs and irritability is noted. Then there is disorientation in the area, numbness in the limbs, and seizures may occur. Left untreated, it can lead to loss of consciousness and coma.

1. Light. It is characterized by the absence of any signs in the periods between attacks, but at the same time continues to organically affect the cerebral cortex. The patient notes the deterioration of the condition at least 1 time during the calendar month. To stop the attack, it is enough to use the appropriate medications or eat sweet food.
2. Average. The frequency of occurrence of seizures is several times a month. The person may lose consciousness at this point or fall into a coma.
3. Heavy. This degree of disease is accompanied by irreversible brain damage. Seizures often occur and almost always lead to loss of consciousness.

The manifestations of hyperinsulism are practically the same in children and adults. A feature of the course of the disease in young patients is the development of seizures against the background of lower glycemia, as well as a high frequency of their recurrence. The result of constant exacerbations and regular relief of this condition with drugs is a violation of mental health in children.

Why is the disease dangerous?

Any pathology can lead to complications if no action is taken in a timely manner. Hyperinsulinemia is no exception, therefore it is also accompanied by dangerous consequences. The disease occurs in acute and chronic forms. Passive flow leads to blunting of brain activity, negatively affects the psychosomatic state.

• violations in the functioning of systems and internal organs;
• development of diabetes;
• obesity;
• coma;
• deviations in the work of the cardiovascular system;
• encephalopathy;
• parkinsonism

Hyperinsulinemia that occurs in childhood adversely affects the development of the child.

Diagnostics

It is often difficult to identify the disease due to the lack of specific symptoms.

If a deterioration in well-being is detected, a doctor's consultation is required, who can determine the source of this condition using the following diagnostic tests:

• analysis for hormones produced by the pituitary gland and pancreas;
• MRI of the pituitary gland to exclude oncology;
• abdominal ultrasound;
• pressure measurement;
• checking the level of glycemia.

The diagnosis is made on the basis of an analysis of the results of the examination and the patient's complaints.

Treatment of the disease

Therapy depends on the characteristics of the course of the disease, therefore it differs during periods of exacerbation and remission. To stop the attacks, the use of drugs is required, and the rest of the time it is enough to follow a diet and treat the underlying pathology (diabetes).

Help with exacerbation:

• eat carbohydrate or drink sweet water, tea;
• inject a glucose solution in a jet to stabilize the condition (maximum amount - 100 ml / 1 time);
• when coma occurs, intravenous glucose should be performed;
• in the absence of improvement, an injection of adrenaline or glucagon should be given;
• apply tranquilizers for convulsions.

Patients in serious condition should be taken to a hospital and treated under the supervision of doctors. With organic damage to the gland, resection of the organ and surgical intervention may be required.

The diet for hyperinsulinemia is selected taking into account the severity of the course of the disease. Frequent and difficult to manage seizures require the presence of an increased amount of carbohydrates in the daily diet (up to 450 g). At the same time, the consumption of fats and protein foods should be maintained within the normal range.

In the normal course of the disease, the maximum amount of carbohydrates received with food per day should not exceed 150 g. Sweets, confectionery, alcohol should be excluded from the diet.

Video from an expert:

To reduce the manifestations of hyperinsulinemia, it is important to constantly control the course of diabetes and follow the main recommendations:

• eat fractionally and balanced;
• constantly check the level of glycemia, adjust it if necessary;
• observe the required drinking regimen;
• lead a healthy and active lifestyle.

If the excessive production of insulin was the result of a specific disease, then the main prevention of the development of seizures is reduced to the treatment of the pathology, which acts as the main cause of their occurrence.

Absolute increase in blood insulin levels, or hyperinsulinism: symptoms, diagnosis and treatment

Hyperinsulinism is a disease that occurs in the form of hypoglycemia, which is an excess of the norm or an absolute increase in the level of insulin in the blood.

An excess of this hormone causes a very strong increase in sugar content, which leads to a deficiency of glucose, and also causes oxygen starvation of the brain, which leads to impaired nervous activity.

Occurrence and symptoms

This disease occurs more often in women and occurs between the ages of 26 and 55 years. Attacks of hypoglycemia, as a rule, manifest themselves in the morning after a fairly long fast. The disease can be functional and it manifests itself at the same time of day, however, after taking carbohydrates.

Not only prolonged fasting can provoke hyperinsulinism. Another important factor in the manifestation of the disease may well be various physical activities and mental experiences. In women, repeated symptoms of the disease may occur only in the premenstrual period.

Hyperinsulinism symptoms are as follows:

• continuous feeling of hunger;
• increased sweating;
• general weakness;
• tachycardia;
• pallor;
• paresthesia;
• diplopia;
• inexplicable feeling of fear;
• mental arousal;
• tremor of the hands and trembling of the limbs;
• unmotivated actions;
• dysarthria.

However, these symptoms are initial, and if they are not treated and continue to ignore the disease further, then the consequences may be more severe.

Absolute hyperinsulinism is manifested by the following symptoms:

• sudden loss of consciousness;
• coma with hypothermia;
• coma with hyporeflexia;
• tonic convulsions;
• clinical seizures.

Such attacks usually appear after a sudden loss of consciousness.

Before the onset of an attack, the following symptoms appear:

• decreased memory efficiency;
• emotional instability;
• complete indifference to others;
• loss of habitual professional skills;
• paresthesia;
• symptoms of pyramidal insufficiency;
• pathological reflexes.

Causes

The causes of hyperinsulinism in adults and children are divided into two forms of the disease:

• pancreatic. This form of the disease develops absolute hyperinsulinemia. It occurs in both malignant and benign neoplasms, as well as hyperplasia of pancreatic beta cells;
• non-pancreatic. This form of the disease causes elevated level insulin.

The non-pancreatic form of the disease develops under such conditions:

• endocrine diseases. They lead to a decrease in counter-insulin hormones;
• liver damage of various etiologies. Liver diseases lead to a decrease in glycogen levels, as well as disrupt metabolic processes and accompanies the development of hypoglycemia;
• lack of enzymes that are directly involved in the processes responsible for glucose metabolism. Leads to relative hyperinsulinism;
• uncontrolled intake of drugs aimed at lowering sugar levels in diabetes mellitus. May cause drug-induced hypoglycemia;
• eating disorders. This condition includes: a prolonged period of fasting, increased loss of fluid and glucose (due to vomiting, lactation, diarrhea), increased physical activity without eating carbohydrate foods, which causes a rapid decrease in blood sugar levels, eating a sufficiently large amount of refined carbohydrates which significantly increases blood sugar levels.

Pathogenesis

Glucose is perhaps the most important nutrient substrate of the human central nervous system and ensures the normal functioning of the brain.

Hypoglycemia can cause inhibition of metabolic and energy processes.

Due to the violation of the redox process in the body, there is a decrease in oxygen consumption by the cells of the cerebral cortex, due to which hypoxia develops.

Hypoxia of the brain manifested as: increased drowsiness, apathy and inhibition. In the future, due to a lack of glucose, a violation of all metabolic processes in the human body occurs, as well as a significant increase in blood flow to the brain, a spasm of peripheral vessels occurs, which often causes a heart attack.

Disease classification

Complications

Early ones occur after a short period of time after an attack, they include:

This happens due to a very sharp decrease in the metabolism of the heart muscle and human brain. A severe case can provoke the development of hypoglycemic coma.

Late complications begin to appear after a sufficiently long period of time. Usually after a few months, or after two or three years. Characteristic features late complications are parkinsonism, encephalopathy, impaired memory and speech.

Hyperinsulinism: treatment and prevention

Depending on the causes that led to the appearance of hyperinsulinemia, the tactics of treating the disease are determined. So, in the case of organic genesis, surgical therapy is prescribed.

It consists in enucleation of the neoplasm, partial resection of the pancreas, or total pancreatectomy.

As a rule, after surgery, the patient has transient hyperglycemia, therefore, subsequent drug treatment and a low-carbohydrate diet are carried out. Normalization occurs a month after the operation.

In cases of inoperable tumors, palliative therapy is prescribed, which is aimed at preventing hypoglycemia. If the patient has malignant neoplasms, then he additionally needs chemotherapy.

If the patient has functional hyperinsulinism, then the initial treatment is directed at the disease that caused it.

In severe attacks of the disease with the subsequent development of coma, therapy is carried out in intensive care units, detoxification is carried out infusion therapy administered adrenaline and glucocorticoids. In cases of convulsions and psychomotor overexcitation, sedatives and injections of tranquilizers are indicated.

Related videos

What is hyperinsulinism and how to get rid of a constant feeling of hunger, you can also find out in this video:

We can say about hyperinsulinism that this is a disease that can lead to severe complications. It occurs in the form of hypoglycemia. In fact, this disease is the exact opposite of diabetes mellitus, because with it there is a weak production of insulin or its complete absence, and with hyperinsulinism - increased or absolute. Basically, this diagnosis is made to the female part of the population.

• Eliminates the causes of pressure violations
• Normalizes blood pressure within 10 minutes after taking

Hyperinsulinemia is a pathological phenomenon, which is essentially an increase in the amount of insulin in the blood. The reasons may be associated with various disorders occurring in the body, but the result is the same - a jump in the peptide hormone that the pancreas produces. What is known about hyperinsulinemia and how can it be avoided?

Why does the disease develop?

Experts identify the following reasons that lead to the occurrence of pathology:

• the pancreas begins to produce an excessive amount of insulin;
• the sensitivity of insulin receptors decreases - insulin resistance occurs;
• the process of transfer of glucose molecules is disturbed;
• there are failures in the transmission of signals in cell system(Certain receptors don't work, so there's no way for glucose to enter the cells.)

In addition, there are a number of factors predisposing to hyperinsulinemia.

The risks are increased in the following patients:

• having a hereditary predisposition and having relatives suffering from diabetes mellitus;
• in case of violation of the center of regulation of such feelings as hunger and satiety;
• more commonly diagnosed in women, especially those with hormonal disorders if diagnosed with polycystic ovary syndrome, as well as with gestational diabetes;
• in people who are not physically active;
• in the presence of addictions;
• in the elderly;
• against the background of obesity - excessive adipose tissue leads to the fact that the receptors lose their susceptibility to the action of insulin, and its synthesis decreases;
• in patients suffering from atherosclerosis;
• during menopause;
• at arterial hypertension;
• against the backdrop of treatment hormonal drugs, thiazide diuretics, beta-blockers.

Exposure to harmful substances also negatively affects the functioning of the endocrine system.

Such phenomena negatively affect the transmission of signals to cells. A sharp increase in insulin can lead to the development of diabetes, obesity, hypoglycemic coma. In addition, there are risks of violations in the work of the cardiovascular system.

How does the disease manifest itself?

There are no symptoms during the initial development of the disease, but after that there are clear signs of a pathological disorder:

• the appearance of fatty deposits in the abdomen and upper body;
• bouts of hypertension;
• feeling of thirst;
• pain in muscle tissues;
• dizziness;
• impaired concentration;
• trembling and chills.

With hyperinsulinemia, a person becomes weak, lethargic, gets tired quickly

If the increase in insulin is due to genetic syndrome or a rare disease, then other symptoms appear:

• vision is impaired;
• the skin becomes dark, dryness occurs;
• noticeable stretch marks form on the skin of the abdomen and thighs;
• the patient is concerned about difficult defecation;
• worries about pain in the bones.

Hyperinsulinemia is a serious condition that requires mandatory medical consultation.

Features of diagnosing the disease

High levels of insulin in the blood affect various body systems and are associated with various diseases Therefore, a comprehensive diagnosis is recommended.

Table number 1. Diagnostic measures to detect hyperinsulinemia

Analysis or survey	Research area and features
Analysis for the detection of certain hormones	Specialists are interested in the level: insulin; cortisol (hormone "stress"); TSH (thyrotropic prolactin); ACTH (adrenocorticotropic hormone); aldosterone (steroid hormone of the adrenal cortex); renin (angiotensinogenase).
Blood pressure measurement	Daily monitoring is prescribed - a special registrar equipped with a sensor is attached to the patient's body, which records the appearance and disappearance of pulse waves.
Computing features of the constitution	The specialist determines the body mass index (the ratio of weight and height), The ratio of the circumferences of the waist and hips is also taken into account.
General urine analysis	Determines microalbuminuria - the presence in the urine of a small amount of protein, which normally should not be here.
Ultrasonography	The pancreas, liver, kidneys are examined.
Biochemistry of blood	Specialists are interested in the level of total cholesterol, triglycerides, low and high density lipoproteins. The analysis also reveals the amount of glucose on an empty stomach and after a meal.
CT (cardiotocography); MRI (magnetic resonance imaging)	The pituitary gland and the adrenal cortex are examined. Diagnostics is prescribed to exclude the presence of hypercortisolism syndrome (Itsenko-Cushing's disease).

How is the disease treated?

In general, as with diabetes, in the first place in the treatment of this disease is a diet aimed at getting rid of extra pounds - not for the sake of beauty, but more for health.

The basis of nutrition is to reduce the caloric content of food consumed

When compiling a diet, several factors are taken into account:

• what type of work the patient is engaged in (mental or physical labor);
• does or does not play sports;
• weight at the time of contacting a specialist, etc.

Make food intake fractional - eat 4-6 times a day in small portions.

With insufficient physical activity they should be increased, this will make the treatment more effective. However, there are some nuances here - a statistical power load can adversely affect the patient's condition and cause a hypertensive crisis. Therefore, with hyperinsulinemia, it is better to choose other activities.

For people suffering from sudden increases in blood glucose, yoga, Pilates, swimming, aerobics, water aerobics, etc. are more suitable.

Correction of nutrition and properly selected workouts, which are based on a gradual increase in load, are the key to improving the patient's condition.

In addition, treatment may also include taking medications.

Table number 2. Drugs prescribed for hyperinsulinemia and their action

Type of drugs	Action
Hypoglycemic drugs: biguanides, thiazolidines	Medicines that lower blood sugar levels.
Drugs with antihypertensive action	They are prescribed to normalize blood pressure, and, thanks to their intake, it is possible to avoid the development of heart attacks and strokes.
ACE inhibitors	They are used to treat arterial hypertension - they reduce both systolic and diastolic pressure.
Beds and fibrates	Means that effectively reduce cholesterol levels.
Serotonin reuptake inhibitors	Medicines that reduce appetite.
Preparations containing alpha-lioic acid	They increase the utilization of excess glucose and remove excess cholesterol from the body.

Preventive measures

Hyperinsulinemia is one of those diseases that, in most cases, can be prevented by following simple rules:

• do not eat excessively fatty and sweet foods;
• include more green vegetables and fruits in the diet;
• provide yourself with sufficient loads - at least walk daily for half an hour;
• give up bad habits that negatively affect your health.

This disease is a high risk factor for the development of more serious diseases and conditions - diabetes mellitus, strokes, heart attacks. Therefore, it is desirable to identify the disease as early as possible and treat it in a timely manner.