Modi diabetes symptoms. Hereditary forms of diabetes mellitus (diabetes mellitus type MODY)

14.07.2020

What is MODY diabetes?

MODY diabetes (Maturity Onset Diabetes of the Young) is a group of diseases that are caused by mutations in one of the genes involved in glucose regulation. For the first time such a term was introduced in 1974 by American scientists to define an atypical, mildly progressive form of diabetes mellitus in young patients with a hereditary predisposition.

MODY diabetes is more often familial in nature, when similar disorders of carbohydrate metabolism are also noted in one of the parents and relatives of the 2nd and 3rd degrees of relationship (grandmothers, grandfathers, etc.).

There are currently 14 known MODY types, the most common of which are MODY 1 (HNF4A / MODY), MODY 2 (GCK / MODY) and MODY 3 (HNF1A / MODY). MODY is diagnosed in 2-5% of cases of the total number of people with different types of diabetes. Diagnosis of different types of MODY based on clinical presentation alone is not possible!

How to suspect MODY?

early onset before 25-35 years; for MODY 2 (GCK / MODY), an increase in blood sugar can be noted from birth)
more often the absence of excess body weight (BMI less than 25 kg / m2).

IMPORTANT:in some MODY subtypes, obesity is a provoking factor against which blood sugar can rise.

there are no classic symptoms of diabetes mellitus (thirst, frequent urination, weight loss, increased appetite) and ketosis at the onset of the disease
negative titer of autoantibodies (GADA, IA-2A, ICA, IIA, ZnT8) at the onset of the disease
no need for insulin, low need for insulin (less than 0.5 U / kg) more than 3-5 years from the onset of the disease
preserved secretion of C-peptide for more than 3-5 years from the onset of the disease
hbA1c level is stable and rarely exceeds 7.5%
non-progressive course or achievement of compensation of the disease against the background of low doses of insulin and the absence of strict self-control of the disease
absence of vascular complications in case of MODY 2 (GCK / MODY). The other types of MODY are characterized by the development of vascular complications and the development of insulin demand.

What tests need to be done in case of a non-standard (for type 1 diabetes) course of diabetes mellitus?

urinalysis to determine the level of glucose in urine (measure blood sugar at the same time)
dynamics of НвА1с for the entire observation period
C-peptide (against the background of a normal diet and a fasting period before blood sampling for no more than 10-12 hours)
autoantibody titer (GADA, IA-2A, ICA, IIA, ZnT8)
for the child's father and mother to examine blood sugar on an empty stomach, 2 hours after a carbohydrate meal (sweet porridge) + НвА1с

What should you check with your relatives?

which of the relatives has diabetes mellitus or other disorders of carbohydrate metabolism?
at what age was the disease detected, what were the height / weight, blood sugar, HbA1c at the time of diagnosis of diabetes
what therapy is used (drug, doses, duration of admission, effectiveness)
to assess the compensation of the disease (dynamics of НвА1с)
the presence of vascular complications (which, when identified, therapy)
the presence of cases of gestational diabetes mellitus and / or the birth of children with a large weight in the family
whether hypoglycemia was observed during the neonatal period in children

How is MODY diabetes diagnosed?

Molecular genetic research using the NGS method allows you to search for mutations in 28 candidate genes at once (of which 13 are MODY genes)

How to treat and monitor MODY diabetes?

therapy depends on a genetic defect (for MODY2 - diet, for MODY 1 and 3 - oral hypoglycemic drugs, with age - insulin therapy) and the preservation of insulin secretion.
the nature of the observation depends on the genetic defect and the therapy received.

IMPORTANT to understand!

MODY diabetes is an RARE disease! The decision on the advisability of carrying out a genetic study and the tactics of treating a child should be endocrinologist.

Is a group of clinically similar forms of diabetes mellitus with an autosomal dominant inheritance pathway. The disease manifests itself in childhood and adolescence. The main symptoms are frequent urge to urinate and an increase in urine volume, increased thirst and appetite, weight loss, reddening of the skin, increased body temperature. The diagnosis is complex, it includes a clinical examination, a set of laboratory tests: glucose on an empty stomach and after a meal, hormonal and genetic blood tests. The treatment program involves taking hypoglycemic drugs, nutritional correction and systematic sports.

ICD-10

E13 Other specified forms of diabetes mellitus

General information

Pathogenesis

Pathology is formed on the basis of mutations in genes that affect the functionality of cells of the islets of Langerhans, is transmitted in an autosomal dominant manner, which causes non-sex-linked inheritance and the identification of close relatives suffering from one form or another of hyperglycemia. MODY is based on mutation of only one gene. Diabetes is manifested by a decrease in the activity of pancreatic cells - a lack of insulin production.

As a result, glucose entering the bloodstream from the stomach is not absorbed by the cells of the body. A state of hyperglycemia develops. Excess sugar is excreted by the kidneys, forming glucosuria (glucose in the urine) and polyuria (increased urine volume). Due to the resulting dehydration, the feeling of thirst increases. Instead of glucose, ketone bodies become a source of energy for tissues. Their excess in plasma provokes the development of ketoacidosis - metabolic disorders with a shift in blood pH to the acidic side.

Classification

MODY diabetes is presented in several forms with genetic, metabolic and clinical heterogeneity. The classification is based on distinguishing between types of disease, taking into account the site of the mutated gene. 13 genes have been identified, changes in which provoke diabetes:

MODY-1. The factor involved in the control of glucose metabolism and distribution is damaged. Pathology is characteristic of newborns, young children.
MODY-2 A mutation in the glycolytic enzyme gene that controls glucose-mediated insulin release from glandular cells is determined. It is considered a favorable form, does not cause complications.
MODY-3. Gene mutations are manifested by progressive dysfunction of insulin-producing cells, this provokes the manifestation of the disease at a young age. The course is progressive, the condition of patients is gradually deteriorating.
MODY-4. The factor that ensures the normal development of the pancreas, the production of insulin, changes. The mutation can lead to persistent diabetes in newborns against the background of underdevelopment of the endocrine organ or to dysfunction of beta cells.
MODY-5. This factor affects embryonic development and the coding of genes in the pancreas and some other organs. Progressive nondiabetic nephropathy is characteristic.
MODY-6. Differentiation of insulin-producing cells, nerve cells of certain parts of the brain is impaired. Mutations are manifested by diabetes in children and adults, neonatal diabetes with neurological pathology.
MODY-7. The factor regulates the formation and activity of the pancreas. The disease is typical for adults, but there are 3 cases with early onset.
MODY-8. Mutations contribute to the development of atrophy, fibrosis and lipomatosis of the pancreas. Hormonal deficiency and diabetes are formed.
MODY-9. The factor is involved in the differentiation of insulin-producing cells. The course of the disease is typical with ketoacidosis.
MODY-10. Genetic changes in the factor are becoming a common cause of neonatal diabetes. Proinsulin production is impaired, programmed death of pancreatic cells is possible.
MODY-11. The factor is responsible for stimulating the synthesis and secretion of the hormone insulin. Diabetes with obesity is characteristic. An extremely rare variant of the disease.
MODY-12. It is based on a change in the sensitivity of the receptors of sulfonylurea and potassium channels of the pancreas. It manifests itself as neonatal, childhood and adult diabetes.
MODY-13. The receptor sensitivity of K + channels decreases. The clinical picture has not been studied.

Symptoms of MODY diabetes

Among all types of diabetes MODI, 50-70% of clinical cases are in MODI 3. The second most prevalent is MODI 2, and the third is MODI 1 (1%). Other variants of the disease are less common, insufficiently studied, and do not represent clinical significance. The second type of illness often manifests itself in childhood. It is asymptomatic or with mild manifestations, is extremely rarely accompanied by complications, therefore, it is diagnosed during screening examinations and during pregnancy, when the gestational form of diabetes develops.

The third type has a progressive course, in most patients it begins at the age of 20 to 40 years. The manifestations are similar to the symptoms of classic type 1 diabetes: the amount of urine increases, thirst increases, appetite increases, body weight decreases, insomnia and seizures are possible at night, hot flashes, agitation, increased blood pressure and temperature during the day.

Without treatment, symptoms progressively increase, and the risk of micro- and macrovascular complications remains high. A long "honeymoon" is characteristic - 3 years or more. This phrase denotes the period after the start of insulin therapy, when the dose of the drug initially selected by the doctor lowers the blood sugar level more than expected, and a treatment adjustment is required up to the complete withdrawal of insulin.

The clinical picture of the first type of diabetes MODI is similar to the third, but manifests itself more often in newborns and young children. Determined by macrosomia and neonatal hypoglycemia of the fetus.

Complications

With MODY type 3 diabetes, there is a gradual progressive increase in symptoms. Therapy with insulin and hypoglycemic drugs gives good results, but patients remain at risk of developing angiopathy. Damage to capillary networks in the retina leads to diabetic retinopathy (decreased vision), in the renal glomeruli - to nephropathy (impaired filtration of urine).

Atherosclerosis of large vessels is manifested by neuropathies - numbness, pain, tingling in the legs, malnutrition of the lower extremities ("diabetic foot"), malfunctioning of internal organs. In expectant mothers, diseases of the second and first types are capable of provoking fetal macrosomia.

Diagnostics

Due to the similarity of the symptoms of various forms of diabetes and the rarity of MODY, the diagnosis is quite complex, voluminous and lengthy. At least a month passes from the moment of the patient's first visit to the confirmation of the diagnosis. The examination is supervised by an endocrinologist; consultations of a geneticist, ophthalmologist, and neurologist are additionally appointed. The main stages are the identification of hyperglycemia, the differentiation of MODY-diabetes from the usual type 1 and 2 diabetes. The complex of diagnostic procedures includes the following methods:

Clinical survey, examination. Modi is characterized by an early onset, no obesity. It is distinguished from type I diabetes by a high hereditary nature of transmission (about 100%) - the patient has at least one close relative with some form of diabetes, prediabetes, mild fasting hyperglycemia. Another differential sign is the absence of symptoms of ketoacidosis (vomiting, abdominal pain, acetone odor from the mouth). Long-term remissions are characteristic.
Standard laboratory tests. The level of glucose, insulin, C-peptide, antibodies (blood) is determined, a glucose tolerance test is performed. With MODI 2, prolonged, but mild or moderate fasting hyperglycemia is found (on average 5.5-8.5 mmol / l). For types 3 and 1, fasting sugar is normal, but after a carbohydrate load it remains elevated for more than 2 hours (from 11.1 mmol / l). There are no antibodies to insulin and pancreatic cells, and there is no correlation with the HLA system. C-peptide levels are relatively normal.
Genetic tests. It is possible to reliably diagnose the type of disease using a molecular genetic study that detects mutations in genes. The procedure is long, all parts of the isolated chromosome are studied in detail, but first of all those changes in which are associated with the development of MODI types 1, 2, 3.

Treatment of MODY diabetes

The principles of therapy for diabetes MODI are the same as for the treatment of common variants of the disease. They are aimed at eliminating hyperglycemia, normalizing metabolic processes in the body. The methods depend on the type of disease and on the presence of pregnancy - when carrying a child, hyperglycemia can negatively affect only the woman, but also the fetus, therefore insulin therapy is used. The general scheme of therapeutic action includes:

Medication correction. These types of diabetes are susceptible to hypoglycemic tablet drugs. Sugar-lowering drugs are prescribed for most patients; in case of a second type of illness, a change in diet is sufficient. Pregnant women, adolescents with puberty, and patients with a long-term third type of illness may require the use of insulin to prevent complications.
Compliance with a diet. Shown nutrition with a reduced carbohydrate content - products containing refined sugar are excluded, sources of complex carbohydrates (cereals, cereals) are acceptable in moderate quantities. The basis of the diet consists of vegetables, dairy and meat products, fish, eggs. Fractional food intake avoids pronounced fluctuations in glucose levels.
Regular physical activity. Most cases of the disease are mild, patients can organize sports on their own. Aerobic exercise is recommended - race walking, jogging, team games, gymnastics. It is undesirable to do weightlifting exercises.

Forecast and prevention

The course of MODY diabetes is considered to be more favorable than other types of diabetes - the symptoms are less pronounced, the disease lends itself well to correction with diet, exercise and taking hypoglycemic drugs. With strict adherence to the appointments and recommendations of the doctor, the prognosis is positive. Since the decrease in insulin production is caused by genetic factors, prevention is ineffective. Patients at risk should have periodic blood tests for early detection of hyperglycemia and prevention of complications.

Hereditary diabetes in children, characterized by dysfunction of beta cells responsible for the production of insulin, as well as a dysfunction of glucose metabolism, is called modi-diabetes.

This disease is a composite group of various forms of diabetes, similar to the course of the disease and the principle of inheritance of the disease.

In comparison with other types of diabetes mellitus, this type proceeds with relative ease, similar to type II diabetes in an adult. This often complicates the diagnostic process, since its main symptoms do not coincide with those of diabetes.

MODY-diabetes is an abbreviation for "Maturity Onset Diabetes of the Young", which translates from English as "mature diabetes in young people", the name characterizes the main feature of the disease. The percentage of diabetics of this type is about 5% of the total number of patients, which is about 70-100 thousand people for every million, but in reality the numbers can be much higher.

Causes and possible complications

The main cause of MODI diabetes is a defect in the insulin-secreting function of beta cells in the pancreas, the location of which is the so-called "islets of Langerhans".

The key feature of any type of this disease is autosomal dominant inheritance, that is, the presence of diabetics in the second or more generation significantly increases the chances of inheriting genetic disorders in a child. Moreover, in this situation, factors such as body weight, lifestyle, etc. do not play a role at all.

Islets of Langerhans

The autosomal type of inheritance involves the transmission of traits with ordinary chromosomes, and not with sex. Therefore, modi-diabetes is hereditarily transmitted to children of both sexes. The dominant type of inheritance implies the manifestation of a dominant gene from two genes obtained from the parents.

If the dominant gene was obtained from a parent with diabetes, then the child will inherit it. If both genes are recessive, then the genetic disorder will not be inherited. In other words, a child with modi-diabetes has one of the parents or one of the relatives - diabetics.

Prevention of pathology is impossible: the disease is genetically determined. The best solution is to avoid excess weight. This, unfortunately, will not prevent the onset of the disease, but will ease the symptoms and delay their progress.

Complications in MODY diabetes can be exactly the same as in type I and II diabetes, among them:

polyneuropathy, in which the limbs almost completely lose sensitivity;
diabetic foot;
various defects in kidney function;
the occurrence of trophic ulcers on the skin;
blindness due to a reason;
diabetic angiopathy, in which blood vessels become brittle and tend to clog.

MODY diabetes is more commonly diagnosed in women than in men, and in women the disease is more severe and more difficult to treat.

Special features

Modi diabetes mellitus has the following features:

modi diabetes, as a rule, is found exclusively in early childhood or adolescence;
it can be diagnosed only by conducting molecular and genetic tests;
MODY diabetes has 6 varieties;
the mutated gene often disrupts the function of the pancreas. As it develops, it seriously affects the kidneys, eyes and circulatory system;
this type of diabetes is passed on from parents and can be inherited in 50% of cases;
the treatment process for modi-diabetes can be different. The key role in determining the strategy is played by the type of disease, determined by the type of mutated gene;
DM type I and II is a consequence of the occurrence of pathologies of several genes. Modi, on the other hand, is monogenic, that is, it disrupts the function of only one gene out of eight.

Subspecies

The disease of this type has 6 subspecies, of which 3 are the most common.

Depending on the type of mutated gene, each type of modi diabetes is assigned the corresponding names: MODY-1, MODY-2, MODY-3, etc.

The most common are the first 3 subspecies. Among them, the lion's share of cases has 3 subspecies, found in 2/3 of patients.

The number of MODY-1 patients, by the way, is only 1 person per 100 patients with the disease. Modi-2 diabetes is associated with mild hyperglycemia, which predicts better outcomes for patients. Unlike other types of modi-diabetes, which tend to progress, this type has favorable rates.

The other subtypes of diabetes are so rare that it makes no sense to mention them. It is worth noting only MODY-5, which is similar to type II diabetes in a sufficiently mild course in the absence of the development of the disease. However, this subspecies often causes diabetic nephropathy - a serious complication of the disease, characterized by serious damage to the arteries and kidney tissue.

How to recognize?

With such an ailment as modi-diabetes, diagnosis requires a special examination of the body; it can be quite difficult to identify the disease. Modi-diabetes symptoms are very different from those of diabetes widely known to endocrinologists.

There are a number of characteristic signs that indicate that the likelihood of the presence of the disease is quite high:

if modi-diabetes is detected in a child or adolescent under 25 years of age, then it makes sense to conduct molecular genetic tests, since type II diabetes mellitus in most cases is detected in people who have reached the age of 50;
in the event that relatives have been diagnosed with diabetes, then the probability of the disease is present, although it remains low. If, however, several generations have had high sugar levels, then the likelihood that modi-diabetes will be detected is much higher;
common forms of diabetes, as a rule, stimulate weight gain, this is especially true for patients with type II diabetes. However, in the case of MODY diabetes, this is not detected;
the period of development of type I diabetes is often accompanied by ketoacidosis. At the same time, the smell of acetone emanates from the patient's oral cavity, ketone bodies are present in the urine, the patient is constantly tormented by thirst and suffers from profuse urination. With regard to MODY diabetes, there is no ketoacidosis at an early stage of the disease;
if the glycemic index 120 minutes after the glucose tolerance test exceeds 7.8 mmol / l, then this with a high degree of probability indicates the presence of an ailment;
a protracted "honeymoon" of the disease, lasting more than a year, also indicates the likelihood of developing MODY-diabetes. As for type I diabetes, the remission time is usually only a few months;
compensation of the level of insulin in the patient's blood occurs with the introduction of the minimum dose in diagnosed type II diabetes.

However, the presence of certain symptoms, as well as their absence, cannot be a sufficient and objective basis for an accurate diagnosis.

MODY diabetes tends to mask its presence, therefore, the disease can only be detected after a series of tests, among which, for example, a glucose tolerance test, a blood test for the presence of autoantibodies to beta cells that produce insulin, etc.

If you skip the onset of modi, diabetes can become decompensated, making it difficult to treat and can cause serious complications.

Treatment

At the beginning of the development of the disease, it will be appropriate to apply regular physical activity and diets drawn up by the attending physician.

Active exercises and breathing exercises are also always relevant. This usually produces tangible results.

At the subsequent stages of the development of the disease, one cannot do without special drugs that lower sugar levels.

If their use turns out to be ineffective, then the treatment is continued using ordinary insulin. It allows you to control the required level of glucose in the patient's blood in the norm.

And, despite the fact that people with modi diabetes can easily make up for the insulin deficiency, it is still actively used in the treatment process. It will also be relevant to include in the diet foods that lower blood sugar levels.

It is worth remembering that the course of treatment is individual in each case! It is established by the attending physician, taking into account the stage, complexity, type and nuances of the disease.

It can also be extremely dangerous to include in the course of various kinds of folk remedies or new drugs that are not provided for in the course.

An increase or decrease in physical activity can also have a detrimental effect on the general condition of the patient and the course of the disease.

Puberty of the patient leads to a change in the hormonal background, therefore insulin therapy is indispensable in this case.

INTRODUCTION

For the first time, MODY diabetes was described by R. Tattersall in 1974 in three families as
- mild diabetes,
- with an autosomal dominant type of inheritance,
- arising in young people.
In 1975 R. Tattersall and S. Fajans first introduced the abbreviation MODY to define mildly progressive diabetes in young people with hereditary burden.
It was not until the 1990s that advances in molecular genetics and the presence of large bloodlines help in the identification of the genes responsible for this form of diabetes.
Currently, MODY diabetes is well documented in European and North American populations, however the prevalence in Asian populations is still unknown.

CLASSIFICATION AND PHENOTYPICAL SIGNS OF MODY-DIABETES

Genetic heterogeneity of MODY

MODY diabetes is a monogenic form of diabetes with

genetic,
metabolic
clinical heterogeneity.

Genes currently known for mutations causing MODY diabetes are:

Gene of nuclear factor of hepatocytes 4α ( HNF4A; MODY1),
Glucokinase gene ( GCK; MODY2),
Gene of nuclear factor of hepatocytes 1α ( HNF1A; MODY3),
The gene for the transcription factor PDX1 ( PDX1; MODY4),
Transcription factor 2 gene ( TCF2) or hepatocyte nuclear factor 1β ( HNF1B; MODY5),
The gene for neurogenic differentiation factor 1 ( NEUROD1; MODY6),
Gene Kruppel-like factor 11 ( KLF11; MODY7),
The gene for carboxyl ether lipase ( CEL; MODY8),
PAX4 gene ( PAX4; MODY9),
Insulin gene ( INS; MODY10),
B-lymphocyte kinase ( BLK; MODY11),
ATP-binding cassette, sub-family C ( CFTR / MRP), term 8 ( ABCC8; MODY12),
Gene KCNJ11 (MODY13).

Currently, 13 known genes do not explain all cases of diagnosed MODY diabetes, which implies the presence of as yet unknown gene mutations.

The most common causes of MODY diabetes are gene mutations:

GCK -32% of all cases of MODY diabetes in the UK,
HNF1A -52%,
HNF4A -10%,
HNF1B -6%.

In patients from Asian countries, the genes whose mutations lead to MODY diabetes differ:

In Korea, only 10% of patients with MODY diabetes or early-onset type 2 diabetes (T2DM) were found to have known MODY gene mutations ( HNF1A5%, GCK 2.5%, and 2.5% HNF1B),
in Japan and China - from 10% to 20%.
This indicates the need to discover new genes, defects in which can lead to diabetes MODY in Asia.

CLINICAL CHARACTERISTICS OF MODY DIABETES TYPES

GCK-MODY (MODY2)

Glucokinase is a glycolytic enzyme

catalyzes the conversion of glucose to glucose-6-phosphate,
controls glucose-mediated insulin release from β-cells.

GCK-MODY, the most common form (approximately 48%) among Caucasians.

However, only a small fraction (<5%) из выявленных случаев диабета MODY в Корее и Китае были вызваны GCK-MODY.

The clinical picture is manifested in the form:

moderate fasting hyperglycemia from birth (from 5.5 to 8.0 mmol / L, glycosylated hemoglobin in the range of 5.8% to 7.6%),
slight deterioration with age,
is asymptomatic - often first diagnosed during routine screening or during pregnancy,
rarely leads to serious complications.

Patients with GCK-MODYs do not require treatment outside of pregnancy, as:

hypoglycemic therapy is ineffective,
no late complications.

During pregnancy, insulin therapy may be needed to prevent overgrowth of the fetus.

HNF1A-MODY (MODY3)

Heterozygous mutations HNF1A lead to progressive β-cell dysfunction, leading to diabetes early in adulthood:

in 63% of carriers of this gene by the age of 25,
almost 100% by the age of 55.

In carriers, glucosuria appears even before the onset of diabetes due to decreased renal glucose reabsorption.

Hyperglycemia can be severe
worsens throughout life
the risks of micro- and macrovascular complications are similar to type 1 diabetes mellitus (T1DM) and type 2 diabetes.

Close glycemic control is required.!

Patients with HNF1A-MODY sensitive to therapy:

sulfonylureas (first-line therapy),
insulin may be needed over time.

HNF4A-MODY (MODY1)

The first described type of diabetes is MODY.
HNF4A - a transcription factor found in the liver, intestines, kidneys and pancreas.
- Participates in the regulation of genes necessary for glucose metabolism and transport.
HNF4A mutations account for less than 10% of MODY cases in Europe, and more than 103 mutations in 173 families have been identified so far.
Heterozygous HNF4A mutations result in
- significant fetal macrosomia, due to increased insulin secretion,
- the development of neonatal hypoglycemia in the fetus.
Characterized by the absence of glucosuria and low apolipoproteins (apoA11, apoCIII and apoB) HNF4A-MODY.
Sulfonylureas are the first line drugs for these patients.

PDX1-MODY (MODY4)

PDX1 (insulin promoter factor 1 [ IPF1]) - transcription factor,
- participates in the development of the pancreas and the expression of the insulin gene.
A homozygous mutation can lead to permanent neonatal diabetes due to underdeveloped pancreas.
Heterozygous mutations PDX1 lead to β-cell dysfunction and MODY4.
PDX1- MODY is a very rare cause of MODY diabetes.

HNF1B-MODY (MODY5)

HNF1B genome encoded TCF2,
expressed in the liver, kidneys, intestines, stomach, lungs, ovaries, β-cells of the pancreas and affects their embryonic development.
Heterozygous mutation in HNF1B characterized by progressive nondiabetic nephropathy, pancreatic atrophy and genital anomalies.
Birth weight can be significantly reduced by reducing insulin secretion.
Half of the gene carriers develop diabetes.
Spontaneous De Novo mutations occur relatively frequently, so the diagnosis is not always supported by family history.
HNF1B-MODY phenotypes differ from HNF1A-MODY due to the fact that diabetes HNF1B-MODY is developing
- as due to insulin resistance,
- and a defect in insulin secretion.
Patients with HNF1B-MODYs generally require early initiation of insulin therapy.

NEUROD1-MODY (MODY6)

NEUROD1 -a transcription factor that regulates the differentiation of β-cells of the pancreas and some neurons of the retina, inner ear, cerebellum and hippocampus.
Heterozygous mutations NEUROD1 can lead to diabetes, both in childhood and adulthood.
Mutations in both alleles can lead to neonatal diabetes mellitus with
- neurological disorders,
- reduced learning ability.

KLF11-MODY (MODY7)

KLF11 -a transcription factor that regulates pancreatic organogenesis and the activity of insulin-producing β-cells of an adult pancreas.
Two rare variants of the gene KLF11 were identified in three French families with early-onset type 2 diabetes.

CEL-MODY (MODY8)

CEL expressed in mammary glands and acinar cells of the pancreas.
Heterozygous mutations in a gene CEL lead to:
- atrophy,
- fibrosis,
- lipomatosis of the pancreas,
  - which in turn leads to exocrine and endocrine insufficiency and diabetes mellitus.

PAX4-MODY (MODY9)

PAX4 - a transcription factor,
participates in the differentiation of insulin-producing β-cells of the pancreas.
With a defect in this gene, diabetes mellitus often occurs with the development of ketoacidosis.

INS-MODY (MODY10)

Mutations INS - a common cause of neonatal diabetes,
but a rare cause of MODY diabetes in childhood or adulthood.
Heterozygous INS mutations disrupt
- proinsulin production,
- can induce apoptosis of β-cells in the endoplasmic reticulum.
Treatment is usually started with insulin, although some patients may be dispensed with taking oral hypoglycemic drugs.

BLK-MODY (MODY11)

BLK- through transcription factors PDX1 and NKX6.1stimulates the synthesis and secretion of insulin in the β-cells of the pancreas.
Persons with MODY11 have a higher prevalence of obesity than other types of MODY.
Currently mutations BLK identified in three families.

ABCC8-MODY (MODY12)

ABCC8 encodes sulfonylurea receptor 1 ( SUR1) the subunit of ATP-sensitive potassium channels (K-ATP) in the β-cells of the pancreas.
Homo- and heterozygous mutations lead to the development of neonatal diabetes mellitus,
heterozygous mutations can also cause MODY diabetes, clinically similar to HNF1A / 4A-MODY.
A thorough molecular genetic diagnosis is required, as it determines the tactics of treating a patient.
It is recommended to start therapy with sulfonylurea preparations.

KCNJ11-MODY (MODY13)

KCNJ11 encodes Kir6.2, part of the K-ATF channel.
Homozygous mutations lead to neonatal diabetes,
heterozygous mutations can lead to a wide variety of manifestations of diabetes mellitus.
- Age at the time of diagnosis ranges from 13 to 59 years.
Treatment of these patients is carried out depending on the severity of the disease:
- diet,
- oral hypoglycemic therapy,
- insulin.

MODY DIABETES STUDIES IN KOREA.

The prevalence of MODY in Korea is still unknown.
In a study of the Korean population, only 10% of 40 cases of MODY or type 2 diabetes with early manifestation had known MODY gene mutations ( HNF1A 5%, GCK 2.5%, and HNF1B 2,5%).
These results are similar to those of China and Japan.
There is a need for MODY diabetes research in Asia to identify unknown mutations.

DIAGNOSTICS MODY

The prevalence of MODY diabetes is 1% to 2% of all diabetes cases.
A properly diagnosed diagnosis determines the optimal treatment strategy.
- Patients on insulin therapy due to an incorrect diagnosis of type 1 diabetes
  - can be switched to oral hypoglycemic therapy (sulfonylureas) when diagnosed HNF1A-MODY or HNF4A-MODY,
  - which will not only improve their quality of life, but also glycemic control.
The genetic diagnosis of MODY can also affect the patient's prognosis.
- For patients with mild hyperglycemia during adolescence and diagnosis GCK-MODY, HNF1A-MODY or T1DM requires a different approach to management and therapy.
Family members of MODY patients should undergo molecular genetic testing to determine whether they are carriage or likely to develop the disease.

According to British diabetologists, 80% of patients with MODY were incorrectly diagnosed with T1DM and T2DM, which led to incorrect treatment tactics with a deterioration in the quality of life of patients.

This diagram shows a diagnostic algorithm for molecular genetic testing for the detection of MODY diabetes in young people with diabetes.

CONCLUSION

MODY diabetes is a common cause of monogenic diabetes,
- accounts for 1% to 2% of all cases of diabetes.
Despite its low prevalence, the identification of MODY genes is important in the diagnosis.
The varied clinical picture of MODY diabetes is explained by genetic heterogeneity.
Only timely diagnosis of MODY diabetes can ensure the correct treatment and management of patients, as well as the identification of gene mutations in patients' relatives.
A nationwide MODY registry and systematic approach are essential to quickly diagnose and determine the correct treatment for MODY diabetes.

Source:

Kim S-H. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know? Diabetes & Metabolism Journal... 2015; 39 (6): 468-477. doi: 10.4093 / dmj.2015.39.6.468.

To diagnose diabetes mellitus and determine its type, taking into account the level of modern medicine, an endocrinologist without much practice and experience will be able to do it. An exception is this form of the disease, like modi diabetes.

Even those who are not a professional physician and generally do not face endocrine system diseases every day, it is known that there are two types of diabetes mellitus:

Insulin-dependent - type 1 diabetes;
Non-insulin dependent - type 2 diabetes.

Features by which the disease of the first type is recognized: its onset occurs in adolescence or adolescence, while insulin must be injected immediately and now for the rest of his life.

The patient cannot do without it, as without air and water. And all because the cells of the pancreas, which are responsible for the production of this hormone, gradually lose their functions and die off. Unfortunately, scientists have not yet found a way to regenerate them.

Type 2 diabetes is more common in older people. It is quite possible to live with him for many more years without insulin injections. But subject to a strict diet and regular physical activity. As a supportive agent, hypoglycemic drugs are prescribed, but they are not always needed.

The disease can be compensated for. How successful depends only on the desire and willpower of the patient himself, on the general state of his health at the time when the diagnosis was made, age and lifestyle.

The doctor only makes appointments, but how much they will be observed, he cannot control, since the treatment is carried out at home on his own.

The development of such a form of the disease as mody diabetes proceeds somewhat differently. What is it, how to recognize it, what features and threat are - below.

Unusual symptoms and features

Мody diabetes is a very special form of pathology. Its symptoms and course do not fall under the standards characteristic of type 1 or type 2 diabetes.

For example: mody diabetes means if in a small child for no apparent reason the concentration of glucose in the blood increases to 8.0 mmol / l, the phenomenon is observed repeatedly, but nothing else happens? That is, there are no other signs of diabetes mellitus.

How can one explain the fact that in some children the initial stage of type 1 diabetes mellitus can last up to several years? Or is it that adolescents diagnosed with type 1 diabetes do not need to increase their insulin dose for many years, even if they do not monitor their blood sugar levels?

In other words, insulin-dependent type 1 diabetes in young patients and children is often completely asymptomatic and not burdensome, much like type 2 diabetes in older patients. It is in these cases that a type of disease such as modi can be suspected.

From 5 to 7 percent of all cases of diabetes mellitus occur in the so-called mody diabetes. But these are only official statistics.

Experts say this form of diabetes is actually much more common. But it remains unrecorded due to the complexity of the diagnosis. What is mody diabetes?

What is this type of disease

Maturity Onset Diabetes of the Young - this is how the English-language abbreviation stands. What in translation means diabetes of a mature type in young people. For the first time such a term was introduced in 1975 by American scientists to define an atypical, mildly progressive form of diabetes mellitus in young patients with a hereditary predisposition.

The disease develops against the background of a gene mutation, as a result of which dysfunctions of the islet apparatus of the pancreas occur. Genetic changes occur most often in adolescence, adolescence and even childhood. But to diagnose a disease, or rather its type, is possible only by the method of molecular genetic research.

In order to be diagnosed with mody diabetes, a mutation in certain genes must be confirmed without fail. To date, 8 genes have been identified that can mutate, which is the reason for the development of this type of disease in different forms. All of them differ in symptomatology and clinical picture, respectively, require different tactics in treatment.

When can this type of disease be suspected?

So, what symptoms and indicators indicate that this rare and difficult to diagnose type of diabetes is taking place? The clinical picture can be very similar to the development and course of type 1 diabetes. But in parallel, the following signs are also noted:

Very long (at least a year) remission of the disease, while periods of decompensation are not observed at all. In medicine, this phenomenon is also called "honeymoon".
On manifestation, there is no ketoacidosis.
The insulin-producing cells retain their function, as evidenced by the normal level of C-peptide in the blood.
With minimal insulin administration, very good compensation is observed.
Indicators of glycated hemoglobin do not exceed 8%.
There is no association with the HLA system.
Antibodies to beta cells and insulin are not detected.

Important: the diagnosis can be made without a doubt only if the patient has close relatives who are also diagnosed with diabetes mellitus, borderline "hungry" hyperglycemia, gestational (during pregnancy) diabetes or impaired cell glucose tolerance.

There are grounds for suspicion of mody-diabetes in cases where the diagnosis was confirmed at the age of less than 25 years, and without obesity symptoms.

Parents should be especially careful if their children have had the following symptoms for two years or more:

Hunger hyperglycemia (no more than 8.5 mmol / l), but without other characteristic concomitant phenomena - weight loss, polydipsia, polyuria;
Impaired carbohydrate tolerance.

Patients, as a rule, do not have any special complaints in such cases. The problem is that if you miss the moment, a variety of complications can develop and diabetes will turn into decompensated diabetes. Then it will be difficult to control the course of the disease.

Therefore, it is required to regularly conduct research and, at the slightest change in the clinical picture and the manifestation of new symptoms, begin therapy to lower blood sugar levels.

Information: it is noted that this unusual type of diabetes mellitus occurs more often in women than in men. It proceeds, as a rule, in a more severe form. There are no scientifically proven explanations for this phenomenon yet.

Varieties of modi-diabetes

Depending on which genes have mutated, there are 6 different forms of the disease. They all proceed differently. They are called respectively Mody-1, Mody-2, etc. The most benign form is considered to be Modi-2 diabetes.

In this case, lean hyperglycemia is rarely higher than 8.0%; progression, like the development of ketoacidosis, is not recorded. There are no other characteristic manifestations of diabetes mellitus. It has been established that this form is most common among the population of France and Spain.

The compensatory state in patients is maintained with a meager dose of insulin, which almost never needs to be increased.

In the northern countries of Europe - England, Holland, Germany - Moby-3 is more common. This variant of the course of the disease is considered the most common. It develops at a later age, usually after 10 years, but at the same time rapidly, often with severe complications.

A pathology such as Modi-1 is extremely rare. Of all cases of diabetes, this form of Modi-1 is only 1%. The course of the disease is severe. The Modi-4 variant of the disease develops in young people over the age of 17. Modi-5 resembles the second variant in its mild flow and lack of progression. But it is often complicated by a disease such as diabetic nephropathy.

Treatment methods

Since this form of pancreatic pathology is not characterized by active progression, the treatment tactics are the same as in type 2 diabetes. At the initial stage, the following measures are enough to control the patient's condition:

Balanced strict diet;
Sufficient physical activity.

At the same time, it has been confirmed in practice that it is precisely the correctly selected and regularly performed physical exercises that give excellent results and contribute to quick, good compensation.

The following approaches and techniques are also used:

Respiratory gymnastics, yoga.
Eating foods that help lower sugar.
Traditional medicine recipes.

Whichever method is chosen, it must always be agreed with the attending physician. When diet and folk recipes are not enough, they switch to