type 1 diabetes

• Type 1 diabetes is an autoimmune disease in which pancreatic β cells are destroyed and insulin secretion stops.and accounts for approximately 5-10% of all diabetes cases.
• G-type mutation in DNA region rs2664170Research shows that people with the disease tend to be at higher risk of developing
• The annual incidence rate in Japan is approximately 2.3 per 100,000 people.Young people/womenThe incidence is concentrated in

Overview Type 1 diabetes is a type of diabetes that has completely different characteristics from type 2 diabetes, which is a lifestyle-related disease. Autoimmune reactions usually do not attack any part of the body, but certain things can cause immune cells to attack your own organs. As a result, pancreatic beta cells are autoimmunely destroyed and insulin, a hormone that lowers blood sugar levels, is no longer produced, resulting in type 1 diabetes. According to an epidemiological survey by the Ministry of Health, Labor and Welfare's research group, the number of patients with type 1 diabetes is approximately 100,000 to 140,000, and it is estimated that approximately 2.3 people per 100,000 will develop the disease in one year. It has been reported that most people who develop the disease are young people, and it is particularly common in women. (Reference link 1) Although genetic factors are not usually involved, recent research has revealed that a certain region near the gene "GAB3" is likely to influence the risk of developing "type 1 diabetes." Young people have fewer opportunities to undergo regular health checkups and other tests, so late detection can lead to complications. Finding out your own genetic type through genetic testing and knowing your risk of developing type 1 diabetes may be useful in preventing the onset and taking early measures. 2. Rationale Research conducted by the Juvenile Diabetes Research Foundation in the UK revealed that the DNA region near the gene GAB3 increases the risk of developing type 1 diabetes. This DNA region is called "rs2664170," and there are three genotypes: "AA type," "AG type," and "GG type." (Reference link 2) Type GG, which has the risk allele G, is more likely to develop type 1 diabetes, and type AG is slightly more likely to develop type 1 diabetes. Regarding the genetic type of Japanese people, the AA type accounts for the most (65.5%), the AG type accounts for 30.9%, and the GG type accounts for the least at 3.6%. (Reference link 3) However, people with type GG or type AG do not necessarily develop type 1 diabetes; the likelihood of developing the disease increases due to a combination of environmental factors. Symptoms of type 1 diabetes often occur suddenly and include dry mouth, excessive urination, and weight loss. As the symptoms progress, insulin may no longer be produced, leading to dangerous conditions such as coma or ketoacidosis due to hyperglycemia. Especially in children, it is difficult to communicate the symptoms well, and there are cases where the symptoms are noticed through bedwetting (bedwetting), so the cooperation of parents is essential for early detection. By understanding the risk of developing type 1 diabetes at an early stage, it becomes possible to manage the risks in terms of lifestyle and environment. 3. Mechanism of action GAB3, a gene involved in the onset of type 1 diabetes, is located on the X chromosome of the 24 chromosomes common to humans. The gene "GAB3" is abundant in tissues such as the spleen and bone marrow, and contains genetic information essential for the growth of immune cells called "macrophages." (Reference link 4) The pathogenic mechanism by which the gene "GAB3" is directly related to "type 1 diabetes" has not been elucidated, but depending on the genotype of the DNA region "rs2664170", the gene "GAB3" may be overexpressed, thereby excessively promoting the growth of leukocytes into "macrophages". It is thought that the proliferated "macrophages" activate the immune system and cause inflammation, and the secreted information transmitting substances activate lymphocytes, thereby destroying the pancreatic beta cells that secrete insulin. In fact, in type 1 diabetes, immune cells such as macrophages infiltrate locally into the islets of Langerhans in the pancreas, causing inflammation, and insulin-secreting beta cells are said to become dysfunctional, so it can be assumed that the mechanism described above is the cause of autoimmune type 1 diabetes. (Reference link 5) As mentioned above, the DNA region "rs2664170" is one of the single nucleotide polymorphisms that is attracting attention as it is closely related to the onset of "type 1 diabetes."

Type 1 diabetes mellitus (T1DM) is a metabolic disease in which an autoimmune reaction destroys pancreatic beta cells and completely stops insulin secretion.It accounts for approximately 5-10% of all diabetic patients and has a pathological condition that is fundamentally different from type 2 diabetes, which is a lifestyle-related disease.

According to an epidemiological survey by the research group of the Ministry of Health, Labor and Welfare, the number of type 1 diabetes patients in Japan isApproximately 100,000 to 140,000 peopleThe annual incidence rate is estimated to be approximately 2.3 per 100,000 people. It has been reported that the onset of the disease is concentrated in young people, and the incidence tends to be particularly high in women.

Causes and mechanisms of type 1 diabetes

Type 1 diabetes develops when immune cells that normally attack foreign invaders mistakenly attack and destroy the body's own pancreatic beta cells. While type 2 diabetes is mainly caused by insulin resistance, type 1 diabetes is characterized by:

• Autoimmune β cell destruction:Immune cells (macrophages and lymphocytes) attack β cells in the pancreatic islets of Langerhans.
• Complete cessation of insulin secretion:Destruction of β cells reduces insulin production ability to zero
• Genetic predisposition:DNA region rs2664170 near gene GAB3 is involved in risk of developing disease

The gene "GAB3" is located on the X chromosome and contains genetic information necessary for the growth of macrophages present in the spleen and bone marrow. It is thought that the G-type mutation in the DNA region rs2664170 overexpresses GAB3, promoting macrophage proliferation and activating autoimmune responses.

Main symptoms of type 1 diabetes

The symptoms areappear suddenly and rapidlyThis contrasts with the slow progression of type 2 diabetes.

• Dry mouth/drinking and urinating too much
• rapid weight loss
• chronic fatigue
• blurred vision
• In children, it may be discovered through bedwetting.

As the symptoms progress, insulin becomes depleted andComa due to hyperglycemiaYaDiabetic ketoacidosis (DKA)There is a risk of causing a life-threatening condition.

Difference between type 1 diabetes and type 2 diabetes

Type 1 diabetes complication risk

Without proper treatment, the following complications may occur:

• Diabetic ketoacidosis (DKA): Acute complications due to insulin deficiency that are life-threatening.
• cardiovascular disease(myocardial infarction/stroke)
• diabetic nephropathy(renal dysfunction)
• diabetic neuropathy(Peripheral nerve disorder)
• diabetic retinopathy(Risk of decreased visual acuity/blindness)

Diagnostic method

It is diagnosed by the following tests.

• Fasting plasma glucose test
• HbA1C (glycated hemoglobin) test
• Autoantibody test (GAD antibody, IA-2 antibody, insulin autoantibody)
• C-peptide measurement (evaluation of insulin secretion ability)

Relationship between DNA region rs2664170 and onset risk

Jeffrey C by Juvenile Diabetes Research Foundation UK A study by Barrett et al. found that the DNA region rs2664170 near the gene GAB3 is associated with the risk of developing type 1 diabetes.

• There are three genotypes of rs2664170: GG, GA, and AA.
• GG type with G type which is Risk Alleleare more likely to develop type 1 diabetes
• GA typetend to be slightly more likely to develop
• Type AA is relatively low risk.

However, people with type GG or GA type do not necessarily develop type 1 diabetes.A combination of environmental factors increases the likelihood of developing the disease.

Genotype distribution in Japanese (rs2664170)

Mechanism of action: Relationship between gene GAB3 and autoimmunity

The gene GAB3 is one of the 24 human chromosomes.X chromosomeLocated in GAB3 is present in the spleen and bone marrow and carries the genetic information necessary for macrophage growth.

The mechanism of G-type mutation in DNA region rs2664170 is as follows.

• Overexpression of GAB3 → excessively promotes growth of leukocytes into macrophages
• Macrophage proliferation → activation of immune function/induction of inflammation
• Secretion of information transmitters → activation of lymphocytes
• Macrophage infiltration into pancreatic islets of Langerhans → destruction of β cells

It is speculated that this mechanism causes autoimmune type 1 diabetes.

Q1. What is type 1 diabetes?

Type 1 diabetes mellitus (T1DM) is a metabolic disease in which an autoimmune reaction destroys pancreatic beta cells and completely stops insulin secretion.It accounts for approximately 5 to 10% of all diabetes cases and occurs acutely, mainly in children and young people. In Japan, it is estimated that approximately 2.3 people per 100,000 people develop the disease annually.

Q2. What is the cause of type 1 diabetes?

The main cause isDestruction of pancreatic beta cells due to autoimmune reactionIt is. Immune cells attack their own beta cells, and they lose their ability to produce insulin. The G-type mutation in the DNA region rs2664170 near gene GAB3 has been identified as a risk factor.

Q3. What is the difference between type 1 diabetes and type 2 diabetes?

Type 1 isInsulin secretion cessation due to autoimmunityIt causes acute onset in young people and requires insulin injections. Type 2 isinsulin resistanceThe main cause is that it develops gradually in middle-aged and elderly people, and lifestyle habits are strongly involved.

Q4. Can genetic testing determine the risk of type 1 diabetes?

By examining the genotype of the DNA region rs2664170,Understanding trends in the risk of developing type 1 diabetesYou can. Studies have shown that people with the G mutation (GG and AG) tend to be at higher risk.

Q5. What are the early symptoms of type 1 diabetes?

Early symptoms of type 1 diabetes aresuddenly appearIt is characterized by this. Typical symptoms include dry mouth, excessive urination, rapid weight loss, and chronic fatigue. In some children, it may be noticed by bedwetting. As it progressesKetoacidosis or comaThere is a risk of causing