Different types of Type 1 diabetes and hereditary diabetes: Classic Type 1, LADA, Idiopathic Type 1, Dual Diabetes and MODY

Type 1 diabetes has several variants, including classic type 1, LADA, idiopathic diabetes, dual diabetes, and hereditary forms such as MODY, each with unique symptoms and treatments

How Ferry discovered he did not have type 2 diabetes, but type 1.

Ferry, a 34-year-old man, noticed that lately he was often tired and thirsty. He first thought it was due to stress, but when he also started losing a lot of weight for no apparent reason, he decided to see his family doctor. The doctor performed a blood sugar test and noted elevated glucose levels. Based on his age, type 2 diabetes was initially considered, and Ferry was prescribed metformin.

Still, Ferry did not feel better. His blood sugar levels continued to fluctuate, and he continued to feel tired. After further testing, including a C-peptide test and a ZnT8 antibody test, it was discovered that his body produced little insulin and that autoantibodies were present. These results confirmed that Ferry did not have type 2 diabetes, but type 1 diabetes.

After this diagnosis, Ferry began insulin therapy. Within a few weeks, he felt much better and had more energy. He learned that it is important to have further testing when symptoms and doubts persist, as misdiagnosis can lead to ineffective treatment.

In Ferry's case, the ZnT8 antibody test, offered by Bloedwaardentest.nl, proved crucial to making the correct diagnosis. This test is specifically aimed at detecting autoimmune diabetes and is especially valuable when other antibody tests are negative or when the diagnosis is in doubt.

Conclusion

Type 1 diabetes takes various forms, each with unique characteristics and challenges. Ferry's story highlights how important it is to get the right diagnosis using tests such as autoantibody testing and C-peptide measurements. If you experience symptoms such as extreme thirst, weight loss or fatigue, do not hesitate to seek medical attention and the proper diagnostics.

Type 1 diabetes is an autoimmune disease in which the immune system attacks the insulin-producing beta cells in the pancreas. This leads to a chronic deficiency of insulin, resulting in elevated blood sugar levels. Although many people are familiar with the classic form of type 1 diabetes, there are several variants within this category that present different symptoms, progression and diagnostic challenges. In this blog, we will discuss the different types of type 1 diabetes, what you notice about it, when to test, and how to make an accurate diagnosis.

The different types of type 1 diabetes

1. Classic type 1 diabetes
• What is it. This is the best known form of type 1 diabetes and often begins at a young age (children and young adults). The immune system destroys the beta cells in the pancreas, leading to a complete loss of insulin production.
• Symptoms:
• Excessive thirst (polydipsia)
• Frequent urination (polyuria)
• Unexplained weight loss
• Fatigue and lethargy
• Blurred vision
2. LADA (Latent Autoimmune Diabetes in Adults)
• What is it. A slower progressive form of type 1 diabetes that manifests in adults (usually over the age of 30). Initially it resembles type 2 diabetes, but the underlying mechanism is autoimmune.
• Symptoms:
• Gradual onset of mild hyperglycemia
• Difficulty controlling blood sugar, even with oral medication
• Increasing dependence on insulin over time
3. Idiopathic type 1 diabetes
• What is it. This is a rare form of type 1 diabetes in which no obvious autoimmune reaction is detected. It is more common in people of Asian or African descent.
• Symptoms:
• Similar to classic type 1 diabetes
• No detectable autoantibodies in blood tests
4. Double diabetes
• What it is. A situation in which a person has characteristics of both type 1 diabetes (autoimmune) and type 2 diabetes (insulin resistance). This can occur in people with type 1 diabetes who are overweight or develop insulin resistance.
• Symptoms:
• Problems controlling blood sugars despite insulin use
• Characteristics of insulin resistance, such as increased abdominal fat
5. MODY (Maturity Onset Diabetes of the Young).
• What is it. MODY is an inherited form of diabetes caused by mutations in specific genes (such as HNF1A, HNF4A or GCK). It usually begins at a young age, often under 25, and is often confused with type 1 or type 2 diabetes.
• Symptoms:
• Mildly elevated blood sugar levels (especially in MODY 2)
• No presence of autoantibodies
• Familial history of diabetes across multiple generations
• Treatment:
• Depends on type of MODY. MODY 2 often requires no treatment, while MODY 3 responds well to sulfonylurea derivatives instead of insulin.

What do you notice with type 1 diabetes?

The symptoms of type 1 diabetes can appear suddenly and vary depending on the severity and progression of the disease. Below are the most common signs:

• Extreme thirst and dryness in the mouth: This is due to dehydration caused by frequent urination.
• Weight loss for no reason: The body burns muscle and fat tissue as a source of energy in the absence of insulin.
• Frequent urination, especially at night: Due to high blood sugar levels, the body tries to get rid of excess sugar through urine.
• Severe fatigue: The body cannot use glucose effectively as an energy source.
• Acute symptoms in severe cases: such as nausea, vomiting, abdominal pain and in severe cases ketoacidosis (accumulation of acids in the blood).

When should you get tested?

It is important to get tested for type 1 diabetes at:

1. Severe symptoms: Such as extreme thirst, weight loss, and frequent urination.
2. Family history of type 1 diabetes or MODY: First-degree relatives of people with type 1 diabetes or MODY are at increased risk.
3. Unexplained hyperglycemia: High blood sugar levels not consistent with other forms of diabetes.
4. Age: Although type 1 diabetes can occur at any age, it is common in children, teens and young adults. MODY is more common in adolescents and young adults with a family history of diabetes.

How can you diagnose type 1 diabetes?

Type 1 diabetes is diagnosed based on clinical symptoms and various blood tests. Here are the most important tests:

1. Blood sugar test (sober or random):
• Blood sugar levels above a certain level (for example, >7 mmol/L sober or >11 mmol/L at random) indicate diabetes.
2. HbA1c test:
• Measure average blood sugar levels over the past 2-3 months.
• A value of ≥6.5% may indicate diabetes.
3. Autoantibody testing:
• Detect autoantibodies characteristic of type 1 diabetes, such as GAD antibodies, IA2 antibodies or ZnT8 antibodies.
• LADA can be detected by performing these tests in adults with a suspected diabetes diagnosis.
4. C-peptide test:
• Measures how much insulin the body produces. Low C-peptide levels indicate type 1 diabetes.
5. Genetic testing:
• Necessary to diagnose MODY. Specific genetic mutations, such as in HNF1A or GCK, can be detected.
6. Urinalysis:
• Can detect ketones in urine, indicating ketoacidosis - a dangerous complication of untreated type 1 diabetes.

Interpretation of genetic variants and SNPs in MODY

In genetic testing, specific SNPs (Single Nucleotide Polymorphisms) can help diagnose hereditary diabetes variants such as MODY. Below are some relevant SNPs and their significance:

1. rs1169288 (HNF1A):
• This variant is linked to MODY 3, one of the most common forms of MODY.
• An abnormality may indicate impaired insulin production. Individuals with this mutation often respond well to sulfonylurea derivatives.
2. rs1800574 (HNF1A):
• Changes in this SNP can negatively affect insulin production.
• This is an important marker in the diagnosis of MODY 3.
3. rs115080759 (HNF4A):
• This SNP is associated with MODY 1. People with abnormalities in this gene often have an increased risk of diabetes at birth or in early adulthood.
4. rs3757840 (GCK):
• Mutations in this gene are associated with MODY 2, which leads to mildly elevated blood sugar levels.
• Often, no treatment is needed because glucose levels remain relatively stable.
5. rs1799884 (GCK):
• This SNP may play a role in regulating glucose metabolism and is important in the diagnosis of MODY 2.

What does it mean when these SNPs deviate?

• Diagnostic understanding: Abnormalities in

these SNPs can indicate that a person has an inherited form of diabetes such as MODY. The specific mutation often determines what type of MODY is present, how severe the symptoms are and what treatment will be most effective. For example:

• MODY 1 (HNF4A): Patients are often at increased risk for diabetes from birth. Treatment may include insulin or oral medication.
• MODY 2 (GCK): This type causes mildly elevated blood sugar levels and usually does not require treatment.
• MODY 3 (HNF1A): This variant often responds well to sulfonylurea tablets, which stimulate insulin production.
• Prognosis and risk assessment: Knowing these genetic abnormalities helps doctors not only diagnose, but also predict the course of the disease and tailor treatment to the patient's specific needs.

For comprehensive evaluation of type 1 diabetes and related conditions, Bloodtesting.nl.com offers several tests. Here are some relevant studies:

1. HbA1c and Glucose Test: This test measures both fasting glucose levels and the HbA1c level, which provides insight into average blood sugar levels over the past few months.
2. Antibodies to GAD65: This test detects the presence of antibodies to glutamate decarboxylase, which can help diagnose autoimmune diabetes such as type 1 and LADA.
3. Antibodies to Insulin (IAA): This test determines if antibodies to insulin are present, which can be useful in differentiating type 1 diabetes.
4. iGene DNA test Health: This comprehensive DNA test identifies part of your genetic predisposition, including susceptibility to certain conditions and medications. Click here for the iGene Health test.

It is advisable to determine, in consultation with a medical professional, which tests are most appropriate for your situation.