Dr Louise Johnson explains the new guidelines for managing early Type 1 diabetes.
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Type 1 diabetes 101
Type 1 diabetes is an autoimmune condition that occurs as a result of destruction of the beta cells of the pancreas. The beta cells produce insulin in normal healthy people. This destruction leads to sever insulin deficiency. Without insulin treatment, this will lead to diabetic ketoacidosis and death. Thus, lifelong insulin therapy is needed for survival. Type 1 diabetes represent 5–10% of all diabetes. The diagnosis classically occurs in children and adolescents but can also occur in adulthood.
Classically Type 1 diabetes present over the course of days or weeks in children and adolescents with drinking a large amount of water and passing a large amount of urine. This is associated with weight loss, dry mouth, and blurred vision. These are all symptoms of high blood glucose and is associated with or without ketones.
Four antibodies that cause Type 1 diabetes
In Type 1 diabetes, there are autoantibodies present in the blood that can be measured to confirm Type 1 diabetes. There are four types of antibodies that can cause Type 1 diabetes. They can all be measured in the blood and are usually present at diagnosis. They are:
- Glutamic acid decarboxylase (GAD) antibody
This antibody is specific against GAD. It’s common as the first detected autoantibody in childhood up to 15 years of age. Adult-onset cases most often present with this antibody. It’s associated with slower progression to Type 1 diabetes and is often found as a single-positive antibody, especially in adults.
- Insulin autoantibody (IAA)
This antibody is specific against insulin. It’s common as a first detected autoantibody in young children. Its frequency declines with age but is of little information in people already injecting insulin as antibodies can develop in response to injected insulin.
- Insulin antigen 2 auto antibody (IA-2A)
Also known as ICA512, this antibody is against tyrosine phosphatase islet antigen-2. Its presence is associated with more advanced islet auto-immunity and a faster progression to Stage 3 Type 1 diabetes.
- Zinc transporter 8 auto antibody (ZnT8A)
This antibody is against transmembrane zinc transporter type 8 protein in the beta cell granule. The presence of this antibody can improve risk stratification in individuals with a single other autoantibody.
Usually more than one antibody is present at diagnosis.
Diagnosis
Type 1 diabetes can de classified in three stages. These stages are determined by the presence of antibodies and the amount of abnormal glucose measurements.
Stage 1
The person’s blood tests positive for two or more antibodies but the person is without symptoms and the oral glucose tolerance test (OGTT) is normal.
An oral glucose tolerance test is a blood test where a person consume 75 gram of glucose and blood is tested at fasting, 30-, 60-, 90-, and 120 minutes.
The fasting plasma glucose is below 5.6 mmol\L and the two-hour OGTT is below 7.8 mmol\L. HbA1c below 5.7%. The person is asymptomatic.
Stage 2
The blood tests positive for two or more antibodies, and the oral glucose tolerance test is impaired but not yet in the diabetes range. This mean the fasting plasma glucose value is below 5.6 and 6.9 mmol/L and the two-hour OGTT is more than 11.1 mmol/L at 30-, 60-, and 90 min. The HbA1c is between 5.7 and 6.4%.
Stage 3
Antibodies are positive, the person is symptomatic, and glucose is in the diabetes range. Fasting glucose more than 7 mmol/L and two hours after meals more than 11.1 mmol\L. HbA1c more than 6.5%. The treatment for Stage 3 diabetes is insulin.
Advice for stages
Stage 1 Type 1 diabetes
- Confirm the autoantibody three months later with a second sample.
- Metabolic monitoring with glucose testing for the first two years after testing positive. Monitor the glucose thereafter every six months or if symptomatic.
Stage 2 Type 1 diabetes
- Use HbA1c every six months to monitor glucose.
- Combine with diabetes diet and exercise.
- The question when to start early insulin to preserve beta cells of the pancreas will be decided by a specialist.
Latent auto immune diabetes of adults
Half of all the new cases of Type 1 diabetes is now occurring in adults. Misclassification due to misdiagnosis (commonly as Type 2 diabetes) occurs in nearly 40% of people.
The term latent autoimmune diabetes of adults (LADA) was introduced 30 years ago to identify adults that developed immune-mediated diabetes. The criteria for the diagnosis of LADA consists of:
- Age older than 30 years
- Lack of the need for insulin for at least six months
- Present of autoantibodies
However, there is a debate whether the term LADA should still be used. The American Diabetes Association standard of care notes that for classification purposes all forms of diabetes mediated by autoimmune destruction are included in the classification of Type 1 diabetes.
The investigation of adults with suspected Type 1 diabetes isn’t always straightforward. The first step is to suspect this in a non-obese patient with high glucose (more than 16.7 mmol/L and can present with mild acidosis). An antibody test should be done to confirm the presence of autoimmunity.
This will mark the progression to severe insulin deficiency. It’s important to remember to only check GAD antibodies in clinically suspected Type 1 diabetes since a low concentration of GAD antibodies can be seen in Type 2 diabetes and thus false positivity is a concern.
Just to make the scenario more interesting, there is 5–10% of Type 1 diabetes that may occur without antibodies and the autoantibodies disappear over time.
Genetic risk scoring (GRS) for Type 1 diabetes has received attention to differentiate people whose classification is unclear. This was developed in 2019 and uses 67 single nucleotide polymorphisms from known autoimmune loci and can predict Type 1 diabetes in children of European and African ancestry. It’s not routinely available yet for clinical use.
Investigating adults with suspected Type 1 diabetes
Step 1
Test for autoantibodies; if this is positive the diagnosis is confirmed.
Step 2
If the autoantibody test is negative, check the age (since 5–10% of Type 1 can test negative). If older than 35 years, the classification is unclear. A trial of non-insulin therapy can be started.
Do a C-peptide blood test to determine the amount of insulin from the pancreas. C-peptide with a value of more than 600 pmol/L confirms the diagnosis of Type 2 diabetes. A value between 200 and 600 makes the diagnosis indeterminate and the C peptide should be followed up in five years. Keep a good eye on glucose management.
A C-peptide value of less than 200 pmol/L moves the scale over to Type 1 diabetes.
Psychosocial care
The testing and positive screening of an autoantibody that predicts Type 1 diabetes can be very stressful to both the patient and their families. Shock, grief, guilt, anger and depression can all be emotions that may be encountered. The TEDDY study and the Autoimmunity Screening for Kids (ASK) study showed these emotions in children testing positive.
Psychosocial care should be integrated into these patients’ routine medical visits. Unfortunately, the medications tested to preserve beta cells of the pancreas in Stage 1 and 2 haven’t shown any results yet.
The quest for insulin beta cell replacement and autoantibody suppression is ongoing. As our understanding of the immunology of Type 1 diabetes expands, development of the next generation of immunotherapy is under active pursuit.
References
- Fourlanos S, Dotta F et al. “Latent autoimmune diabetes in adults (LADA) should be less latent.” Diabetologia 2005; 48:2206-12
- Lynam A, McDonald T et. al.” Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults age 18-50 years.” BMJ 2019;9
- Holt RIG et.al. Investigating suspected type 1 diabetes. Diabetes care 2021;44:2589-625
- Philip M, Achenbach P et al. “Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes.” diabetology, 2024;67:1731-1759
MEET THE EXPERT

Dr Louise Johnson is a specialist physician passionate about diabetes and endocrinology. She enjoys helping people with diabetes live a full life with optimal quality. She is based in Pretoria in private practice.
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