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Stages of type 1 diabetes

Author: Dr Sorin Ioacara | Last update: November 9th, 2020

All moon phases on a sky above a city.

Discover here: When does type 1 diabetes start? | Stage 1 | Stage 2 | Stage 3 | Stage 4

The stages of type 1 diabetes are generally little known to both the patients and doctors. The very concept of staging type 1 diabetes is a notion that has gained more shape only in the last 10-15 years. The diagnosis of type 1 diabetes is not very difficult in a child with a blood glucose of 400 mg/dl (22.2 mmol/l). If the child has been drinking a lot of water and urinating a lot for the last two weeks, things are even more straightforward.

However, our discussion refers to the possibility of diagnosing type 1 diabetes many years before this hyperglycemic moment, when the child is perfectly healthy.

There are four stages in the natural course of type 1 diabetes:

  1. Autoimmunity, asymptomatic, normoglycemia
  2. Autoimmunity, asymptomatic, prediabetes
  3. Autoimmunity, symptomatic, hyperglycemia
  4. Type 1 diabetes evolving for a long time

You can get the diagnosis of type 1 diabetes in any of these stages of evolution.

The stages of type 1 diabetes begin with the second specific antibody

An infant with a toy in his mouth.

The stages of type 1 diabetes can begin only at least a few months after birth. Therefore, diabetes that starts in the first six months of life is never type 1 diabetes, but neonatal diabetes. At birth, you already have a constellation of genes, which can pose a low, medium or high risk for type 1 diabetes. Even though these genes will stay for the rest of your life, they are not enough to trigger the disease.

The primary cause of type 1 diabetes triggers autoimmunity

The risk of developing type 1 diabetes varies widely in the population. Current evidence is much better for risk factors acting after birth.

The cause of type 1 diabetes is that one that can trigger the immune system’s response against pancreatic beta cells. So, it is very likely that initially, this response of the immune system is not constant, but in waves. The immune system attacks the pancreatic beta cells for a specified period. Then, a break will follow and so on.

The mechanisms of progression to type 1 diabetes differ from its cause

Gradually, the attack of the immune system becomes permanent, without periods of pause. The cause can sometimes disappear quickly after the initial aggression. Thus, only the mechanisms of progression to type 1 diabetes remain active in the long term, not its primary cause.

Current technology does not allow direct detection of immune system damage in the Langerhans Islands, which harbour the pancreatic beta cells. At least not in the living man. Only the pathologic examination can reveal the pancreatic beta cells. However, this type of examination is usually done in the deceased patient or if at least one pancreas fragment is surgically removed. Pancreatic biopsy is extremely risky. That’s why it can’t be a routine option.

An indirect method of highlighting the attack of the immune system against pancreatic beta cells is the dosing of specific antibodies. The presence of a single antibody is not sufficient to diagnose the stage 1 of the type 1 diabetes.

The risk of type 1 diabetes in the presence of a single antibody is about 10%. The stages of type 1 diabetes start from the moment the second specific antibody appears.

Type 1 diabetes, stage 1

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The diagnosis of stage 1 of the type 1 diabetes involves the detection of at least two of the four specific antibodies. Also, all blood glucose levels must be within the normal range, including glycosylated hemoglobin. The particular symptoms of type 1 diabetes are not present at this stage. This phase is the real onset of type 1 diabetes. Type 1 diabetes stage 1 usually lasts for several years, sometimes even decades. Rarely, progression to stage 2 can be quick, in just 1-3 months.

Most children (90%) who have a clinical onset of type 1 diabetes (stage 3) by the age of ten could have been diagnosed with stage 1 of the type 1 diabetes before the age of five. Once in stage 1, type 1 diabetes is a self-sustaining disease.

He will progress to stage 2, 3 and 4 no matter what we attempt to do. Indeed, most interventions tried so far could only slow down the progression, not stop it. Most, but not all! Of great interest is the use of a drug, called teplizumab, in an attempt to slow the progression from stage 2 to 3. A recent study showed a doubling of the time required to reach stage 3 of type 1 diabetes (clinical onset) with the use of this drug.

Type 1 diabetes, stage 2

A road sign with the number 2

The diagnosis of type 1 diabetes mellitus stage 2 means the presence of at least two specific antibodies plus glucose values in the range of prediabetes. As in stage 1, the particular symptoms of type 1 diabetes are absent. Phase 2 of type 1 diabetes usually lasts 1-2 months. For this reason, it isn’t easy to recognize it. At this stage, the immune system already destroyed about 20% of pancreatic beta cells. An additional 10% completely stopped working. Only 70% of the beta cells are still functional. However, these remaining 70% beta cells do not work at optimal parameters. An intravenous glucose test can highlight this lack of efficiency.

In this stage of type 1 diabetes, there is a reduction in the amplitude of phase 1 of insulin secretion. Phase 1 of insulin secretion refers to the rapid discharge of insulin in the first 1-3 minutes in response to intravenous glucose. Towards the end of stage 2 of the type 1 diabetes, the phase 1 of insulin secretion melts down gradually into phase 2 of the insulin secretion.

Blood glucose in the prediabetes range means any of the following:

  • 100-125 mg/dl (5.6-6.9 mmol/l) fasting
  • 140-199 mg/dl (7.8-11 mmol/l) at 2 hours in a test of glucose tolerance test
  • glycosylated hemoglobin 5.7-6.4% (39-47 mmol / l)

Type 1 diabetes, stage 3

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The clinical hyperglycemic onset of type 1 diabetes is the entry into stage 3 of the disease. Children previously diagnosed with stage 1 or 2 of the type 1 diabetes generally have only slightly elevated blood glucose and glycosylated hemoglobin levels at the onset (stage 3). This mild onset is due to the training received in recognizing the specific symptoms of unbalanced type 1 diabetes. These children have a significantly lower risk of developing diabetic ketoacidosis at onset. Besides, education received in stage 1 or 2 of the type 1 diabetes and insulin therapy promptly initiated in stage 3 is associated with a lower risk of long-term complications.

Ways of the clinical onset of type 1 diabetes

At the time of diagnosis of stage 3 of type 1 diabetes, most children have intense thirst, frequent and high amount urination and weight loss. These symptoms specific to type 1 diabetes are generally present for 2-4 weeks, but have worsened in the last 3-5 days.

Rarely, the evolution is fast, in just 2-3 days. Such rapid development is often associated with diabetic ketoacidosis at onset. Dehydration, nausea and vomiting are additional signs of severity, announcing the start of diabetic ketoacidosis. The younger the child, the higher the risk of rapid progression to ketoacidosis. When the child is in ketoacidosis, he takes deep breaths, saying that he is “short of air”. Also, ketone bodies can cause abdominal pain.

The fact that he urinates often should not be confused in this context with a urinary tract infection. Under no circumstances should this child be stopped from drinking as much water as he feels needed. A simple finger or urine glycemia (with coloured strips) can quickly point to the source of the problem.

At the other extreme are some children who have an unusually slow course of the disease. They may have high blood sugar only postprandially (after a meal) for already a few months. Then follows a slow rise in fasting blood sugar (in the morning). Glycosylated hemoglobin generally stays below 8% throughout this period.

The remission phase in paediatric type 1 diabetes

The period of transient remission of type 1 diabetes is also known as the “honeymoon phase”. Temporary remission is of two kinds:

  • partial
  • complete

Partial remission means a reduction in the need for insulin after the first 5-14 days from onset below 0.5 U/Kg body-weight. Prandial insulin can sometimes be stopped entirely, keeping only the basal insulin. The basal insulin requirement in monotherapy may in some cases be only 2-4 U/day.

Complete remission involves the possibility of stopping insulin therapy entirely while maintaining the metabolic control. This “honeymoon” can last between two weeks and two years, whether it is partial or complete.

The only thing that can slightly prolong the period of transient remission is the systematic, daily, high-intensity physical effort. Unfortunately, there is nothing you can do to extend the transitional remission period indefinitely.

Type 1 diabetes, stage 4

A syringe floats over a hand with a laptop on in the far background

At the end of the transient remission period, the insulin requirement begins to increase significantly. There will be a parallel decrease in insulin secretion from your body. You can measure the blood C peptide to evaluate your insulin secretion. A value below 0.4 ng/dl indicates a low insulin secretion. However, any amount above 0.05 ng/dl is associated with a lower risk of chronic complications of diabetes. Stage 4 of type 1 diabetes begins after the end of the remission period (if any), when the need for insulin in basal-bolus treatment has stabilized. This insulin requirement stabilization usually happens 6-12 months after the onset. The duration of stage 4 of the type 1 diabetes is currently for the rest of your life.

The existence of stage 4 is not universally recognized. There are some opinions that it is enough to maintain stage 3 designation even beyond the 6-12 months from the onset (and the end of a possible remission period). I find the use of stage 4 useful to separate phases after the first year from the beginning. In this way, we can better focus our clinical and research efforts on the period within one year after onset, defined as stage 3 and then separately for the next period.

References

  1. American Diabetes Association Guideline 2020
  2. ISPAD Clinical Practice Consensus Guidelines 2018
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