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Diabetes Qualified

The evolution of diabetes classifications

The evolution of diabetes classifications

Most people know of type 1 diabetes, type 2 diabetes and gestational diabetes. But have you ever heard of monogenic diabetes? LADA? What about mitochondrial diabetes? Is there such a thing as type one-and-a-half? And what is atypical diabetes, type 1b, type 3. Credentialled Diabetes Educator Carolien Koreneff explains all.

Diabetes classifications

Different types of diabetes have had different names over the years. For example, type 1 diabetes was once called juvenile diabetes, before it changed names to Insulin Dependent Diabetes Mellitus or IDDM. Type 2 diabetes used to be referred to as mature onset diabetes and later became Non-Insulin Dependent Diabetes Mellitus or NIDDM. This caused some confusion when people with NIDDM changed to insulin treatment; did this mean they were now IDDM? No, they would have been referred to as “Non-Insulin Dependent Diabetes Mellitus-Insulin requiring”. Some health professionals still like using these terms.

What we know now is that diabetes is not clear cut. It is not just black and white. I tend to consider types of diabetes as being on a spectrum; with beta cell loss and insulin deficiency on one end and insulin resistance on the other end.

A proposed new division of diabetes conditions

A few years ago, I came across an article that was published in The Lancet, that suggested changing diabetes classifications. The article, authored by academics from Swedish and Finnish universities, proposed an entirely new division of diabetes conditions, because diabetes is not simply one disease. Diabetes is several conditions, each with different causes, treatments and outcomes.

Before we take a look at the subgroup these Scandinavians suggested, I will highlight a few other points, and other types of diabetes.

Diabetes in the early 1900s

Diabetes has traditionally been considered one condition: that of abnormally high blood glucose levels. The first treatment for diabetes was insulin, introduced in 1922. It was only a few years later, in 1936, that researchers published an article in The Lancet, that showed some people were sensitive to the insulin injections, whereas others were not. They started speculating that there may be different types of diabetes, and they were not wrong!

The previous classification of diabetes mentioned earlier (IDDM and NIDDM) were clumsy. They really only looked at whether or not a person needed insulin. The logical conclusion was that there are only two types of diabetes.

It was around 1998 that the American Diabetes Association (ADA) and the World Health Organization (WHO) recommended changing the classification to four main subtypes of diabetes: type 1, type 2, type 3 and gestational diabetes.

Type 1 diabetes

We now know that some people have an insulin deficiency, where they cannot produce enough insulin themselves. We consider type 1 diabetes to be an auto-immune condition. A condition where your own immune system attacks and destroys the beta cells in the pancreas, the cells that usually produce insulin.

Why the immune system of some people turns on the person themselves remains unknown to this day. But we do know that the auto-immune attack leaves those people being unable to produce (enough) insulin themselves, making them insulin deficient.

Insulin resistance

Other people are less sensitive to insulin; a condition currently referred to as insulin resistance. The underlying causes remain unclear in many cases. Although major social changes that have taken place over the past 50 or so years have contributed to the development of insulin resistance, including reduced physical activity levels and changes in food intake. Where we once walked or cycled to work, we now take the car or public transport. We favour lifts over stairs and generally have more sedentary jobs. Most people now work in offices instead of ploughing our lands. Food has become cheaper; portions have become bigger. Food is faster to access, and often highly processed.

Once the ability to store energy in our bodies was an evolutionary advantage. When food was plentiful we stored it as fat, in order to be able to access this energy at times of famine. But now, this is doing us harm. Research has shown that being above your most optimal weight increases insulin resistance and increases the risk of developing type 2 diabetes, as well as other medical conditions. But why is it that not everyone who becomes overweight develops diabetes?

Type 2 diabetes

The current ADA and WHO classification defines type 2 diabetes as being related to insulin resistance. However, people with type 2 diabetes may also have a relative insulin deficiency. One hypothesis is that type 2 diabetes is triggered by an inflammatory process.

Type 3 diabetes

According to the ADA and WHO type 3 diabetes covers a wide range of specific types of diabetes, including the various genetic defects of beta cell function, genetic defects in insulin action and diseases of the exocrine pancreas. The National Diabetes Services Scheme (NDSS) currently refers to this group of people with diabetes as “other diabetes”, for diagnostic purposes.

Gestational diabetes

As the foetus is very sensitive to glucose, blood glucose targets in pregnancy are much lower. In gestational diabetes (GDM) the blood glucose levels of a woman can become elevated due to an increased requirement of insulin whilst she is pregnant. Gestational diabetes can also be considered a form of insulin resistance, as some of the pregnancy hormones make the woman less sensitive to her own insulin.

Women with GDM will be advised to follow a healthy eating plan and do regular physical activity, to manage glucose levels. If this is not enough to keep their glucose levels in their target range, insulin injections may be needed. Although in some countries a tablet for diabetes, called Metformin, is prescribed in this setting, we currently don’t recommend tablet treatment for GDM in Australia.

Changing classifications

The move from the ADA and WHO to a classification that allowed for subgrouping by pathogenesis was forward looking. It created a framework that could accommodate the increasing number of specific causes for diabetes, which have since been discovered. Let’s look a a few of these.


Although most people develop type 1 diabetes earlier in life, around 5-15 years of age, there are some who develop an auto-immune reaction which presents in adulthood, and which is much slower to progress. This type of diabetes is currently referred to as Latent Auto-immune Diabetes in Adults, or LADA.

Many people with LADA are diagnosed with diabetes later in life. As many are above their most optimal weight for their bodies, LADA can be misdiagnosed as type 2 diabetes. However, most people with LADA have better cholesterol levels and less problems with blood pressure. People with LADA generally will need insulin injections over time, as their immune system destroys more and more of their insulin producing cells. Therefore, one could argue that LADA is a mixture of type 1 and type 2 diabetes.

It is now estimated that the group of people with LADA is around the same size as those with type 1 diabetes.


Some people develop a type of type 2 diabetes at a young age due to mutations in a dominant gene. So far there have been 13 of these hereditary conditions identified. This group of diabetes, which is common in some families, is referred to as Mature Onset Diabetes in the Young, or MODY. Treatment will depend on the type of mutation and can consist of tablets or insulin injections.

Secondary diabetes

Some people develop diabetes due to damage to the pancreas by other causes. These can include surgery, cancer and infections, such as pancreatitis.

The treatment of this type of diabetes depends on the cause and the extent of the damage. Many people will require insulin injections.

Other types of diabetes

Type 1b diabetes is an unusual form of type 1 diabetes reported mainly in Africa and Asia. People with type 1b have almost complete insulin deficiency. There is a strong hereditary component and importantly there is no evidence of auto-immunity.

Type 3c diabetes can develop when the pancreas gets damaged in such a way that it is unable to produce insulin. This could be due to conditions such as cystic fibrosis or chronic pancreatitis, a chronic infection of the pancreas. Having a pancreatectomy can also result in type 3c.

Monogenic diabetes are the least common forms of diabetes that result from mutations or changes in a single gene. Most cases of monogenic diabetes are inherited from a parent who also has the condition. It mostly affects young people, mainly under the age of 25. MODY, mentioned before, is a type of monogenic diabetes. Another example of monogenic diabetes is neonatal diabetes, where the baby develops hyperglycaemia within the first 6 months of life.

Monogenic diabetes conditions used to be numbered relating to the timing of the discovery of the genetic problem. Now they are referred to by their genetic mutations. The most common mutations are to hepatocyte nuclear factor-1-alpha (HNF1A, MODY3) and glucokinase (GCK, MODY2).

NODAT, or New Onset Diabetes After Transplant, is the development of diabetes following a solid organ transplantation, such as a kidney transplant, liver transplant or heart transplant. People at high risk of developing type 2 diabetes are more prone to develop NODAT, particularly if they have a first-degree relative with diabetes. Steroid treatment, as part of the anti-rejection therapy, increases the risk of developing NODAT, as do low magnesium levels. NODAT is almost the same as type 2 diabetes, in as far as the person tends to have insulin resistance and a decrease in insulin secretion. However, in NODAT hyposecretion seems to have a more important role in the glucose intolerance.

New subgroups?

Let’s go back to the research I mentioned earlier. The researchers suggested that the classification of diabetes could be refined, which might help to individualise treatment and identify people who may be at higher risk of developing certain diabetes-related complications. They identified five clusters of people with diabetes. Each with significantly different characteristics and different risks of diabetes complications. They suggested the following five subgroups:

  1. Severe auto-immune diabetes (SAID)
  2. Severe insulin-deficient diabetes (SIDD)
  3. Severe insulin-resistant diabetes (SIRD)
  4. Mild obesity-related diabetes
  5. Mild age-related diabetes

The authors used body-mass index, age at diabetes diagnosis, and two very specific blood tests for these classifications. One of the blood tests was C-peptides, which estimates how much insulin the body makes. If C-peptide levels are low it could show that little beta-cell function is left. If C-peptide levels are high it might mean that there is insulin resistance present. The other blood test they looked at is called glutamic acid decarboxylase (GAD) antibody status. In Australia we do not do these tests routinely as they are very expensive and not widely available.

As with most things in life, there are advantages and disadvantages to changing the diabetes classification. For starters, this proposed new classification may make it easier for some people to access continuous glucose monitoring (CGM) supplies or insulin pump consumables through the NDSS.

There are also limitations with this proposed re-classification of diabetes. For example, it does not account for other forms of diabetes such as steroid-induced diabetes or NODAT. Most importantly there would be huge costs involved in re-classifying diabetes. Hence it will no doubt take many more years before changes (if any) to the current naming of types of diabetes takes place.