From sciencefocus.com
By Prof Craig Beall
Misdiagnosis rates for this rare type of diabetes could be complicating treatment for patients
You might be surprised to learn that there are more than two types of diabetes. We're all familiar with types 1 and 2, but you may have seen another one – type 1.5 – making headlines recently.
Type 1.5 diabetes, or latent auto-immune diabetes (LADA) to use its official name, is not a new form of diabetes, but it is somewhat rare. It’s been medically recognised as a distinct form of diabetes since 1993 and accounts for 3–12 per cent of all cases of diabetes in adults.
But as LADA shares similarities with its two, more famous, cousins, it's also trickier to identify. Hence, it's often misdiagnosed – a recent study suggests that as many as 14 per cent of people diagnosed with type 2 diabetes may actually have LADA.
Like type 1 and 2 diabetes, LADA is classed as a disorder of too much sugar, or glucose, in the blood.
When this occurs, it doesn’t matter what kind of diabetes you have – the symptoms remain the same: extreme thirst, frequent visits to the toilet, fatigue and unexplained weight loss. Diabetes UK, the leading UK charity for the disease, describe these as ‘the four Ts’: thirst, toilet, tired and thinner.
Once these symptoms appear, it's important to seek a diagnosis as soon as possible. Untreated diabetes can lead to a host of severe complications, impacting the kidneys, eyes and feet, as well as the nerve cells in your body.
But if the symptoms for these diseases are all the same, how can experts tell which kind of diabetes you really have? And how does it affect the way you treat it?
How type 1.5 diabetes compares to types 1 and 2
Diabetes, in its many forms, has ailed humans throughout history. A peculiar symptom often alerted healers in Ancient Greece, India and Egypt to the condition: the patient's urine smelled sweet. Hence the name Diabetes mellitus, taken from the Greek word ‘diabetes’, which means to pass through, and the Latin word ‘mellitus’, meaning sweet.
This aromatic side effect is caused by a build-up of glucose in the body. Glucose is meant to be broken down by a hormone called insulin, which is produced in the pancreas and converts glucose into a form that can be used as an energy source in cells.
A build-up of glucose happens when a person’s body either:
- isn’t producing enough insulin (as is usually the case in type 1 diabetes)
- or isn’t reacting to insulin the way it should (as in type 2 diabetes)
In either case, a lot of extra strain is put on the kidneys, which try to reabsorb the excess glucose floating around in the blood. When the kidneys can’t remove any more glucose, the excess sugar spills into the urine, offering a sign of the disease.
ADA shares a lot of similarities with these two main types of diabetes, but it has more in common with type 1 than type 2.
One of the main reasons people with type 1 diabetes don’t produce enough insulin is that their immune system attacks the cells in their pancreas that make the insulin. When a substantial number of these cells are lost, they can no longer make enough insulin to keep glucose levels in check.
The same is true in LADA – a swarm of immune cells attack the pancreas, leading to a drop in insulin production, which causes glucose levels to steadily increase. The two differ, however, when it comes to how long the disease takes to have an effect.
Type 1 diabetes takes effect rapidly, and is likely to be diagnosed in childhood or in a clinical emergency. LADA has a slower burn – hence the ‘latent’ in latent auto-immune diabetes – and doesn’t kick in until adulthood, commonly occurring in people above the age of 30.
As you age, a protective scaffold known as the peri-islet basement membrane (BM) forms around the insulin-making cells in your pancreas. Current thinking suggests that this scaffold helps to keep your immune cells from attacking your pancreas.
By the time that “autoimmunity starts in LADA, the pancreatic [cells] have already formed into larger structures and they’re better protected. They’re better able to resist the immune attack,” says Sarah Richardson, professor of cellular biomedicine at the University of Exeter.
The onset of LADA is therefore more similar to type 2, which usually rears its head during adulthood. It’s because of this similarity that up to 14 per cent of people diagnosed with type 2 diabetes are actually misdiagnosed cases of LADA.
Why misdiagnosis matters
The first line of treatment for type 2 diabetes is a medication called metformin. Given in tablet form, metformin works in two ways. Not only does it stop the liver from too much glucose, but it also increases the body’s sensitivity to insulin.
There isn’t, however, a definite, agreed-upon way of managing LADA yet. Metformin can be prescribed, as can insulin replacement therapy. If a person is misdiagnosed with type 2 diabetes when they really have LADA, they could be put on a course of metformin when they really need insulin.
The longer a person takes the wrong medication, the higher their glucose levels can climb. Over the longer term, high glucose levels increase the risk of heart disease and stroke, eye problems (retinopathy), foot problems (which can range from a higher risk of infection and ulcers to a loss of sensation), kidney disease (nephropathy) and nerve disease (neuropathy).
A 2018 study published in Diabetic Medicine found that people with LADA were more prone to developing severe neuropathy than people with type 2 diabetes.
LADA can also cause damage to small blood vessels, known as microvascular disease. A 2020 study found that implementing strict glucose control from the time a person was diagnosed with LADA could significantly reduce the later risk of microvascular disease.
Cutting down rates of misdiagnosis is therefore crucial for people with LADA, and thankfully there are a few key ways to tell it apart from type 1 and type 2 diabetes.
The first and most important thing doctors can do to differentiate the disease is to check for antibodies. These falsely tell immune cells to attack the insulin-producing cells in the pancreas. The presence of at least one antibody indicates autoimmune diabetes. If antibody levels are high, LADA may progress more quickly.
The same is true if multiple antibodies are found. In this case, insulin injections should be the first course of treatment, giving immediate and better control over glucose levels.
Doctors can also directly check a person’s insulin production. This is done by measuring a protein in their blood, called c-peptide, that’s made during pancreatic insulin production. Higher levels of c-peptide can be treated with metformin tablets, and very low or undetectable levels mean that insulin should be started immediately. In LADA, C-peptide levels decline with time – the current recommendation is to get them checked every six months.
A person’s body type can also be an indicator of LADA. If someone developed an increase in the ‘four Ts’ – thirst, toilet trips, tired and thinner – but had relatively low fat levels or body weight, they’re generally more likely to have LADA than type 2 diabetes. People with LADA also typically have better cholesterol, which can be used to narrow down a diagnosis.
Once the correct diagnosis has been made, LADA can be treated appropriately. It’s getting to this place, with the help of a medical professional, that’s critical.
https://www.sciencefocus.com/the-human-body/how-to-recognise-lada
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