An old line, often repeated with variations, holds that the world is divided into two groups of people: those who divide the world into two kinds of people and those who don’t. It might also be said that in the world of diabetes clinical care and research, the world is divided into two groups: those who divide diabetes into two types and those who don’t.
For the first group, there is Type 1 diabetes and there is Type 2 diabetes, both of which impair the body’s ability to produce insulin and metabolize blood sugar. Each type has specific causes, symptoms and treatments. The second group holds that some patients with diabetes have characteristics that do not fit neatly into either group. They argue that these patients have a distinct condition they have labeled latent autoimmune diabetes of adults, or LADA.
In considering the question of categorizing diabetes, Dr. Cecilia Low Wang divides the world in yet another way. There are “lumpers” and “splitters.” Lumpers look for common characteristics between entities — like disease — while splitters look for differences and create new categories.
Low Wang, professor of medicine in the Division of Endocrinology, Metabolism and Diabetes at the University of Colorado School of Medicine and director of the Glucose Management Team at UCHealth University of Colorado Hospital on the Anschutz Medical Campus, is a self-described lumper. She spoke with UCHealth Today to explain the often subtle differences between the two – or three – types of diabetes and how those differences affect the diagnosis and treatment of the disease.
Let’s start with Type 1 and Type 2 diabetes. How are they different?
“That absolutely comes up in every conversation when someone is newly diagnosed with diabetes as well as when we first see a person in clinic,” Low Wang said. “It’s something that we are always thinking about and reevaluating because there are a significant proportion of people who are misdiagnosed with Type 2 diabetes and actually end up having Type 1.”
Type 2 diabetes, or what was once called adult-onset diabetes, is far more common than Type 1 — about 90% of all people diagnosed with diabetes, Low Wang said.
“One of the basic features of it is the body has insulin resistance, or an inability to use insulin very well or efficiently,” she explained. “Your body has to make more insulin to maintain good [blood sugar levels], and your pancreas has to work harder to make more insulin.”
In contrast, Type 1 diabetes, formerly called juvenile-onset diabetes, is an autoimmune disease in which the body produces auto-antibodies that attack the pancreas and the clusters of cells, called islets, that produce insulin, Low Wang said.
“Most people [with Type 1 diabetes] have profound destruction of the islets as part of the process of developing Type 1 diabetes,” she said. As a result, “People with Type 1 diabetes need insulin to survive.”
Another important difference is that Type 2 diabetes runs strongly in families, while the risk for Type 1 diabetes is less strongly inherited, Low Wang said.
How do the treatments for Type 2 diabetes and Type 1 diabetes differ?
As Low Wang mentioned, Type 1 diabetes destroys the insulin-producing cells that break down sugar, so patients with the disease must take insulin regularly, either through shots or pumps. People with Type 2 diabetes can often manage their insulin resistance and higher need for insulin with exercise, diet and non-insulin drug treatments, like Jardiance and Ozempic and many others that work in different ways to restore the body’s ability to produce insulin or manage blood sugar levels.
So far, these differences sound pretty straightforward. But are they? For example, can a person with Type 2 diabetes be misdiagnosed and actually have Type 1?
Yes. “I have seen patients who have been misdiagnosed with Type 2 diabetes for decades, and then they come to me and I diagnose them with Type 1 diabetes,” Low Wang said. “Then your entire frame of mind shifts because they need completely different treatments.”
According to the American Diabetes Association (ADA) and European Association for the Study of Diabetes EASD), more than 40% of people who develop Type 1 diabetes after they are 30 receive treatment initially for Type 2 diabetes.
Why does diabetes misdiagnosis occur?
There are several reasons, Low Wang said. To start, the lines between Type 1 and Type 2 diabetes are not clear-cut. For instance, terms like “juvenile-onset diabetes” for Type 1 and “adult-onset diabetes” for Type 2 have been mostly discarded, and for good reason, she noted.
“A significant proportion of people with Type 1 diabetes are diagnosed when they are below the age of 20,” Low Wang said. “But probably half are diagnosed over the age of 20. And there is a significant second peak of Type 1 diabetes when people are around their 50s, so certainly it’s something we should be thinking about.”
In addition, a patient may have some features of both Type 1 diabetes and Type 2 diabetes, Low Wang said. As the ADA and EASD report explains it, an older adult (on the surface a characteristic of a Type 2 diabetes patient) might at the same time have a normal or low body mass index (which is more typically characteristic of a Type 1 diabetes patient). Conversely, a young adult patient may have a higher-than-normal body mass index, a characteristic that again could point to either type of diabetes, the report notes.
“We have some patients diagnosed with Type 2 diabetes who look like they are clearly insulin resistant, but their diabetes is also acting like they are not making very much insulin at all,” Low Wang added.
One important test to confirm a diagnosis of Type 1 diabetes measures levels of the GAD (glutamic acid decarboxylase) auto-antibody, which targets an enzyme that helps the pancreas produce insulin. But Low Wang said the GAD does not always provide the answer, particularly when the disease has gone undetected for a long time. In a large percentage of these people, the GAD auto-antibodies have become undetectable or “faded away,” as she put it. The question for a clinician, then, is whether the patient has Type 1 diabetes and has lost the auto-antibodies or whether they never had them in the first place.
“Those antibody-negative Type 1 diabetes patients are probably the biggest conundrum that we face,” Low Wang said.
Are there other tests to confirm a Type 1 diabetes diagnosis?
Yes. Low Wang said clinicians can use other autoantibody tests to “drill down” on a possible diagnosis if the GAD test is negative. These are often checked to determine whether a family member of an individual is at risk for Type 1 diabetes. In addition, the C-peptide level test measures the body’s actual production of insulin. That test should be used along with simultaneously monitoring glucose levels in the blood, she added.
Low Wang said she bases decisions on whether to conduct the tests on listening to her patients describe their symptoms and histories, and on her “clinical suspicion” that a person might have Type 1 diabetes. The higher her suspicion, the more likely she will use one or more tests to confirm or rule out the diagnosis.
What are the clues that lead to suspicion of Type 1 diabetes in these difficult-to-diagnose cases?
Low Wang listed a number of factors that can point to Type 1 diabetes in patients who have been diagnosed with Type 2 diabetes:
- Age of 30 or younger
- No or little excess body weight (body mass index less than 30)
- No family history of diabetes
- Lack of response to non-insulin therapies and lifestyle changes (e.g., diet and exercise)
I’ve been diagnosed with T1 diabetes later in life. Will I be treated differently than someone diagnosed earlier?
The treatment — insulin — is the same, but Type 1 diabetes affects people differently depending on the age at diagnosis, Low Wang said. A toddler with Type 1 diabetes may be sicker and may be more likely to have diabetic ketoacidosis (DKA) when they are first diagnosed. DKA is a condition that can lead to coma, hospitalization and death without insulin and other treatments.
In school age children, the problems develop a little more slowly than in toddlers, Low Wang said. They typically have a “honeymoon period” of less than six months or more before they require insulin treatment. In adults, the honeymoon is often more prolonged, she said. But for the reasons discussed earlier, starting the medication as quickly as possible when there is insulin deficiency is important.
Why is it so important that people diagnosed with Type 1 diabetes later in life act on the diagnosis?
Low Wang emphasized that uncontrolled blood sugar levels pose significant risks for people with either Type 1 or Type 2 diabetes. The risks of complications differ depending on the type, but include cardiovascular disease, kidney problems, nerve pain, vision loss, and foot damage.
However, as an autoimmune disease, Type 1 diabetes puts patients at risk for other autoimmune disorders, such as hypothyroidism (low thyroid function) and Addison’s disease, a life-threatening condition that affects the adrenal glands, Low Wang said.
In general those who have Type 1 diabetes “need to be thinking about and screening for other autoimmune disorders, in addition to screening for diabetes complications,” Low Wang said.
What is the most important message for patients diagnosed with Type 1 diabetes later in life?
“You can’t assume that you have Type 2 diabetes,” Low Wang said. “As clinicians, we are always thinking about what is going on with the diabetes process because we want to make sure that we get the diagnosis correct.” Low Wang noted that it’s important for patients to review what was happening when they were diagnosed and how the diagnosis was made.
“For people who have struggled after making lifestyle changes – let’s say they’ve lost weight, and their blood sugars are still out of whack – that’s the most classic clue that you might have Type 1 diabetes,” Low Wang said. “You would for sure need to talk to your clinician and find out,” she said. It’s also important that patients make sure their provider has any updated information about medications they are taking and changes in their health, such as weight loss, she added.
OK. About the term ‘latent autoimmune diabetes of adults,’ or LADA. What does it refer to, and does it encapsulate the difficulties of diagnosing Type 1 diabetes that you describe?
Low Wang said most of the research that supports the idea of LADA has come from other parts of the world. “What they are trying to describe is people who have autoimmune diabetes that developed when they were adults,” she said. “That, to me, is still Type 1 diabetes.”
Some researchers put LADA in a separate category because Type 1 diabetes that appears later in life affects people differently than those who have it at a much younger age, as she explained earlier.
“It’s a way of naming something that is basically autoimmune Type 1 diabetes that manifests or shows up in adulthood,” Low Wang said. “But it’s one group. I don’t find it helpful to define this as a different type of diabetes.”
She also pointed out that the American Diabetes Association agrees. In 2022, the organization listed LADA as Type 1 diabetes that “evolves more slowly than the classic disease” but added that it “does not recognize it as a specific type of diabetes.”
If LADA isn’t a separate type of diabetes, is it worth considering?
“In my mind, it is,” Low Wang said. “There are still a lot of people using the term. Even a lot of clinicians are still using it. When you hear it, you really need to know what we’re talking about. It is Type 1 autoimmune diabetes but the individual may have other treatment options initially.”
In general, how can patients with diabetes help to manage their own health?
“I think it’s really important to be as honest and complete [with your provider] as you can,” Low Wang said. “If you’ve missed [medication] doses, just let them know because if they don’t know, they might raise your medication dose, and that could be a problem.”
It’s also very important for patients to get involved in their care and seek out reliable sources of information, Low Wang said.
“I love it when people come in and are engaged and ask questions,” she said. “I always encourage that.” But she also cautioned patients to be selective in what they read and whom they listen to.
“There is some very convincing misinformation out there,” Low Wang said. “It’s sometimes very difficult to distinguish between what is reliable and what isn’t. There are many reliable sources such as the American Diabetes Association, the Endocrine Society, and the American Association of Clinical Endocrinology, as well as many academic medical institutions and the Centers for Disease Control and Prevention.”