In recent years some medical providers and diabetes advocates have been publically discussing LADA and Alzheimer’s, and yet no organization has formally classified either as their own unique forms of diabetes. Beverly Thomassian RN, MPH, CDE, BC-ADM talks about what she believes both are and how she addresses them in the clinical setting.  

By: John Parkinson, Clinical Content Coordinator,
A 37 year old lean patient diagnosed with “type 2” diabetes is referred to your clinic because he can’t get his A1c below 9 percent. He is exercising regularly, on metformin at maximum dose and has lost 10 plus pounds. He is restricting his carb intake to 45 gms a day in an attempt to get his blood glucose to goal, but he is still running in the mid 200s. The patient is frustrated and discouraged.

This patient had been unaware his body was in need of insulin therapy, and he could possibly be someone with type 1.5 or Latent Autoimmune Diabetes of Adults (LADA). This scenario is a hyperglycemic crisis, especially when a person is misdiagnosed with type 2 diabetes initially. 

The reason a problem like this exists is that there is no formal consensus or classification for people who exhibit the characteristics of LADAs. There are a growing number of clinicians who believe LADA should be acknowledged and would like to see more attention being paid to it to help get these people on earlier insulin therapy and help them with better  patient outcomes.

The problem is, according to Beverly Thomassian, RN, MPH, CDE, BC-ADM, is without the official classification or at the very least guidance by the healthcare community that this unique subset of diabetes exists, it can lead to ongoing unmanaged hyperglycemia and lead to the development of comorbidities due to maintaining unnecessarily high blood sugars in the absence of insulin therapy.  

Thomassian (pictured, lower right) says she suspects her patients have LADA, first by their body weight, age and history of diabetes onset. If the patient is not overweight and describes a sudden onset of hyperglycemia, this increases her suspicion. In addition, she performs a comprehensive family history with a special focus on any history of autoimmune disease in the patient and their immediate family to determine if this person is a likely candidate for being a LADA. Overall, she says patients with LADA present with elements more indicative of type 1 than type 2 diabetes; since often, inspite of weight loss and carbohydrate restriction, their blood sugars are still elevated.

Thomassian has her own consulting business, Diabetes Educational Services, and manages a recognized American Diabetes Association (ADA) education program, Diabetes Survival Camp, in Paradise, Calif. In addition to seeing LADA patients, she also sees seniors and she believes in the diabetes connection to Alzheimer’s or what some are referring to as type 3 diabetes.

And so Thomassian takes a holistic, clinical approach with these patients who are at risk of Alzheimer’s; she sees the preservation of brain health as vital to staving off dementia and Alzheimer’s. spoke with Thomassian about which patients might be potential LADA candidates, provides some insights about the link between Alzheimer’s and diabetes, and how she treats both subsets of patients therapeutically. Can you define LADA?
Thomassian: LADA or 1.5 is a gradual, autoimmune destruction of the pancreas. To determine if someone has 1.5 diabetes, I usually rely on clinical presentation and their lack of response to oral agents and weight loss. If further confirmation is needed, I suggest that we check for autoantibodies, which would confirm an autoimmune attack, With 1.5, you are drawing the three major autobodies: glutamic acid decarboxylase antibodies (GAD), insulin antibodies (IAA), and islet cell antibodies (ICAs), and one result comes back positivie is the person has LADA . 

I refer to LADA as a slow moving type 1. The pathology is autoimmune based, but the person can still have some remnant beta cells left. It is hard to determine how many of these cells exist but it can as anywhere from 10 to 30 percent of them. 
The reason it is so important to differentiate between 1.5 versus type 1 or type 2 is that the studies being done are indicating if we can identify 1.5 we can preserve or save those remaining cells by initiating early insulin therapy. However, this theory is so new and emerging that we don’t know how long we can delay the destruction of the beta cells since it is an autoimmune process. If you are interviewing a new patient for the first time who presents with what you suspect to be LADA or 1.5. What are the clinical parameters you use to determine this?
Thomassian: These people might be average weight or a littleoverweight, but they are not obese. They will likely have had pretty good A1cs six months ago, but their A1cs went up very quickly, and unexpectedly. The patient might tell you, ‘I was trying to make some changes to my diet and eat less food,’ and their blood sugars are not coming down.

When people with type 2 diabetes lose weight, their sugars often come down; in people with LADA, their blood sugars are not affected that much by weight loss or carbohydrate restriction.

You want to find out about their family history. Maybe their family doesn’t have diabetes, but they may have other autoimmune illnesses. I will ask them about a history of thyroid, rheumatoid arthritis, celiac disease or other autoimmune conditions in their families.
These LADA people are older, have blood sugars that go up quickly in a short amount of time, and they don’t look like type 2s. And they might respond minimally to oral medications. These are signs that this is not the typical diabetes, so we need to investigate further. Do you recommend panel testing in these patients?
Thomassian: You can look at their glucose and it may be elevated, but I don’t recommend c-peptide testing in this situation. Their c-peptide could be normal, and they could still be making some insulin. C-peptide levels don’t get at the underlying pathology of this autoimmune process. 

I believe doing a very good family history, observing the blood glucose response to weight loss, exerciseand medications and getting a detailed history of the onset of diabetes will usually reveal the true nature. If based on all that data, I am still not sure, I will request to draw at antibodies How do you begin to treat a 1.5 as opposed to other people who present with classic symptoms of type 1 diabetes?  
Thomassian: If the 1.5s are experiencing glucose toxicity initially (blood sugars of 300s or more) then they may need more than expected quantities of insulin based on their body weight. Then once they start to take insulin on a regular basis and their blood sugars start to normalize, you will see they need about 0.5 units of insulin per kilogram of body weight. In general, they do not display characteristics of insulin resistance; they are insulin deficient and tend to be insulin sensitive.

The best thing to do when they stabilize is to put them on daily basal insulin to help their overall blood sugars under control. In many instances, they will also need bolus insulin twice to three times a day depending on how much beta cell mass they have left. So you believe in putting LADA patients on insulin right away, and you don’t advocate waiting?
Thomassian: When you lose beta cells you not only lose insulin production, you lose hypoglycemia protection too. Beta cells have such an important role in stopping glucose fluctuation.
I believe in getting them on basal insulin right away. And if their sugars are running high during the day, I would add some bolus insulin to their regimen. If they are heavier and do show some insulin resistance you can add metformin, but it may or may not be helpful. Why do you think LADA is not formally recognized by any medical organizations? 
Thomassian: I think there has been some breakthrough in this area. Irl Hirsh, MD, a leader in the field, has written on it and the ADA had a cover article on LADA in Diabetes Forecast, their magazine for patients.

Even TrialNet is seeing 1.5 as its own unique clinical feature, and they are enrolling people with LADA for their clinical trials.

I also think we didn’t had good science on it before. Now we see more information and research emerging on it. We are understanding autoimmunity and better able to map out the genetics that are associated with diabetes with the work of the Human Genome Project  and with the Natural History research compiled by the TrialNet group. What advice would you give to other clinicians in terms of treatment for LADAs?

Thomassian: If a person walks in with the diagnosis of type 2 and is not fitting the typical type 2 mold, investigate further. If they don’t look or exhibit symptoms of a classic type 2—they don’t have that central abdominal obesity, for example—they could be a LADA. Trust your professional instincts.

Complete a comprehensive family history, and if you are still not sure, draw for antibodies.

And I believe in administering early insulin therapy to get them out of glucose toxicity and to protect beta cells. And initially, oral agents might work in conjunction with basal insulin, but they may need complete insulin therapy over time. You had a discussion in your recent newsletter where you had mentioned type 3 diabetes. Can you explain what type 3 means?

Thomassian: With type 3 diabetes, they are talking about as it is associated with Alzheimer’s disease and insulin resistance. It may be its own unique type of diabetes.

While this term has not be accepted in the medical world, clinicians and researchers have been noticing people with diabetes do have double the risk of developing Alzheimer’s. And it seems to be related to insulin resistance in the brain. With insulin resistance in the brain there is an amyloid formation and decreased neurotransmission.

We know there is a link between diabetes and Alzheimer’s and we have been trying to figure out what it is exactly. It seems like there is a genetic link between the two conditions. In both Alzheimer`s and diabetes there is insulin resistance. It appears that this insulin resistance in the brain reducesneurotransmission. With diabetes, there is also vascular disease, so there might be a vascular dimension where the brain is not getting enough circulation. It could be a combination of insulin resistance and poor vascularization of the brain. Does the healthcare community need to reclassify forms of diabetes into this new number system where it is includes 1.5 and type 3 diabetes?

Thomassian: There is no doubt, 1.5 diabetes is underdiagnosed; even in clinical trials such at the UKPDS, people with LADA were misdiagnosed with type 2 diabetes.

It does need to be recognized as its own separate entity—as a slow moving, autoimmune diabetes. If we recognize it, and treat it early there might be some beta cell preservation associated with it. And we might be able to have people with LADA feel healthier. They may go for many years with undertreated hyperglycemia because they are not receiving the insulin replacement therapy their body needs.

So if we have a better understanding of the pathology, we can provide better treatment and outcomes. Quite frequently, LADAs who are diagnosed with type 2, are put on oral medications and told to exercise and lose weight. These patients are compliant and are taking their medicine and eating right and yet their blood sugars are still high. When their blood sugars don’t come down, they feel like failures; these people are not failures, their pancreas is failing. They have autoimmune destruction. I can look at them and say, ‘your body is screaming for insulin.’

As far as type 3 diabetes classification, the only good thing about calling it this is that it will bring attention to it. So many people don’t realize that diabetes, Alzheimer’s and dementia are linked. And there are some things to keep the brain healthy, like crossword puzzles, exercise, and reading. Anytime people can do right-left brain hemisphere activities, it can help slow down dementia and Alzheimer’s. Dancing is particularly helpful, since there it requires a lot of right-left brain connection and quick decision making.  
Bringing attention to these health issues helps us as providers to keep people as healthy as long as possible. Can you talk about your patients who might be at risk of Alzheimer’s and what you do to improve outcomes?

Thomassian: Most of the patients in my clinic are mature (60 and above), but we are seeing more in the 30-50 age range as the incidence of diabetes affects younger people. I love my patients. Even though they may be older and suffering with other chronic illnesses, they amaze and impress me with their great attitudes and willingness to do the work required to manage diabetes. During my classes, I focus not only on body health but also brain health and prevention of dementia and Alzheimer’s. We do brain gymnastics, including balancing exercise and the Macarena.  I have 80 and 90 year old people in my classes doing the Macarena dance, and they love it!  

Thomassian is doing a free webinar on World Diabetes Day (November 14) on New Horizons in Diabetes, where she will be talking about this topic. Interest persons can go here to view it.