Think Autoimmune: Connecting the Dots

The Connection Between Autoimmunity & T1D

In this section, Jodi Lavin-Tompkins asks Lucia Novak questions about how she puts Type 1 diabetes (T1D) screening into practice and how Diabetes Care and Education Specialists (DCESs) and other health care professionals (HCPs) can advocate and educate people with diabetes about the connection between autoimmunity and T1D.

Making Recommendations Around T1D Screening in Your Practice

Jodi Lavin-Tompkins: What is the traditional thinking about T1D and how it needs to change to better address screening?

Lucia Novak: Type 1 diabetes is typically associated with children and adolescents. This is when we see the initial peak incidence of T1D. It is the most common chronic disease of childhood. But we see another increase later in life, in individuals in their 40s through 60s. More than 50% of all new cases diagnosed each year are adults. However, because T1D is usually not on our radar in people over age 30, somewhere between 5% to 15% of adults with T1D are misclassified as having Type 2 diabetes (T2D).

In addition, we have seen a global rise in autoimmune disorders, in general, by about 3% to 4% across the globe, and that includes T1D. As mentioned in section 1 of this series, many autoimmune disorders are associated with a higher risk of developing T1D. 

If you are a DCES or another HCP for adults, you may ask, "Some of the individuals I see may be at greater risk, but I cannot screen everybody — how do I figure this out?"

The goal of this section is to help practitioners identify individuals with whom they may need to go that extra step and screen for T1D — and/or recommend their family members to be screened for T1D.

Jodi Lavin-Tompkins: What do DCESs and other HCPs need to know about T1D and its connection to other autoimmune disorders?

Lucia Novak: Many autoimmune disorders — including T1D — share the same risk-associated HLA haplotypes, often resulting in comorbidity. Autoimmune disorders tend to coexist in one person and cluster in families.  

If a person has one autoimmune disorder, they are likely to have at least one other; and if there is a family history, the individual is also at greater risk. Therefore, it is crucial to ask individuals about their personal and family medical history, including any autoimmune conditions — not just T1D.   

Not screening for other autoimmune conditions in these cases is very similar to not checking cholesterol in someone who is known to have a family history of heart disease.  

Jodi Lavin-Tompkins: What are the most common autoimmune disorders you see?

Lucia Novak: T1D is a common autoimmune disorder, but not the most common. The more common autoimmune conditions that are seen where I practice are thyroid conditions: Hashimoto's thyroiditis (autoimmune hypothyroidism), and Graves' disease (autoimmune hyperthyroidism).

Other related autoimmune diseases are described in section 1 and include celiac, intrinsic factor vitamin B12 deficiency (pernicious anemia), vitiligo, rheumatoid arthritis, autoimmune atrophic gastritis, and Addison’s disease, to name a few. Autoimmune disorders in general affect females more often than males at a rate of 2:1, and 80% of those with an autoimmune disorder are female. The sex-biased association is unknown, but research is being done to better understand it.  While T1D specifically is not associated with gender, people who tend to have more than one autoimmune disorder (i.e., Hashimoto’s thyroiditis and T1D) are more often women between ages 40 to 60 years.

Jodi Lavin-Tompkins: Why is it important to know about these other autoimmune disorders when it comes to T1D screening and diagnosis?

Lucia Novak: As I mentioned earlier, T1D is being underdiagnosed, or in many cases, it is being misdiagnosed as T2D, especially in adults where 5% of 15% are being misclassified as having T2D. According to the ADA Standards of Care in Diabetes, soon after the diagnosis of T1D, individuals need to be screened for autoimmune thyroid disorders because there is such a high association between T1D and autoimmune thyroid disease. While the reverse is not as clear, we need to keep in mind the connection between autoimmune diseases.

Overall, practitioners need to trust their gut when the pieces do not seem to fit.

Examples of Connecting T1D to Autoimmunity in Practice

Jodi Lavin-Tompkins: Can you give us a couple of examples?

Lucia Novak: As you know, every adult aged 35 years and older needs to be screened for diabetes, regardless of risk factors.  The type of diabetes we are most often looking for is T2D — especially in the adult population. However, T2D is a disease of insulin resistance and there are clinical manifestations and/or other diseases that are associated with this classification (acanthosis nigricans, hypertension, elevated triglycerides, low HDL, history of PCOS, fatty liver). Therefore, when you are screening for diabetes and the values are abnormal but the person 1) has another known autoimmune disorder or family history (such as Hashimoto’s thyroiditis or vitiligo), and/or 2) does not have any signs, symptoms, or other disorders related to insulin resistance, we need to determine if this person has autoimmune T1D.

Therefore, when I am repeating the A1C or glucose, I will add a T1D autoimmune profile which includes the GAD65, IA-2, IAA, and ZnT8 autoantibodies. The one most likely to be positive in an adult will be the GAD65 autoantibodies as it is the most sensitive and specific biomarker associated with latent autoimmune diabetes of adulthood (LADA).

Jodi Lavin-Tompkins: What about individuals who have been living with an incorrect diagnosis; what would that look like?

Lucia Novak: If you have a suspicion that something is not right, follow up with that. It could be someone diagnosed with T2D years ago and they are saying that they have had it for 30 years and their glucose has never been well managed. Their A1C has never been less than 8, let alone less than 7. So, I am looking at their labs, and the picture does not add up. For example, they might be on a very low dose of lisinopril 2.5 mg. Yet they inform you that they do not have high blood pressure but were told they need it to “protect their kidneys.” Perhaps they are not on a statin or a very low dose of one and they are without elevated TG and have normal HDL and TG and their LDL is under 100. It has been my experience that someone with 30 years of T2D needs a high-intensity dose of a statin to achieve an LDL of < 70 and they typically have low HDL with elevated TG. As you can see, the clinical picture does not add up to this person having T2D.

Additionally, it is up to us to make sure their life story has no missing pieces. For instance, they may be aware that their mother, sister, or aunt have “thyroid problems” but do not know if it is an autoimmune disorder. This would become a homework assignment for that person — to try to clarify that family history — it is so important!

Jodi Lavin-Tompkins: Are some individuals being misdiagnosed with T2D in part due to assumptions made because of factors like weight and ethnicity?

Lucia Novak: Yes — traditionally, individuals of color are considered at high risk for developing T2D compared to their White counterparts. Therefore, if an adult is Black, Hispanic, or Asian and/or has overweight or obesity, it is often assumed they have T2D.

Practitioners need to dig a little deeper into that personal and family medical history for the pieces of that autoimmune puzzle. What should drive determining who to screen is listening to the person and getting their full personal and family history. They are the experts in who they are and what they and their families have experienced. We are the experts in putting those pieces of information together to determine the risk/potential for diseases/disorders. We are instrumental in connecting the “diagnostic dots,” but we cannot do it without their input.

The Value of Screening for Family Members

Jodi Lavin-Tompkins: How do you recommend individuals with T1D talk to their families about screening?

Lucia Novak: When individuals are seen in the clinic and have T1D, they often will say they have no known family history of T1D. But when you start asking about thyroid disorders, they will commonly say something like, "Yeah, my mom has this." Then you discover there are other endocrine or glandular issues going on. We must pause as DCESs and other HCPs and say, "OK, this patient does not match someone showing evidence of insulin resistance, impaired glucose tolerance, or impaired fasting glucose, and they have all of this other ‘stuff’ going on."

I strongly advise and encourage the individuals I see with T1D to discuss screening with family members, certainly first-degree relatives like parents, siblings, and their children.

It also works the other way — someone with T1D needs to be screened for other autoimmune disorders upon or shortly after diagnosis. I encourage their family members to be screened for an autoimmune etiology if they have an unclear diagnosis (i.e., hypothyroidism but not known if it is autoimmune; or a history of stomach issues/food intolerances) with no real idea of the cause.

When it comes to autoimmunity disorders, it takes a village to figure it out — and that village includes the health care team, the patient, and their family.  Once one autoimmune disorder has been diagnosed, it should remain high on the list of differential diagnoses for other complaints, illnesses, and disorders.

Jodi Lavin-Tompkins: How do you convince individuals and family members of the value of screening for T1D and/or autoimmune disorders, beyond potentially getting bad news?

Lucia Novak: If they ask why they would want to find out if they have got this, you can tell them, "It's really important that you identify whether or not anyone else in your family has this so we can closely monitor and reduce the risk or delay an acute, life-threatening hyperglycemic event. Another reason would be to ensure the correct diagnosis has been made between T1D and T2D as these two diseases are managed very differently."

The conversation might sound like, “Look, you (or a family member) have one autoimmune disorder and the chances of having another are high compared to someone without this type of disorder. Knowing if you are at risk for T1D will allow you to prepare and enable you to live your best life."

Screening Coverage & Coding 

Jodi Lavin-Tompkins: What do What do patients, DCESs, and other HCPs need to know about the cost of screenings?

Lucia Novak: Tests such as screening the A1C or fasting glucose, getting a B12 level, and the autoimmune panel are usually covered by health insurance. I have been practicing for 30 years, and I have never had an individual say their insurance did not cover their diabetes autoimmune screening. I might get that for some other tests like a vitamin D level if I did not have the appropriate diagnostic code, but I have not to this day had them come back and say they had to pay out-of-pocket for autoimmune screening, but that may not be everyone’s experience.  If they are informed that they will be charged, there is free testing for T1D antibodies available to eligible individuals through certain centers or research studies.

Jodi Lavin-Tompkins: How should practitioners code these tests in their EHR?

Lucia Novak: Use the ICD code for screening; it is going to be a Z code. "Screening for other suspected endocrine disorders" is one of the ICD 10 codes that I use. Then I put in my rationale, such as: "A history of autoimmunity/need to rule out." Then I list what I am ruling out.

Diagnosing T1D

Jodi Lavin-Tompkins: If someone comes back with one positive antibody for T1D, does that mean they have T1D?

Lucia Novak: Well — we are still speaking about screening — which is done in asymptomatic people.  Therefore, keeping this in mind, when screening for T1D in someone who is asymptomatic (euglycemic) — we are looking for the presence of autoantibodies to determine risk for T1D. The presence of at least 2 autoantibodies is associated with an almost 70% conversion to overt T1D. They will progress more rapidly to stage 2 and then to stage 3. Those screened and found to have only 1 positive autoantibody have less than 15% conversion to T1D — and may revert to negative and not progress at all. However, these individuals will need to be monitored.

If there is a family history of T1D, and initial screening detects no autoantibodies it is recommended that individuals be periodically rescreened for autoantibodies — perhaps every 1 to 3 years — depending on other risk factors (such as the number of family members with T1D, prevalence of other autoimmune disorders, history of hyperglycemia (i.e., when exposed to glucocorticoid, illness).

If one autoantibody is detected, rescreen annually to observe for others to become positive — and begin to monitor glucose to determine the transition to early metabolic decompensation (stage 2).

If two or more autoantibodies are detected, you are no longer screening for risk of T1D — this is diagnostic for stage 1 T1D. Additional and future testing would focus on monitoring for early metabolic decompensation (progression from stage 1 to stage 2) and once in stage 2, to reduce the risk or delay DKA when progressing to stage 3.

Once someone has progressed to stage 2, the ADA recommends monitoring for clinical T1D (stage 3) by performing A1C testing every 6 months and obtaining 75 g oral glucose tolerance test (i.e., fasting and 2 h plasma glucose) every year.  Some DCESs and other HCPs may be inclined to place patients on CGM to closely monitor glucose patterns and initiate insulin as soon as dysglycemia is recognized.

Key Takeaways

• Autoimmune disorders cluster in families.
• When an individual has one autoimmune disorder, have a higher degree of suspicion that other autoimmune disorders are present.
• All adults aged 35 years and older should be screened for diabetes. If results identify prediabetes, consider other comorbid conditions and question if a diagnosis of stage 2 T1D should be considered.