Lance Bass’ diabetes misdiagnosis: Controversies of type 1.5
Key Takeaways
Lance Bass recently announced that he was misdiagnosed with type-2 diabetes (T2DM) during the pandemic. Despite being prescribed treatment, his symptoms failed to improve.
His true diagnosis was latent autoimmune diabetes (LADA), a controversial clinical entity that shares features of T1DM and T2DM.
LADA should be a differential diagnosis for patients of normal weight with hypothyroidism and other autoimmune disorders; C-peptide levels can guide the diagnosis and treatment of LADA, which includes insulin.
During the COVID-19 pandemic, Lance Bass (of the celebrated boy band NSYNC) was diagnosed with type-2 diabetes (T2DM). He initially struggled with getting his glucose levels under control, despite changing his diet and workout regimen and taking medication as prescribed.[]
Bass recently learned that he, in fact, had latent autoimmune diabetes (LADA), a controversial clinical entity also known as type 1.5 diabetes.
LADA defined
The American Diabetes Association (ADA) defines LADA as T1DM that evolves more slowly, and does not list it as its own form of diabetes. In Japan, it’s termed slowly progressive insulin-dependent T1DM. The WHO refers to LADA as a slowly evolving immune-related diabetes.[]
The Immunology for Diabetes Society proposes the following three criteria for the LADA diagnosis:[]
Age greater than 30 years
Positive autoantibodies to islet β cells
Insulin independence for at least the initial 6 months after initial diagnosis
A controversial diagnosis
LADA exhibits overlapping features of T1DM and T2DM, with autoimmunity against insulin-producing pancreatic cells.
No consensus exists as to whether LADA is a different clinical diagnosis, or a subtype of T1DM with the slower destruction of insulin-producing cells. Depending on studies and geography, the prevalence of LADA ranges from 3% to 12% of all patients with diabetes.[]
Although the criteria defined by the Immunology for Diabetes Society are appealing, they are debated; the choice of insulin treatment depends on the specialist.
LADA is similar to T1DM because antibodies to islet β cells are present—but at lower levels. Moreover, immune destruction advances at a slower clip vs typical T1DM.
Most patients present with hyperglycemia that is less drastic than that in T1DM and are diagnosed and mismanaged as having T2DM, as was the case with Bass. It’s only later that their specialists realize these patients are having trouble controlling their symptoms with standard treatments—including sulfonylureas—and eventually require insulin.[]
LADA that is undiagnosed or misdiagnosed raises the risk of microvascular (eg, nephropathy, retinopathy, and neuropathy) and macrovascular (coronary artery disease, stroke, and peripheral artery disease) complications.[] Although it’s tempting to think that patients with LADA might exhibit a decreased risk of macrovascular complications secondary to improved metabolic profiles vs T2DM, data indicate that T2DM and LADA predict similar cardiovascular outcomes.[]
Symptoms and diagnosis
Metabolic syndrome is more pronounced in patients with LADA than those with T1DM, and triglyceride levels are higher in LADA patients than those with T2DM.[]
As for BMI, while people with T2DM are typically overweight or obese, individuals with LADA are usually of normal weight.
Bass, for instance, is quite fit, and maintains a consistent exercise routine.[]
The biggest challenge with regard to LADA is differentiating the diagnosis from T2DM. Compared with patients who have T2DM, those with LADA exhibit at least one autoantibody, including islet cell antibodies or glutamic acid decarboxylase antibodies (GADAs). People with LADA usually have low levels of C-peptide, whereas those with T2DM have normal to high levels. To help differentiate LADA from T2DM, C-peptide can be a cost-effective test.[]
LADA should be a differential diagnosis for normal-weight patients with hypothyroidism and other autoimmune disorders, as well as those with deteriorating glycemic control despite the higher doses of oral treatments and the prescription of incretin mimetics.[]
“In LADA, the most frequently found antibodies are GADAs, and many authors recommend performing this measure in all newly diagnosed diabetic patients,” wrote authors publishing in PLoS One.[] “However, the costs involved in following this recommendation would be high and hardly acceptable in [primary healthcare].”
Treatment options
Despite receiving treatment, Bass had difficulty controlling his diabetes, which is typical for T1.5DM.
“[W]hen I was first diagnosed, I had a difficult time getting my glucose levels under control even though I made adjustments to my diet, medication, and my workout routine,” he recently told People.[]
Using the 2020 consensus guidelines for T2DM issued by the ADA and the European Association for the Study of Diabetes (EASD), and recognizing the heterogeneity within autoimmune diabetes, an expert panel developed appropriate “deviations” from those guidelines as recommendations for LADA.
Specifically, panel members suggested C-peptide values should serve as a proxy for β-cell function and should guide therapeutic decisions.[] The panel proposed the following three categories and corresponding treatments.
C-peptide levels <0.3 nmol/L: A multiple-insulin regimen is recommended as for T1DM.
C-peptide values ≥0.3 and ≤0.7 nmol/L: This was defined by the panel as a “gray area” in which a modified ADA/EASD algorithm for T2DM is recommended: “The modification consists of avoiding the use of hypoglycemic drugs that may have an effect in deteriorating β-cell function."[]
C-peptide values >0.7 nmol/L: The panel suggests a slightly modified ADA/EASD algorithm as for T2DM, with patients receiving repeated C-peptide measurements, to allow for the potentially progressive nature of LADA; monitoring C-peptide levels permits treatment adjustments.
The panel also recommended that newly diagnosed patients with non-insulin-requiring diabetes be screened for LADA.[]
Fortunately, Bass’s health improved after he started taking insulin, modified his diet, maintained a consistent exercise routine, and made other lifestyle changes.[]
Experts typically agree that sulfonylureas are a poor option for patients with LADA. These drugs deplete β-cells, drop C-peptide levels, allow for the persistence of antibodies, and are associated with earlier progression to insulin therapy.[]
On the other hand, thiazolidinediones may enhance insulin sensitivity by triggering nuclear peroxisome proliferator-activated gamma receptors. Furthermore, by preserving β-cell function, dipeptidyl peptidase (DPP) 4 inhibitors could be effective when either used alone or combined with insulin in LADA.[]
What this means for you
LADA should be considered in newly diagnosed patients with non-insulin-requiring diabetes. C-peptide levels are an inexpensive way to test for the condition. The prognosis of LADA is akin to that for T2DM. Hyperglycemia appears to predict death due to heart disease. Therefore, strict glycemic control is integral to improving prognosis.