By Cecilia D., Lagniappe Wellness Dietetic Intern
Diabetes mellitus is a disease so common worldwide just about every person walking down the streets of wherever you are reading this from could tell you something about it. Maybe you have seen commercials on television for medicines to aid in diabetes management, heard the common misconception that carbs are “bad” for people with diabetes, or that celebrities including Nick Jonas and Rosie O’Donnell have diabetes. There are two well studied commonly known variations of diabetes: type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). T1DM is typically diagnosed in children and adolescents; it is an autoimmune disease, which describes an automatic response initiated by the immune system that results in the body’s immune, or “defender” cells, attacking healthy native cells. Often, this attack disrupts a process required for normal bodily functions to occur and keep the individual healthy. In the circumstances of T1DM, the beta cells of the pancreas, which produce insulin, are destroyed by this autoimmune response, and insufficient insulin production results (Nolasco-Rosales et al., 2023). Detection of these autoantibodies are helpful in diagnosing T1DM ( (Nolasco-Rosales et al., 2023)T2DM is developed later on in life usually after the age of thirty, but certainly can be diagnosed in childhood and adolescence. However, in T2DM, insulin resistance is the functional problem and it is perceived as preventable as it is often attributed to the presence of excess adipose tissue, poor diet, and physical inactivity (Nolasco-Rosales et al., 2023). A less commonly known form of diabetes which develops later in life like T2DM, yet presents with similar complications and physical traits to T1DM, is known as latent autoimmune diabetes in adults (LADA) or type 1.5 diabetes mellitus (Buzetti et al., 2020). Some may describe LADA as the most extreme version of T1DM (Nee et al., 2022). LADA is estimated to impact 2-12% of people in the world, but it is speculated the number of afflicted may be even higher as misdiagnosis is likely (Buzzetti et al., 2020).
LADA can be confusing to both professionals and patients and for good reason, too! Part of the confusion has to do with poorly outlined parameters for defining LADA. Inconclusive phenotypic criteria regarding age of detection as over the age of thirty (Lee & Hudda, 2021) or over the age of twenty, thirty, thirty five, or the upper limit of seventy years of age depending on where in the world one may be diagnosed make picking and choosing between a T2DM and LADA diagnosis difficult when primarily concerning age (Chen & Chen, 2019). Thankfully, there are other considerations for diagnosis beyond age. The detection of different autoantibodies which may be present in T1DM, T2DM, and LADA or C-peptide levels which are markedly decreased in both T1DM and LADA (Buzzetti et al., 2020) The presence of C-peptide indicates insulin production, therefore lower C-peptide indicates lower insulin production. Depending on the timing of screening for LADA, use of C-peptide as diagnostic criteria may not be the most accurate marker, especially if the screening is timed between late adolescence and early adulthood when T1DM is most likely to be diagnosed (El Sayed et al., 2023).While insulin resistance is the clear etiology in T2DM and beta cells lacking in numbers and effectiveness due to an autoimmune response is the etiology in T1DM, there is no one key to answer the “Why?” of LADA (Li et al., 2021). Research suggests that LADA diagnosis is associated with less oxidative stress than T2DM, but further analysis and repeat studies must be conducted to solidify this as a risk factor and/or marker with defining ranges of LADA; prevalence of oxidative stress has been well defined in inflammation and related inflammatory conditions including diabetes mellitus, heart diseases, and various cancers (Li et al., 2021). Back in 2016, researchers at AHEPA University Hospital in Thessaloniki, Greece found evidence to suggest combining treatment of sitagliptin with Metformin and vitamin D improved blood sugar control in just 8 weeks in a patient with LADA who had presented with lab values associated with long term relatively poor blood sugar management, thereby preserving remaining beta cell function (Rapti et al., 2016)Researchers and diabetes interventionists have been able to agree on some broad term characteristics of the LADA outlined by Buzzetti and colleagues in 2020, including:
- Insulin is not required for management within at least the first 6 months of diagnosis, but soon after becomes a necessary intervention as beta cells continue to trend down.
- GADA, an autoantibody, is the most sensitive marker for defining LADA.
- Familial and/or individual history of the diagnosed is positive for autoimmune diseases.
Unfortunately, major barriers to diagnosing LADA lie in the high prices for testing for GADA, serum insulin levels, and C-peptide volume. Additionally, these tests are not commonly available in most clinics, and typically require secondary referrals many patients fail to receive in the first place (Buzzetti et al., 2020). Additionally, LADA is not the type of diabetes at the forefront of the diagnosing practitioner’s mind due to its rarity and novelty in the medical world. It usually requires assertion that some beta-cell function remains and is worthy of preservation. The average practitioner is unlikely to investigate beta-cell functionality when diagnosing a patient beyond the age of thirty, as diagnostic criteria are met with cheaper tests for T2DM, the most common form of diabetes (Buzzetti et al., 2020). This does not mean the physician is not doing her due diligence, rather it means the diagnostic criteria may require changes to include ruling out LADA.Treatment for LADA varies by presence of markers as well. For example, low C-peptide levels may indicate there is no longer beta cell functionality (Buzzetti et al., 2020). Having this marker for reference can be helpful in determining that insulin use is indicated to achieve adequate glycemic control. If C-peptide levels are higher, it may be useful to take the first line of defense in treating T2DM and use Metformin for blood sugar management paired with diet modifications (Buzzetti et al., 2020). The primary goal in LADA management first and foremost is to preserve any remaining beta cell functionality for as long as possible with improved glycemic control, also known as blood sugar management (Buzzetti et al., 2020). Again, if misdiagnosis occurs, it is likely any treatment options will prove to be enough to achieve glycemic control for at least some satisfactory period of time, further masking the true prevalence of LADA. Many motivated researchers are conducting studies about LADA, the diagnostic criteria, gathering evidence to support solidifying standard screening options, and defining treatment objectives to improve the lives of those living with LADA, unbeknownst and aware.LADA is a less common form of diabetes which presents in adulthood with characteristics of T1DM and T2DM such as low C-peptide levels, impaired beta cell function, poor glycemic control, and increased risks for microvascular complications. Definitive tests are often expensive and may lead to misdiagnosis of type 2 diabetes and/or underdiagnosis of LADA. Preventive approaches may be developed with further genetic and familial history analysis. The reason for LADA onset still remains a mystery, but research suggests contributing factors may include, but not be limited to, oxidative stress, vitamin D deficiency, and genetic risk with high prevalence of autoimmune diseases in LADA sufferers families. The best way to improve consistency in diagnostic criteria and treatment options is by getting the word out about the existence of LADA.
Buzzetti, R., Tuomi, T., Mauricio, D., Pietropaolo, M., Zhou, Z., Pozzilli, P., & Leslie, R. D. (2020). Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel. Diabetes, 69(10), 2037–2047. https://doi.org/10.2337/dbi20-0017.
El Sayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B.S., Hilliard, M. E., Isaacs, D., Johnson, E. L., Kahan, S., Khunti, K., Leon, J., Lyons, S. K., Perry, M. L., Prahalad, P., Pratley, R. E., Seley, J.J., Stanton, R. C., Gabbay, R. A.; on behalf of the American Diabetes Association, 2. Classification and Diagnosis of Diabetes: Standards of Care in Diabetes—2023. Diabetes Care 1 January 2023; 46 (Supplement_1): S19–S40. https://doi.org/10.2337/dc23-S002.
Li, J., Zhang, Y., Zhang, J., Dong, R., Guo, J., & Zhang, Q. (2021). Oxidative Stress and Its Related Factors in Latent Autoimmune Diabetes in Adults. BioMed research international, 2021, 5676363. https://doi.org/10.1155/2021/5676363.
Nee, L. Y., Yee, Y. Y., Ci, G. Q., & Voon, T. C. (2022). Type 1 diabetes and latent autoimmune diabetes in adults: Are they the same?. Journal of the ASEAN Federation of Endocrine Societies, 37, 37. Retrieved from https://www.asean-endocrinejournal.org/index.php/JAFES/article/view/2367.
Nolasco-Rosales, G. A., Ramírez-González, D., Rodríguez-Sánchez, E., Ávila-Fernandez, Á., Villar-Juarez, G. E., González-Castro, T. B., Tovilla-Zárate, C. A., Guzmán-Priego, C. G., Genis-Mendoza, A. D., Ble-Castillo, J. L., Marín-Medina, A., & Juárez-Rojop, I. E. (2023). Identification and phenotypic characterization of patients with LADA in a population of southeast Mexico. Scientific reports, 13(1), 7029. https://doi.org/10.1038/s41598-023-34171-2.
Rapti, E., Karras, S., Grammatiki, M., Mousiolis, A., Tsekmekidou, X., Potolidis, E., Zebekakis, P., Daniilidis, M., & Kotsa, K. (2016). Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults. Endocrinology, diabetes & metabolism case reports, 2016, 150136. https://doi.org/10.1530/EDM-15-0136.