It can be challenging to distinguish latent autoimmune diabetes in adults (LADA) from either type 1 or type 2 diabetes. The overlap in age of onset, rate of progression, and metabolic features often blurs the boundaries. Clinicians usually rely on several indicators, including body mass index, age at diagnosis, family history, HLA typing, clinical presentation, degree of glucose variability, insulin reserve, and C-peptide levels. The presence of autoantibodies, particularly against glutamic acid decarboxylase (GAD65), pancreatic islet cells (ICA), or insulin (IAA), remains central to confirming autoimmune involvement.
However, emerging research suggests that additional inflammatory markers may refine diagnostic accuracy. The article highlights several candidates such as adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFR2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and total leukocyte count. These biomarkers reflect the immune-metabolic interplay behind LADA, bridging autoimmune mechanisms with insulin resistance and chronic inflammation. Their combined use could potentially help clinicians identify patients earlier, guide therapy choices, and predict disease progression more precisely.
Integrating these novel markers into everyday clinical practice will require further validation through longitudinal studies. Establishing standardized cut-off values, assessing cost-effectiveness, and determining how such results influence treatment decisions remain essential next steps. As research evolves, a multi-marker approach, combining traditional autoantibody panels with inflammatory and metabolic profiling, may ultimately clarify the spectrum between autoimmune and insulin-resistant diabetes forms.
About Dr. Gerti Tashko, MD
Dr. Gerti Tashko, MD, is an endocrinologist in Montgomery County, Maryland. He is uniquely quadruple board-certified in endocrinology, lipidology, hypertension, and obesity medicine. His practice delivers root-cause-focused metabolic and endocrine care, available virtually and in person. He uses advanced diagnostics, personalized nutrition, and preventive medicine to improve long-term health.
Diabetes Care
cross-sectional
April 2018
OBJECTIVE
To test whether differences in serum concentrations of adiposity-related low-grade inflammatory mediators could help to differentiate patients with latent autoimmune diabetes in adults (LADA), classic adult-onset type 1 diabetes, and type 2 diabetes.
Methods
This cross-sectional study involved 75 patients with LADA, 67 with classic adult-onset type 1 diabetes, and 390 with type 2 diabetes. Serum concentrations of adiponectin, soluble tumor necrosis factor-α receptor 2 (sTNFR2), interleukin-6, hs-CRP, and total leukocyte number were measured. To evaluate the differences of these markers among diabetes types, we performed logistic regression models and evaluated area under the receiver-operating characteristic curve (AUCROC) values.
RESULTS
The profile of innate immunity-related inflammatory markers correlated with metabolic syndrome components.
LADA versus classic adult-onset type 1 diabetes was independently related to sTNFR2 (odds ratio 1.9, p = 0.047) and hs-CRP levels (OR 0.7, p = 0.019)
And a higher number of total leukocytes lowered the risk of LADA compared with type 2 diabetes (OR 0.98, p = 0.036).
The logistic regression model including explanatory biomarkers explained 35% of the variation for LADA versus classic adult-onset type 1 diabetes (AUCROC 0.83, p < 0.001) and 15% of the variation for LADA versus type 2 diabetes (AUCROC 0.73, p < 0.001).
CONCLUSIONS
Inflammatory, adiposity, and immune-related markers could help to differentiate a LADA diagnosis from that of classic adult-onset type 1 diabetes, and also LADA from that of type 2 diabetes, along with islet autoantibody positivity.