Management of Latent Autoimmune Diabetes in Adults: A Consensus Statement From an International Expert Panel

Abstract

A substantial proportion of patients with adult-onset diabetes share features of both type 1 diabetes (T1D) and type 2 diabetes (T2D). These individuals, at diagnosis, clinically resemble T2D patients by not requiring insulin treatment, yet they have immunogenetic markers associated with T1D. Such a slowly evolving form of autoimmune diabetes, described as latent autoimmune diabetes of adults (LADA), accounts for 2-12% of all patients with adult-onset diabetes, though they show considerable variability according to their demographics and mode of ascertainment. While therapeutic strategies aim for metabolic control and preservation of residual insulin secretory capacity, endotype heterogeneity within LADA implies a personalized approach to treatment. Faced with a paucity of large-scale clinical trials in LADA, an expert panel reviewed data and delineated one therapeutic approach. Building on the 2020 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus for T2D and heterogeneity within autoimmune diabetes, we propose "deviations" for LADA from those guidelines. Within LADA, C-peptide values, proxy for β-cell function, drive therapeutic decisions. Three broad categories of random C-peptide levels were introduced by the panel: 1) C-peptide levels <0.3 nmol/L: a multiple-insulin regimen recommended as for T1D; 2) C-peptide values ≥0.3 and ≤0.7 nmol/L: defined by the panel as a "gray area" in which a modified ADA/EASD algorithm for T2D is recommended; consider insulin in combination with other therapies to modulate β-cell failure and limit diabetic complications; 3) C-peptide values >0.7 nmol/L: suggests a modified ADA/EASD algorithm as for T2D but allowing for the potentially progressive nature of LADA by monitoring C-peptide to adjust treatment. The panel concluded by advising general screening for LADA in newly diagnosed non-insulin-requiring diabetes and, importantly, that large randomized clinical trials are warranted.

Figure 1

Algorithm for LADA diagnostic pathway based on autoantibody screening and C-peptide levels at diagnosis (to be used when financial restriction does not apply). **Consider also pancreatitis or monogenic diabetes.

Figure 2

Algorithm for glucose-lowering medications in LADA patients with C-peptide <0.3 mmol/L or with C-peptide ≥0.3 and ≤0.7 nmol/L. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HF, heart failure.

Figure 3

Algorithm for glucose-lowering medications in LADA patients with C-peptide levels ≥0.3 and ≤0.7 nmol/L without established ASCVD (atherosclerotic cardiovascular disease) or CKD (chronic kidney disease). *Deviation from ADA/EASD T2D algorithm. **Increased risk of diabetic ketoacidosis, especially in patients with BMI ≤27.