Distinct Interplay Between β-Cell Function and Insulin Resistance in Latent Autoimmune Diabetes in Adults Versus Type 2 Diabetes

Unlabelled: We conducted a cross-sectional study to explore the interplay between β-cell function and peripheral insulin resistance in latent autoimmune diabetes in adults (LADA) compared with type 2 diabetes. Thirty-one people with LADA were matched for sex, BMI, and disease duration with 31 people with type 2 diabetes. Insulin resistance was estimated using established surrogate indexes, and serum C-peptide levels were measured by ELISA. Despite the similar BMI, the LADA group exhibited lower mean values of estimated insulin resistance compared with the type 2 diabetes group. Among individuals with similar insulin resistance, the LADA group consistently showed lower C-peptide values compared with the type 2 diabetes group. C-peptide levels showed a direct relationship with the majority of insulin resistance indexes exclusively in type 2 diabetes, but not in LADA. Our findings show that people with LADA exhibit a blunted insulin secretory capacity compared with people with type 2 diabetes, even at similar levels of insulin resistance, being unable to mount a meaningful compensatory response to insulin resistance. This discrepancy may explain the worse glycemic control often observed in people with LADA, placing these people at higher risk of suboptimal glycemic control and highlighting the importance of early and accurate classification of adult-onset diabetes and tailored therapeutic strategies. Article highlights: The identification of differences in the relationship between insulin secretion and resistance among different diabetes types will help inform clinical decisions. The interplay between insulin secretion and resistance may distinguish latent autoimmune diabetes in adults (LADA) from type 2 diabetes. Individuals with LADA are less capable of mounting a sustained compensatory insulin secretion compared with those with type 2 diabetes, even at similar insulin resistance levels. Distinct pathophysiology characterizes LADA and type 2 diabetes. The defect in insulin secretion for similar levels of insulin resistance might contribute to the higher risk of poor glycemic control often observed in LADA, arguing for accurate diagnosis of adult-onset diabetes types.