Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Latent Autoimmune Diabetes of Adults (LADA): Islet-related Autoimmunity Identifies a Unique Pattern of Impaired Beta -Cell Function and Pathology. (#80)

Roberto Gianani 1 2 , Angela Subauste 2 , Massimo Pietropaolo 2
  1. Pathology, University of Illinois at Chicago, Stroger Hospital Surgical Pathology Fellowship Program, Chicago, Illinois, USA
  2. MEND, University of Michigan, Ann Arbor, MI, United States

Detailed metabolic and histological investigations in LADA are still lacking. We therefore evaluated indexes of insulin secretion, pancreatic pathology, and metabolic assessment in clinically diagnosed T2D patients with and without the presence of humoral islet autoimmunity (Ab). A total of 18 patients with clinically diagnosed T2D with at least 5-year duration of diabetes were evaluated in this study. In those 18 subjects we assessed acute insulin responses to arginine, euglycemic clamp study, and assessment of whole-body fat mass and fat-free mass. The presence of islet Ab correlated with severely impaired β-cell function as demonstrated by remarkably low AIRmax as compared to the Ab negative group. Glucose clamp studies indicated that both Ab positive and Ab negative patients developed peripheral insulin resistance in a similar fashion. These findings were reinforced by pathology data evaluated in the pancreatic pathology of fifteen organ T2D donors and twenty four controls. In this group, four express either islet autoantibodies or the DR3/D34 HLA class II allelic combination which is increased in prevalence in patients with autoimmune diabetes. The beta cell mass in these four organ donors (hence referred as organ donors with T2D and markers of autoimmunity) was significantly lower than in donors without markers of autoimimunity. (p = 0.02). Furthermore, all T2D donors with markers of autoimmunity vs. three of eleven donors without markers of autoimmunity, expressed the autoimmune associated pattern A pathology (characterized by the presence of pseudo-atrophic islets). In conclusion, long-term LADA patients exhibit profound impairment of insulin secretion as well as reduced beta cell mass seemingly determined by an immune-mediated injury of pancreatic β-cells. Understanding the mechanisms underlying beta cell destruction in LADA will provide insights into the pathogenesis and may lead to the development of new therapies to halt progression in the early phase of the disease process.