High GADA titer increases the risk of insulin requirement in LADA patients: A 7-year follow-up (NIRAD study 7)

Objective: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. Methods: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. Results: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes ( P<0.0001 for both). A BMI of ≤ 25 kg/m² and IA-2<inf>IC</inf> and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, ORZ6.95). Conclusions: High GADA titer, BMI ≤ 25, ZnT8 and IA-2<inf>IC</inf> positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.