GADA and anti‐ZnT8 complicate the outcome of phenotypic type 2 diabetes of adults

Background A proportion of phenotypic type 2 diabetes (T2D) patients produce pancreatic autoantibodies and a majority of T2D patients develop serious life-disabling complications over time despite the implementation of adequate clinical interventions. This study determined whether the presence of pancreatic autoantibodies (GADA, IA-2A, anti-ZnT8, or ICA) was associated with serious complications or concomitant diseases of adult patients diagnosed with T2D (N = 305). Main results In the study population, 22·3% (N = 68) of subjects were positive for at least 1 of the 4 of the markers associated with autoimmune diabetes (presence of pancreatic autoantibody – pAb), followed by GADA (14·1%, N = 43), ICA (8·9%, N = 27), anti-ZnT8 (5·6%, N = 17) and IA-2A (2·0%, N = 6). Logistic regression analysis adjusted for patient's age, gender and duration of T2D revealed that (i) pAb was associated with higher prevalence of adiposity (odds ratio of adjusted regression model (adOR) 2·51, P = 0·032); (ii) pAb, GADA and anti-ZnT8 were associated with autoimmune thyroid disease (adORs 3·07, P = 0·012; 6·29, P < 0·001 and 3·52, P = 0·052, respectively); (iii) pAb and GADA, in particular, were risk factors for neurological complications (adORs 2·10, P = 0·036; 2·76, P = 0·009, respectively) and polyneuropathy in particular (adORs 2·60, P = 0·012; 3·10, P = 0·007, respectively); and (iv) anti-ZnT8 was a risk factor for developing nephropathy (adOR 4·61, P = 0·022). In addition, adiposity was associated with 5·3-year earlier onset of disease (adjusted linear regression model, P = 0·006). Conclusions These results suggest that GADA and anti-ZnT8 are associated with progression of serious T2D complications, including polyneuropathy and nephropathy. In addition, adiposity represents a significant risk for autoimmunity development in T2D patients.