Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes

Abstract

AimsTo assess the prevalence of ZnT8-ab and its correlation to other autoimmune markers and diabetic ketoacidosis occurrence in children and adults with T1DM onset. MethodsThe study included 367 patients (218 children; 149 adults) at the T1DM onset. Selected diabetes-related autoantibodies such as GAD-ab, IA2-ab, ZnT8-ab were tested before the initiation of insulin therapy. Diabetic ketoacidosis was defined as glucose concentration > 13.9 mmol/l, pH < 7.30, concentration of HCO3 < 15 mmol/l, presence of ketone bodies in the blood and urine.ResultsThe autoantibodies pattern differs in both study groups. Children were mostly positive for two (37.8%) and three (49.5%) autoantibodies, whereas adults for one (32.2%) and two (30.7%). The most frequently detected autoantibodies in youth were ZnT8-ab (81.1%) and IA2-ab (80.7%), while in adults GAD-ab (74.8%). ZnT8-ab (p < 0.0001) titers were significantly higher in children, but adults had higher titer of GAD-ab (p < 0.0001) and IA2-ab (p < 0.0001). Children developed more frequently diabetic ketoacidosis (28.4 vs. 10.7%, p = 0.0002). ZnT8-ab (p = 0.002) and IA2-ab (p = 0.008) were reported mostly in individuals with ketoacidosis. A correlation between the number of positive antibodies and the severity of ketoacidosis was observed (Rs − 0.129 p = 0.014). ZnT8-ab were associated with a greater risk of ketoacidosis independent of gender, age group and the autoantibodies number [OR = 2.44 (95% CI 1.0–5.94), p = 0.04]. ConclusionsChildren are at greater risk of ketoacidosis at the diagnosis of diabetes. ZnT8-ab and IA2-ab are commonly detected in children, while adults have frequently higher titer of GAD-ab. ZnT8-ab are associated with more acute diabetes onset.Electronic supplementary materialThe online version of this article (10.1007/s00592-017-1091-x) contains supplementary material, which is available to authorized users.

Association of Zinc Transporter-8 Autoantibody (ZnT8A) with Type 1 Diabetes Mellitus

“…The mean age at the onset of diabetes was similar to an Indian population, and the distribution of gender was also similar [8]. There was a higher frequency of ZnT8A in males in the current study, which contrasts with a number of studies that reported a higher frequency in women or even documented no difference between genders with T1DM that was noticed by Eisenbarth et al probably because of difference in gender distribution in these studies [15,[19][20][21].…”

Prevalence of islet autoantibodies in Thai juvenile‐onset type 1 diabetes

“…In addition, the prevalence of islet autoantibody positivity in T1DM appeared to be correlated with age and clinical presentation. In a recent study in Caucasian subjects, ZnT8A and IA2A were commonly detected in children with T1DM, whereas adults had a significantly frequently higher GADA titer . Furthermore, ZnT8A are associated with more acute diabetes onset and DKA .…”

“…In a recent study in Caucasian subjects, ZnT8A and IA2A were commonly detected in children with T1DM, whereas adults had a significantly frequently higher GADA titer. 18 Furthermore, ZnT8A are associated with more acute diabetes onset and DKA. 18 Similarly, ZnT8A are more prevalent in younger (≤20 years) new-onset Japanese patients, compared with patients with age at onset >20 years.…”

“…18 Furthermore, ZnT8A are associated with more acute diabetes onset and DKA. 18 Similarly, ZnT8A are more prevalent in younger (≤20 years) new-onset Japanese patients, compared with patients with age at onset >20 years. 14 Islet antibody-negative or type 1B (idiopathic) diabetes comprises approximately 10% of recent-onset T1DM in Caucasian subjects.…”

Commentary on the Impact of Obesity on Pediatric Diabetes

“…Although the majority of those with T1DM have positive antibodies at presentation, some do not and presumably develop them later. 22,29 Thus, obese individuals with negative autoantibodies may be mistaken for having T2DM but may in fact have T1DM. In patients with negative antibodies at presentation but a clinical course suggestive of T1DM, the authors recommend rechecking antibodies to help determine the actual diagnosis.…”