Test ID: EZNT8    
Zinc Transporter 8 (ZnT8) Antibody, Serum

Clinical distinction of type 1 from type 2 diabetes mellitus

Identification of individuals at risk of type 1 diabetes (including high-risk relatives of patients with diabetes, and those with gestational diabetes)

Prediction of future need for insulin treatment in adult-onset diabetic patients

Islet cell autoantibodies have been known to be associated with type 1 diabetes mellitus since the 1970s.(1) Since 1988, several autoantigens against which islet antibodies are directed have been identified. These include the insulinoma-associated protein 2 (IA-2), glutamic acid decarboxylase 65 (GAD65), insulin, and, most recently, the zinc transporter ZnT8. Only 4% to 7% of patients with type 1 diabetes are autoantibody negative, fewer than 10% have only 1 marker, and around 70% have 3 or 4 markers. These findings have been confirmed in multiple specialty laboratories internationally.

One or more of these autoantibodies are detected in 93% to 96% of patients with type 1 diabetes, both adults and children. These antibodies are also detectable in relatives of type 1 diabetic patients at risk for developing diabetes, before clinical onset. Because of symptom-onset in adulthood, societal obesity, and initial insulin-independence, some patients with type 1 diabetes are initially diagnosed as having type 2 diabetes,. These patients with either "latent autoimmune diabetes in adulthood" or type 1 diabetes mellitus, may be distinguished from those patients with type 2 diabetes by detection of 1 or more islet autoantibodies, including ZnT8 antibody.(2-5) Patients with gestational diabetes can also be stratified for future diabetes risk by detection of 1 or more islet autoantibodies (including ZnT8 antibody).

<15.0 U/mL

Seropositivity for ZnT8 autoantibody (> or =15 IU/mL) is supportive of:

-A diagnosis of type 1 diabetes

-A high risk for future development of diabetes

-A current or future need for insulin therapy in patients with diabetes

Negative results do not exclude the diagnosis of or future risk for type 1 diabetes mellitus. The risk of developing type 1 diabetes may be stratified further by testing for: 1) antibodies targeting insulin, IA2, and GAD65 and 2) HLA genetic markers. Careful monitoring of hyperglycemia is the mainstay of determining the requirement for insulin therapy

1. Bingley PJ: Clinical applications of diabetes antibody testing. J Clin Endocrinol Metab 2010;95:25-33

2. Andersson C, Vaziri-Sani F, Delli A, et al: Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatr Diabetes 2013;14:97-105

3. Dereke J, Nilsson C, Landin-Olsson M, Hillman M: Prevalence of zinc transporter 8 antibodies in gestational diabetes mellitus. Diabet Med 2012;29:e436-439

4. Gorus FK, Balti EV, Vermeulen I, et al: Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients. Clin Exp Immunol 2013;171:82-90

5. Petruzelkova L, Ananieva-Jordanova R, Vcelakova J, et al:  The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus. Diabet Med 2014;31:165-171