Test ID: DBS1    
Diabetes Mellitus Type 1 Evaluation, Serum

Distinguishing type 1 from type 2 diabetes mellitus

Identifying individuals at risk of type 1 diabetes (including high-risk relatives of patients with diabetes)

Predicting future insulin requirement treatment in patients with adult-onset diabetes

Islet cell autoantibodies have been known to be associated with type 1 diabetes mellitus since the 1970s. 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.(1) 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.(2) Some patients with type 1 diabetes are initially diagnosed as having type 2 diabetes because of symptom-onset in adulthood, societal obesity, and initial insulin-independence. 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). Patients with gestational diabetes can also be stratified for future diabetes risk by detection of 1 or more islet autoantibodies.

GLUTAMIC ACID DECARBOXYLASE (GAD65) ANTIBODY

< or =0.02 nmol/L

Reference values apply to all ages.

 INSULIN ANTIBODIES

< or =0.02 nmol/L

Reference values apply to all ages.

 ISLET ANTIGEN 2 (IA-2) ANTIBODY

< or =0.02 nmol/L

Reference values apply to all ages.

ZINC Transporter 8 (ZnT8) ANTIBODY

< 15.0 U/mL

Reference values apply to all ages.

Seropositivity for 1 or more islet cell autoantibodies is supportive of:

-A diagnosis of type 1 diabetes. Only 2% to 4% of patients with type 1 diabetes are antibody negative; 90% have more than 1 antibody marker, and 70% have 3 or 4 markers.(1) Patients with gestational diabetes who are antibody seropositive are at high risk for diabetes postpartum. Rarely, diabetic children test seronegative, which may indicate a diagnosis of maturity-onset diabetes of the young in clinically suspicious cases.

-A high risk for future development of diabetes. Among 44 first-degree relatives of patients with type 1 diabetes, those with 3 antibodies had a 70% risk of developing type 1 diabetes within 5 years.(2)

-A current or future need for insulin therapy in patients with diabetes. In the UK Prospective Diabetes Study, 84% of those classified clinically as having type 2 diabetes and seropositive for glutamic acid decarboxylase 65 required insulin within 6 years, compared to 14% that were antibody negative.(3)

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 HLA genetic markers. Careful monitoring of hyperglycemia is the mainstay for determining the requirement for insulin therapy.

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

2. Bingley PJ, Gale EA: Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial: the role of additional immune, genetic and metabolic markers of risk. Diabetologia 2006;49:881-890

3. Turner R, Stratton I, Horton V, et al: UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997;350:1288-1293