The Diabetes Autoimmune Reactivity screen –Cyrex Array 6 evaluates antibodies against Glutamic Acid Decarboxylase 65 (GAD65), Insulin and the islet cells. This screen can be used to help identify the onset of autoimmune diabetes. It may also be useful in monitoring a current diagnosis of diabetes and the effectiveness of treatment.
Recommended if you:
- Have Type 1 Diabetes or severe/atypical manifestations of Type 2 Diabetes
- Have a family history of Type 1 Diabetes or Metabolic Syndrome
- Have Gluten-Reactivity,
- Dairy-Sensitivity and/or Cerebellar Ataxia
What is being measured – IgG and IgA of:
- Glutamic Acid Decarboxylase 65 (GAD65)
- Insulin and Islet Cell Antigen
Function of Glutamic Acid Decarboxylase 65 (GAD65)
Glutamic Acid Decarboxylase (GAD) a neuronal protein is an enzyme responsible for the conversion of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter g-aminobutyric acid (GABA). GAD is also expressed by pancreatic beta cells.
Glutamic Acid Decarboxylase 65 Antibodies Appear:
- Battan disease (6)
- Celiac disease (3)
- Cerebellar ataxia (4)
- Gluten sensitivity (3)
- Polyendocrine autoimmune syndrome (2)
- Stiff-person syndrome (2)
- Type 1 Diabetes (2, 4, 7)
Clinical Significance of Glutamic Acid Decarboxylase 65:
This enzyme is the major auto-antigen in Type I Diabetes. Researchers speculate that as a target antigen, GAD65 may directly, or indirectly, produce the T cell response cascade that results in insulin-dependent (type 1) diabetes mellitus.7 In addition to patients with autoimmunity against islet cell antigen (Type I Diabetes), patients with neurological disorders (low GABA) may also produce high levels of antibodies against GAD.2, 4, 6 Anti-GAD autoantibodies may result in an excess of excitatory neurotransmitters, which can lead to seizures.5 Due to cross-reactivity between gliadin and casein,1 patient with antibodies against GAD65 should implement a dairy-free diet. Additionally, in a study of Celiac patients,3 60% of the participants with Celiac disease produced GAD65, which may explain the relationship between Celiac disease and type-1 diabetes.
Function of Insulin and Islet cells:
Islet cells are found in the region of the pancreas that contains its hormone-producing cells. Hormones produced in the islets are secreted directly into the blood flow by different types of cells including the beta-cell. Insulin is a hormone that plays a role in the regulation of carbohydrate and fat metabolism. Insulin triggers cells in the liver, muscle, and fat tissue to take up glucose from the blood and store it as glycogen in the liver and muscle.
Insulin and Islet Cell Antigen Antibodies Appear:
- Insulin Autoimmune Hypoglycaemia (3)
- Insulinoma (3)
- Type 1 Diabetes (1, 4, 5)
- Unexplained Hypoglycaemia (3)
- Banchuin, et al. Cell-mediated immune responses to GAD and beta-casein in type 1 diabetes mellitus in Thailand. Diabetes Res Clin Pract, 2002; 55(3):237-245.
- Ellis and Atkinson. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med, 1996; 2:148-153.
- Hadjivassiliou et al. Gluten sensitivity: from gut to brain. Lancet Neurol, 2010; 9:318-330.
- Honnorat, et al. Cerebellar ataxia with anti-glutamic acid decarboxylase antibodies. Arch Neurol, 2001; 58:225-230.
- LeRoth, et al (eds.). Diabetes Mellitus (3rd ed.). Lippincott Williams & Wilkins: Philadelphia, PA; 2004.
- Pearce, et al. Glutamic acid decarboxylase autoimmunity in Batten disease and other disorders. Neurology, 2004; 63:2001-2005.
- Vojdani and Tarash. Cross-reaction between gliadin and different food and tissue antigens, Food Nutri Sci, 2013; 4:20-32.
- Wilson, et al. Therapeutic alteration of insulin-dependent diabetes mellitus progression by T cell tolerance to glutamic acid decarboxylase 65 peptides in vitro and in vivo1. J Immunol, 2001; 167:569-577.
- Honeyman, et al. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol, 2010; 184(4):2204-2210.
- Hiemstra,etal.Cytomegalovirusinautoimmunity: Tcellcrossreactivitytoviralantigenandautoantigenglutamicacid decarboxylase. Proc Natl Acad Sci U S A, 2001; 98(7):3988-3991.
- Roep,etal.Molecularmimicryintype1diabetes:immunecross-reactivitybetweenisletautoantigenandhuman cytomegalovirus but not Coxsackie virus. Ann N Y Acad Sci, 2002; 958:163-165.
- Ou,etal.Cross-reactiverubellavirusandglutamicaciddecarboxylase(65and67)proteindeterminantsrecognisedbyTcells of patients with type I diabetes mellitus. Diabetologia, 2000; 43(6):750-762.
- Kharrazian,etal.Detectionofisletcellimmunereactivitywithlowglycemicindexfoods:isthisaconcernfortype1diabetes? J Diabetes Res, 2017; 2017:4124967.
Beta cells in the islets are selectively destroyed by an autoimmune process in type 1 diabetes. Multiple islet cell antibodies (ICAs) at diagnosis of diabetes can predict future complete beta-cell failure; after diagnosis
ICA development in patients who were antibody negative at diagnosis indicate decreasing beta-cell function.1
ICAs may precede diabetic symptoms by several years, even in people with normal glucose tolerance, but these titers are not always followed by diabetes; ICAs are often present at or soon after the clinical onset of insulin-dependent diabetes, but their prevalence decreases thereafter.4, 5
Insulin antibodies have been part of the first-line assessments for patient who fulfill Whipple’s triad.2 Coupling insulin C-peptide antibodies can assist in the differential diagnosis.
For example, an elevated concentration of insulin, C-peptide and proinsulin raises the possibility of insulinoma; on the other hand, inappropriately raised serum insulin with low or very low C-peptide in unexplained hypoglycaemia can justifiably raise the possibility of surreptitious insulin self.
- Borg, et al. A 12-year prospective study of the relationship between islet antibodies and b-cell function at and after the diagnosis in patients with adult-onset diabetes. Diabetes, 2002; 51:1754–1762.
- Cryer, et al. Evaluation and management of adult hypoglycemic disorders: An endocrine society clinical practice guidline. J Clin Endocrinol Metab, 2009; 94:709-28.
- Ismail. Testing for insulin antibodies is mandatory in the differential diagnosis of hypoglycaemia in non-diabetic subjects. J Clin Endocrinol, 2011; Accepted Article:doi: 10.1111/j.1365-2265.2011.04259.x.
- Lendrum, et al. Islet-cell, thyroid, and gastric autoantibodies in diabetic identical twins. Br Med J, 1976; 1:553-556.
- Schölin, et al. Islet antibodies and remaining b-cell function 8 years after diagnosis of diabetes in young adults: a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden. J Intern Med, 2004; 255:384-391.
- Alder, et al. Insulin autoantibodies with high affinity to bovine milk protein alpha casein. Clin Exp Immunol, 2001; 164:42-49.
- Kharrazian, et al. Detection of islet cell immune reactivity with low glycemic index foods: is this a concern for type 1 diabetes? J Diabetes Res, 2017; 2017:4124967.
- Härkönen, et al. Enterovirus infection can induce immune responses that cross-react with beta-cell autoantigen tyrosine phosphatase IA-2/IAR. J Med Virol, 2002; 66(3):340-350.