Presence of GAD and IA-2 Antibodies in Youth With a Type 2 Diabetes Phenotype: Results from the TODAY study

• Published in: Diabetes care Vol. 33; no. 9; pp. 1970 - 1975
• Main Authors: Klingensmith, Georgeanna J, Pyle, Laura, Arslanian, Silva, Copeland, Kenneth C, Cuttler, Leona, Kaufman, Francine, Laffel, Lori, Marcovina, Santica, Tollefsen, Sherida E, Weinstock, Ruth S, Linder, Barbara
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.09.2010
• Subjects: Adolescent; adolescents; Autoantibodies; Autoantibodies - metabolism; Autoimmunity; Biological and medical sciences; blood lipids; blood pressure; body mass index; c-peptide; C-Peptide - metabolism; Child; children; Cholesterol; clinical examination; Design; Development and progression; Diabetes; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 2 - immunology; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diabetics; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; fasting; Female; Genetic aspects; Glutamate Decarboxylase; Glutamate Decarboxylase - immunology; Health sciences; high density lipoprotein cholesterol; Hospitals; Humans; immunology; Islets of Langerhans; Islets of Langerhans - metabolism; Kidney diseases; Lipids; Male; Medical sciences; Metabolic diseases; metabolic syndrome; metabolism; Miscellaneous; National Institutes of Health; noninsulin-dependent diabetes mellitus; Obesity; Original Research; patients; phenotype; Public health. Hygiene; Public health. Hygiene-occupational medicine; Studies; Teenagers; triacylglycerols; Triglycerides; Young adults; Youth; Endocrinopathy; Human; Type 2 diabetes; Nutrition; Enzyme; Phosphoric monoester hydrolases; Trend; Metabolic diseases; Esterases; Result; Glutamic acide decarboxylase antibody; Phenotype; Adolescent; Hydrolases; Endocrinology; Protein-tyrosine-phosphatase
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc10-0373

OBJECTIVE: To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings. RESEARCH DESIGN AND METHODS: Children (10-17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations. RESULTS: Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects. CONCLUSIONS: Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes.