The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study.
OBJECTIVE
To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings.


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.
Klingensmith
Georgeanna J
GJ
Barbara Davis Center and the Children's Hospital, University of Colorado Denver, Aurora, Colorado, USA. georgeanna.klingensmith@ucdenver.edu
Pyle
Laura
L
Arslanian
Silva
S
Copeland
Kenneth C
KC
Cuttler
Leona
L
Kaufman
Francine
F
Laffel
Lori
L
Marcovina
Santica
S
Tollefsen
Sherida E
SE
Weinstock
Ruth S
RS
Linder
Barbara
B
D000293:Adolescent; D001323:Autoantibodies / Q000378:metabolism*; D002096:C-Peptide / Q000378:metabolism; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male
D001323:Autoantibodies; D002096:C-Peptide; C096322:ICA512 autoantibody; D005968:Glutamate Decarboxylase