The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00081328.

Figure 1

Fasting C-peptide vs. antibody titer. Antibody levels are represented in NIDDK/NIH standardized DK units, and C-peptide values are measured as nanograms per milliliter. A: GAD-65 antibody titers vs. fasting C-peptide. △, GAD-65 values for IA-2–negative subjects; +, GAD-65 values for IA-2–positive subjects. GAD-65 values ≥45 DK units/ml are positive. B: IA-2 antibody titers vs. fasting C-peptide. △, IA-2 values for GAD-65–negative subjects; +, IA-2 values for GAD-65–positive subjects. IA-2 values ≥5.0 DK units/ml are positive. The normal range for fasting C-peptide is 0.5–3.0 ng/ml.

Figure 2

Box-and-whisker plots of BMI z score (A) and fasting C-peptide (B) by antibody (Ab) status. + identifies the mean, and the line through the middle of the box is the median. The upper and lower edges of the box are the 75th and 25th percentiles, respectively. The upper whisker is drawn between the 75th percentile (upper edge of the box) and the largest observed value <1.5 times the interquartile range, above the 75th percentile. The lower whisker is drawn between the 25th percentile and the smallest observed value >1.5 times the interquartile range below the 25th percentile. ○, outliers.