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Diabetes Care. 2015 Mar;38(3):513-20. doi: 10.2337/dc14-1638. Epub 2015 Jan 7.

Tyrosine phosphatase-related islet antigen 2(256-760) autoantibodies, the only marker of islet autoimmunity that increases by increasing the degree of BMI in obese subjects with type 2 diabetes.

Author information

1
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy raffaella.buzzetti@uniroma1.it.
2
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
3
Diabetes Unit, Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.

Abstract

OBJECTIVE:

Since patients with type 2 diabetes and positive for type 1 diabetes-specific antibodies have wide variations in BMI, this study evaluated whether the frequency and pattern of islet autoantibody positivity is related to BMI.

RESEARCH DESIGN AND METHODS:

Clinical and biochemical characteristics and islet autoantibodies including GAD and protein tyrosine phosphatases islet antigen-2 (IA-2)IC and IA-2(256-760) were evaluated in 1,850 patients with type 2 diabetes from the Non-Insulin Requiring Autoimmune Diabetes study cohort. BMI was evaluated in all patients, who were then subdivided in three groups according to BMI (<25, ≥25 to <30, and ≥30 kg/m(2)).

RESULTS:

Out of 1,850, 120 (6.5%) patients were positive for at least one of the following antibodies: GAD (4.1%), IA-2(256-760) (3.3%), or IA-2IC (1.1%). GAD and IA-2IC antibodies showed decreasing frequencies with increasing BMI (P < 0.0001 and 0.0006, respectively, for trend); in contrast, the frequency of IA-2(256-760) antibodies increased with increasing BMI (P = 0.005 for trend). Patients with type 2 diabetes positive for IA-2(256-760) alone showed a phenotype resembling classical obese type 2 diabetes, with higher BMI, waist circumference, and uric acid (P < 0.005 for all), lower thyroid peroxidase antibodies, and lower progression to insulin requirement than GAD antibody-positive patients (P = 0.04 and P = 0.0005, respectively).

CONCLUSIONS:

The IA-2(256-760) antibody appears to represent an antibody marker that mainly identifies a clinical phenotype very similar to obese type 2 diabetes, suggesting a possible different pathogenetic mechanism.

PMID:
25567348
DOI:
10.2337/dc14-1638
[Indexed for MEDLINE]

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