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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/m²). 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Evidence has been reported for a new susceptible locus for type 1 diabetes, the protein tyrosine phosphatase nonreceptor type 2 (PTPN22), which encodes a lymphoidspecific phosphatase. The aim of the study was to evaluate the influence of the C1858T variant of the PTPN22 gene on βcell function as measured by C-peptide levels from time of disease diagnosis through 12 months follow-up in a prospective series of 120 consecutive type 1 diabetic subjects. RESEARCH DESIGN AND METHODS -- The C1858T polymorphism was genotyped using TaqMan. Fasting C-peptide, A1C, and insulin requirements were determined at diagnosis and every 3 months for 12 months;-their change during follow-up was analyzed using the general linear model repeated-measures procedure. RESULTS -- Fasting C-peptide levels were significantly lower and A1C levels were significantly higher in subjects carrying the PTPN22 1858T variant than in subjects homozygous for C 1858 from time of disease diagnosis through 12 months of intensive insulin therapy follow-up (P =. 0.008 and P = 0.01, respectively). These findings were independent of age at onset, sex, and HLA risk groups. The trend in C-peptide and AIC levels in the 12-month period did not differ significantly between subjects with or without the 1858T variant. Insulin dose was similar in the 1858T carriers and noncarriers. CONCLUSIONS -- Type 1 diabetic subjects carrying the 1858T variant show significantly lower/β-cell function and worse metabolic control at diagnosis and throughout the study period than subjects homozygous for C1858; these differences remain unchanged over the course of the first year after diagnosis. [ABSTRACT FROM AUTHOR]

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., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)