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foxl

LADA and HLA genotype

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foxl

Eur J Endocrinol. 2010 Jul 5. [Epub ahead of print]

Number of autoantibodies and HLA Genotype, more than high titers of glutamic acid decarboxylase autoantibodies (GADA65Ab), predict insulin dependence in latent autoimmune diabetes of adults (LADA).

 

Maioli M, Pes GM, Delitala G, Puddu L, Falorni A, Tolu F, Lampis R, Orru' V, Secchi G, Cicalò A, Floris R, Madau G, Pilosu RM, Whalen M, Cucca F.

 

M Maioli, INTERNAL MEDICINE, UNIVERSITY OF SASSARI, SASSARI, I-07100, Italy.

Abstract

 

Objective: In LADA the progression into insulin-dependent diabetes is usually faster than in Type 2 Diabetes (T2D) but the factors influencing this progression are incompletely known. In this study we searched for sensitive markers associated with early development of insulin-dependence. Design: The screening of 5,568 T2D patients for glutamic acid-decarboxylase (GAD65Ab) antibodies identified 276 LADA patients (M=131; F=145) and in 251 of them tyrosine phosphatase-2 (IA-2Ab) and thyreoperoxidase (TPOAb) autoantibodies, some clinical features and genotype variation at the main type 1 diabetes (T1D) disease susceptibility loci (HLA-DRB1, HLA-DQB1) were analysed. Results: After 4 years from diagnosis of diabetes, high GAD65Ab titer was not significantly associated with faster progression towards insulin deficiency (p=0.104). Patients with GAD65Ab and TPOAb or IA-2Ab or triple positivity for both islet and thyroid peroxidase antibodies (GAD65Ab/IA-2Ab/TPOAb) showed a significantly faster disease progression (p=0.002). Among 104 TPOAb-positive LADA patients 10 received replacement therapy (L-thyroxine), 43 showed high TSH levels (62.7% developed insulin-dependence) and 3 had hyperthyroidism treated with methimazole. Multivariate analysis revealed a significant effect on disease progression only for TPOAb (p=0.022), female gender (p=0.036), low BMI (p=0.001) and T1D high/intermediate risk HLA-DRB1/DQB1 genotypes grouped (p=0.020). Conclusions: High GAD65Ab titers per se are not a major risk factor for disease progression in LADA, while the number of positive autoantibodies and HLA DRB1-DQB1 genotypes at high risk for T1D are significant predictors. Moreover, clinical characteristics such as low BMI and female gender are more likely to identify patients who will require insulin therapy within 4 years from diagnosis.

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foxl
I don't have a low BMI....hah!.......for once it may be a good thing?.....at least in this regard!:D

 

Yes ... just what I was thinking, myself. I am doing okay, but was not, pre-dx. Now ... think we can get HLA testing? HAH!

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momof3
Now ... think we can get HLA testing? HAH!

 

 

Exactly what I was thinking! I know the MD's I have seen (even the Endo) would not order it and think it was a waste of money for us and insurance companies.

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foxl
Exactly what I was thinking! I know the MD's I have seen (even the Endo) would not order it and think it was a waste of money for us and insurance companies.

 

Well until AACE issues guidelines pertaining to the predictive value of genetic testing ... which no doubt will come long after they issue guidelines pertaining to the predictive value of antibody testing ... :eek: :eek: :eek:

 

I got distracted, this morning ... I mostly posted this because it again reinforces the relationship of GAD and TPO antibodies ... ie, this is the same disease process ongoing, in people with thyroid autoimmune disease.

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