This study reveals a positive correlation between age at diagnosis of type 1 diabetes and FCP with a more rapid decline of β-cell function in the very young patients. These data can inform the design of clinical trials using C-peptide values as an end-point for the effect of a given treatment.

OBJECTIVE -To compare the clinical parameters, C-peptide levels, pattern of islet cellspecific autoantibodies, and prevalence of predisposing genotypes in subjects with latent autoimmune diabetes in adults (LADA) and those with adult-onset type 1 diabetes with rapid progression.RESEARCH DESIGN AND METHODS -We evaluated the clinical parameters, Cpeptide levels, and islet cell-specific autoantibodies in 54 LADA, 57 adult-onset type 1 diabetic, and 190 type 2 diabetic patients. Islet cell autoantibodies were also compared between subgroups of newly diagnosed patients with LADA and those with newly diagnosed adult-onset and childhood-onset type 1 diabetes. The genetic study was performed in subjects with LADA and those with adult-onset type 1 diabetes in comparison with a control population.RESULTS -There were no differences in the clinical parameters between LADA and adultonset type 1 diabetes. Patients with LADA had lower BMI (P Ͻ 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P ϭ 0.001), and triglycerides (P ϭ 0.001); higher HDL cholesterol levels (P Ͻ 0.0001); and lower prevalence of hypertension (P ϭ 0.0028) compared with patients with type 2 diabetes. C-peptide levels were similar at onset (P ϭ 0.403) but decreased less rapidly in LADA than in adult-onset type 1 diabetes (P ϭ 0.0253). Single-autoantibody positivity was more often seen in LADA than in type 1 diabetes (P ϭ 0.0001). The prevalence of predisposing HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 genotypes and the DR4-DQB1*0302 haplotype were increased in both LADA and adult-onset type 1 diabetic subjects compared with the control population. There were no differences in the frequencies of these risk alleles and haplotypes between the two patient groups.CONCLUSIONS -Subjects with LADA had clinical characteristics similar to those with adult-onset type 1 diabetes with rapid progression. C-peptide levels did not differ at onset but decreased less rapidly in LADA. Patients with LADA rather had single islet cell-specific autoantibody positivity. The prevalence of HLA-DQB1*0302, -DR4, -DR3, and -DR3/DR4 risk alleles and the DR4-DQB1*0302 high-risk haplotype did not differ in the two forms of autoimmune diabetes.

Administration of DiaPep277 seems safe and may have beneficial effects on C-peptide levels over time in some patients with T1D, but this finding was not accompanied by reduced HbA1c or insulin requirement. Studies with more patients and longer follow-up are needed to further study the effect of DiaPep277.

Aims/hypothesis The variants of transcription factor 7-like 2 (TCF7L2) gene have been proposed to be associated with latent autoimmune diabetes in adults (LADA). We sought to confirm the possible association in Europeans and to examine the interaction between one gene variant and clinical data. Methods The TCF7L2 rs7903146 C-to-T polymorphism was genotyped in 211 LADA, 1,297 type 2 diabetic, 545 type 1 diabetic and 1,497 control individuals from Hungary. A meta-analysis of our and previously published studies was performed to evaluate the size and the heterogeneity of the gene effect.Results The meta-analysis yielded a significant effect of TCF7L2 T allele (OR 1.28; p<0.0001) on LADA risk without heterogeneity among Europeans. The T allele conferred equally strong susceptibility to LADA and type 2 diabetes. In the Hungarian dataset, the T allele was associated with LADA and type 2 diabetes, but not with type 1 diabetes.T allele carriers had significantly lower BMI than patients with the CC genotype in the LADA and type 2 diabetes groups (p=0.0021 and p=0.0013, respectively). In both diseases, the diabetes risk was significantly higher in the non-overweight than in the overweight BMI category (p=0.0013 and p<0.0001, respectively); susceptibility to LADA was increased by 2.84-fold in non-overweight individuals compared with overweight ones. Conclusions/interpretation The meta-analysis demonstrates that TCF7L2 rs7903146 polymorphism is a populationindependent susceptibility locus for LADA in Europeans. The effect size is similar for LADA and type 2 diabetes. The gene effect on diabetes risk may be modulated by BMI, such that the lower the BMI, the higher the gene effect.

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