Similar genetic features and different islet cell autoantibody pattern of latent autoimmune
diabetes in adults (LADA) compared with adult-onset type 1 diabetes with rapid progression
OBJECTIVE - To compare the clinical parameters, C-peptide levels, pattern of islet
cell-specific 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, C-peptide 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 adult-onset type 1 diabetes. Patients with LADA
had lower BMI (P < 0.0001), waist-to-hip ratio (0.0029), total cholesterol (P = 0.001),
and triglycerides (P = 0.001); higher HDL cholesterol levels (P < 0.0001); and lower
prevalence of hypertension (P = 0.0028) compared with patients with type 2 diabetes.
C-peptide levels were similar at onset (P = 0.403) but decreased less rapidly in LADA
than in adult-onset type 1 diabetes (P = 0.0253). Single-autoantibody positivity was
more often seen in LADA than in type 1 diabetes (P = 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.