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

Abstract

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.

Common variants in the TCF7L2 gene help to differentiate autoimmune from non-autoimmune diabetes in young (15–34 years) but not in middle-aged (40–59 years) diabetic patients

“…Genetically, young and middle-aged antibody-positive patients were similar with respect to increased prevalence of risk genotypes HLA-DQB1, PTPN22 CT + TT, INS VNTR classI/I and INS VNTR classIIIA/IIIA. These findings are consistent with previous reports [3,41,42]. Although HLA genotyping together with measurements of islet antibodies has been used to identify individuals at risk of type 1 diabetes, until now no genetic markers have been available for type 2 diabetes.…”

High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial?Type 1 Diabetes

“…In this regard, it is important to note that DQB1*0602 may not protect subjects from LADA, as one report has shown that these patients have the same frequency of this allele as seen in the general population [27]. Others report no differences in the frequency of highrisk alleles between LADA and older, but more typical type 1 patients [34].…”

GAD autoantibodies and epitope reactivities persist after diagnosis in latent autoimmune diabetes in adults but do not predict disease progression: UKPDS 77

“…LADA patients may otherwise be clinically indistinguishable from those with type 2 diabetes (diagnosed as adults, can be obese) and can be adequately managed for many years with diet/oral agent therapy [3]. However, the GADA-positive cohort contained fewer individuals with features of the metabolic syndrome, a characteristic more typical of classic type 2 diabetes than LADA [27,28]. It has been proposed that LADA patients with high GADA levels have a more 'type 1 diabetic' phenotype (reduced residual beta cell function, lower BMI and lower frequency of hypertension), and those with low levels a more type 2 diabetes phenotype [29].…”