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Background: To assess the prevalence of markers of autoimmune insulitis (AII) in patients classified originally as having Type-2 diabetes mellitus (Type-2 DM). 386 patients subdivided according to the BMI, C-peptide and type of treatment., Methods and Results: Age, BMI, C-peptide, Glutamic acid decarboxylase autoantibodies (GADA), HLA-DR/,-DQ alleles. Prevalence of GADA varied from < 5% in obese patients with normal/increased C-peptide to > 30% in non-obese patients with low C-peptide. In majority of GADA positive patients, the Type-1 DM high-risk HLA-DRB1*, HLA-DQB1* alleles have been found. Among them HLA-DRB1*0302 and HLA-DRB1*0201 were more frequent than HLA-DRB1*040x and HL:A-DQB1*0302., Conclusions: Significant fraction of patients classified initially as Type-2 DM may have in fact Type-1 DM. Such patients can be recognized on the basis of assessment of serological (GADA) and immuno-genetical (HLA-DR/,-DQ alleles) markers. In some patients clinical, metabolic, immune, and immunogenetic markers may disagree. This divergence stresses multifactorial genesis of diabetes. Moreover, it can also suggest that both autoimmune insulitis and insulin resistance may coexist in parallel.

Aim of Study: To assess some immunological and immunogenetic aspects in patients with latent autoimmune (Type-1) diabetes mellitus (DM) of adults (LADA)., Subjects: 24 patients with LADA, 11 patients with Type-2 DM and 20 healthy volunteers (Pilot study). PARAMETERS TESTED: HLA-DRB1* and HLA-DQB1* alleles, parameters of cellular immunity (CD4+, CD8+, CD3/HLA-DR+, CD8/HLA-DR+, CD45RA+[CD4], CD16+CD56), CD19+, IL-4, INF-gamma and organ specific (OSA) autoantibodies (against thyroid gland, gastric parietal cells, tubuli, basal membranes of glomerulus, AMA and ABBA)., Results and Discussion: Type-1 DM HLA-DRB1* and HLA-DQB1* risk alleles have been found in a majority of patients with LADA. The most frequent were HLA-DRB1*0301 and DQB1*0201. Assessement of parameters of cellular immunity and cytokine profiles (IL-4 a INF-gamma) in peripheral blood did not reveal any contribution to a differentiation between Type-1 and Type-2 DM). We confirmed increased occurence of OSA in patients with LADA, what stress importance of routine screening for OSA in patients with LADA.

Results on HLA-DRB1* and HLA-DQB1* allele frequencies in the Slovak population by PCR-SSP method are presented. HLA-DRB1* alleles were determined in 130 and HLA-DQB1* alleles in 143 healthy unrelated individuals. The highest frequency was observed for the alleles HLA-DRB1*1101-13 (0.203), HLA-DRB1*0701 (0.142), HLA-DQB1*0301 (0.244), and HLA-DQB1*0201 (0.209). The least frequent alleles were HLA-DRB1*1402-6-9, HLA-DRB1*0901 (both 0.0038), HLA-DQB1*0401 (0.007), and HLA-DQB1*0601 (0.0035). The results obtained by DNA-typing were compared with those calculated from the serological study. No statistically significant differencies were found. The allele frequencies obtained in our study were also compared with those of the Czech and Austrian populations. No statistically significant differencies were observed. (Fig. 2, Tab. 3, Ref. 13.)

The polymorphism at the HLA-DPB1 locus was established in 146 unrelated persons. The polymerase chain reaction (PCR) in combination with restriction fragment length polymorphism (RFLP) technique was used. After PCR amplification of the second exon of the HLA-DPB1 locus, the PCR products were digested with seven allele specific endonucleases. The alleles DPB1*0401 (43.29%), DPB1*0402 (20.89%), DPB1*0201 (14.39%) and DPB1*0301 (9.25%) were the most common among 15 DPB1 alleles detected in the tested group. The least frequent alleles were DPB1 *0202, *0601, *1101 and *1501 (0.34%). The comparison with allele frequencies in Austrian and German populations showed no statistically significant differences. (Tab. 2, Ref. 18.)