The aim of this study was to evaluate the impact of TNFα and their receptor in autoimmune diabetes. It was found the most pronounced inhibition of production of soluble forms of the receptor for TNFα in the background of an increased number of lymphocytes bearing membrane-associated receptors for TNFα in patients with manifested variant of diabetes type 1, compared to patients with latent autoimmune diabetes of adults.

Aim. To elucidate the role of Th1/Th2 polarization of immune response in LADA patients in the realization of the clinical phenotype of the disease. Materials and methods. 70 patients aged 21-61 (mean 41.3?1.0 yr) with DM diagnosed based on WHO criteria (1999). Groups 1 and 2 included 13 DM1and 57 DM2 patients (34.6?7.2 and 43.6?7.6 yr respectively). 27 DM2 patients (41.2?1.6 yr) presumably had LADA (P. Zimmet's criteria).Serum anti-GAD65, ICA, and IAA antibodies along with C-peptide were measured in fasting sera and 120 min after GTT by solid phase immunoenzymeassays following manufacturer's instructions with the use of a photometer for Multiscan EX microplates (ThermoLabSystems, Finland) at405 nm (for GAG and ICA) and 450 nm (for IAA and C-peptide). GAD, IAA, and C-peptides levels were calculated automatically from calibrationcurves. Mononuclear leukocytes were isolated by centrifugation in the ficoll-verographin density gradient. The cells thus obtained were resuspendedin the complete nutritient medium reducing their concentration to 2.0x10^6/ml. Phytohemagglutinin (Difco, Germany) was added (10 mcg/1 ml) tothe samples to stimulate mononuclear leukocytes; cell suspensions were further incubated for 24 hr. Initial and PGA-induced levels of IL-2, 4, 10 insupernatants of cell cultures were measured by solid phase immunoassay at 450 nm. Results. At least one type of autoantibodies (GAD, ICA or IAA) was identified in 24.3% of all DM patients (17/70) and in 18% of the DM2 patients(10/57). The level of anti-GAD and ICA ABs and percentage of AB-positive patients were higher in the LADA group while that of anti-IAA ABs amongDM1 patients without LADA. Two AB types at a time were found in 17% (4/23) of the patients with autoimmune DM in the absence of significantdifference between LADA and DM1. Patients with LADA had a significantly lower basal C-peptide level than DM2 patients. The was a tendencytoward lower level of stimulated C-peptide secretion in LADA patients compared with DM2 ones. It suggests impairment of beta-cell secretory functionaffected by the autoimmune process. We observed enhanced basal production of IFN-y by blood mononuclear leukocytes in all DM patients in theabsence of significant difference between the groups. Mitogen-activated production in all CD patients was lower than normal without inter-groupdifferences. Patients with DM2 had the inverted type of IL-2 secretion unlike those with autoimmune diabetes. In both cases it was significantly differentfrom normal values. There was a tendency toward higher basal production of IL-4 by mononuclear leukocytes in LADA and DM2 comparedwith CD1 which reflects pathogenetic peculiarities of beta-cell function in LADA differing from those in DM1 and responsible for slower impairment ofbeta-cell function in this condition. Basal and PGA- induced production of IL-10 was higher in LADA and DM2 than in DM1. It suggests enhancedsuppressor activity of leukocytes that may protect beta-cells from autoimmune destruction and determines gradual development of clinical symptoms ofinsulin deficiency. In contrast, low production of IL-10 in DM1 gives evidence of polarization of the immune response. Conclusion. The loss of functional parenchyma and manifestation of insulin deficiency in LADA occur at a relatively low rate due to the peculiarcharacter of cytokine-mediated cell interactions. It suggests the necessity of an active and careful diagnostic strategy with the use of immunologicalmethods for examination of elder patients presenting with a variety of pathogenetic variants of DM.

Some researchers found that the development of microvascular complications (nephropathy, retinopathy) with latent autoimmune diabetes adults (LADA) occurs much earlier than in type 1 diabetes mellitus. The research devoted to the study of the spectrum and the time of development of microangiopathy in patients with latent autoimmune diabetes of adults, compared to patients with type 1 and 2 diabetes mellitus. Also studied immunological factors (cytokine secretion of mononuclear leukocytes) as one of the possible mechanisms of diabetic angiopathy progression. It has been shown that in LADA, as in patients with type 2 diabetes mellitus, the development of microvascular complications (nephropathy, retinopathy) occurs much earlier than in type 1 diabetes mellitus (after a 4-year course of the disease) due to a sharp decline in the serum concentration of C peptide. Thus in patients with LADA, having microvascular complications in the supernatants of cell cultures of mononuclear leukocytes determined a significant increase in the concentrations of cytokines IL-2, IL-4, TNFα.

The review devotes to studying the role of cytokines in development of autoimmune diabetes mellitus, latent autoimmune diabetes in adults included. Therapeutic approaches to prevent the loss of endogenous insulin secretion are discussed. There is review of clinical trials of immunosuppressive agents and modulators of immune tolerance in autoimmune diabetes mellitus.