The effect of insulin antibodies of various orders on the course of type 1 diabetes mellitus before and during pregnancy
Abstract
Background. Women with type 1 diabetes mellitus (DM1) are at an increased risk of having children with congenital abnormalities. The association has been demonstrated of the worst neonatal outcomes with the presence of autoantibodies (aAB) to pancreatic islet cells of mother. First-order insulin antibodies (AB1) are currently recognized as the most informative immunological markers in the diagnosis and monitoring of the pathological process in DM1. Second-order antibodies (AB2) exert a significant effect on features of the course of DM1, however, these antibodies are poorly understood. No studies of insulin AB3 in DM1 have been conducted.
Aim. To study the consequences of the imbalanced production of insulin AB1, AB2, and AB3 for the course of DM1 in women during pregnancy.
Methods. Anti-insulin antibodies of various orders (AB1, AB2, AB3) were determined by a standard solid-phase enzyme-linked immunosorbent assay (ELISA). The blood glucose concentration of pregnant women was measured in 20-µl samples of whole blood by the glucose oxidase method using a semi-automatic glucose analyzer (AGKM-01, Russia). Glycemia of pregnant women was monitored 2-3 times per week and, if necessary, daily. Glycosylated hemoglobin (HbAlc) was measured with an AU480 biochemical analyzer (Beckman Coulter, USA) using Beckman Coulter Diagnostics reagent kits (USA).
Results. Pregnant women with DM1 were divided into groups based on their set of anti-insulin ABs of various orders before pregnancy. Each group was characterized by a specific clinical picture of DM1. In cases, when concentrations of anti-insulin AB1, AB2, and AB3 did not exceed normal levels, or in cases of isolated AB1 overproduction (groups 1 and 2), the course of DM1 was characterized by the absence of significant fluctuations of glycemia and insulin requirements throughout pregnancy. This category of patients was characterized by a stable, subcompensated course of DM1. The most severe course of DM1 was typical for patients with a predominant production of insulin receptor AB2 (group 3). Women of this group had abnormally high levels of glycemia and an increased requirement for insulin almost throughout pregnancy, particularly in the 2nd and 3rd trimesters. The associated hyperglycemic conditions were severe. With overproduction of anti-insulin AB3 (group 4), DM1 was usually subcompensated, most often manifested in the 2nd and 3rd trimesters. These states often alternated with periods of decompensation. Patients of this group had a high (but lower than in group 3) insulin requirement, that reached a maximum in the 3rd gestation period. The unstable, subcompensated course of DM1 in pregnant women of group 4 is apparently due to imbalanced effects of AB2 and AB3.
Conclusion. During pregnancy with DM1, there is a clear dependence of the course of DM1 on the production of anti-insulin ABs of various orders: severe, often uncompensated course of diabetes is associated with a high level of AB2, whereas the most favorable, easily controlled course of DM1 is associated with prevailing biosynthesis of AB1.
