Study of T-cell activation in type I diabetic patients and pre-type I diabetic subjects by cytometric analysis: antigen expression defect in vitro.

In Type I diabetes the observation of a decreased release of interleukin-2 (IL-2) and soluble IL-2 receptors by means of stimulated lymphocytes in vitro indicates that a primary immunoregulatory defect may be involved. To confirm this hypothesis we investigated the T-cell activation trend, evaluating the surface expression of IL-2 receptor (CD25), transferrin (CD71), HLA class II (DR), and CD69 phenotypes after in vitro stimulation with phytohemagglutinin (PHA; 1 and 10 micrograms/ml) and concanavalin A (12.5 micrograms/ml) in six newly diagnosed Type I diabetics and six islet cell- and insulin autoantibody-positive first-degree relatives. As controls were studied six long-standing Type I diabetics and six healthy subjects. T-cell cultures from the four groups were performed on the same day and examined at 0, 24, 48, 96, 120, and 144 hr. Cytometric analysis was performed, keeping PBMC gating constant on the basis of physical parameters (scatter and volume). Using both PHA concentrations, a lower level of CD25, CD71, CD69, and DR antigen expression was found in newly diagnosed patients at all observation times with respect to control cultures (P < 0.001). Unexpectedly, pre-Type I diabetic subjects, after 1 microgram/ml of PHA, showed a significantly reduced expression of CD69 (P < 0.001) and CD71 (P < 0.001). The levels remained low, also with high PHA, at the different observation periods, while CD25 expression was found to be reduced in prediabetics only after 1 micrograms/ml of PHA (P < 0.001). The long-standing patients showed a T cell activation trend very close to the latter. Our data show that in Type I diabetes and in the early phases of the disease, the initial activation signal(s) appears to be affected, particularly with one or more subsequent events necessary to initiate the appearance of "activation antigens." This study suggests that the natural history of immunoregulation in pre-Type I and Type I diabetes is characterized by a primary defect in this system, which also persists in patients with long-standing disease.

Analysis of T-lymphocyte subsets after phytohemagglutinin stimulation in normal and type 1 diabetic mothers and their infants.

PROBLEM: Our aim was to investigate the immunological status of diabetic pregnancy, which is an overlap of diabetic immunity abnormalities and the immunological modifications normally occurring during pregnancy. METHOD: We studied lymphocyte subpopulations and lymphokine production, after 96 h of phytohemagglutinin (PHA) stimulation, from normal and Type I diabetic pregnant women at delivery time and from the respective cord blood. RESULTS: Peripheral blood mononuclear cells (PBMC) from both normal and Type I diabetic mothers showed an increase in CD8+ and a decrease in CD4+ cells compared to the respective cord blood mononuclear cells (CBMC). Moreover, Type I PBMC showed a lower number of "activated" CD3+ DR+ cells and a higher number of CD8+ CD25+ cells with respect to normal women, which may reflect the dysregulatory pattern due to the autoimmune condition. Type I CBMC showed a big increase in the number of CD4+ Leu8+ cells, a cell subpopulation characterized by inhibitory activity. Finally, as regards lymphokine release in culture supernatants, type I diabetes seemed to be associated with an over-production of IL1 and IL6, although the latter increase is less evident in CBMC cultures. CONCLUSIONS: The present study shows that diabetic pregnancy is associated with major alterations of cell-mediated immunity leading to a state of immunodepression. Moreover, our study suggests that the maternal immunological status influences fetal immunity, as demonstrated by the increase in the number of regulatory cells and by the altered pattern of lymphokine production (IL1 and IL6) by lymphocytes derived from diabetic CBMC. The latter phenomenon perfectly mirrors maternal PBMC characteristics.

[Fetal macrosomia in children of diabetic mothers: relationship with excess weight in early years of life]. / Macrosomia fetale nei figli di madre diabetica: relazione con l'eccedenza ponderale nei primi anni di vita.

One hundred children (4.1 +/- 1.9 years) were examined: 31 of type I diabetic mothers, 25 of type II diabetic mothers and 44 of gestational diabetic mothers. The fetal body weight index at delivery was determined according to Babson. The weight/height index was determined according to Tunner's Centiles, when the children were examined. At delivery 41% of babies examined was greater than 90 degrees C for gestational age; when the babies were reexamined 23% was greater than 90 degrees C. On the contrary, during the early years of life we found that the 51% of children is greater than 90 degrees C and of this, the 27% became obese. The diabetic mother's children develop obesity more frequently than those of non diabetic mother's ones. The body weight at birth influences but is not the cause of obesity in the early years of life.

[Residual hyperinsulinism after glucose oral load in obese subjects with normal glucose tolerance]. / Iperinsulinismo residuo dopo carico orale di glucosio in obesi a normale tolleranza glicidica.

Forty-five NGT obese subjects were submitted to OGTT with IRI and CPR determinations and to euglycemic hyperinsulinemic clamp, and divided into two groups: A) those with return of insulinemia toward basal values, and B) those with residual hyperinsulinism, in order to evaluate possible differences in insulin secretion and/or insulin action among them. Our data show the younger age of those with residual hyperinsulinism, that also seems related to insulin secretion, represented by IRI and CPR basal values, but not to insulin resistance parameters.