Insulin immunogenicity in pregnancy: maternal and fetal studies

Abstract

Antibodies to insulin were found in 92% of the 138 insulin-treated pregnant diabetic patients studied. No effect of pregnancy was shown on insulin antibody levels. Higher insulin antibody levels were significantly associated with the previous use of conventional insulins. Change from conventional to highly purified porcine insulin during pregnancy produced a significant reduction in insulin antibody levels. The combination of protamine zinc and soluble insulin used before pregnancy was found to be the most immunogenic. Insulin antibodies were freely transferred to the fetus but not detectable after the first 8 months of life. No insulin antibodies were found in the cord blood or during the next few weeks in the infants of mothers who had no antibodies to their injected insulin. There was a tendency for higher insulin antibody levels to be associated with indices of neonatal morbidity but not with percentile birth weights and C-peptide levels in cord sera.

Diabetes-Related Autoantibodies and Gestational Diabetes

“…Menon et al (63) reported that the concentration of animal insulin in cord serum correlated with birth weight, but this observation has not been confirmed by other authors (42,64,65,70,71). The underlying mechanism would be an IAfacilitated maternal insulin transfer and, as a consequence, an enhancement of fetal hyperinsulinism and related morbidity (72).…”

“…They are mainly IgG and are actively transported by the placenta (67,68). Maternal and fetal levels are highly correlated for IAs (42,60,(63)(64)(65), ICAs (60), GADAs (60,69), and IA-2As (60). This transplacental passage of antibodies lies behind the higher prevalence of DRA in cord blood from infants of diabetic mothers compared with infants of diabetic fathers (66).…”

“…Maternal insulin-IA complexes have been associated with toxemia (18,73,74), HELLP syndrome (75), hypoglycemia (18,76), respiratory distress (18), and high hematocrit in the newborn (76). Nevertheless, other investigators have not observed a relationship between maternal levels of IAs and cord blood levels of insulin (71), 32-33 split proinsulin (71), or C-peptide (64). In our experience, fetal outcomes were not influenced by the presence or titers of IAs, IAAs, or ICAs (77).…”

Autoimmunity and familial risk of type 1 diabetes

“…It has been shown that IA levels in women with type 1 diabetes remain quite stable during pregnancy [11,12] or decrease only slightly toward term [13,14]. At the time of delivery, it has been shown that around 74% to 90% of mothers with type 1 diabetes are IA-positive [15,16].…”

Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum

“…Controversially, some studies have reported stable IA titres during pregnancy [7,8], while a slight decrease in IA levels has been documented in others [9,10]. No detailed data are available on IAA levels in nondiabetic women during pregnancy.…”