Glutamate Decarboxylase Antibodies in Non-Diabetic Pregnancy Precedes Insulin-Dependent Diabetes in the Mother but not Necessarily in the Offspring

Abstract

We studied the risk for diabetes of glutamate decarboxylase (GAD65Ab) and islet cell (ICA) autoantibodies in non-diabetic pregnant mothers and their children. Pregnancy and cord blood sera were collected in 1970-87 from about 35,000 mothers who delivered a child in the city of Malmö, Sweden. A total of 42 mothers were identified in 1988 who, 1-18 years after their pregnancies, had developed either insulin-dependent (n = 22) or non-insulin dependent (n = 20) diabetes mellitus. First, in 123 pregnant mothers selected as controls, 0.8% had GAD65Ab and 0.8% ICA. Second, among the mothers with non-insulin dependent diabetes, 7/20 (35%) had GAD65Ab eight months to 13 years, 10 months before clinical diagnosis. Third, in mothers who later developed insulin-dependent diabetes, 12/22 (55%) had GAD65Ab and 10/22 (45%) had ICA in pregnancies preceding the clinical diagnosis by 13 months to 9 years, 4 months. In 1996, none of the children born to the 42 mothers have developed diabetes. GAD65Ab and ICA in non-diabetic pregnancies may predict insulin-dependent diabetes in the mother but not necessarily in the offspring.

Cord blood islet autoantibodies and seasonal association with the type 1 diabetes high-risk genotype

“…As previously demonstrated for GAD65Ab and ICA, 31 levels of islet Abs in the offspring tended to be higher than in the serum sample obtained from the mother at the time of delivery. It is possible that the levels appear high in the offspring due to the hemodilution that takes place during pregnancy.…”

“…However, after 1 year all children had undetectable levels. It has been speculated that the presence of islet Abs during pregnancy in nondiabetic mothers may reflect subclinical islet autoimmunity which would not only put the mother 31 at increased postnatal risk for T1D but also the offspring. 28 As part of the Diabetes Prediction in Skåne (DiPiS) project, 32 our aim is to identify nongenetic factors that improve positive prediction of T1D.…”

Is islet autoimmunity really detectable at birth?

“…One of these children, who had IAA and GAD at birth, presumably from the mother's circulation developed Type I diabetes at age 4 years. These data further suggest that islet autoantibodies found at birth are likely to be acquired through transplacental exchange of the mother's immunoglobulin and support other reports [4,5] which indicate that in utero production of islet autoantibodies is likely to be a relatively rare occurrence.…”

“…Blood spots were also obtained from 37 control neonates born in the same hospital on the same day and with no family history Type I diabetes in the mother and from 20 newborns of mothers with Type I diabetes. Blood spots were extracted and eluate measured for antibodies to glutamic acid decarboxylase (GADA), IA±2 (IA±2A), and insulin (IAA) as described previously [3,4]. None of the birth blood spots from children who developed diabetes or control children had detectable islet autoantibodies, whereas at least one autoantibody was detected in 7 of 20 children from mothers with Type I diabetes.…”

Is Presence of Islet Autoantibodies at Birth Associated With Development of Persistent Islet Autoimmunity?

“…The relationship of cord blood autoantibodies and islet autoimmunity has been explored in previous studies (12)(13)(14)(15). However, to assess the predictive value of cord blood autoantibodies in newborns, large prospective studies would be most useful.…”