On the appearance of islet associated autoimmunity in offspring of diabetic mothers: a prospective study from birth

Abstract

For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n = 113) and gestational diabetes (n = 55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies > or = 20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies > 49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies > or = 20 JDF-U, 76% insulin antibodies > 49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies > or = 20 JDF-U, 18% insulin antibodies > 49 nU/ml; neonates: 13% islet cell antibodies > or = 20 JDF-U, 55% insulin antibodies > 49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal growth is increased by maternal type 1 diabetes and HLA DR4-related gene interactions

“…Subjects Children followed prospectively from birth in the German BABYDIAB [16][17][18] and BABYDIET [19] studies were included. Recruitment into the studies began in 1989 (BABYDIAB) and 2000 (BABYDIET).…”

“…Since 1989, we have prospectively followed from birth children of parents or siblings with type 1 diabetes [16,17]. In these children anthropometric data such as weight and height are obtained throughout childhood.…”

Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with Type I diabetes: The German BABYDIAB study

“…Since 1989 we have conducted a prospective German multicentre study of infants followed from birth. The ªBABY-DIABº study of children from mothers or fathers with Type I diabetes investigates the temporal development of the responses of insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), the antibodies to the protein tyrosine phosphatase IA-2 (IA2A), and islet cell autoantibodies (ICA) at birth (cord blood) and at 9 months, 2, 5 and 8 years of age in all children [8,9]. At 2 years of age, EDTA blood is requested from parents and the index child for HLA typing.…”

“…We have shown previously that persistent autoantibodies often appear by the age of 2 years in offspring of parents with Type I diabetes [8,9]. Recent genome-wide mapping has confirmed that HLA class II genes confer the greatest genetic risk for Type I diabetes [10±12].…”

Natural History of Type 1 Diabetes

“…Over the last 15 years, several groups have initiated prospective studies from birth examining the development of islet autoimmunity and diabetes (5)(6)(7)(8), providing an opportunity to test such theoretical models in patients developing type 1 diabetes. Findings from these studies have significantly contributed to our current understanding of the pathogenesis of childhood diabetes.…”