Endocrine autoimmunity in families with type 1 diabetes: frequent appearance of thyroid autoimmunity during late childhood and adolescence.

AIMS/HYPOTHESIS: Thyroid autoimmunity clusters with other endocrine and non-endocrine forms of autoimmunity. The aim of this study was to determine the chronological appearance of thyroid autoantibodies in relation to other forms of autoimmunity in at-risk children. METHODS: The BABYDIAB study follows children of parents with type 1 diabetes. Children born in Germany between 1989 and 2000 were recruited at birth and followed up at 9 months and at 2, 5, 8, 11, 14 and 17 years. Antibodies to thyroid peroxidase were measured in samples taken at the last study visit in 1,489 children and in all previous samples in children who tested positive. Islet antibodies and antibodies to 21-hydroxylase and transglutaminase were also measured in all children. Median follow-up was 8 years. RESULTS: The cumulative risk for developing antibodies to thyroid peroxidase was 20.3% (95% CI 12.3-28.3) by age 14 years. The risk was increased in girls (adjusted HR 2.0; 95% CI 1.2-3.4; p = 0.008), in children who had multiple first-degree family history of type 1 diabetes (adjusted HR 3.3; 95% CI 1.4-8.0; p = 0.006) and in children who also had antibodies to GAD (adjusted HR 3.0; 95% CI 1.5-5.9; p = 0.001). Thyroid peroxidase antibody appearance was most common from age 8 years and was often the last autoantibody to develop in children with other autoantibodies. CONCLUSIONS/INTERPRETATION: Among children of patients with type 1 diabetes, the appearance of thyroid autoantibodies is frequent, is not synchronous to the appearance of other autoantibodies and is most common in late childhood and adolescence.

[Breastfeeding in women with gestational diabetes]. / Stillverhalten bei Frauen mit Gestationsdiabetes.

BACKGROUND AND OBJECTIVE: Children born to mothers with gestational diabetes are at an increased risk of developing obesity. Breastfeeding is acknowledged as beneficial for child development and it is suggested that breastfeeding protects against becoming obese. The aim of this study was to document breastfeeding habits of women with gestational diabetes and to identify factors that affect breastfeeding habits. METHODS: Breastfeeding habits (breastfeeding of any duration) were recorded of 257 mothers with gestational diabetes (mean age 31.4 +/- 4.8 years) who participated in a prospective post-partum study between 1989 and 1999 and compared to breastfeeding habits of 527 healthy mothers (mean age 30.3 +/- 4.2 years), all enrolled in the prospective BABYDIAB study between the years 1989 and 2000. Breastfeeding data were prospectively obtained by questionnaire and interview. RESULTS: Compared to children of healthy mothers, fewer children of mothers with gestational diabetes were breastfed (75% vs 86%; P<0.0001). Among breastfed children the duration of full or any breastfeeding was shorter in children of mothers with gestational diabetes (median for full breastfeeding 9 weeks. [mothers with gestational diabetes] vs. 17 weeks. [healthy mothers]; p<0.0001; median duration of any breastfeeding 16 weeks. vs. 26 weeks.; p<0.0001). After stratification for other risk factors the duration of breastfeeding significantly differed between mothers with gestational DM and those who were healthy (hazard ratio [HR] 1.4; p<0.05 for full breastfeeding; HR 1.5; p<0.0001 for any breastfeeding). Full and any breastfeeding was shorter in women with insulin-dependent gestational diabetes than in those with diet-controlled gestational diabetes (full breast-feeding 4 weeks. vs. 12 weeks.; p<0.01 and any breastfeeding 10 weeks. vs. 20 weeks,; p<0.0001). Fewer women with gestational diabetes and a body weight index (BMI) >30 kg/m2 breastfed (65% vs 80%; p=0.01) and for a shorter duration than women with a BMI <30 kg/m2 (any breastfeeding 12 weeks. vs. 17 weeks; p=0.02). The type of DM therapy independently correlated with reduced breastfeeding duration (HR 1.7; p=0<0.01). CONCLUSIONS: Mothers with gestational diabetes, especially mothers with insulin-dependent gestational diabetes, and obese mothers breastfed their children significantly less and for a shorter duration than healthy mothers. These findings could explain the higher risk of their children developing obesity later in life and should be considered when counselling women with gestational diabetes.

Breastfeeding habits in families with Type 1 diabetes.

AIMS: Breastfeeding is acknowledged to be beneficial for child development. Women with diabetes may be more likely not to breastfeed their children because of neonatal morbidity and instability in diabetes control. The aim of this study was to assess the effect of maternal Type 1 diabetes on breastfeeding habits. METHODS: Full breastfeeding and any breastfeeding were reported in the first year of life in 1560 children born in Germany between 1989 and 2004. Of those, 997 children had a mother with Type 1 diabetes, and the remaining 563 children had a father or sibling with Type 1 diabetes. RESULTS: Fewer children of mothers with Type 1 diabetes were breastfed than children of non-diabetic mothers (77 vs. 86%; P < 0.0001) and, amongst breastfed children, there was a shorter duration of full breastfeeding (12 vs. 17 weeks; P < 0.0001) and any breastfeeding (20 vs. 26 weeks, P < 0.0001) in children of mothers with Type 1 diabetes compared with children of non-diabetic mothers. Other factors associated with reduced frequency and duration of breastfeeding were pre-term delivery (P < 0.0001), young maternal age (P < 0.0001), and firstborn children (P < 0.0001). After stratification for each of these factors, breastfeeding remained significantly less frequent and of less duration in children of mothers with Type 1 diabetes as compared with children of non-diabetic mothers. CONCLUSIONS: Mothers with Type 1 diabetes breastfeed their children less than international recommendations. Counselling to increase frequency and duration of breastfeeding may be warranted in this population.

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

AIMS/HYPOTHESIS: Intrauterine growth in non-diabetic pregnancies is reported to be influenced by type 1 diabetes susceptibility genes. In particular, the high-risk HLA DR4_DQB1*0302 haplotype is associated with increased birthweight. The aim of this study was to determine whether HLA DR4 was associated with increased birthweight in a maternal diabetes environment and whether effects persisted during early childhood. SUBJECTS AND METHODS: Birthweight and gestational age were obtained in singleton births from mothers with type 1 diabetes (n = 1161) or whose fathers or siblings have type 1 diabetes (n = 872). Weight and height at ages 2 and 5 years were obtained from paediatric records. Data were adjusted for (gestational) age and sex and expressed as percentiles of German reference data. HLA DR typing was obtained for all children and 1090 children also had insulin gene (INS) variable number of tandem repeats (VNTR) typing. RESULTS: Maternal type 1 diabetes was associated with increased birthweight, gestational age and birthweight percentiles (all p < 0.0001). In children of mothers with type 1 diabetes, birthweight percentile was further related to maternal HbA(1c) during pregnancy (r = 0.26; p < 0.0001) and was independently increased if children had HLA DR4 alleles (76th vs 64th percentile; p < 0.0001). HLA DR4 was not associated with birthweight in children of non-diabetic mothers. Birthweight was not associated with INS VNTR genotypes. High birthweight, but not HLA DR4 was associated with increased weight and BMI at ages 2 and 5 years (p < 0.0001). CONCLUSIONS/INTERPRETATION: Our findings are consistent with the hypothesis that a diabetic intrauterine environment interacts with gene(s) marked by the type 1 diabetes susceptibility HLA DR4 alleles to increase fetal growth.

Immune responses to glutamic acid decarboxylase and insulin in patients with gestational diabetes.

Pregnancy is a natural state of immunoprotection and tolerance. We studied subjects with gestational diabetes (GDM) to evaluate the influence of pregnancy on the humoral immune response to the autoantigen GAD and to injected insulin. Antibodies against glutamic acid decarboxylase (GADA) subclasses and epitope reactivity were determined in 34 GADA-positive pregnant patients with GDM, in 20 GADA-positive relatives of people with TID and in 25 GADA-positive patients with newly diagnosed TID. Partum levels of insulin antibodies (IA), IgG1- and IgG4-IA were measured in 131 women with GDM treated with human insulin from the time of diabetes diagnosis (including 22 with GADA) and were compared to 19 patients with TID after 3 months of insulin treatment. GADA titre and subclasses were similar among all groups. GADA in GDM patients bound fewer epitopes than GADA in relatives of patients with TID (all epitopes being present in 23%versus 65%, P < 0.01). In particular, antibodies to the minor GADA epitopes GAD6596-249, GAD651-100 and GAD67 were less frequent in patients with GDM compared to relatives (P < 0.01). Antibodies to insulin (IA) were found in 17% of patients with GDM. They were more frequent in GDM patients with GADA compared to GADA-negative patients (41%versus 12%, P < 0.005). IgG1 was the dominant insulin antibody subclass response in both patients with GDM and TID but levels of IgG1-IA and IgG4-IA were significantly lower in patients with GDM compared to patients with TID (P < 0.004). Antibody responses in women with gestational diabetes appear to be dampened and restricted, but without change in subclass usage.