Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA1c

Bonifacio, Ezio; Pflüger, Maren; Marienfeld, S.; Winkler, Christiane; Hummel, Michael; Ziegler, Anette G.

doi:10.1007/s00125-008-1022-z

Cited by 36 publications

(44 citation statements)

References 40 publications

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“…While there are some data suggesting that birthweight differs according to HLA genotype, including increased birthweight in children with certain type 1 diabetes-susceptibility HLA alleles [9][10][11], there is no clear relationship between birthweight and risk of type 1 diabetes [12,13]. Moreover, in our BABYDIAB study, the highest risks for autoimmunity appeared to be associated with normal birthweight [23]. There have also been reports of associations between BMI and autoantibody concentration, but these studies had very few autoantibody-positive cases, and the correlations were made between BMI and antibody concentrations that were largely at the upper end of the normal range, values that are extremely difficult to reproduce in multiple laboratories, i.e.…”

Section: Discussioncontrasting

confidence: 54%

Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

et al. 2009

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Aims/hypothesis It has been suggested that metabolic demand and insulin resistance play a role in the development of type 1 diabetes, including the onset of autoimmunity. The aim of the present study was to determine whether insulin demand is increased in children with islet autoantibodies. Methods BMI standard deviation score (BMI-SDS) was measured from 2 years of age in 1,650 prospectively followed children of mothers or fathers with type 1 diabetes, including 135 who developed persistent islet autoantibodies. HOMA of insulin resistance (HOMA-IR) was determined using fasting samples from 777 of the children starting from age 5 years. Results An increased HOMA-IR was associated with female sex (p=0.0004), older age (p<0.0001) and increased BMI-SDS (p<0.0001). Children with islet autoantibodies did not have an increased HOMA-IR compared with agematched islet autoantibody-negative children (age 8 years: mean 0.61 vs mean 0.72, respectively, p=0.21; age 11 years: mean 0.96 vs mean 1.21, respectively, p=0.07). Furthermore, after correction for age and sex, autoantibody positivity was associated with decreased HOMA-IR values (p=0.01). BMI-SDS was similar between islet autoantibodypositive and -negative children at age 2 (mean 0.07 vs mean 0.16, respectively), 5 (mean 0.06 vs 0.08, respectively), 8 (mean −0.09 vs mean 0.02, respectively), and 11 years (mean 0.22 vs mean 0.16, respectively) and similar to that of national reference values. Conclusions/interpretation Islet autoantibody-positive children in the BABYDIAB cohort are not insulin resistant and do not have an increased BMI around and early after islet autoantibody seroconversion. These findings are inconsistent with the notion that insulin resistance is a risk factor for islet autoimmunity.

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Section: Discussioncontrasting

confidence: 54%

Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

et al. 2009

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“…Therefore, screening only for IA-2A and ZnT8A can be generalized as a costeffective strategy to identify potential participants in secondary immunomodulatory prevention trials with similar antibody-inferred risk in children, adolescents and adults. Omission of relatives with genetic [31] and/or maternal [35] protective factors further improves screening efficiency in all age groups.…”

Section: Discussionmentioning

confidence: 99%

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

Gorus

Balti

Vermeulen

et al. 2012

Clinical and Experimental Immunology

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SummaryIn first-degree relatives of type 1 diabetic patients, we investigated whether diabetes risk assessment solely based on insulinoma antigen 2 (IA-2) and zinc transporter 8 (ZnT8) antibody status (IA-2A, respectively, ZnT8A) is as effective as screening for three or four autoantibodies [antibodies against insulin (IAA), glutamate decarboxylase 65 kDa (GAD) glutamate decarboxylase autoantibodies (GADA) and IA-2A with or without ZnT8A] in identifying children, adolescents and adults who progress rapidly to diabetes (within 5 years). Antibodies were determined by radiobinding assays during follow-up of 6444 siblings and offspring aged 0-39 years at inclusion and recruited consecutively by the Belgian Diabetes Registry. We identified 394 persistently IAA + , GADA + , IA-2A + and/or ZnT8A + relatives (6·1%). After a median follow-up time of 52 months, 132 relatives developed type 1 diabetes. In each age category tested (0-9, 10-19 and 20-39 years) progression to diabetes was significantly quicker in the presence of IA-2A and/or ZnT8A than in their joint absence (P < 0·001). Progression rate was age-independent in IA-2A + and/or ZnT8A + relatives but decreased with age if only GADA and/or IAA were present (P = 0·008). In the age group mainly considered for immune interventions until now (10-39 years), screening for IA-2A and ZnT8A alone identified 78% of the rapid progressors (versus 75% if positive for Ն 2 antibodies among IAA, GADA, IA-2A and ZnT8A or versus 62% without testing for ZnT8A). Screening for IA-2A and ZnT8A alone allows identification of the majority of rapidly progressing prediabetic siblings and offspring regardless of age and is more cost-effective to select participants for intervention trials than conventional screening.

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“…The risk is twofold greater in children of a father than a mother with type 1 diabetes [19,21,22]. The reason for this finding is not known, but it could be due to differences in susceptibility genes.…”

Section: Discussionmentioning

confidence: 95%

Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study

et al. 2015

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Aims/hypothesis Some studies have revealed a relationship between Caesarean section (CS) and type 1 diabetes, while other studies have not. By using the Swedish paediatric quality register we investigated whether birth by CS is related to the risk of developing type 1 diabetes during childhood.Methods All children diagnosed with type 1 diabetes from 2000 to 2012 and included in the register (n=9376) were matched with four controls by year, day of birth, sex and county of birth from the Swedish Medical Birth Register.Results Overall, 13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1 diabetes were delivered by CS compared with 13.5% of control children (p<0.001). Mothers with diabetes more often gave birth by CS than mothers without diabetes (78.8% vs 12.7%, p<0.001). In a logistic regression model adjusting for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was 1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes at the time of delivery had the highest OR to have been born by CS. Children of mothers without diabetes, delivered by CS, had no increased risk of developing type 1 diabetes. Maternal diabetes was the strongest predictor of childhood diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54).Conclusions/interpretation CS had no influence on the risk of type 1 diabetes during childhood or adolescence. However, maternal diabetes itself strongly increased the risk of offspring developing type 1 diabetes.

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Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA1c

Cited by 36 publications

References 40 publications

Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients

Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study

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