Background: Gestational weight gain (GWG) is known to be a potential risk factor for short-term postpartum weight retention (PPWR) and thus for overweight in women. Does GWG also determine the long-term risk of overweight in women? Objective: We aimed to study the short-and long-term effects of GWG in accordance with the Institute of Medicine (IOM) recommendations on postpartum weight retention. Design: We systematically reviewed 5 databases and bibliographies of various publications supplemented by hand search for relevant articles published in English or German and performed meta-analyses to quantify the effect estimate of PPWR by using a random-effects model. We split the data into 4 categories of follow-up: ,0.5, 0.5-1, ;3, and 15 y. Results: Of 1770 search hits, 9 observational studies remained suitable for the analysis. PPWR increased after longer time spans after delivery irrespective of whether GWG had been below, within, or above the guidelines. Compared with women with GWG within the recommendations, those with a GWG above the recommendations retained an additional 3.06 kg (95% CI: 1.50, 4.63 kg) after 3 y and 4.72 kg (95% CI: 2.94, 6.50 kg) on average after 15 y postpartum. Inadequate GWG was associated with less PPWR (22.99 kg; 95% CI: 23.72, 22.27 kg) ,6 mo after pregnancy. This association faded over time and became nonsignificant (21.41 kg; 95% CI: 23.03, 0.21 kg) after 15 y. The results remained stable in sensitivity analyses that accounted for changes in IOM criteria over time and potential effect modification by low social class. A funnel plot did not suggest publication bias. Conclusion: GWG in accordance with the IOM recommendations is associated with long-term effects on PPWR.Am J Clin Nutr 2011;94:1225-31.

Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β–inducible genes in vitro and then used this set of genes to define an IFN-inducible transcriptional signature in peripheral blood mononuclear cells from a group of active systemic lupus erythematosus patients (n = 25). Using this predefined set of 225 IFN signature genes, we investigated the expression of the signature in cohorts of healthy controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed samples). Expression of the IFN signature was increased in genetically predisposed children before the development of autoantibodies (P = 0.0012) but not in patients with established T1D. Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14+ monocytes. DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease. These findings identify transient increased expression of type I IFN genes in preclinical diabetes as a risk factor for autoimmunity in children with a genetic predisposition to T1D.

Background: Excessive gestational weight gain (GWG) increases the risk of a number of adverse pregnancy outcomes and was recently identified as a potential risk factor for childhood obesity. It is therefore of interest whether GWG can be modified by an intervention combining dietary counseling and physical activity. Objective: The objective was to review published data on interventions to reduce GWG by modulating diet and physical activity during pregnancy. Design: We systematically reviewed 4 databases and bibliographies of various publications supplemented by a hand-search for relevant articles published in English or German and performed a metaanalysis to quantify the effect estimate by a random-effects model. Results: Four randomized controlled trials and 5 nonrandomized trials with a total of 1549 women enrolled were identified as being relevant. Meta-analyses of all 9 trials indicated a lower GWG in the intervention groups, with a standardized mean difference of 20.22 units (95% CI: 20.38, 20.05 units). We observed no indication for publication bias. Conclusions: Interventions based on physical activity and dietary counseling, usually combined with supplementary weight monitoring, appear to be successful in reducing GWG. The results are of particular interest with respect to the objective of preventing excessive GWG.Am J Clin Nutr 2010;92:678-87.

Background High gestational weight gain (GWG) has been found to be associated with a number of adverse perinatal and long-term outcomes.Objectives We aimed to perform a systematic review and metaanalysis to find out whether physical activity in pregnancy might help avoid high GWG.Search strategy A literature search in relevant databases and an additional search by hand through bibliographies of various publications were performed.Selection criteria We included randomised controlled trials on healthy women, with increased physical activity as the only intervention. GWG had to be documented for the intervention and control group separately.Data collection and analysis Two reviewers independently extracted data and performed quality assessment. Data from the included trials were combined using a random-effects model. The effect size was expressed as mean difference (MD).Main results Of 1380 studies identified, 12 trials met the inclusion criteria. In seven trials, GWG was lower in the exercise group compared with the control group, whereas five trials showed a lower GWG in the control groups. The meta-analysis resulted in an MD of GWG of )0.61 (95% CI: )1.17, )0.06), suggesting less GWG in the intervention groups compared with the control groups. We found no indication for publication bias or dose effects.Author's conclusions In summary, our analyses suggest that physical activity during pregnancy might be successful in restricting GWG.

Considerably wider optimal GWG ranges than recommended by the Institute of Medicine might be tolerated with respect to avoidance of adverse birth weight outcome. Stratification by maternal body mass index category alone might not be sufficient.

BackgroundAround 0.3% of newborns will develop autoimmunity to pancreatic beta cells in childhood and subsequently develop type 1 diabetes before adulthood. Primary prevention of type 1 diabetes will require early intervention in genetically at-risk infants. The objective of this study was to determine to what extent genetic scores (two previous genetic scores and a merged genetic score) can improve the prediction of type 1 diabetes.Methods and findingsThe Environmental Determinants of Diabetes in the Young (TEDDY) study followed genetically at-risk children at 3- to 6-monthly intervals from birth for the development of islet autoantibodies and type 1 diabetes. Infants were enrolled between 1 September 2004 and 28 February 2010 and monitored until 31 May 2016. The risk (positive predictive value) for developing multiple islet autoantibodies (pre-symptomatic type 1 diabetes) and type 1 diabetes was determined in 4,543 children who had no first-degree relatives with type 1 diabetes and either a heterozygous HLA DR3 and DR4-DQ8 risk genotype or a homozygous DR4-DQ8 genotype, and in 3,498 of these children in whom genetic scores were calculated from 41 single nucleotide polymorphisms. In the children with the HLA risk genotypes, risk for developing multiple islet autoantibodies was 5.8% (95% CI 5.0%–6.6%) by age 6 years, and risk for diabetes by age 10 years was 3.7% (95% CI 3.0%–4.4%). Risk for developing multiple islet autoantibodies was 11.0% (95% CI 8.7%–13.3%) in children with a merged genetic score of >14.4 (upper quartile; n = 907) compared to 4.1% (95% CI 3.3%–4.9%, P < 0.001) in children with a genetic score of ≤14.4 (n = 2,591). Risk for developing diabetes by age 10 years was 7.6% (95% CI 5.3%–9.9%) in children with a merged score of >14.4 compared with 2.7% (95% CI 1.9%–3.6%) in children with a score of ≤14.4 (P < 0.001). Of 173 children with multiple islet autoantibodies by age 6 years and 107 children with diabetes by age 10 years, 82 (sensitivity, 47.4%; 95% CI 40.1%–54.8%) and 52 (sensitivity, 48.6%, 95% CI 39.3%–60.0%), respectively, had a score >14.4. Scores were higher in European versus US children (P = 0.003). In children with a merged score of >14.4, risk for multiple islet autoantibodies was similar and consistently >10% in Europe and in the US; risk was greater in males than in females (P = 0.01). Limitations of the study include that the genetic scores were originally developed from case–control studies of clinical diabetes in individuals of mainly European decent. It is, therefore, possible that it may not be suitable to all populations.ConclusionsA type 1 diabetes genetic score identified infants without family history of type 1 diabetes who had a greater than 10% risk for pre-symptomatic type 1 diabetes, and a nearly 2-fold higher risk than children identified by high-risk HLA genotypes alone. This finding extends the possibilities for enrolling children into type 1 diabetes primary prevention trials.

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Very little is known about the role of the innate immune system in the course of human type 1 diabetes. Here we investigated neutrophil numbers along with other leukocyte populations in patients at diagnosis of type 1 diabetes and during prediabetes. Complete and differential blood counts were analyzed from 107 adult patients with newly diagnosed type 1 diabetes, 21 children with persistent islet autoantibodies and a family history of type 1 diabetes, and 1 238 age and gender matched control subjects, all individuals without any signs of acute infection.Adult patients with newly diagnosed type 1 diabetes had significantly lower total WBC (p<1×10⁻⁶), neutrophil (p<1×10⁻⁶), basophil (p<1×10⁻⁶), monocyte (p=4×10⁻⁶) and lymphocyte (p<1×10⁻⁶) counts compared to control subjects. Erythrocyte, eosinophil and platelet counts did not differ between groups. Similarly, children with persistent islet autoantibodies had decreased WBC (p=0.001), neutrophils (p=0.003), and lymphocytes (p=0.006) in comparison to control children. Our findings demonstrate a perturbation of leukocyte homeostasis at and prior to onset of type 1 diabetes suggesting a general involvement of the innate immune system in the pathogenesis of type 1 diabetes.