Vitamin D and probiotics supplement use in young children with genetic risk for type 1 diabetes.

BACKGROUND/OBJECTIVES: Vitamin D and probiotics are nutrients of interest in the context of type 1 diabetes (T1D). We assessed the prevalence of and factors associated with vitamin D and probiotic supplementations among young children with genetic risk of T1D. SUBJECTS/METHODS: Use of supplements during the first 2 years of life was collected prospectively from 8674 children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. RESULTS: Single and/or multivitamin/mineral (MVM) supplements were reported by 81% of the children. The majority of participants in Finland, Germany and Sweden (97-99%) and 50% in the United States received vitamin D supplements that were mostly MVMs. Probiotics use varied from 6% in the United States to 60% in Finland and was primarily from probiotics-only preparations. More than 80% of the vitamin D and probiotics supplementation was initiated during infancy, and more than half of the uses lasted longer than a year. Being the first child, longer duration of breastfeeding, born in a later year, older maternal age and higher maternal education level were associated with both vitamin D and probiotics use. Shorter gestational age and mother not smoking during pregnancy were associated with a higher likelihood of probiotics supplementation only. CONCLUSIONS: Vitamin D and probiotics supplementations are popular in children 0-2 years old and are associated with common factors. Data documented here will allow evaluation of the relationship between early childhood dietary intake and the development of islet autoimmunity and progression to T1D.

Risks of Adverse Perinatal Outcomes after Repeat Terminations of Pregnancy by their Methods: a Nationwide Register-based Cohort Study in Finland 1996-2013.

BACKGROUND: Repeat terminations of pregnancy (TOPs) are associated with an increased risk of adverse outcomes in the subsequent birth. The perinatal outcomes after repeat TOPs by their methods have not yet been properly studied. This study aimed to examine perinatal outcomes in subsequent pregnancy among the women with a singleton birth and a history of TOPs. METHODS: All the first-time mothers (n = 419 879) with a singleton birth during 1996-2013 in Finland were identified from the Medical Birth Register and linked to the Abortion Register. Adjusted multivariable logistic regression analysis was used to estimate risks of adverse perinatal outcomes. RESULTS: The increased incidence of adverse perinatal outcomes was found with increasing number of surgical TOPs. After adjusting for confounders, the women with one surgical TOP had slightly increased but significant odds of 1.07 (95% CI 1.02, 1.13) for being small for gestational age compared with the women having no TOP. A significantly high risk for extremely preterm birth (OR 1.51, 95% CI 1.03, 2.23) was found among the women having had repeat surgical TOPs when compared to the women with no TOP. Non-significant risks were found for adverse perinatal outcomes after women's repeat surgical TOPs than repeat medical TOPs. CONCLUSION: Information regarding the consequences of repeat induced TOPs will be significant in sexual health education as well as counselling women after first termination.

Serum carotenoid and tocopherol concentrations and risk of asthma in childhood: a nested case-control study.

BACKGROUND: The antioxidant hypothesis regarding the risk of asthma in childhood has resulted in inconsistent findings. Some data indicate that the role of antioxidants in childhood asthma risk may have a critical time window of effect, but only a well-designed longitudinal cohort study can clarify this hypothesis. OBJECTIVE: To study the longitudinal associations between serum carotenoid and tocopherol concentrations during the first 4 years of life and asthma risk by the age of 5 years. METHODS: Based on a case-control design nested within a Finnish birth cohort, 146 asthma cases were matched to 270 controls on birth time, sex, genetic risk, and birth place. Non-fasting blood samples were collected at the ages of 1, 1.5, 2, 3, and 4 years and serum carotenoids and tocopherols were analysed. Parents reported the presence and age at start of persistent doctor-diagnosed asthma in the child at the age of 5 years. Data analyses were conducted using generalized estimating equations. RESULTS: We did not find strong associations between serum carotenoids and tocopherols and the risk of asthma based on age-specific and longitudinal analyses. Both lower and higher quarters of α-carotene and γ-tocopherol increased the risk of asthma. CONCLUSIONS: The current findings do not support the suggestion that the increased prevalence of asthma may be a consequence of decreased intake of antioxidant nutrients. Moreover, we did not confirm any critical time window of impact of antioxidants on asthma risk. Replication of these findings in similar longitudinal settings will strengthen this evidence base.

Maternal fatty acid intake during pregnancy and the development of childhood overweight: a birth cohort study.

BACKGROUND: Maternal diet during pregnancy may contribute to the risk of offspring adiposity. OBJECTIVES: The objective of the study is to explore the associations between maternal antenatal dietary fatty acid intake and the risk of offspring overweight and obesity at the ages of 2 to 7 years. METHODS: In a prospective Finnish birth cohort with 3807 mother-child pairs, maternal diet in late pregnancy was assessed with a food frequency questionnaire. Intakes of total fatty acids and individual saturated, monounsaturated and polyunsaturated fatty acids (PUFAs) were calculated. Generalized estimating equation models were used to study the associations of maternal dietary variables with repeatedly measured offspring overweight and obesity. RESULTS: In girls, maternal intake ratio of n-6:n-3 PUFAs had a U-shaped association with obesity (adjusted OR for the lowest 2.0 [95% CI 1.27-3.20] and the highest 1.7 [1.03-2.73] vs. the two middle quartiles of n-6:n-3 PUFAs, p = 0.01). In boys, arachidonic acid (20:4n-6): docosahexaenoic acid + eicosapentaenoic acid ratio was associated with obesity (adjusted OR for the lowest 1.0 [0.60-1.57] and the highest 0.5 [0.26-0.88] vs. the two middle quartiles, p = 0.02). Saturated fatty acids and monounsaturated fatty acids were not associated with overweight or obesity in either sex. CONCLUSIONS: Maternal intakes of PUFAs in late pregnancy were associated with risk of later obesity differently in girls and boys.

Maternal diet during pregnancy and lactation and cow's milk allergy in offspring.

BACKGROUND/OBJECTIVES: Diet during pregnancy and lactation may have a role in the development of allergic diseases. There are few human studies on the topic, especially focusing on food allergies. We sought to study the associations between maternal diet during pregnancy and lactation and cow's milk allergy (CMA) in offspring. SUBJECTS/METHODS: A population-based birth cohort with human leukocyte antigen-conferred susceptibility to type 1 diabetes was recruited in Finland between 1997 and 2004 (n=6288). Maternal diet during pregnancy and lactation was assessed by a validated, 181-item semi-quantitative food frequency questionnaire. Register-based information on diagnosed CMA was obtained from the Social Insurance Institution and completed with parental reports. The associations between maternal food consumption and CMA were assessed using logistic regression, comparing the highest and the lowest quarters to the middle half of consumption. RESULTS: Consumption of milk products in the highest quarter during pregnancy was associated with a lower risk of CMA in offspring (odds ratio (OR) 0.56, 95% confidence interval (CI) 0.37-0.86; P<0.01). When stratified by maternal allergic rhinitis and asthma, there was evidence of an inverse association between high use of milk products and CMA in offspring of non-allergic mothers (OR 0.30, 95% CI 0.13-0.69, P<0.001). Cord blood IgA correlated positively with the consumption of milk products during pregnancy, indicating exposure to CMA and activation of antigen-specific immunity in the infant during pregnancy. CONCLUSIONS: High maternal consumption of milk products during pregnancy may protect children from developing CMA, especially in offspring of non-allergic mothers.

Maternal intake of fatty acids and their food sources during lactation and the risk of preclinical and clinical type 1 diabetes in the offspring.

AIMS: We examined maternal dietary intake of fatty acids and foods which are sources of fatty acids during lactation and whether they are associated with the risk of preclinical and clinical type 1 diabetes in the offspring. METHODS: The subjects comprised a cohort of 2,939 mother-child pairs from the prospective Type 1 Diabetes Prediction and Prevention Study. Composition of maternal diet during the third month of lactation was assessed by a validated food frequency questionnaire. Among the children with HLA-conferred susceptibility to type 1 diabetes, 172 developed preclinical and 81 clinical diabetes. Average follow-up for preclinical type 1 diabetes was 7.5 years (range 0.2-14.0 years) and for clinical type 1 diabetes 7.7 years (0.2-14.0 years). RESULTS: Maternal intake of fatty acids during lactation was not associated with the risk of type 1 diabetes in the offspring. After adjusting for putative confounders, maternal total consumption of red meat and meat products during lactation was associated both with increased risk for preclinical [hazard ratio (HR) 1.19, 95 % CI 1.02-1.40, p = 0.038] and clinical type 1 diabetes (HR 1.27, 95 % CI 1.06-1.52, p = 0.025). In particular, consumption of processed meat products showed an association with increased risk for type 1 diabetes (HR 1.23, 95 % CI 1.02-1.48, p = 0.045). Maternal use of vegetable oils was associated with increased risk for preclinical type 1 diabetes (HR 1.21, 95 % CI 1.03-1.41, p = 0.023). CONCLUSIONS: Maternal consumption of red meat, especially processed meat, during lactation may increase the risk of type 1 diabetes.

Prenatal and post-natal exposure to antibiotics and risk of asthma in childhood.

BACKGROUND: Evidence on the association between post-natal exposure to antibiotics and the development of asthma is extensive, but inconsistent and even less is known about prenatal exposure. OBJECTIVE: The aim of this study was to examine the associations between prenatal and post-natal exposure to different antibiotics and the risk of childhood asthma in a population- and register-based nested case-control study. METHODS: All children who were born in 1996-2004 in Finland and diagnosed with asthma by 2006 were identified from a national health register. For each case, one matched control was selected. Information on asthma diagnoses, purchased anti-asthmatic drugs and antibiotics as well as putative confounders was obtained from national health registries. The associations were analysed using conditional logistic regression for children diagnosed at the age of 3 years or later (n = 6 690 case-control pairs). RESULTS: Maternal use of any antibiotics during pregnancy was associated with an increased risk of asthma in the offspring [adjusted odds ratio (OR) = 1.31 (95% confidence interval (CI): 1.21-1.42)]. Several maternal specific antibiotics were associated with the risk of asthma, and the strongest association was observed for cephalosporins [OR = 1.46 (95% CI 1.30-1.64)]. Child's use of antibiotics during the first year of life was associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48-1.73)]. Child's use of cephalosporins [OR = 1.79 (95% CI 1.59-2.01)], sulphonamides and trimethoprim [OR = 1.65 (95% CI 1.34-2.02)], macrolides [OR = 1.61 (95% CI 1.46-1.78)] and amoxicillin [OR = 1.46 (95% CI 1.35-1.58)] was associated with an increased risk of asthma. CONCLUSIONS AND CLINICAL RELEVANCE: Both prenatal and post-natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.

No association between vitamin D and ß-cell autoimmunity in Finnish and Estonian children.

BACKGROUND: Vitamin D has immunomodulatory properties, such as regulation of FOXP3 expression and regulatory T-cell activity. Our aim was to investigate whether plasma 25-hydroxyvitamin D [25(OH)D] concentrations associate with the development of ß-cell autoimmunity and the transcriptional activity of FOXP3 or vitamin D3 convertase gene (CYP27B1) in CD4+ memory T cells. METHODS: We studied 83 Finnish and 32 Estonian children participating in the DIABIMMUNE and DIPP studies. Twenty-nine Finnish and six Estonian children tested positive for at least one diabetes-associated autoantibody. The plasma concentrations of 25(OH)D and 1,25(OH)2D were analysed with an enzyme immunoassay. Gene expression of FOXP3 and CYP27B1 in the isolated CD4+ memory T cells was studied with reverse transcription quantitative polymerase chain reaction. RESULTS: Vitamin D status did not differ between subjects positive and negative for ß-cell autoantibodies. Finnish children had higher vitamin D status than Estonian children (p < 0.001). FOXP3 expression was higher in Estonian CD4+ memory T-cell samples than in Finnish samples (p < 0.01) even when including in both groups only children with serum 25(OH)D concentrations in the range of 50-80 nmol/L (p < 0.001). CONCLUSIONS: These findings do not support a crucial role of circulating 25(OH)D as a regulator of ß-cell autoimmunity or FOXP3 expression.

Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study.

BACKGROUND: Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. OBJECTIVE: To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. METHODS: The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). RESULTS: At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). CONCLUSIONS: Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.

Introduction of complementary foods in infancy and atopic sensitization at the age of 5 years: timing and food diversity in a Finnish birth cohort.

OBJECTIVE: To study the associations between timing and diversity of introduction of complementary foods during infancy and atopic sensitization in 5-year-old children. METHODS: In the Finnish DIPP (type 1 diabetes prediction and prevention) birth cohort (n = 3781), data on the timing of infant feeding were collected up to the age of 2 years and serum IgE antibodies toward four food and four inhalant allergens measured at the age of 5 years. Logistic regression was used for the analyses. RESULTS: Median duration of exclusive and total breastfeeding was 1.4 (interquartile range: 0.2-3.5) and 7.0 (4.0-11.0) months, respectively. When all the foods were studied together and adjusted for confounders, short duration of breastfeeding decreased the risk of sensitization to birch allergen; introduction of oats <5.1 months and barley <5.5 months decreased the risk of sensitization to wheat and egg allergens, and oats additionally associated with milk, timothy grass, and birch allergens. Introduction of rye <7.0 months decreased the risk of sensitization to birch allergen. Introduction of fish <6 months and egg ≤11 months decreased the risk of sensitization to all the specific allergens studied. The introduction of <3 food items at 3 months was associated with sensitization to wheat, timothy grass, and birch allergens; the introduction of 1-2 food items at 4 months and ≤4 food items at 6 months was associated with all endpoints, but house dust mite. These results were particularly evident among high-risk children when the results were stratified by atopic history, indicating the potential for reverse causality. CONCLUSIONS: The introduction of complementary foods was consecutively done, and with respect to the timing of each food, early introduction of complementary foods may protect against atopic sensitization in childhood, particularly among high-risk children. Less food diversity as already at 3 months of age may increase the risk of atopic sensitization.

Maternal dietary fat and fatty acid intake during lactation and the risk of asthma in the offspring.

AIM: To explore the association between maternal dietary fat and fatty acid (FA) intake during lactation, and the risk of asthma in the offspring by the age of 5 years. METHODS: The subjects comprised 1798 mother-child pairs from the Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Dietary intake was assessed by a validated 181-item food frequency questionnaire, which covered the third month of lactation. The cumulative incidence of asthma was assessed at the age of 5 years with a questionnaire modified from the International Study of Asthma and Allergies in Childhood (ISAAC). Cox proportional hazards regression was used for statistical analysis. RESULTS: The maternal use of margarines during lactation was associated with a marginally increased risk of asthma [hazard ratio (HR) for user vs. nonuser 1.96, 95% confidence interval (CI) 1.01-3.82, p = 0.047] after adjusting for putative confounders. The maternal intakes of n-3 polyunsaturated FA (PUFA) and fish during lactation were not associated with the risk of asthma. CONCLUSION: Maternal use of margarines during lactation was weakly associated with an increased risk of asthma in the offspring at the age of 5 years. Other fats or FAs during lactation were not associated with the risk of asthma. However, the nonadherence to dietary recommendations regarding especially fats of our study population may restrict the generalizability of our results.

Dietary acrylamide exposure among Finnish adults and children: the potential effect of reduction measures.

A deterministic exposure assessment using the Nusser method that adjusts for within-subject variation and for nuisance effects among Finnish children and adults was carried out. The food consumption data covered 2038 adults (25-74 years old) and 1514 children of 1, 3 and 6 years of age, with the data on foods' acrylamide content obtained from published Finnish studies. We found that acrylamide exposure was highest among the 3-year-old children (median = 1.01 µg kg(-1) bw day(-1), 97.5th percentile = 1.95 µg kg(-1) bw day(-1)) and lowest among 65-74-year-old women (median = 0.31 µg kg(-1) bw day(-1), 97.5th percentile = 0.69 µg kg(-1) bw day(-1)). Among adults, the most important source of acrylamide exposure was coffee, followed by casseroles rich in starch, then rye bread. Among children, the most important sources were casseroles rich in starch and then biscuits and, finally, chips and other fried potatoes. Replacing lightly roasted coffee with dark-roasted, swapping sweet wheat buns for biscuits, and decreasing the acrylamide content of starch-based casseroles and rye bread by 50% would result in a 50% decrease in acrylamide exposure in adults. Among children, substituting boiled potatoes for chips and other friend potatoes and replacing biscuits with sweet wheat buns while lowering the acrylamide content of starch-based casseroles by 50% would lead to acrylamide exposure that is only half of the original exposure. In conclusions, dietary modifications could have a large impact in decreasing acrylamide exposure.

Intake of antioxidants during pregnancy and the risk of allergies and asthma in the offspring.

BACKGROUND/OBJECTIVES: The potential immune functions related to the damages induced by oxygen-free radicals suggest that antioxidants may have a role in the development of allergies. The objective was to investigate the association between maternal intake of antioxidants during pregnancy and the risk of asthma, rhinitis and eczema in 5-year-old children. SUBJECTS/METHODS: This study was on the basis of the Finnish Type 1 Diabetes Prediction and Prevention Nutrition Study, a population-based birth cohort study with 5-year follow-up. Complete information on maternal food frequency questionnaire data and ISAAC (International Study of Asthma and Allergies in Childhood)-based allergic outcomes were available for 2441 children. Cox proportional regression and logistic regression were used for the analyses. RESULTS: Maternal intake of any of the antioxidants was not significantly associated with the risk of asthma, rhinitis or eczema in the offspring, except for dietary intake of magnesium, which was independently associated with protection against eczema (OR 0.78; 95% CI 0.62-0.97). CONCLUSION: Maternal intake of dietary magnesium during pregnancy may protect against the risk of eczema in the offspring. We did not confirm previous observations concerning other antioxidants. This may be due to the variable amount of antioxidant intake across studies and also indicative of the hypothesis that there may be a critical time window in pregnancy during which antioxidants might modify the risk of allergies in the offspring.

Maternal food consumption during pregnancy and risk of advanced ß-cell autoimmunity in the offspring.

BACKGROUND: Evidence for a putative role of maternal diet during pregnancy in the development of ß-cell autoimmunity in the child is scarce. The authors study the association of food consumption during pregnancy and the development of ß-cell autoimmunity in the offspring. SUBJECTS AND METHODS: A prospective Finnish birth cohort of 4297 infants with human leukocyte antigen (HLA)-DQB1-conferred susceptibility to type 1 diabetes and their mothers. Blood samples were collected from the children at 3-12 months intervals to measure type 1 diabetes-associated antibodies: antibodies against islet cells (ICA), insulin, glutamate dehydroxylase, and islet antigen 2. The mothers completed a validated food frequency questionnaire. The end-point was repeated positivity for ICA together with at least one of the other three antibodies. Piecewise-exponential survival models were used. The effective sample size was 3723, with 138 end-points. The median follow-up time was 4.4 years. RESULTS: Maternal consumption of butter, low-fat margarines, berries, and coffee were inversely associated with the development of advanced ß-cell autoimmunity in the offspring, adjusted for genetic risk group and familial diabetes. These associations for low-fat margarines (use vs. non-use HR 0.60, 95% CI: 0.38-0.93, p = 0.02), berries (continuous variable HR 0.90, 95% CI: 0.83-0.98, p = 0.02) and coffee (highest quarter vs. lowest HR 0.62, 95% CI: 0.40-0.97, p = 0.04), remained significant when adjusting for potential confounding sociodemographic, perinatal, and other dietary factors. CONCLUSIONS: In this study assessing total food consumption of the mother during pregnancy, only few among the 27 food groups tested were weakly related to the development of advanced ß-cell autoimmunity in Finnish children.

Early introduction of root vegetables in infancy associated with advanced ß-cell autoimmunity in young children with human leukocyte antigen-conferred susceptibility to Type 1 diabetes.

AIMS: Early introduction of supplementary foods has been implicated to play a role in the development of ß-cell autoimmunity. We set out to study the effects of breastfeeding and age at introduction of supplementary foods on the development of ß-cell autoimmunity. METHODS: A prospective birth cohort of 6069 infants with HLA-DQB-conferred susceptibility to Type 1 diabetes was recruited between 1996 and 2004. Antibodies against islet cells, insulin, glutamate dehydroxylase and islet antigen 2 were measured at 3- to 12-month intervals. The families recorded at home the age at introduction of new foods and, for each visit, completed a structured dietary questionnaire. The endpoint was repeated positivity for islet cell antibodies plus at least one other antibody and/or clinical Type 1 diabetes (n = 265). RESULTS: Early introduction of root vegetables (by the age of 4 months) was related to increased risk of developing positivity for the endpoint [hazard ratio (95% CI) for the earliest third 1.75 (1.11-2.75) and for the middle third 1.79 (1.22-2.62) compared with the last third (> 4 months), likelihood ratio test P = 0.006], independently of the introduction of other foods and of several putative socio-demographic and perinatal confounding factors. Introducing wheat, rye, oats and/or barley cereals (P = 0.013) and egg (P = 0.031) early was related to an increased risk of the endpoint, but only during the first 3 years of life. CONCLUSIONS: Early introduction of root vegetables during infancy is independently associated with increased risk of ß-cell autoimmunity among Finnish children with increased genetic susceptibility to Type 1 diabetes.

Voxelwise analysis of diffusion tensor imaging and structural MR imaging in patients with the m.3243A>G mutation in mitochondrial DNA.

BACKGROUND AND PURPOSE: The m.3243A>G mutation is the most common pathogenic mutation in mtDNA; tissues with high dependence on aerobic energy metabolism, such as the brain, heart, and skeletal muscle, are most affected by the ensuing mitochondrial dysfunction. We hypothesized that the m.3243A>G mutation manifests as disturbances in white matter microstructural integrity and volumetric changes in the brain. MATERIALS AND METHODS: DTI and structural MR imaging were performed on 15 adult patients with the m.3243A>G mutation and 14 healthy age-matched controls. Voxelwise analysis of the DTI data was performed to reveal possible differences in FA and MD values. Additionally, normalized brain tissue volumes of the subjects were measured, and voxelwise analysis of gray matter was performed to assess volumetric changes in the brain. RESULTS: Among patients with m.3243A>G mutation, voxelwise analysis of the DTI data revealed significantly reduced FA in several areas located mainly in the occipital lobes, thalami, external and internal capsules, brain stem, cerebellar peduncles, and cerebellar white matter. There were no differences in MD values between the patients and the controls. Analysis of the structural MR imaging data revealed reduced total volume of gray and white matter in patients with m.3243A>G mutation, and VBM analysis identified areas of significant gray matter loss mainly in the occipital lobes and cerebellum. CONCLUSIONS: Our findings show that patients with m.3243A>G mutation have mild microstructural damage leading to loss of directional organization of white matter and reduced brain volumes.

Are serum α- and ß-carotene concentrations associated with the development of advanced beta-cell autoimmunity in children with increased genetic susceptibility to type 1 diabetes?

AIM: Reactive oxygen intermediates have been implicated in mediating the destruction of insulin-producing beta cells and antioxidant nutrients thought to protect against such a process. This study aimed to assess the associations between serum α- and ß-carotene concentrations, and the risk of advanced beta-cell autoimmunity, in children with HLA-conferred susceptibility to type 1 diabetes. METHODS: This case-control study, comprising 108 case children with advanced beta-cell autoimmunity and 216 matched control children, was nested within the nutrition study of the Type 1 Diabetes Prediction and Prevention (DIPP) birth cohort. Serum α- and ß-carotene samples were collected each year from the age of 1 to 6 years. For each case-control group, serum samples were analyzed up to the time of seroconversion in the case children. Associations were studied using a conditional logistic-regression model. RESULTS: Neither serum α- nor ß-carotene concentration was significantly associated with the risk of advanced beta-cell autoimmunity. There was marginal evidence (P=0.049) of an inverse association between serum ß-carotene concentration and the risk of developing advanced beta-cell autoimmunity at a time closest to seroconversion after adjusting for parental education, maternal age, duration of gestation, diabetes in first-degree relatives, number of earlier deliveries and maternal smoking during pregnancy. CONCLUSION: The present study data provided no clear evidence to support an association between serum α- or ß-carotene concentration and advanced beta-cell autoimmunity.

The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study: recruitment, intervention and follow-up.

AIMS/HYPOTHESIS: The Trial to Reduce IDDM in the Genetically at Risk (TRIGR) study was designed to establish whether weaning to a highly hydrolysed formula in infancy subsequently reduces the risk of type 1 diabetes. METHODS: The study population comprises newborn infants who have first-degree relatives with type 1 diabetes and meet the increased risk HLA inclusion, but not exclusion criteria. The study is being performed in 15 countries in three continents. First-degree relatives of patients with type 1 diabetes were identified from diabetes clinics, diabetes registries, and from other endocrinology or obstetrics offices and websites. HLA typing was performed at birth from cord or heel stick blood, and the results sent to the study's Data Management Unit within 2 weeks for communication of eligibility to the clinical study centre. All mothers recruited were encouraged to breastfeed. The intervention lasted for 6 to 8 months, and weaning formulas based on hydrolysed casein and standard cow's milk were compared. RESULTS: TRIGR recruited 5,606 infants, of whom 2,160 were enrolled as eligible participants, 6% more than the target of 2,032. Of those enrolled, 80% were exposed to the study formula. The overall retention rate over the first 5 years is 87%, with protocol compliance at 94%. The randomisation code will be opened when the last recruited child turns 10 years of age, i.e. in 2017. CONCLUSIONS/INTERPRETATION: The TRIGR experience demonstrates the feasibility and successful implementation of an international dietary intervention study. TRIGR is the first ever primary prevention trial for type 1 diabetes and, if completed successfully, will provide a definite answer to the research question. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777 FUNDING: The study was funded by the National Institute of Child Health and Development (NICHD) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) (grant numbers HD040364, HD042444 and HD051997), Canadian Institutes of Health Research, the Juvenile Diabetes Research Foundation International and the Commission of the European Communities (specific RTD programme 'Quality of Life and Management of Living Resources', contract number QLK1-2002-00372 'Diabetes Prevention'. Other funding came from the EFSD/JDRF/Novo Nordisk Focused Research Grant, Academy of Finland, Dutch Diabetes Research Foundation and Finnish Diabetes Research Foundation).

Feasibility and compliance in a nutritional primary prevention trial in infants at increased risk for type 1 diabetes.

AIM: The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) was launched to determine whether weaning to a highly hydrolysed formula in infancy reduces the incidence of type 1 diabetes in children at increased genetic disease susceptibility. We describe here the findings on feasibility and compliance from the pilot study. METHODS: The protocol was tested in 240 children. The diet of the participating children was assessed by self-administered dietary forms, a structured questionnaire and a food record. Blood samples were taken and weight and height measured at birth and at 3, 6, 9, 12, 18 and 24 months. RESULTS: A majority of the subjects (84%) were exposed to the study formula at least for 2 months. Linear growth or weight gain over the first 2 years of life was similar in the two study groups. The levels of IgA and IgG antibodies to cow's milk and casein were higher in the cow's milk-based formula group than in the hydrolysed formula group during the intervention period (p<0.05), reflecting the difference in the intake of cow's milk protein. CONCLUSION: This randomized trial on infant feeding turned out to be feasible, and dietary compliance was acceptable. Valuable experience was gained for the planning and sample size estimation of the study proper.

Diet and weight gain characteristics of pregnant women with gestational diabetes.

BACKGROUND/OBJECTIVES: To determine if women with gestational diabetes (GD) modify their diet and nutrient intake in late pregnancy and gain more weight during pregnancy compared with women without GD. SUBJECTS/METHODS: Food and nutrient intake of 3613 pregnant women was studied using food frequency questionnaires from the Type I Diabetes Prediction and Prevention Nutrition Study. RESULTS: D was reported in 4.8% of the participating women (n=174). Women with GD gained less weight during pregnancy than those unaffected by GD (mean 9.4 vs 12.6 kg, P<0.001). Women with GD consumed more milk products (84 vs 76 g/MJ, P=0.002), cereal products (21 vs 18 g/MJ, P<0.001), vegetables (32 vs 22 g/MJ, P<0.001) and meat (16 vs 14 g/MJ, P<0.001) than unaffected women. The intake of protein (18 vs 16 percent of total daily energy intake, P<0.001) and dietary fibre (3.1 vs 2.4 g/MJ, P<0.001) was higher, whereas the intake of sugars (13.3 vs 15.0 g/MJ, P<0.001) and saturated fatty acids (3.49 vs 3.98 g/MJ, P<0.001) was lower among women with GD. The nutrient density of the diet was higher in women with GD with higher intakes of vitamins A and D, folate and iron. CONCLUSIONS: The late pregnancy diet of women with GD differed considerably from that of unaffected women. Women with GD had a higher body weight at the beginning of the pregnancy, but they gained less weight during pregnancy. These findings indicate that abnormal glucose tolerance during pregnancy encourages women to modify their dietary habits towards healthier food choices.