Dietary fatty acid intake in childhood and the risk of islet autoimmunity and type 1 diabetes: the DIPP birth cohort study.

PURPOSE: The aim was to study the associations between dietary intake of fatty acids in childhood and the risk of islet autoimmunity and type 1 diabetes (T1D). METHODS: The prospective Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study included children with genetic susceptibility to T1D born between 1996 and 2004. Participants were followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Dietary intake of several fatty acids at the age of 3 months to 6 years was assessed 1-8 times per participant with a 3-day food record. Joint models adjusted for energy intake, sex, HLA genotype and familial diabetes were used to investigate the associations of longitudinal intake of fatty acids and the development of islet autoimmunity and T1D. RESULTS: During the 6-year follow-up, 247 (4.4%) children of 5626 developed islet autoimmunity and 94 (1.7%) children of 5674 developed T1D. Higher intake of monounsaturated fatty acids (HR 0.63; 95% CI 0.47, 0.82), arachidonic acid (0.69; 0.50, 0.94), total n-3 fatty acids (0.64; 0.48, 0.84), and long-chain n-3 fatty acids (0.14; 0.04, 0.43), was associated with a decreased risk of islet autoimmunity with and without energy adjustment. Higher intake of total fat (0.73; 0.53, 0.98), and saturated fatty acids (0.55; 0.33, 0.90) was associated with a decreased risk of T1D only when energy adjusted. CONCLUSION: Intake of several fatty acids was associated with a decreased risk of islet autoimmunity or T1D among high-risk children. Our findings support the idea that dietary factors, including n-3 fatty acids, may play a role in the disease process of T1D.

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study.

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring's risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997-2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.

Maternal antioxidant intake during pregnancy and the development of cows' milk allergy in the offspring.

Cows' milk allergy (CMA) is the most common food allergy in young children, and it is often the first manifestation of atopic diseases. Accordingly, very early environmental factors, such as maternal diet during pregnancy, may play a role in the development of CMA, but the evidence is limited. The aim of this study was to investigate the association between maternal intake of antioxidant nutrients during pregnancy and the subsequent development of CMA in the offspring in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Maternal dietary information during pregnancy was collected with a detailed, validated FFQ. The maternal dietary information and the information on putative confounding factors were available for 4403 children. Information on diagnosed CMA (n 448) was obtained from a medical registry and queried from the parents up to child's age of 3 years. The Finnish food composition database was used to calculate the average daily intake of nutrients. Logistic regression was applied for statistical analyses, and the nutrient intakes were adjusted for energy intake. OR are presented per 1 sd increment of the particular nutrient intake. Maternal total and dietary intake of ß-carotene was associated with an increased risk of CMA in the offspring when adjusted for the putative confounding factors (total OR 1·10, 95 % CI 1·02, 1·20; dietary OR 1·10; 95 % CI 1·01, 1·19). Using dietary supplements containing antioxidants in addition to a balanced diet may not confer any additional benefits.

Vitamin D intake during the first 4 years and onset of asthma by age 5: A nested case-control study.

BACKGROUND: Early-life vitamin D intake has been linked to asthma risk in childhood, but the role of longitudinal vitamin D exposure has not been previously evaluated. We investigated the association between vitamin D intake during the first 4 years of life and asthma risk by age 5. METHODS: Within a Finnish population-based birth cohort, 182 incident asthma cases were matched to 728 controls on sex, genetic risk for type 1 diabetes, delivery hospital, and time of birth. Vitamin D intake was assessed by age-specific 3 day food records. Parents completed a validated version of the International Study of Asthma and Allergies in Childhood questionnaire at 5 years. RESULTS: At 3 months, supplements were the main source of vitamin D intake; intake from foods increased from 3 months on, mainly from fortified milk products. Vitamin D intake at each specific age was associated with an increased risk of any asthma, atopic, and non-atopic asthma, but only intake at 1 and 2 years was statistically significantly associated with asthma. Longitudinal vitamin D intake was associated with an increased risk of asthma (OR 1.24; 95%CI 1.00-1.53). CONCLUSIONS: Increased vitamin D intake in childhood, particularly intake at 1 and 2 years of age, may increase risk of childhood asthma. This might reflect a true effect or residual confounding by lifestyle or environmental factors. Repeated assessment of vitamin D intake allowed evaluation of the longitudinal and age-dependent impact of vitamin D on the risk of asthma. Further longitudinal studies are required to confirm or question these findings.

Fatty acid status in infancy is associated with the risk of type 1 diabetes-associated autoimmunity.

AIMS/HYPOTHESIS: We investigated the association of early serum fatty acid composition with the risk of type 1 diabetes-associated autoimmunity. Our hypothesis was that fatty acid status during infancy is related to type 1 diabetes-associated autoimmunity and that long-chain n-3 fatty acids, in particular, are associated with decreased risk. METHODS: We performed a nested case-control analysis within the Finnish Type 1 Diabetes Prediction and Prevention Study birth cohort, carrying HLA-conferred susceptibility to type 1 diabetes (n = 7782). Serum total fatty acid composition was analysed by gas chromatography in 240 infants with islet autoimmunity and 480 control infants at the age of 3 and 6 months. Islet autoimmunity was defined as repeated positivity for islet cell autoantibodies in combination with at least one of three selected autoantibodies. In addition, a subset of 43 infants with primary insulin autoimmunity (i.e. those with insulin autoantibodies as the first autoantibody with no concomitant other autoantibodies) and a control group (n = 86) were analysed. A third endpoint was primary GAD autoimmunity defined as GAD autoantibody appearing as the first antibody without other concomitant autoantibodies (22 infants with GAD autoimmunity; 42 infants in control group). Conditional logistic regression was applied, considering multiple comparisons by false discovery rate <0.05. RESULTS: Serum fatty acid composition differed between breastfed and non-breastfed infants, reflecting differences in the fatty acid composition of the milk. Fatty acids were associated with islet autoimmunity (higher serum pentadecanoic, palmitic, palmitoleic and docosahexaenoic acids decreased risk; higher arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Furthermore, fatty acids were associated with primary insulin autoimmunity, these associations being stronger (higher palmitoleic acid, cis-vaccenic, arachidonic, docosapentaenoic and docosahexaenoic acids decreased risk; higher α-linoleic acid and arachidonic:docosahexaenoic and n-6:n-3 acid ratios increased risk). Moreover, the quantity of breast milk consumed per day was inversely associated with primary insulin autoimmunity, while the quantity of cow's milk consumed per day was directly associated. CONCLUSIONS/INTERPRETATION: Fatty acid status may play a role in the development of type 1 diabetes-associated autoimmunity. Fish-derived fatty acids may be protective, particularly during infancy. Furthermore, fatty acids consumed during breastfeeding may provide protection against type 1 diabetes-associated autoimmunity. Further studies are warranted to clarify the independent role of fatty acids in the development of type 1 diabetes.

Maternal dietary folate, folic acid and vitamin D intakes during pregnancy and lactation and the risk of cows' milk allergy in the offspring.

Maternal nutrient intake during pregnancy and lactation potentially influences the development of allergic diseases. Cows' milk allergy (CMA) is often the first manifestation of atopic diseases, but the impact of early nutritional influences on CMA has not been explored. The associations between maternal intakes of folate, folic acid and vitamin D during pregnancy and lactation were addressed in a prospective, population-based birth cohort within the Finnish Type 1 Diabetes Prediction and Prevention Study. Mothers of 4921 children during pregnancy and 2940 children during lactation provided information on maternal dietary intake during the 8th month of pregnancy and the 3rd month of lactation using a detailed, validated FFQ. Information on diagnosed CMA in the offspring was obtained from a medical registry as well as queried from the parents. The Finnish food composition database was used to calculate nutrient intake. Logistic regression was applied for statistical analyses. Folate intake and folic acid and vitamin D supplement use were associated with an increased risk of CMA in the offspring, whereas vitamin D intake from foods during pregnancy was associated with a decreased risk of CMA. Thus, maternal nutrient intake during pregnancy and lactation may affect the development of CMA in offspring. Supplementation with folic acid may not be beneficial in terms of CMA development, especially in children of allergic mothers. The association between dietary supplement use and CMA risk can at least partly be explained by increased health-seeking behaviour among more educated mothers who also use more dietary supplements.

Food consumption and risk of childhood asthma.

BACKGROUND: The consumption of foods rich in n-3 polyunsaturated fatty acids has been proposed to protect against childhood asthma. This study explores the association of food consumption (including cow's milk (CM)-free diet) in early life and the risk of atopic and non-atopic asthma. METHODS: Food intake of 182 children with asthma and 728 matched controls was measured using 3-day food records, within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study cohort. The diagnoses of food allergies came both from the written questionnaire and from the registers of the Social Insurance Institution. Conditional logistic regression with generalized estimating equations framework was used in the analyses. RESULTS: The diagnosis of cow's milk allergy (CMA) led to multiple dietary restrictions still evident at 4 yr of age. Even after adjusting for CMA, higher consumption of CM products was inversely associated with the risk of atopic asthma and higher consumption of breast milk and oats inversely with the risk of non-atopic asthma. Early consumption of fish was associated with a decreased risk of all asthma. CONCLUSIONS: Dietary intake in early life combined with atopy history has a clear impact on the risk of developing asthma. Our results indicate that CM restriction due to CMA significantly increases and mediates the association between food consumption and childhood asthma risk.

An increase in serum 25-hydroxyvitamin D concentrations preceded a plateau in type 1 diabetes incidence in Finnish children.

CONTEXT: In Finland the world-record for the highest incidence of type 1 diabetes has risen steeply over the past decades. However, after 2006 the incidence rate has plateaued. We showed earlier, that despite the strong genetic disease component, environmental factors are driving the increasing disease incidence. OBJECTIVE: Since vitamin D intake has increased considerably in the country since 2003, we analyzed how serum 25-hydroxyvitamin D (25[OH]D) concentration changed over time in healthy children, and the timely relation of these changes to disease incidence. DESIGN, SETTING AND PARTICIPANTS: The birth cohort of the Finnish Type 1 Diabetes Prediction and Prevention project was used to explore longitudinal changes in serum 25-hydroxyvitamin concentrations. The sampling period was limited to children born from 1994 to 2004, with serum samples collected during 1998-2006 in the Turku area, Southwest Finland (60 °N). MAIN OUTCOME MEASURE: 25(OH)D concentrations were measured every 3-6 months from birth, ages ranging from 0.3 to 12.2 years (387 subjects, 5334 measurements). RESULTS: Serum 25(OH)D concentrations were markedly lower before 2003 than after (69.3 ± 1.0 nmol/L vs 84.9 ± 1.3 nmol/L, respectively, P < .001) in both genders. The mean difference between the periods was 15.7 ± 1.3 nmol/L (P < .001). Importantly, the frequency of children with low serum 25(OH)D levels (< 50 nmol/L) was reduced to almost half from 2003 (37.3% vs 69.9 %; P < .001). Similarly, severe vitamin D deficiency (<25 nmol/L) also decreased (2.7% vs 7.7%; P = .005). In addition, we detected higher 25(OH)D concentrations in young children (< 2 years) as compared to older children, which is explained by higher vitamin D intake in this group. CONCLUSIONS: We provide evidence that an increase in circulating concentrations of 25(OH)D shows a delayed temporal association with leveling off of type 1 diabetes incidence in Finland after 2006.

Nutrient intake variability and number of days needed to assess intake in preschool children.

The duration of the period of time during which diet should be recorded for sufficiently accurate results on the usual intake of an individual is an especially challenging issue in prospective studies among children. We set out to describe nutrient intake variability in preschoolers and to determine the number of record days required (D) to estimate intake of energy and thirty-two nutrients. The diet and the use of dietary supplements were assessed with three consecutive daily food records including one weekend day in 1639 children participating in the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention Project (DIPP) in Finland. Variance ratios and D stratified by sex and age groups were calculated for 455 (1-year-old), 471 (3-year-old) and 713 (6-year-old) children (born between 1998 and 2003). Within:between variance ratios and D increase with increasing age, and are slightly higher for girls. Vitamin A, cholesterol, n-3 and n-6 fatty acids, ß-carotene and folate intakes require the most replicates. Including supplemental intake has an impact on the variance estimates according to the proportion of supplement users. In the DIPP Nutrition Study with 3 d food records, the correlation coefficients between observed and true intakes of energy and thirty-two nutrients averaged 0·91 in 1-year-old children, 0·79 in 3-year-old children and 0·74 in 6-year-old children. For providing accurate nutrient intake estimates, three replicates of food records are reasonable in 1-year-old children but must be questioned for several nutrients in 3- and 6-year-old children. The accuracy of ranking boys is greater than that for girls.

Intake of antioxidant vitamins and trace elements during pregnancy and risk of advanced beta cell autoimmunity in the child.

BACKGROUND: Type 1 diabetes may have its origins in the fetal period of life. Free radicals were implicated in the cause of type 1 diabetes. It was hypothesized that antioxidant nutrients could protect against type 1 diabetes. OBJECTIVE: We assessed whether high maternal intake of selected dietary antioxidants during pregnancy is associated with a reduced risk of advanced beta cell autoimmunity in the child, defined as repeated positivity for islet cell antibodies plus >/=1 other antibody, overt type 1 diabetes, or both. DESIGN: The study was carried out as part of the population-based birth cohort of the Type 1 Diabetes Prediction and Prevention Project. The data comprised 4297 children with increased genetic susceptibility to type 1 diabetes, born at the University Hospital of Oulu or Tampere, Finland, between October 1997 and December 2002. The children were monitored for diabetes-associated autoantibodies from samples obtained at 3-12-mo intervals. Maternal antioxidant intake during pregnancy was assessed postnatally with a self-administered food-frequency questionnaire, which contained a question about consumption of dietary supplements. RESULTS: Maternal intake of none of the studied antioxidant nutrients showed association with the risk of advanced beta cell autoimmunity in the child. The hazard ratios, indicating the change in risk per a 2-fold increase in the intake of each antioxidant, were nonsignificant and close to 1. CONCLUSION: High maternal intake of retinol, beta-carotene, vitamin C, vitamin E, selenium, zinc, or manganese does not protect the child from development of advanced beta cell autoimmunity in early childhood.

Dietary intake and use of dietary supplements in relation to demographic variables among pregnant Finnish women.

Proper nutrition during pregnancy may be important for maternal health and fetal growth and development. In Finland, targeted recommendations are given to guide pregnant women in their food choice and dietary supplement use so that they may obtain adequate nutritional status and meet the increased need for nutrients. The aims of the present study were to examine food choices, nutrient intake and dietary supplement use of pregnant Finnish women in association with demographic variables. One thousand and seventy-five families were invited to a birth cohort study during 1998-9. Mothers of 797 newborns completed a validated 181-item food-frequency questionnaire from which the food and nutrient intakes were calculated. The information about supplement use was collected concerning the whole pregnancy. The results of the present study suggest that healthy food choices are rather common among pregnant Finnish women and the choices are positively correlated with age and education. Nutrient supplements were used by 85 % of the women. Supplements were favoured by the older and well-educated women and by those who had normal weight before pregnancy. Of the women in the present study, 31 % received vitamin A-containing supplements, although it is not recommended during pregnancy. Taking food and supplementation into account, the intake of vitamin D did not meet the dietary recommendation and folic acid intake was below recommendation in 44 % of the women. Therefore there seemed to be unnecessary nutrient supplementation and at the same time lack of relevant supplementation among these pregnant women.

Enteral virus infections in early childhood and an enhanced type 1 diabetes-associated antibody response to dietary insulin.

Enteral virus infections may trigger the development of beta-cell-specific autoimmunity by interacting with the gut-associated lymphoid system. We analyzed the effect of three different virus infections on immunization to dietary insulin in children carrying increased genetic risk for type 1 diabetes. Forty-six of 238 children developed multiple diabetes-associated autoantibodies and 31 clinical diabetes (median follow-up time 75 months). Insulin-binding antibodies were measured with EIA method (median follow-up time 24 months). Antibodies to enteroviruses, rotavirus and adenovirus were measured with EIA in samples drawn at birth and the ages of 3 and 6 months. Nineteen enterovirus, 14 rotavirus and 8 adenovirus infections were diagnosed. At the ages of 6, 12, and 18 months, the concentrations of insulin-binding antibodies were higher in children with postnatal entero-, rota- and/or adenovirus infections than in children without these infections. Children who subsequently developed ICA or IA-2 antibodies or clinical type 1 diabetes had higher concentrations of insulin-binding antibodies than children who remained autoantibody negative. Our data suggest that enteral virus infections can enhance immune response to insulin, induced primarily by bovine insulin in cow's milk. An enhanced antibody response to dietary insulin preceded the development of beta-cell specific autoimmunity and type 1 diabetes.

Use of vitamin D and other dietary supplements by Finnish children at the age of 2 and 3 years.

The aims of this study were to investigate the frequency of the use of vitamin D and other dietary supplements by Finnish children at the age of 2 and 3 years, to evaluate daily nutrient intake from supplements, and to investigate the relation between supplement use and various sociodemographic factors. The families of 534 newborn infants were invited to a birth cohort study in 1996-1997. Families of 292 children at the child's age of 2 years and families of 263 children at the age of 3 years completed a three-day food record from which the daily use of dietary supplements was calculated. The frequency of dietary supplement use was 50% among the two-year-olds, and 37% among the three-year-old children. The most commonly used supplements among the two-year-olds were vitamin D or vitamin A + D combination (38%) and fluoride (16%) and among the three-year-olds fluoride (19%) and multivitamins (16%), respectively. Intake of nutrients other than vitamin D or fluoride from supplements was rare among two-year-olds, whereas 16% of the three-year-olds received also vitamin A, C, E, and several group B vitamins. Mean daily intake of vitamin D from supplements was 6.7 micrograms at the age of 2 years and 5.3 micrograms at the age of 3 years, respectively. The level of parental education was positively associated with the child's vitamin D supplementation at the age of 2 years. As the compliance with national recommendations of vitamin D supplementation was low, intensified counseling of the parents is needed at the well-baby clinics in Finland.

Vitamin D receptor polymorphisms: no association with type 1 diabetes in the Finnish population.

OBJECTIVE: The effect of polymorphisms of the vitamin D receptor (VDR) gene on susceptibility to type 1 diabetes has recently been investigated extensively. Several findings on positive disease associations have been observed and, in addition, a protective effect of vitamin D supplementation has been reported. DESIGN: We studied the effect of three vitamin D receptor gene polymorphisms (VDRA, VDRB, VDRF) on susceptibility to type 1 diabetes in a large case-control series (more than 2000 controls and about 1000 patients) from the Finnish population. METHODS: A combination of case-control and affected-family based approaches was used. Subjects were genotyped for VDRA (ApaI), VDRB (BsmI) and VDRF (FokI) single nucleotide polymorphisms using a minisequencing reaction. RESULTS: A few borderline significant associations were observed with both approaches used. In the case-control association analyses we found significant differences between cases and controls in frequencies of VDRB (P=0.024, all subjects and P=0.016, HLA DQB1*0302-positive subjects) and VDRF (P=0.0063, Turku cohort). In the total family set a decreased (39.3%) transmission of the VDRA-VDRB-VDRF haplotype 1-1-2 and an increased (60.3%) transmission of haplotype 2-1-2 to sons was seen (P=0.0059 and P=0.024 respectively). Transmission of the haplotype 2-2-1 to daughters was decreased (37.6%, P=0.022). Interestingly, we also observed significant differences in allele frequencies of the polymorphisms studied between populations from three different regions in Finland. CONCLUSIONS: All these differences disappeared after correction for multiple testing. We conclude that the single nucleotide polymorphisms analysed are unlikely to be associated with type 1 diabetes in the Finnish population.