Infant Feeding, Gut Permeability, and Gut Inflammation Markers.

OBJECTIVES: Increased gut permeability and gut inflammation have been linked to the development of type 1 diabetes. Little is known on whether and how intake of different foods is linked to these mechanisms in infancy. We investigated whether the amount of breast milk and intake of other foods are associated with gut inflammation marker concentrations and permeability. METHODS: Seventy-three infants were followed from birth to 12 months of age. Their diet was assessed with structured questionnaires and 3-day weighed food records at the age of 3, 6, 9, and 12 months. Gut permeability was assessed with the lactulose/mannitol test and fecal calprotectin and human ß-defensin-2 (HBD-2) concentrations were analyzed from stool samples at the age of 3, 6, 9, and 12 months. The associations between foods and gut inflammation marker concentrations and permeability were analyzed using generalized estimating equations. RESULTS: Gut permeability and gut inflammation marker concentrations decreased during the first year of life. Intake of hydrolyzed infant formula ( P = 0.003) and intake of fruits and juices ( P = 0.001) were associated with lower intestinal permeability. Intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and oats ( P = 0.003) were associated with lower concentrations of HBD-2. Higher intake of breast milk was associated with higher fecal calprotectin concentrations ( P < 0.001), while intake of fruits and juices ( P < 0.001), vegetables ( P < 0.001), and potatoes ( P = 0.007) were associated with lower calprotectin concentrations. CONCLUSIONS: Higher intake of breast milk may contribute to higher calprotectin concentration, whereas several complementary foods may decrease gut permeability and concentrations of calprotectin and HBD-2 in infant gut.

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.

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.

Iron intake, haemoglobin and risk of gestational diabetes: a prospective cohort study.

OBJECTIVE: To investigate the possible association between total daily iron intake during pregnancy, haemoglobin in early pregnancy and the risk of gestational diabetes mellitus (GDM) in women at increased risk of GDM. DESIGN: A prospective cohort study (based on a cluster-randomised controlled trial, where the intervention and the usual care groups were combined). SETTING: Primary healthcare maternity clinics in 14 municipalities in south-western Finland. PARTICIPANTS: 399 Pregnant women who were at increased risk of GDM participated in a GDM prevention trial and were followed throughout pregnancy. MAIN OUTCOME MEASUREMENTS: The main outcome was GDM diagnosed with oral glucose tolerance test at 26-28 weeks' gestation or based on a diagnosis recorded in the Finnish Medical Birth registry. Data on iron intake was collected using a 181-item food frequency questionnaire and separate questions for supplement use at 26-28 weeks' gestation. RESULTS: GDM was diagnosed in 72 women (18.1%) in the study population. The OR for total iron intake as a continuous variable was 1.006 (95% CI 1.000 to 1.011; p=0.038) after adjustment for body mass index, age, diabetes in first-degree or second-degree relatives, GDM or macrosomia in earlier pregnancy, total energy intake, dietary fibre, saturated fatty acids and total gestational weight gain. Women in the highest fifth of total daily iron intake had an adjusted OR of 1.66 (95% CI 0.84 to 3.30; p=0.15) for GDM. After excluding participants with low haemoglobin levels (≤120 g/l) already in early pregnancy the adjusted OR was 2.35 (95% CI 1.13 to 4.92; p=0.023). CONCLUSIONS: Our results suggest that high iron intake during pregnancy increases the risk of GDM especially in women who are not anaemic in early pregnancy and who are at increased risk of GDM. These findings suggest that routine iron supplementation should be reconsidered in this risk group of women.

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.