Diet in early life and antibody responses to cow's milk and type 1 diabetes associated autoantigens

Tyypin 1 diabetes eli ns. nuoruustyypin diabetes kuuluu suomalaislasten yleisimpien kroonisten sairauksien joukkoon heti allergisten sairauksien jälkeen. Nuoruustyypin diabetekseen sairastutaan ennen murrosikää Suomessa yleisemmin kuin missään muualla maailmassa. Ensimmäiset merkit sairaudesta voivat elimistössä ilmetä jo ensimmäisinä elinvuosina. Tyypin 1 diabeteksessa haiman insuliinia tuottavat saarekesolut tuhoutuvat ja diabeetikot tarvitsevat insuliinin pistoksina. Diabeteksen puhkeamisen määrää osittain perinnöllinen alttius, mikä voidaan todeta määrittämällä HLA-riskigeenit vastasyntyneen napaverinäytteestä. Lisäksi tarvitaan joitakin toistaiseksi tuntemattomia tekijöitä käynnistämään ja vauhdittamaan haimasolujen tuhoutumista. Kun insuliinia tuottavien solujen tuhoutuminen alkaa, lapsen vereen kehittyy vasta-aineita haiman saarekesoluja kohtaan. Näitä saarekevasta-aineita mittaamalla voidaan perinnöllisesti alttiista lapsista löytää erityisen suuren sairastumisriskin omaavat lapset. Väitöskirjatyössä arvioitiin raskausajan ja imeväisiän ruokavaliota sekä niiden yhteyttä lapsen vasta-aineisiin haiman saarekesoluille ja lehmänmaidolle. Tutkimuksessa seurattiin yhteensä 3565 Tyypin 1 diabeteksen ennustaminen ja ehkäisy (DIPP) ­tutkimukseen osallistuneen lapsen varhaisvaiheen ruokintaa (menetelminä ruokapäiväkirja, lisäruokien aloitusikälomake sekä kyselylomake) ja diabeteksen esiasteen kehittymisestä kertovien vasta-aineiden ilmaantuvuutta. Imeväisruokinnan kansalliset ja kansainväliset suositukset ovat Suomessa vielä saavuttamatta. Yksinomaisen imetyksen kesto oli keskimäärin 1.5 kk, kun suositus on puolen vuoden ikään saakka. Vain joka toinen lapsi sai vielä puolen vuoden iässä äidinmaitoa (osittaista imetystä suositellaan vuoden ikään saakka). Ensimmäisiä lisäruokia ja maitovalmisteita lapset saivat suositeltua aiemmin. Perheiden sosioekonomiset erot heijastuvat vahvasti imeväisruokintaan; yli 30-vuotiaan, hyvin koulutetun ja tupakoimattoman äidin tyttövauvalla on suurin todennäköisyys tulla ruokituksi suositusten mukaisesti imeväisiässä. Suosituksia aikaisempi eli ennen neljän kuukauden ikää aloitettu marjojen, hedelmien ja juuresten käyttö oli yhteydessä tyypin 1 diabetekseen kytkeytyvien autovasta-aineiden ilmaantuvuuteen. Tämä täysin uusi havainto vaatii lisätutkimuksia. Seuraava askel on tutkia löydöksen toistettavuus isommalla aineistolla. Lisäksi on pyrittävä selvittämään heijastaako kyseisten ruoka-aineiden varhainen aloitusikä joitakin muita, vielä määrittelemättömiä ympäristö- tai elintapatekijöitä. Tutkimustulokset tukevat nykyisiä imeväisikäisten imetykseen ja lisäruokien aloittamiseen liittyviä valtakunnallisia ravitsemussuosituksia, joiden käytännön tasolle saattamisessa näyttäisi vielä riittävän haastetta. Niistä poikkeaviin ruokavaliomuutoksiin ei toistaiseksi ole aihetta edes suuren diabetesriskin omaavilla lapsilla. Suomalaisnaisten raskaudenaikaista ruoankäyttöä ja ravinnonsaantia selvitettiin 224 raskaana olevan oululaisäidin otoksesta frekvenssikyselyllä ja ruokakirjanpidolla. Monipuolisesti ja tasapainoisesti koostettu ruokavalio tyydyttää raskauden ajan lisääntyneen tarpeen D-vitamiinia ja rautaa lukuun ottamatta. Myös folaatin saanti jää helposti suositeltua pienemmäksi. Ravintovalmisteiden käyttö oli runsasta, mutta osittain väärin painottunutta. D-vitamiinivalmisteiden talvikautisesta käytöstä annettu suositus toteutui huonosti, kun taas monivitamiinivalmisteita käytettiin yli tarpeen. Nuorten, vähän koulutettujen ja tupakoivien äitien ruokavalio oli kauimpana suosituksista. Äitiyshuollon ravitsemusneuvonnan haasteita ovat tarkoituksenmukaiseen valmisteiden käyttöön ohjaaminen, sosiaalisten riskiryhmien varhainen tunnistaminen ja heidän elintapojensa tukeminen lapsen terveyttä rakentavaksi ja suojelevaksi sekä raskaudenaikaisten paino-ongelmien ehkäisy ja hoito. Äidin raskauden ja imetyksen aikaisen maidon kulutuksen yhteyttä lapsen immuunivasteisiin maitoproteiineille selvitettiin lapsuusiän diabeteksen ravintoperäisen ehkäisytutkimuksen (TRIGR) esitutkimusaineistossa. Ainutlaatuisessa tutkimusasetelmassa, jossa lasten ruokavaliosta puuttuivat kaikki lehmänmaitoaltisteet ensimmäisen puolen vuoden aikana, löydettiin vain muutama yhteys äidin raskauden tai imetyksenaikaisen maitotuotteiden käytön ja lapsen immuunivasteiden välillä. Ravinnon ja sairauksien välisten tutkimusten painotus on viimeaikoina vahvasti suuntautunut elämänkaaren alkupäähän; sikiökauden sekä ensimmäisten elinvuosien ravitsemuksen mahdolliseen yhteyteen lapsen myöhempään sairastumisriskiin. Tämän väitöstutkimuksen merkittävimmät tulokset kertovat, että raskausajan ja imeväisiän ruokavalio Suomessa ei kaikilta osin yllä suositusten tasolle. Äidin koulutus, ikä ja tupakointi sekä lapsen sukupuoli määrittävät vahvasti ruokavalion koostumusta sekä imetyksen kestoa. Täysin uusi tulos on ensimmäisten kiinteiden lisäruokien suosituksia varhaisemman aloittamisiän mahdollinen yhteys tyypin 1 diabetekseen.This study evaluated diet during pregnancy and infancy and assessed the relation between the early dietary exposures and the humoral immune responses to cow s milk and type 1 diabetes associated autoantigens in the offspring. Research questions were assessed in three different populations. Altogether 113 pregnant women in the city of Oulu between August 1995 and April 1996 participated in a validation study and 111 in a reproducibility study. In the framework of the validation study, the diet of 118 women for whom we had complete food records was assessed. Humoral immune responses to cow s milk in the offspring were assessed among 97 infants, born between 1995 ­ 1997 randomized to receive hydrolysed infant formula in the Trial to Reduce Insulin dependent diabetes mellitus in the Genetically at Risk (TRIGR) study. The diet during infancy and humoral immune responses to type 1 diabetes -associated autoantigens in the offspring was assessed among a cohort of infants in the Type1 Diabetes Prediction and Prevention (DIPP) Nutrition Study (children born between 1996 - 2001) in Oulu and Tampere University hospital areas in Finland. Subjects in TRIGR and DIPP studies have a genetically determined increased risk for type 1 diabetes. The first aim of the present doctoral thesis was to evaluate the validity and reproducibility of a self-administered food frequency questionnaire developed to be used as a dietary instrument, which could be administered after delivery to effectively study the putative effects of the maternal diet during pregnancy on the development of type 1 diabetes. The validity and reproducibility of our 181-item food frequency questionnaire were found to be reasonably good. On average, 70% of the foods and 69% of the nutrients fell into same or adjacent quintiles, according to the food frequency questionnaire and the food record as a comparative method. Pregnancy seemed to be an incitement for dietary over-reporting. Our study represents an internationally important contribution to the methodological field of studies into diet during pregnancy. The second aim was to measure food consumption and nutrient intake during pregnancy, and to evaluate dietary habits and nutrient intake of pregnant women. The results showed that a balanced diet met the increased nutrient requirements during pregnancy, except for vitamin D, folate, and iron. An increase in the consumption of whole grain cereals, vegetables, and fish, and a decrease in the consumption of foods rich in sugar and saturated fatty acids represent the strategy for improving the intake of critical nutrients: essential fatty acids, dietary fibre, vitamin D, folate, and thiamine. This is also a strategy for reducing the risk of overweight. Our findings suggest that the use of dietary supplements increases during pregnancy, but unfortunately their use is focused on the wrong nutrients. Supplementation is needed to ensure an overall adequate intake of iron and vitamin D. Young, less well educated and smokers were less likely to adhere to dietary recommendations. The third aim was to assess whether maternal consumption of milk and milk products could affect the development of cow s milk antibodies in infants. In a unique intervention setting, in which the infants did not receive any intact cow s milk proteins during the first 6 months of life, few relationships were established. Protein intake from raw milk products and cheese tended to slightly inhibit the humoral immune responses to cow s milk proteins in the offspring: cheese during the first 6 months and raw milk later, close to 2 years, with the impact being stronger during lactation than pregnancy The fourth aim was to investigate infant feeding patterns during the first two years of life, and to study the effects of breastfeeding and age at introduction of complementary foods on the development of type 1 diabetes associated autoantibodies. The results on infant feeding indicated that national and international goals have not been achieved. The median duration of exclusive breast feeding among 3565 infants was 1.5 months, and only every second child was still receiving breast milk at the age of six months. Of the children, 63% were introduced to complementary foods (including cow s milk formula) before the age of 4 months. The diet during infancy was strongly influenced by sociodemographic factors; maternal age and education had a positive and infant s male gender and maternal smoking exhibited an inverse association with the duration of breast feeding and the age at introduction of supplementary foods. In the largest cohort series so far reported, an early introduction of fruits and berries was related to the risk of advanced β-cell autoimmunity. The finding of the independent association of fruits and berries with β-cell autoimmunity is novel. The next step will be to assess whether these findings can be replicated, and if so, whether they are proxies for other life style characteristics, or reflect a causal relationship

Sosiaalilääketieteen pitkä linja : väestön kivuloisuudesta globaaliin terveyteen

Non peer reviewe

Preschool children's context-specific sedentary behaviours and parental socioeconomic status in Finland : a cross-sectional study

Objectives This study examined the associations of parental socioeconomic status (SES) with preschoolers' objectively measured sedentary time (SED) over the course of a week and with parent-reported children's screen and reading times at home as indicators of sedentary behaviours (SB). Design Cross-sectional. Setting In years 2015 and 2016 in Finland. Participants 864 children, aged 3-6 years, with their parents. Outcome measures Children's accelerometer data were transformed into average SED minutes per hour in different contexts (preschool, home during preschool days, weekend and total). Parent-reported children's screen and reading times were expressed as average daily minutes. The SES indicators (maternal and paternal education and relative household income) were grouped into three categories. Linear or logistic regression analyses were used, with municipality, season, and children's gender and age as covariates. CIs were adjusted for clustering at the preschool group level. Results Children with low maternal (beta=17.21, 95% CI: 8.71 to 25.71) and paternal (beta=10.54, 95% CI: 0.77 to 20.30) education had more overall screen time at home than their more advantaged counterparts. SES differences in overall screen time were mostly explained by TV viewing. Children with low as opposed to high maternal education (beta=-2.66, 95% CI: -4.95 to -0.38) had less reading time at home. Children whose fathers were on the middle (beta=-1.15, 95% CI: -2.01 to -0.29) educational level had less weekend SED than those with high paternal education. Otherwise, parental SES was not related to objectively measured SED. Conclusions The results of this study highlight the fact that the associations between parental SES and preschoolers' SB are dependent on the indicators of SES and SBs, and vary between different contexts. Generally, parental SES was not associated with SED, whereas some SES differences existed in screen time and reading time at home. Interventions aiming to diminish SES differences in children's SB should focus on home hours.Peer reviewe

Large-scale loyalty card data in health research

Objective To study the characteristics of large-scale loyalty card data obtained in Finland, and to evaluate their potential and challenges in health research. Methods We contacted the holders of a certain loyalty card living in a specific region in Finland via email, and requested their electronic informed consent to obtain their basic background characteristics and grocery expenditure data from 2016 for health research purposes. Non-participation and the characteristics and expenditure of the participants were mainly analysed using summary statistics and figures. Results The data on expenditure came from 14,595 (5.6% of those contacted) consenting loyalty card holders. A total of 68.5% of the participants were women, with an average age of 46 years. Women and residents of Helsinki were more likely to participate. Both young and old participants were underrepresented in the sample. We observed that annual expenditure represented roughly two-thirds of the nationally estimated annual averages. Customers and personnel differed in their characteristics and expenditure, but not so much in their most frequently bought items. Conclusions Loyalty card data from a major retailer enabled us to reach a large, heterogeneous sample with fewer resources than conventional surveys of the same magnitude. The potential of the data was great because of their size, coverage, objectivity, and long periods of dynamic data collection, which enables timely investigations. The challenges included bias due to non-participation, purchases in other stores, the level of detail in product grouping, and the knowledge gaps in what is being consumed and by whom. Loyalty card data are an underutilised resource in research, and could be used not only in retailers' activities, but also for societal benefit.Peer reviewe

Alcohol expenditure in grocery stores and their associations with tobacco and food expenditures

Peer reviewe

Suitability of random forest analysis for epidemiological research: Exploring sociodemographic and lifestyle-related risk factors of overweight in a cross-sectional design.

Aims: Factors that contribute to the development of overweight are numerous and form a complex structure with many unknown interactions and associations. We aimed to explore this structure (i.e. the mutual importance or hierarchy of sociodemographic and lifestyle-related risk factors of being overweight) using a machine-learning technique called random forest (RF). The results were compared with traditional logistic regression (LR) analysis. Methods: The cross-sectional FINRISK 2007 Study included 4757 Finns (aged 25-74 years). Information on participants' lifestyle and sociodemographic characteristics were collected with questionnaires. Diet was assessed, using a validated food-frequency questionnaire. Height and weight were measured. Participants with a body mass index (BMI) 25 kg/m(2) were classified as overweight. R-statistical software was used to run RF analysis (randomForest') to derive estimates for variable importance and out-of-bag error, which were compared to a LR model. Results: In total, 704 (32%) men and 1119 (44%) women had normal BMI, whereas 1502 (69%) men and 1432 (57%) women had BMI 25. Estimated error rates for the models were similar (RF vs. LR: 42% vs. 40% for men, 38% vs. 35% for women). Both models ranked age, education and physical activity as the most important risk factors for being overweight, but RF ranked macronutrients (carbohydrates and protein) as more important compared to LR. Conclusions: RF did not demonstrate higher power in variable selection compared to LR in our study. The features of RF are more likely to appear beneficial in settings with a larger number of predictors.Peer reviewe

Vitamin D Fortification of Fluid Milk Products and Their Contribution to Vitamin D Intake and Vitamin D Status in Observational Studies—A Review

Fluid milk products are systematically, either mandatorily or voluntarily, fortified with vitamin D in some countries but their overall contribution to vitamin D intake and status worldwide is not fully understood. We searched the PubMed database to evaluate the contribution of vitamin D-fortified fluid milk products (regular milk and fermented products) to vitamin D intake and serum or plasma 25-hydroxyvitamin D (25(OH)D) status in observational studies during 1993-2017. Twenty studies provided data on 25(OH)D status (n = 19,744), and 22 provided data on vitamin D intake (n = 99,023). Studies showed positive associations between the consumption of vitamin D-fortified milk and 25(OH)D status in different population groups. In countries with a national vitamin D fortification policy covering various fluid milk products (Finland, Canada, United States), milk products contributed 28-63% to vitamin D intake, while in countries without a fortification policy, or when the fortification covered only some dairy products (Sweden, Norway), the contribution was much lower or negligible. To conclude, based on the reviewed observational studies, vitamin D-fortified fluid milk products contribute to vitamin D intake and 25(OH)D status. However, their impact on vitamin D intake at the population level depends on whether vitamin D fortification is systematic and policy-based.Peer reviewe

Alle kouluikäisten ruoankäytön väestöryhmittäiset erot

Erot ruoankäytössä väestöryhmien välillä lähtevät kehittymään jo synnytyssairaalassa. Lapsena opitut ruokatottumukset, joita vahvimmin määrittävät vanhempien koulutus ja ikä, perheen koko ja lapsen hoitopaikka, jatkuvat usein aikuisuuteen saakka. Varhaislapsuuden ravitsemus on yhteydessä useiden lapsuuden ja aikuisiän kroonisten sairauksien ja lihavuuden riskiin. Lasten ruoankäytön suurimmat väestöryhmittäiset erot löytyvät imetyksen kestossa, kiinteiden lisäruokien aloitusiässä ja kasvisten kulutuksessa. Myös rasvojen, kalaruokien ja makeiden juomien kulutus sekä ravintoaineista rasvojen, sokerin, ravintokuidun, vitamiinien ja kivennäisaineiden saanti vaihtelevat väestöryhmittäin. Vanhempien pitkä koulutus, äidin korkea ikä, pieni perhekoko, äidin tupakoimattomuus sekä päivähoito kodin ulkopuolella ovat yhteydessä lasten suositustenmukaisempaan imeväisruokintaan ja ruokavalioon ennen kouluikää. Lasten ruoankäyttö vaihtelee myös lapsen sukupuolen ja perheen asuinalueen mukaan