Early Growth and Adult Health : Programming of postprandial responses, food intake and salt sensitivity

Epidemiological studies have shown that low birth weight and slow growth during infancy predict an increased risk of metabolic diseases, including type 2 diabetes and cardiovascular disease, in adult life. Unhealthy dietary habits are also closely linked with these diseases. However, few results are available on whether dietary habits play a role in the association between birth size and disease risk in later life. The aim of this thesis was to determine whether body size at birth is associated with food and nutrient intake later in life and whether birth weight modifies the relationship between salt intake and blood pressure. In addition, the impact of early growth on postprandial metabolism was examined. These studies included 2003 men and women born in Helsinki between 1934 and 1944 with detailed information of their birth weight and childhood growth. They participated in a clinical examination between 2001 and 2004. In the clinic, their weight, height and blood pressure were measured and they filled a validated food-frequency questionnaire. Of those who attended the clinical study, 12 obese individuals with a slow increase in body mass index (BMI) during the first year of life and 12 BMI- and age-matched controls were recruited to participate in the postprandial studies. Each participant consumed six different test meals in random order. Body size at birth was positively associated with consumption of fruits and berries and intake of carbohydrates, sugars and fibre, and inversely associated with intake of fat. Salt intake was related to systolic blood pressure among low birth weight participants (birth weight ≤ 3050 g) but not among participants whose birth weight was > 3050 g. Salt intake was not significantly associated with diastolic blood pressure, either in the low birth weight or high birth weight groups. Early growth affected the postprandial responses, and insulin and triglyceride responses were significantly higher in the group that grew slowly during early life than in the controls. Individuals with slow early growth also showed higher appetite regulatory hormone peptide YY responses than did the controls. This study showed that individuals born with small body size may be programmed towards unhealthy dietary habits. In addition, they are sensitive to the blood pressure-raising effect of salt and therefore, may especially benefit from a reduction in salt intake. Slow growth during early life adversely affects postprandial insulin and triglyceride responses. Unhealthy dietary habits and elevated postprandial responses may be one underlying mechanism explaining the increased risk of metabolic diseases associated with nonoptimal early growth. Early growth may also alter appetite regulatory hormone secretion, which could be one explanation why individuals born small or who grow slowly during infancy are unlikely to become obese in later life.Sikiökautinen kasvu voi vaikuttaa läpi elämän ruoankäyttöön ja suolan saannista johtuvaan verenpaineen nousuun. Varhaisella kasvulla näyttäisi olevan vaikutusta myös aterian nauttimisen jälkeisiin aineenvaihdunnan vasteisiin. Väitöstutkimuksessa todettiin, että suuri syntymäkoko oli yhteydessä runsaampaan hedelmien ja marjojen kulutukseen; 1 kg:n syntymäpainon lisäys oli yhteydessä noin 80 g runsaampaan hedelmien ja marjojen kulutukseen. Suuri syntymäkoko oli yhteydessä myös runsaampaan hiilihydraattien ja kuidun saantiin sekä vähäisempään rasvan saantiin. Tulokset viittaavat siihen, että pienikokoisina syntyneillä voi olla epäterveellisemmät ruokatottumukset. Tutkimuksessa havaittiin myös, että ihmisillä jotka olivat syntyessään pienipainoisia, oli suolan saanti yhteydessä systoliseen verenpaineeseen. Sen sijaan ihmisillä, jotka olivat syntyessään painavampia, suolan saanti ei ollut yhteydessä systoliseen verenpaineeseen. Suolan saannin ja diastolisen verenpaineen välillä ei havaittu yhteyttä kummallakaan ryhmällä. Tulos osoittaa, että pienipainoisina syntyneet ovat herkempiä suolan saannista johtuvalle verenpaineen nousulle, minkä vuoksi he voisivat erityisesti hyötyä suolan saannin rajoittamisesta. Tutkimuksessa osoitettiin, että ensimmäisen elinvuoden aikaisella hitaalla kasvulla voi olla haitallisia vaikutuksia aterianjälkeiseen insuliini- ja rasva-aineenvaihduntaan myöhemmällä aikuisiällä. Hidas varhainen kasvu voi myös lisätä kylläisyyden tunnetta lisäävien hormonien eritystä. Tutkimus vahvistaa käsitystä siitä, että ensimmäisen elinvuoden aikana tapahtuva kehitys mahdollisesti muokkaa aikuisiän aineenvaihdunnallisia vasteita ja voi siten lisätä riskiä sairastua sydän- ja verisuonitauteihin sekä tyypin 2 diabetekseen myöhemmällä iällä. Tutkimukseen osallistui 2 003 ihmistä, jotka syntyivät Helsingissä vuosina 1934 1944, ja joiden syntymä-, neuvola- ja koulutiedot kasvumittoineen olivat saatavilla. He osallistuivat kliinisiin yksityiskohtaisiin terveystarkastuksiin vuosien 2001 2004 aikana keskimäärin 61-vuotiaina. Kliinisen tutkimuskäynnin yhteydessä mm. heidän painonsa, pituutensa ja verenpaineensa mitattiin ja he täyttivät validoidun 128-kohtaisen ruoankäytön frekvenssikyselyn. Heidän joukostaan 12 ylipainoista henkilöä, jotka olivat kasvaneet hitaasti ensimmäisen elinvuoden aikana syntymäkokoonsa nähden, ja 12 samanikäistä ja vastaavan painoindeksin omaavaa kontrollihenkilöä osallistui ateriatestaukseen. Ateriatestauksissa tutkittavat nauttivat 6 erilaista testiateriaa, jonka jälkeen veren sokeri- ja rasva-aineenvaihdunnan vasteita sekä kylläisyyttä säätelevien hormonien pitoisuuksia mitattiin 4 tunnin ajan

Impact of Early Growth on Postprandial Responses in Later Life

Peer reviewe

Telomere Length and Frailty : The Helsinki Birth Cohort Study

Objectives: Telomere length is associated with aging-related pathologies. Although the association between telomere length and frailty has been studied previously, only a few studies assessing longitudinal changes in telomere length and frailty exist. Design: Longitudinal cohort study. Setting and participants: A subpopulation of the Helsinki Birth Cohort Study consisting of 1078 older adults aged 67 to 79 years born in Helsinki, Finland, between 1934 and 1944. Measures: Relative leukocyte telomere length (LTL) was measured using quantitative real-time polymerase chain reaction at the average ages of 61 and 71 years, and at the latter the participants were assessed for frailty according to Fried criteria. Results: The mean +/- SD relative LTLs were 1.40 +/- 0.29 (average age 61 years) and 0.86 +/- 0.30 (average age 71 years) for the cohort. A trend of shorter mean relative LTL across frailty groups was observed at 61 years (P =.016) and at 71 years (P =.057). Relative LTL at age 61 years was significantly associated with frailty: per 1-unit increase in relative LTL, the corresponding relative risk ratio (RRR) of frailty was 0.28 (95% confidence interval [CI] 0.08-0.97), adjusting for several confounders. Also, LTL at age 71 years was associated with frailty (RRR 0.18, 95% CI 0.04-0.81) after adjustment for sex, age, and adult socioeconomic status, but further adjustment attenuated the association. No associations between telomere shortening and frailty were observed during the 10-year follow-up. Conclusions: Shorter relative LTL was associated with frailty in cross-sectional and longitudinal analyses, but telomere shortening was not, suggesting that short LTL may be a biomarker of frailty. (C) 2018 AMDA - The Society for Post-Acute and Long-Term Care Medicine. This is an open access article under the CC BY-NC-ND license.Peer reviewe

Body composition as a predictor of physical performance in older age : A ten- year follow-up of the Helsinki Birth Cohort Study

Background: This study assessed how different measures of body composition predict physical performance ten years later among older adults. Methods: The participants were 1076 men and women aged 57 to 70 years. Body mass index (BMI), waist circumference, and body composition (bioelectrical impedance analysis) were measured at baseline and physical performance (Senior Fitness Test) ten years later. Linear regression analyses were adjusted for age, education, smoking, duration of the follow-up and physical activity. Results: Greater BMI, waist circumference, fat mass, and percent body fat were associated with poorer physical performance in both sexes (standardized regression coefficient [beta] from -0.32 to -0.40, p <0.001). Lean mass to BMI ratio was positively associated with later physical performance (beta = 0.31 in men, beta = 0.30 in women, p <0.001). Fat-free mass index (lean mass/height(2)) in both sexes and lean mass in women were negatively associated with later physical performance. Lean mass residual after accounting for the effect of height and fat mass was not associated with physical performance. Conclusions: Among older adults, higher measures of adiposity predicted poorer physical performance ten years later whereas lean mass was associated with physical performance in a counterintuitive manner. The results can be used when appraising usefulness of body composition indicators for definition of sarcopenic obesity.Peer reviewe

Telomere length and physical performance among older people – the Helsinki Birth Cohort Study

Telomere length has been suggested a biomarker of aging and is associated with several chronic diseases. However, the association between telomere length and physical performance is not well known. Using both cross-sectional and longitudinal data, we studied 582 women and 453 men from the Helsinki Birth Cohort Study at two time-points; a baseline examination in 2001-2004 at a mean age of 61 years and a follow-up examination approximately 10 years later in 2011-2013. Telomere length was measured both at baseline and at follow-up using real-time quantitative polymerase chain reaction. Physical performance was evaluated only at follow-up using the Senior Fitness Test (SFT), which assesses strength, flexibility and endurance. In women, shorter telomere length at follow-up (p = 0.044) and greater telomere attrition during follow-up time (p = 0.022) were associated with poorer physical performance after adjusting for covariates (age at baseline, smoking status, body mass index at baseline, follow-up time and educational attainment). No similar associations were found for men. This indicates that, at least in women, telomere length could potentially be used as a biomarker for physical performance, however, more longitudinal studies are needed to confirm this association.Peer reviewe

A healthy Nordic diet and physical performance in old age : findings from the longitudinal Helsinki Birth Cohort Study

Epidemiological studies have shown that a number of nutrients are associated with better physical performance. However, little is still known about the role of the whole diet, particularly a healthy Nordic diet, in relation to physical performance. Therefore, we examined whether a healthy Nordic diet was associated with measures of physical performance 10 years later. We studied 1072 participants from the Helsinki Birth Cohort Study. Participants' diet was assessed using a validated 128-item FFQ at the mean age of 61 years, and a priori-defined Nordic diet score (NDS) was calculated. The score included Nordic fruits and berries, vegetables, cereals, PUFA:SFA and trans-fatty acids ratio, low-fat milk, fish, red and processed meat, total fat and alcohol. At the mean age of 71 years, participants' physical performance was measured using the Senior Fitness Test (SFT), and an overall SFT score was calculated. Women in the highest fourth of the NDS had on average 5 points higher SFT score compared with those in the lowest fourth (P-for trend 0.005). No such association was observed in men. Women with the highest score had 17% better result in the 6-min walk test, 16% better arm curl and 20% better chair stand results compared with those with the lowest score (all P values <0.01). In conclusion, a healthy Nordic diet was associated with better overall physical performance among women and might help decrease the risk of disability in old age.Peer reviewe

Genome-wide association meta-analysis of fish and EPA plus DHA consumption in 17 US and European cohorts

Background Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (Freq(A) = 0.015) was associated with 0.029 servings/day (similar to 1 serving/month) lower fish consumption (P = 1.96x10(-8)). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10(-7)). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.Peer reviewe

Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits

OBJECTIVE Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations. RESEARCH DESIGN AND METHODS We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. RESULTS We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m2 higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h). CONCLUSIONS Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet—specifically higher carbohydrate and lower fat composition—and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants

Gene × dietary pattern interactions in obesity: Analysis of up to 68 317 adults of European ancestry

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist-hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GR

Gene × dietary pattern interactions in obesity: analysis of up to 68 317 adults of European ancestry

Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. Totally, 32 body mass index (BMI)- and 14 waist–hip ratio (WHR)-associated single nucleotide polymorphisms were genotyped, and genetic risk scores (GRS) were calculated in 18 cohorts of European ancestry (n = 68 317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages and fried potatoes (unfavorable). Multivariable adjusted, linear regression within each cohort followed by inverse variance-weighted, fixed-effects meta-analysis was used to characterize: (a) associations of each GRS with BMI and BMI-adjusted WHR and (b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P = 0.006–0.04) were observed between the diet score and WHR-GRS (but not BMI-GRS), two WHR loci (GRB14 rs10195252; LYPLAL1 rs4846567) and two BMI loci (LRRN6C rs10968576; MTIF3 rs4771122), for the respective BMI-adjusted WHR or BMI outcomes. Although the magnitudes of these select interactions were small, our data indicated that associations between genetic predisposition and obesity traits were stronger with a healthier diet. Our findings generate interesting hypotheses; however, experimental and functional studies are needed to determine their clinical relevance