The relevance of dietary insulin demand and dietary protein intake during adolescence for the development of body composition and the adult GH-IGF axis

Obese children are likely to stay obese, resulting comorbidities may emerge already in childhood and tend to persist until adulthood. So-called critical periods for overweight development are early life, the time around the adiposity rebound, and puberty. The growth hormone insulin-like growth factor (GH-IGF) axis plays an important role during growth. It remains to be clarified whether it can be programmed by protein intake during growth. The first aim of this thesis was to examine the associations between dietary insulin demand during adolescence and its relevance for both adult body composition among healthy individuals and weight loss among obese adolescents with clinical features of insulin resistance. Under the second aim, prospective relations between dietary protein intake during different potentially critical, developmental periods and body composition as well as the GH-IGF axis in adulthood were investigated. Data came from two studies conducted in Germany and Australia; an ongoing, open cohort study, the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study and a randomised controlled trial, the Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers (RESIST) study, respectively.Study I revealed that among 262 DONALD participants, a higher pubertal dietary insulin demand was associated with higher body fat percentage in young adulthood. In Study II, a higher dietary insulin demand was related to less weight loss expressed as BMI as percentage of the 95th percentile (BMI %95 centile) among 91 RESIST participants. Inclusion of total energy intake in the model explained the observed associations between dietary insulin demand and change in BMI %95 centile. Study III, including 262 DONALD participants, indicated that a higher pubertal animal protein intake was independently associated with higher adult fat-free mass index (FFMI), but not fat mass index (FMI), in women. Among men, a higher pubertal animal protein intake was related to higher FFMI and lower FMI only after adjusting FFMI for FMI levels in young adulthood and vice versa. Plant protein intake was not associated with adult body composition among either sex. Study IV, also based on data from the DONALD study (n=213 and n=201, respectively), showed that a habitually higher animal protein intake during puberty was related to higher levels of adult IGF-I, IGFBP-3, and lower IGFBP-2, but not to IGFBP-1 among women. In turn, animal protein intake in early life (n=130) was inversely related to IGF-I levels in younger adulthood among males only. However, no association was observed between animal protein intake around adiposity rebound (n=179) and IGF-I in younger adulthood. No relations were observed between plant protein intakes in all three periods and adult GH-IGF axis.In conclusion, results indicate that a lower dietary insulin demand and a higher dietary protein intake may be favourably related to adult body composition. Among women, a higher pubertal animal protein intake may induce an up-regulation of the GH-IGF axis which persists until adulthood. By contrast, inverse associations between higher animal protein intakes in early life and IGF-I concentrations among men support the idea that habitually higher animal protein intakes in this period may trigger an early programming of the GH-IGF axis. Although these findings need to be confirmed in other populations, a reduction of dietary insulin demand and a moderate increase in dietary protein intake may have beneficial effects in the prevention of obesity. Moreover, it needs to be identified which mechanisms lie behind observed associations between dietary animal protein intake and the GH-IGF axis so as to determine to what extent they reflect physiological adaptations or whether these associations indicate higher or lower risks of future diseases.Die Relevanz des ernährungsbedingten Insulinbedarfs und der Proteinaufnahme in der Jugend für die Entwicklung der Körperzusammensetzung und der GH-IGF Achse Adipöse Kinder und Jugendliche haben ein hohes Risiko adipös zu bleiben und sind zudem anfälliger, bereits in jungen Jahren chronische Erkrankungen zu entwickeln, die bis ins Erwachsenenalter bestehen bleiben. Als sogenannte kritsche Phasen der Adipositasentwicklung werden die frühe und mittlere Kindheit sowie die Pubertät diskutiert. Erstes Ziel dieser Arbeit war Assoziationen zwischen dem ernährungsbedingten Insulinbedarf und der Körperzusammensetzung von gesunden Erwachsenen sowie der Gewichtsreduktion bei adipösen Jugendlichen mit Insulinresistenz und/oder Prädiabetes zu untersuchen. Zweites Ziel war, den prospektiven Zusammenhang zwischen der Proteinzufuhr in verschiedenen, potentiell kritischen Entwicklungsphasen und der Körperzusammensetzung sowie der Wachstumshormon-insulin-like growth factor (GH-IGF) Achse bei gesunden Erwachsenen zu untersuchen. Als Datengrundlage dienten sowohl die deutsche DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Studie, eine offene, prospektive Kohortenstudie, als auch die australische Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers (RESIST) Studie, eine randomisierte, kontrollierte Interventionsstudie zur Gewichtsreduktion.Studie I zeigte, dass bei 262 Probanden der DONALD Studie ein höherer ernährungsbedingter Insulinbedarf in der Pubertät mit einem höheren Körperfettanteil im jungen Erwachsenenalter assoziiert war. In Studie II war bei 91 Probanden der RESIST Studie ein höherer ernährungsbedingter Insulinbedarf mit weniger Gewichtsverlust ausgedrückt als BMI in Prozent der 95. Perzentile (BMI %95 Perzentile) assoziiert. Dieser Zusammenhang wurde durch die Berücksichtigung der Gesamtenergieaufnahme im Modell erklärt. Studie III zeigte an 262 DONALD Probanden, dass eine höhere Aufnahme an tierischem Protein während der Pubertät bei Frauen mit einem höheren Fettfreie-Masse- Index (FFMI), aber nicht dem Fettmasse-Index (FMI) im jungen Erwachsenenalter assoziiert war. Bei Männern hing eine höhere Aufnahme an tierischem Protein mit einem höheren FFMI und niedrigerem FMI nur nach Adjustierung des FFMI für FMI im jungen Erwachsenenalter und vice versa zusammen. Die Aufnahme von pflanzlichem Protein in der Pubertät war dagegen weder bei Frauen noch bei Männern mit der Körperzusammensetzung assoziiert. Studie IV basierte ebenso auf Daten der DONALD Studie (n=213 bzw. n=201) und zeigte, dass nur bei Frauen eine höhere Aufnahme an tierischem Protein während der Pubertät mit höheren IGF-I und IGF-Bindungsprotein(BP)-3, niedrigeren IGFBP-2, aber nicht IGFBP-1 Konzentrationen im frühen Erwachsenenalter zusammenhing. Die Aufnahme von tierischem Protein in der frühen Kindheit (n=130) war wiederum nur bei Männern invers mit IGF-I Konzentrationen im frühen Erwachsenenalter assoziiert.Zusammenfassend legen die Resultate nahe, dass ein geringerer Insulinbedarf und eine höhere tierische Proteinaufnahme in der Pubertät vorteilhaft mit der Körperzusammensetzung im jungen Erwachsenenalter assoziiert sind. Bei Frauen bedingte ein höherer Verzehr an tierischem Protein in der Pubertät eine Hochregulation der GH-IGF Achse bis ins frühe Erwachsenenalter. Bei Männern hingegen deutet der inverse Zusammenhang zwischen einer höheren tierische Proteinaufnahme in der frühen Kindheit und niedrigeren IGF-I Spiegeln im frühen Erwachsenalter auf eine langfristige Program-mierung der GH-IGF Achse hin. Obwohl diese Ergebnisse noch in anderen Populationen bestätigt werden müssen, könnten eine Reduktion des Insulinbedarfs und eine moderate Erhöhung der Proteinaufnahme positive Auswirkungen in der Adipositasprävention haben

Dietary Patterns in Primary School are of Prospective Relevance for the Development of Body Composition in Two German Pediatric Populations

This study performed comparative analyses in two pediatric cohorts to identify dietary patterns during primary school years and examined their relevance to body composition development. Nutritional and anthropometric data at the beginning of primary school and two or four years later were available from 298 and 372 participants of IDEFICS-Germany (Identification and prevention of Dietary-induced and lifestyle-induced health Effects In Children and infants Study) and the KOPS (Kiel Obesity Prevention Study) cohort, respectively. Principal component analyses (PCA) and reduced rank regression (RRR) were used to identify dietary patterns at baseline and patterns of change in food group intake during primary school years. RRR extracted patterns explaining variations in changes in body mass index (BMI), fat mass index (FMI), and waist-to-height-ratio (WtHR). Associations between pattern adherence and excess gain in BMI, FMI, or WtHR (>75th percentile) during primary school years were examined using logistic regression. Among PCA patterns, only a change towards a more Mediterranean food choice during primary school years were associated with a favorable body composition development in IDEFICS-Germany (p < 0.05). In KOPS, RRR patterns characterized by a frequent consumption of fast foods or starchy carbohydrate foods were consistently associated with an excess gain in BMI and WtHR (all p < 0.005). In IDEFICS-Germany, excess gain in BMI, FMI, and WtHR were predicted by a frequent consumption of nuts, meat, and pizza at baseline and a decrease in the consumption frequency of protein sources and snack carbohydrates during primary school years (all p < 0.01). The study confirms an adverse impact of fast food consumption on body composition during primary school years. Combinations of protein and carbohydrate sources deserve further investigation

Use of dietary supplements in pregnant women in relation to sociodemographic factors - a report from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

OBJECTIVES: The aim of the present study was to examine the prevalence and associated factors of dietary supplement use, particularly supplements containing vitamin D and fatty acids, in pregnant women enrolled in a multi-national study. DESIGN: The Environmental Determinants of Diabetes in the Young (TEDDY) study is a prospective longitudinal cohort study. Maternal dietary supplement use was self-reported through questionnaires at month 3 to 4 postpartum. SETTING: Six clinical research centres; three in the USA (Colorado, Georgia/Florida and Washington) and three in Europe (Sweden, Finland and Germany). SUBJECTS: Mothers (n 7326) to infants screened for high-risk HLA-DQ genotypes of type 1 diabetes. RESULTS: Ninety-two per cent of the 7326 women used one or more types of supplement during pregnancy. Vitamin D supplements were taken by 65 % of the women, with the highest proportion of users in the USA (80·5 %). Overall, 16 % of the women reported taking fatty acid supplements and a growing trend was seen in all countries between 2004 and 2010 (P < 0·0001). The use was more common in Germany (32 %) and the USA (24 %) compared with Finland (8·5 %) and Sweden (7·0 %). Being pregnant with the first child was a strong predictor for any supplement use in all countries. Low maternal age (<25 years), higher education, BMI ≥ 25·0 kg/m2 and smoking during pregnancy were factors associated with supplement use in some but not all countries. CONCLUSIONS: The majority of the women used dietary supplements during pregnancy. The use was associated with sociodemographic and behavioural factors, such as parity, maternal age, education, BMI and maternal smoking

Breastfeeding and its prospective association with components of the GH-IGF-Axis, insulin resistance and body adiposity measures in young adulthood--insights from linear and quantile regression analysis.

BACKGROUND: Breastfeeding may lower chronic disease risk by long-term effects on hormonal status and adiposity, but the relations remain uncertain. OBJECTIVE: To prospectively investigate the association of breastfeeding with the growth hormone- (GH) insulin-like growth factor- (IGF) axis, insulin sensitivity, body composition and body fat distribution in younger adulthood (18-37 years). DESIGN: Data from 233 (54% female) participants of a German cohort, the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study, with prospective data on infant feeding were analyzed. Multivariable linear as well as quantile regression were performed with full breastfeeding (not: ≤ 2, short: 3-17, long: >17 weeks) as exposure and adult IGF-I, IGF binding proteins (IGFBP) -1, -2, -3, homeostasis model assessment of insulin resistance (HOMA-IR), fat mass index, fat-free mass index, and waist circumference as outcomes. RESULTS: After adjustment for early life and socio-economic factors, women who had been breastfed longer displayed higher adult IGFBP-2 (p(trend) = 0.02) and lower values of HOMA-IR (p(trend) = 0.004). Furthermore, in women breastfeeding duration was associated with a lower mean fat mass index (p(trend) = 0.01), fat-free mass index (p(trend) = 0.02) and waist circumference (p(trend) = 0.004) in young adulthood. However, there was no relation to IGF-I, IGFBP-1 and IGFBP-3 (all p(trend) > 0.05). Associations for IGFBP-2 and fat mass index were more pronounced at higher, for waist circumference at very low or high percentiles of the distribution. In men, there was no consistent relation of breastfeeding with any outcome. CONCLUSIONS: Our data suggest that breastfeeding may have long-term, favorable effects on extremes of adiposity and insulin metabolism in women, but not in men. In both sexes, breastfeeding does not seem to induce programming of the GH-IGF-axis

Development of a harmonized food grouping system for between-country comparisons in the TEDDY Study

The Environmental Determinants of Diabetes in the Young (TEDDY) is an international study aiming to investigate associations between dietary and other environmental factors and the risk of developing islet autoimmunity and type 1 diabetes. Dietary intake was assessed using a 24-h recall and repeated 3-day food records and analyzed using country-specific food composition databases (FCDBs) in Finland, Germany, Sweden, and the U.S. with respective in-house calculation programs. A food grouping harmonization process between four country-specific FCDBs was conducted to evaluate and achieve comparability on food group definitions and quantification of food consumption across the countries. Systematic review revealed that the majority of existing food groups of the TEDDY FCDBs were not comparable. Therefore, a completely new classification system of 15 mutually exclusive main food groups (e.g. vegetables) and 89 subgroups (e.g. root vegetables, leafy vegetables) was developed. Foods and beverages were categorized into basic foods (single ingredient) and composite dishes (multiple ingredients). Composite dishes were broken down to ingredients using food composition data available in the FCDBs or generic recipes created for the harmonization effort. The daily consumption of every food group across FCDBs was quantified consistently as either raw or prepared weight depending on the food group to achieve maximal comparability

Dietary glycemic load, insulin load, and weight loss in obese, insulin resistant adolescents: RESIST study

Background & aims The optimal dietary approach for weight loss and improving insulin sensitivity in adolescents is unknown. This study aimed to explore the association between the estimated insulin demand of the diet, as measured by glycemic and insulin load, weight loss, percentage body fat and insulin sensitivity index (ISI) in obese adolescents with clinical features of insulin resistance and/or prediabetes after a 3 month lifestyle and metformin intervention. Methods Secondary data analysis of 91 adolescents (median age 12.7 years (range 10.1-17.4) participating in a randomized controlled trial, known as RESIST; ACTRN12608000416392. Weight change between baseline and 3 months was measured by BMI expressed as percentage of the 95th centile (BMI %95). Body composition was measured by dual energy X-ray absorptiometry and ISI was determined by an oral glucose tolerance test. Results Higher dietary glycemic load and insulin load were associated with less weight loss (BMI %95), adjusted for sex and pubertal stage, β = 0.0466, P = 0.007 and β = 0.0124, P = 0.040, respectively. Inclusion of total energy intake in the model explained observed associations between dietary glycemic load and insulin load and change in BMI %95. Neither dietary glycemic load nor insulin load were associated with changes in percentage body fat or ISI. Dietary glycemic index and macronutrient content (% of total energy) were not associated to changes in BMI %95, percentage body fat or ISI. Conclusion Reduced energy diet contributes to weight loss in obese, insulin resistant adolescents. Diets with a lower insulin demand were associated with a lower energy intake and may hence assist with weight loss

GH-IGF-axis and HOMA-IR in young adulthood according to breastfeeding duration in multivariable quantile regression models.

<p>Displayed are point estimates (95% CI) for IGF-I (A), IGFBP-1 (B), IGFBP-3 (C), IGFBP-2 (D) and HOMA-IR (E) differences between women and men breastfed for a long duration (i.e. >17 weeks) vs. those not breastfed (i.e. ≤2 weeks) for specific percentiles (10^th, 25^th, 50^th, 75^th and 90^th percentiles). Models included age in adulthood, maternal overweight (yes/no), paternal university degree (yes/no), firstborn status (yes/no), smoking in the household (yes/no) in the case of FMI and WC; in the case of FFMI: age in adulthood, maternal overweight (yes/no), paternal university degree (yes/no), birth weight and length (appropriate for gestational age yes/no), firstborn status (yes/no), smoking in the household (yes/no). DONALD Study, n = 228-232. * p<0.05 DONALD, Dortmund Nutritional and Anthropometric Longitudinally Designed; IGF-I, insulin-like growth factor 1, IGFBP, insulin-like growth factor binding protein, HOMA-IR, homeostasis model assessment for insulin resistance.</p

Body composition and body fat distribution in young adulthood according to breastfeeding duration in infancy, DONALD Study (n = 125 women, 108 men)^a.

a<p>Data are adjusted means (95% CI). Abbreviations used: DONALD, Dortmund Nutritional and Anthropometric Longitudinally Designed. Missing values: n = 1 for firstborn status.</p>b<p>Model 1: adjusted for age in adulthood.</p>c<p>Model 2 for FMI, WC: adjusted for age in adulthood, maternal overweight (yes/no), paternal university degree (yes/no), firstborn status (yes/no), smoking in the household (yes/no). Model 2 for FFMI: adjusted for age in adulthood, maternal overweight (yes/no), paternal university degree (yes/no), birth weight and length (appropriate for gestational age yes/no), firstborn status (yes/no), smoking in the household (yes/no).</p