MONETIZACIÓN DEL DAÑO

4.1 DONALD study

The DONALD study is an ongoing, open cohort study conducted at the Research Institute of Child Nutrition in Dortmund. The major aims of the DONALD study are [317, 318]:

• Analysis of interrelations between dietary intake, metabolism, development and growth • Determination of intra- and inter-individual trends of dietary intake and nutritional

behaviour

• Provision of metabolic reference data from healthy children and adolescents • Provision of dietary intake data for specific assessments of exposures

Since recruitment started in 1985, detailed data on diet, growth, development, and metabolism have been collected from over 1300 children who are systematically followed up until adulthood. Every year, 35 to 40 healthy infants are newly recruited and first examined at the age of 3 months. Each child returns every 3 months in the first year of life, twice a year in the second year of life and then once annually until adulthood (Figure 5). Assessments include medical examinations, anthropometric measurements, parental questionnaires, and 3-day weighed dietary records. Since 2005, participants are asked to provide fasting blood samples from the age of 18 years, until then the study is purely observational and non-invasive. Moreover, parental information including weight and height is repeatedly assessed [317, 318]. The DONALD study was approved by the Ethics Committee of the University of Bonn, and all examinations are performed with parental and participant’s consent.

Ages (years) 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 21 25 30 35 Study Modules Parents Medical examination and anamnesis Anthropometry 3-day weighed dietary record 24h-urine Blood sample Anamnesis, Anthropometry

The 3-day weighed dietary records are analysed using the continuously updated in-house nutrient database LEBTAB (Lebensmitteltabelle) [319], which provides information on energy and nutrients including total protein, animal protein and plant protein. To also allow the examination of dietary GI, GL and insulin demand, the database was extended by the dietary GI according to existing standard procedures [320] and FII, for which a standardized assignment procedure was developed and implemented [321]1. Composite foods are entered as recipes, therefore, providing comprehensive data on ingredients [319]. In order to create the food groups “dairy products” and “meat products”, foods were broken down into their ingredients as appropriate (e.g. pizza was broken down into dairy products, meat products and other product groups). All foods and ingredients were then assigned to their respective food groups, i.e. meat products, dairy products, and miscellaneous.

Venous blood samples are drawn after an overnight fast. IGF-I and IGFBP measurements are not included in the DONALD routine and were measured at the Laboratory of Translational Hormone Analytics in Pediatric Endocrinology Center of Child and Adolescent Medicine at the Justus-Liebig-University in Giessen, Germany. Anthropometric measurements performed in the DONALD study are based on simple measurements only. The estimation of body fat is derived from skinfold measurements. Detailed description of the study methods can be found in the original articles (appendices 1, 3, and 4).

Different, potentially critical, developmental periods comprise the following ages: Early life 0.5-2 years, adiposity rebound 4-6 years, and puberty as 9-14 years for girls and 10-15 years for boys. It should be noted that puberty was defined according to chronological age. Chronological age might be confounded because children of the same age may differ substantially in their pubertal stage. However, the chronological age range we used starts at the same time point at which DONALD participants on average are undergoing puberty according to the age at take-off (onset of pubertal growth spurt). Furthermore, the chronological age range ends where most girls and boys included in the DONALD study have already experienced their first menarche and their voice break, respectively [322, 323]. Therefore, we supposed that chronological age as defined, adequately covers the period of puberty. In addition, preliminary analyses using age at take-off and peak height velocity to define puberty were run and yielded similar results for the relationships of the dietary GI, GL,

1 _{Contribution of Gesa Joslowski: Complementation of assignment of GI values, development and}

implementation of a standardized procedure to assign FII values to recorded foods, assignment of all FII values to the 3-day weighed dietary records (together with Janina Goletzke)

and insulin demand with %BF. Thus, chronological age was used to define puberty in order to not reduce the sample size too much.

4.2 RESIST study

The RESIST study is a randomised control trial (Australian New Zealand Clinical Trial Registration Number 12608000416392) conducted at the Children’s Hospital at Westmead in Sydney. The primary aim of the RESIST study was to determine the effectiveness of two structured lifestyle interventions differing in diet composition on insulin sensitivity in adolescents with clinical features of insulin resistance and/or prediabetes treated with metformin [324].

In total, 111 participants (66 girls) from 10 to 17 years of age were recruited and randomised to either a high carbohydrate, low fat or a moderate carbohydrate, increased protein diet and commenced on metformin. The study is structured in 3 Phases: dietary intervention, intensive exercise, and maintenance phase (Figure 6). Assessments include medical examinations, oral glucose tolerance tests (OGTT) and blood tests, anthropometric measurements, questionnaires, and 24h dietary recalls using a standardized three-pass methodology [324]. To assist with estimating the amounts of foods a food model booklet was used [117].The study was approved by The Children’s Hospital at Westmead Human Research Ethics Committee (07/CHW/12), Sydney South West Area Health, Western Zone (08/LPOOL/195) and Sydney South West Area Health Service, Royal Prince Alfred Hospital (08/RPAH/455). Written informed consent from parents and assent from the young people was sought prior to their enrolment in the study.

Phase 1 (0-3 months) Phase 2 (4-6 months) Phase 3 (7-12 months)

At baseline, randomisation to one of two study diets and commencement of metformin treatment, n=111

Allocation to a high carbohydrate, low fat diet

(in E%), n=55

Allocation to a moderate carbohydrate, increased protein

diet (in E%), n=56

Dietary intervention

(medical consultation, dietitian consultation and support,

24hour dietary recall)

Dietary intervention

(medical consultation, dietitian consultation and support,

24hour dietary recall)

Intensive exercise intervention

(Gym sessions: 2 x per week, home based physical activity: 1 x per week, participants continue with their prescribed diet,

medical consultation, dietitian consultation and support)

Maintenance

(Participants continue with their prescribed diet and their exercise routine, medical consultation, dietitian consultation and support)

Figure 6 Design of the RESIST study (modified after [324]). %En, percentage energy

For this thesis, 24h dietary recalls at weeks 6, 9, and 12 were used and analysed using FoodWorks 2009 which uses the Australian Food and Nutrient Database (AusNut) compiled and regularly updated by Food Standards Australia and New Zealand. GI and FII values have been assigned to each food recorded according to standard procedures [321, 325]2. After an overnight fast, OGTTs were performed and venous blood samples were drawn. Anthropometric measurements are based on single measurements for weight and two measurements for height, using the average value for data analysis. Body composition was analysed using dual-energy X-ray absorptiometry (DEXA). All outcomes were assessed at baseline and after 12 weeks. Detailed description of the study methods can be found in the original article (appendix 2).

All statistical analyses were carried out using the Statistical Analyses System SAS (versions 9.1.3, SAS Institute Inc., Cary, NC). A p-value <0.05 was considered statistically significant. Detailed description of the analytical approaches can be found in the original articles (appendices 1-4).

2

Contribution of Gesa Joslowski: Complementation of assignment of GI values, assignment of all FII values to the 24hour recalls (together with Janina Goletzke)