Study populations

The DONALD and RESIST study comprise both a longitudinally designed cohort study and an intervention study. Even though a longitudinal, prospective cohort study is purely observational, a group of individuals can be followed over time and it is possible to study different exposures in order to determine how these factors are related to specific outcomes. By contrast, an intervention study examines the direct effect of a random or non-random assigned exposure on an outcome. However, the analysis included in this thesis was secondary data analysis of the RESIST study and hence also purely observational.

DONALD Study

The prospective and longitudinal nature of the DONALD study entails the possibility to investigate periods from 3 months of age until adulthood. This design is superior to cross- sectional studies which can only assess an association at a certain time point. Prospective cohort studies are able to identify occurrences of diseases and/or their development. Furthermore, risk factors for specific populations can be identified and give clues of possible causal relations [353].

The DONALD study is an appropriate but non-representative sample, as discussed in the original articles (OA1, OA2, and OA4). Only Caucasians are included and participants display a higher education and a generally high interest in nutrition and health-related topics [318]. However with regards to anthropometrics, former comparisons of the BMI distribution in the DONALD study with the German reference population did not suggest major deviations [354]. DONALD participants included in the analyses of this thesis had slightly lower or comparable BMI values during puberty compared to the German reference population [92]. Furthermore, DONALD participants appeared to have slightly higher BMI values during early life and comparable BMI values around the adiposity rebound than the German reference population [92].

Participants included in the DONALD sub-sample for the body composition analyses (OA1 and OA3) had a median %BF of 17% for men and 29% for women in young adulthood (median age was 19 years (the age range was 18 to 25 years)). Among men, 30.3% were overweight and 4.1% obese; among women, 12.2% were overweight and 4.3% obese. Similarly, men and women who were included in the DONALD sub-sample for the IGF analysis (OA4) had a median %BF of 18% and 31% in younger adulthood (median age was 22 years (the age range was 18 to 36)), respectively. Among men, 33.7% were overweight and 7.4% obese; among women 17.8% were overweight and 5.9% obese. These prevalence are lower, especially for women, than compared to the results of the German Health Interview and Examination Survey for Adults (DEGS1; conducted from 2008 to 2011) for 18-29 year old men and women where 35.3% of men and 30.0% of women were overweight, 8.6% of men and 9.6% of women were obese [113]. This large nationwide survey used BMI to identify overweight and obesity since it can be measured relatively quickly, easy and highly standardised compared to other indicators of overweight. Therefore, no data on %BF were available.

The KiGGS study included a nutrition module, so-called EsKiMo (Ernährungsstudie als KiGGS Modul) [355], providing representative data on dietary intake among children and adolescents. The median daily macronutrient intakes during puberty were 13%En protein, 51%En carbohydrates, and 36%En fat among girls and boys in the DONALD sub-samples (median age was 12 years). Therefore, dietary protein intake of boys and girls was comparable to that of 12 year old boys and girls in EsKiMo. The dietary carbohydrate intake in the DONALD sub-samples was a bit lower for boys and girls (i.e. 1%En for boys and 1.5%En for girls), while dietary fat intakes were higher for boys and girls (i.e. around 3%En for boys and girls), compared to the results of EsKiMo. The median energy intake in the DONALD samples was around 9MJ for boys and 7MJ for girls, thus around 1MJ lower compared 12 year old boys and girls in EsKiMo.

Longitudinal cohort studies may in general have the problem of non-representativeness, as only participants who are really interested in a study will participate over the long-term and this may be often associated with a higher education and socioeconomic status. The DONALD study focusses on details, as it includes repeated, closely spaced measurements, which allow the investigation of relations between habitual dietary intakes in childhood and adolescence (see also chapter 6.2.2, Dietary assessment) and health-related outcomes later in life. With these multiple assessments during growth, potentially critical developmental periods for later disease risk are covered and made it possible to consider them within the

analyses, i.e. early life, adiposity rebound and puberty. This is an advantage compared to other large studies, which are less detailed.

RESIST study

The RESIST study included obese adolescents with clinical features of insulin resistance and/or prediabetes. This is a clinical population at risk of developing type 2 diabetes and other chronic diseases, not meant to be representative for the general population.

The vast majority of the RESIST participants (91%) were born in Australia, but only 27% of participants (n=30) reported having both parents born in Australia [337]. Of these, 6 had at least 1 parent who was an Aboriginal or Torres Strait Islander. The country of birth of the remaining participants’ parents included North African/Middle Eastern (16%), Southern/Central Asia (12%), Southern/Eastern Europe (8%), New Zealand (Maori)/Pacific Islands (6%), and South American (6%). One fifth (20%) reported speaking a language other than English at home. In addition, most participants (87%) reported a family history of obesity [337].

The secondary data analysis included in this thesis was not clearly prospective. This is due to the fact that the average dietary intake was calculated from 24h dietary recalls at weeks 6, 9, and 12 to examine associations with outcomes at 3 months and not all participants completed 3 recalls. It is not possible to draw a conclusion with regards to cause and effect, as discussed in the original article (see OA2). On the other hand, the RESIST sample is the sample of particular interest. RESIST participants are obese and have features of clinical insulin resistance and/or prediabetes, thus they are at risk of developing type 2 diabetes. Especially among adolescents, development of type 2 diabetes is of concern as complications are common and may appear early in children and adolescents with type 2 diabetes [356, 357]. The recruitment of this sample was difficult and it is therefore remarkable that overall 96% and 88% of participants completed the 3 and 6 months visit of the study, respectively [337]. With both studies and their specific characteristics it was possible to study and answer the underlying research questions of this thesis (see chapter 3). Even though the studies are non- representative, it should be noted that representativeness is of minor importance when examining internal associations between exposure and outcome, since it does not affect internal validity. Unquestionably, the results cannot be generalised. In addition, the study samples drawn from the DONALD and RESIST study were both relatively small. This specifically applies to the sub-samples of the DONALD study examining early life and the adiposity rebound (OA3 and OA4) and hence statistical power might not have been sufficient.

With regards to the secondary data analysis of the RESIST study, explanatory power may be limited due to the small sample size and the not clearly prospective design.

6.2.2 Data assessment