The fieldwork of the second follow-up to the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) was completed in August 2017. KiGGS is part of the Robert Koch Institute’s Federal Health Monitoring. The study consists of the KiGGS cross-sectional component (a nationally representative, periodic cross-sectional survey of children and adolescents aged between 0 and 17) and the KiGGS cohort (the follow-up into adulthood of participants who took part in the KiGGS baseline study). KiGGS collects data on health status, health-related behaviour, psychosocial risk and protective factors, health care and the living conditions of children and adolescents in Germany. The first interview and examination survey (the KiGGS baseline study; undertaken between 2003 and 2006; n=17,641; age range: 0-17) was carried out in a total of 167 sample points in Germany. Physical examinations, laboratory analyses of blood and urine samples and various physical tests were conducted with the participants and, in addition, all parents and participants aged 11 or above were interviewed. The first follow-up was conducted via telephone-based interviews (KiGGS Wave 1 2009-2012; n=11,992; age range: 6-24) and an additional sample was included (n=4,455; age range: 0-6). KiGGS Wave 2 (2014-2017) was conducted as an interview and examination survey and consisted of a new, nationwide, representative cross-sectional sample of 0- to 17-year-old children and adolescents in Germany, and the second KiGGS cohort follow-up. The completion of the cross-sectional component of KiGGS Wave 2 means that the health of children and adolescents in Germany can now be assessed using representative data gained from three study waves. Trends can therefore be analysed over a period stretching to over ten years now. As the data collected from participants of the KiGGS cohort can be individually linked across the various surveys, in-depth analyses can be conducted for a period ranging from childhood to young adulthood and developmental processes associated with physical and mental health and the associated risk and protective factors can be explored. As such, KiGGS Wave 2 expands the resources available to health reporting, as well as policy planning and research, with regard to assessing the health of children and adolescents in Germany.

<p>Immunohistochemistry staining protocols</p>

<p>Supplementary methods</p>

<div>AbstractPurpose:<p>Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth <i>in vitro</i>. Presurgical window studies allow rapid <i>in vivo</i> assessment of antitumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin <i>in vivo</i> using a robust window study design.</p><p><b>Patients and Methods:</b> A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850 mg daily for 3 days, and twice daily thereafter) or placebo for 1 to 5 weeks until surgery. The primary outcome was posttreatment IHC expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K–Akt–mTOR and insulin signaling pathways and obesity.</p>Results:<p>Eighty-eight women received metformin (<i>n</i> = 45) or placebo (<i>n</i> = 43) and completed treatment. There was no overall difference in posttreatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference −0.57%; 95% CI, −7.57%–6.42%; <i>P</i> = 0.87). Metformin did not affect expression of markers of the PI3K–Akt–mTOR or insulin signaling pathways, and did not result in weight loss.</p>Conclusions:<p>Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.</p></div>

<div>AbstractPurpose:<p>Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth <i>in vitro</i>. Presurgical window studies allow rapid <i>in vivo</i> assessment of antitumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin <i>in vivo</i> using a robust window study design.</p><p><b>Patients and Methods:</b> A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850 mg daily for 3 days, and twice daily thereafter) or placebo for 1 to 5 weeks until surgery. The primary outcome was posttreatment IHC expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K–Akt–mTOR and insulin signaling pathways and obesity.</p>Results:<p>Eighty-eight women received metformin (<i>n</i> = 45) or placebo (<i>n</i> = 43) and completed treatment. There was no overall difference in posttreatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference −0.57%; 95% CI, −7.57%–6.42%; <i>P</i> = 0.87). Metformin did not affect expression of markers of the PI3K–Akt–mTOR or insulin signaling pathways, and did not result in weight loss.</p>Conclusions:<p>Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.</p></div>