@phdthesis{Polemiti2022,
  author    = {Polemiti, Elli},
  title     = {Identifying risk of microvascular and macrovascular complications of type 2 diabetes},
  doi       = {10.25932/publishup-57103},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-571038},
  school      = {Universit{\"a}t Potsdam},
  pages     = {xii, 292},
  year      = {2022},
  abstract  = {Diabetes is hallmarked by high blood glucose levels, which cause progressive generalised vascular damage, leading to microvascular and macrovascular complications. Diabetes-related complications cause severe and prolonged morbidity and are a major cause of mortality among people with diabetes. Despite increasing attention to risk factors of type 2 diabetes, existing evidence is scarce or inconclusive regarding vascular complications and research investigating both micro- and macrovascular complications is lacking. This thesis aims to contribute to current knowledge by identifying risk factors - mainly related to lifestyle - of vascular complications, addressing methodological limitations of previous literature and providing comparative data between micro- and macrovascular complications. To address this overall aim, three specific objectives were set. The first was to investigate the effects of diabetes complication burden and lifestyle-related risk factors on the incidence of (further) complications. Studies suggest that diabetes complications are interrelated. However, they have been studied mainly independently of individuals' complication burden. A five-state time-to-event model was constructed to examine the longitudinal patterns of micro- (kidney disease, neuropathy and retinopathy) and macrovascular complications (myocardial infarction and stroke) and their association with the occurrence of subsequent complications. Applying the same model, the effect of modifiable lifestyle factors, assessed alone and in combination with complication load, on the incidence of diabetes complications was studied. The selected lifestyle factors were body mass index (BMI), waist circumference, smoking status, physical activity, and intake of coffee, red meat, whole grains, and alcohol. Analyses were conducted in a cohort of 1199 participants with incident type 2 diabetes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam, who were free of vascular complications at diabetes diagnosis. During a median follow-up time of 11.6 years, 96 cases of macrovascular complications (myocardial infarction and stroke) and 383 microvascular complications (kidney disease, neuropathy and retinopathy) were identified. In multivariable-adjusted models, the occurrence of a microvascular complication was associated with a higher incidence of further micro- (Hazard ratio [HR] 1.90; 95\% Confidence interval [CI] 0.90, 3.98) and macrovascular complications (HR 4.72; 95\% CI 1.25, 17.68), compared with persons without a complication burden. In addition, participants who developed a macrovascular event had a twofold higher risk of future microvascular complications (HR 2.26; 95\% CI 1.05, 4.86). The models were adjusted for age, sex, state duration, education, lifestyle, glucose-lowering medication, and pre-existing conditions of hypertension and dyslipidaemia. Smoking was positively associated with macrovascular disease, while an inverse association was observed with higher coffee intake. Whole grain and alcohol intake were inversely associated with microvascular complications, and a U-shaped association was observed for red meat intake. BMI and waist circumference were positively associated with microvascular events. The associations between lifestyle factors and incidence of complications were not modified by concurrent complication burden, except for red meat intake and smoking status, where the associations were attenuated among individuals with a previous complication. The second objective was to perform an in-depth investigation of the association between BMI and BMI change and risk of micro- and macrovascular complications. There is an ongoing debate on the association between obesity and risk of macrovascular and microvascular outcomes in type 2 diabetes, with studies suggesting a protective effect among people with overweight or obesity. These findings, however, might be limited due to suboptimal control for smoking, pre-existing chronic disease, or short-follow-up. After additional exclusion of persons with cancer history at diabetes onset, the associations between pre-diagnosis BMI and relative annual change between pre- and post-diagnosis BMI and incidence of complications were evaluated in multivariable-adjusted Cox models. The analyses were adjusted for age, sex, education, smoking status and duration, physical activity, alcohol consumption, adherence to the Mediterranean diet, and family history of diabetes and cardiovascular disease (CVD). Among 1083 EPIC-Potsdam participants, 85 macrovascular and 347 microvascular complications were identified during a median follow-up period of 10.8 years. Higher pre-diagnosis BMI was associated with an increased risk of total microvascular complications (HR per 5 kg/m2 1.21; 95\% CI 1.07, 1.36), kidney disease (HR 1.39; 95\% CI 1.21, 1.60) and neuropathy (HR 1.12; 95\% CI 0.96, 1.31); but no association was observed for macrovascular complications (HR 1.05; 95\% CI 0.81, 1.36). Effect modification was not evident by sex, smoking status, or age groups. In analyses according to BMI change categories, BMI loss of more than 1\% indicated a decreased risk of total microvascular complications (HR 0.62; 95\% CI 0.47, 0.80), kidney disease (HR 0.57; 95\% CI 0.40, 0.81) and neuropathy (HR 0.73; 95\% CI 0.52, 1.03), compared with participants with a stable BMI. No clear association was observed for macrovascular complications (HR 1.04; 95\% CI 0.62, 1.74). The impact of BMI gain on diabetes-related vascular disease was less evident. Associations were consistent across strata of age, sex, pre-diagnosis BMI, or medication but appeared stronger among never-smokers than current or former smokers. The last objective was to evaluate whether individuals with a high-risk profile for diabetes and cardiovascular disease (CVD) also have a greater risk of complications. Within the EPIC-Potsdam study, two accurate prognostic tools were developed, the German Diabetes Risk Score (GDRS) and the CVD Risk Score (CVDRS), which predict the 5-year type 2 diabetes risk and 10-year CVD risk, respectively. Both scores provide a non-clinical and clinical version. Components of the risk scores include age, sex, waist circumference, prevalence of hypertension, family history of diabetes or CVD, lifestyle factors, and clinical factors (only in clinical versions). The association of the risk scores with diabetes complications and their discriminatory performance for complications were assessed. In crude Cox models, both versions of GDRS and CVDRS were positively associated with macrovascular complications and total microvascular complications, kidney disease and neuropathy. Higher GDRS was also associated with an elevated risk of retinopathy. The discrimination of the scores (clinical and non-clinical) was poor for all complications, with the C-index ranging from 0.58 to 0.66 for macrovascular complications and from 0.60 to 0.62 for microvascular complications. In conclusion, this work illustrates that the risk of complication development among individuals with type 2 diabetes is related to the existing complication load, and attention should be given to regular monitoring for future complications. It underlines the importance of weight management and adherence to healthy lifestyle behaviours, including high intake of whole grains, moderation in red meat and alcohol consumption and avoidance of smoking to prevent major diabetes-associated complications, regardless of complication burden. Risk scores predictive for type 2 diabetes and CVD were related to elevated risks of complications. By optimising several lifestyle and clinical factors, the risk score can be improved and may assist in lowering complication risk.},
  language  = {en}
}
@misc{IgualGilOstKaschetal.2019,
  author    = {Igual Gil, Carla and Ost, Mario and Kasch, Juliane and Schumann, Sara and Heider, Sarah and Klaus, Susanne},
  title     = {Role of GDF15 in active lifestyle induced metabolic adaptations and acute exercise response in mice},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1090},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-46054},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460541},
  pages     = {11},
  year      = {2019},
  abstract  = {Physical activity is an important contributor to muscle adaptation and metabolic health. Growth differentiation factor 15 (GDF15) is established as cellular and nutritional stress-induced cytokine but its physiological role in response to active lifestyle or acute exercise is unknown. Here, we investigated the metabolic phenotype and circulating GDF15 levels in lean and obese male C57BI/6J mice with long-term voluntary wheel running (VWR) intervention. Additionally, treadmill running capacity and exercise-induced muscle gene expression was examined in GDF15-ablated mice. Active lifestyle mimic via VWR improved treadmill running performance and, in obese mice, also metabolic phenotype. The post-exercise induction of skeletal muscle transcriptional stress markers was reduced by VWR. Skeletal muscle GDF15 gene expression was very low and only transiently increased post-exercise in sedentary but not in active mice. Plasma GDF15 levels were only marginally affected by chronic or acute exercise. In obese mice, VWR reduced GDF15 gene expression in different tissues but did not reverse elevated plasma GDF15. Genetic ablation of GDF15 had no effect on exercise performance but augmented the post exercise expression of transcriptional exercise stress markers (Atf3, Atf6, and Xbp1s) in skeletal muscle. We conclude that skeletal muscle does not contribute to circulating GDF15 in mice, but muscle GDF15 might play a protective role in the exercise stress response.},
  language  = {en}
}
@misc{WeiskirchenWeiperTolbaetal.2020,
  author    = {Weiskirchen, Sabine and Weiper, Katharina and Tolba, Ren{\´e} H. and Weiskirchen, Ralf},
  title     = {All you can feed},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1066},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-47246},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-472460},
  pages     = {42},
  year      = {2020},
  abstract  = {The laboratory mouse is the most common used mammalian research model in biomedical research. Usually these animals are maintained in germ-free, gnotobiotic, or specific-pathogen-free facilities. In these facilities, skilled staff takes care of the animals and scientists usually don't pay much attention about the formulation and quality of diets the animals receive during normal breeding and keeping. However, mice have specific nutritional requirements that must be met to guarantee their potential to grow, reproduce and to respond to pathogens or diverse environmental stress situations evoked by handling and experimental interventions. Nowadays, mouse diets for research purposes are commercially manufactured in an industrial process, in which the safety of food products is addressed through the analysis and control of all biological and chemical materials used for the different diet formulations. Similar to human food, mouse diets must be prepared under good sanitary conditions and truthfully labeled to provide information of all ingredients. This is mandatory to guarantee reproducibility of animal studies. In this review, we summarize some information on mice research diets and general aspects of mouse nutrition including nutrient requirements of mice, leading manufacturers of diets, origin of nutrient compounds, and processing of feedstuffs for mice including dietary coloring, autoclaving and irradiation. Furthermore, we provide some critical views on the potential pitfalls that might result from faulty comparisons of grain-based diets with purified diets in the research data production resulting from confounding nutritional factors.},
  language  = {en}
}
@misc{DietrichJacobsZhengetal.2019,
  author    = {Dietrich, Stefan and Jacobs, Simone and Zheng, Ju-Sheng and Meidtner, Karina and Schwingshackl, Lukas and Schulze, Matthias Bernd},
  title     = {Gene-lifestyle interaction on risk of type 2 diabetes},
  series = {Obesity reviews : an official journal of the International Association for the Study of Obesity},
  volume    = {20},
  journal   = {Obesity reviews : an official journal of the International Association for the Study of Obesity},
  number    = {11},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1467-7881},
  doi       = {10.1111/obr.12921},
  pages     = {1557 -- 1571},
  year      = {2019},
  abstract  = {The pathophysiological influence of gene-lifestyle interactions on the risk to develop type 2 diabetes (T2D) is currently under intensive research. This systematic review summarizes the evidence for gene-lifestyle interactions regarding T2D incidence. MEDLINE, EMBASE, and Web of Science were systematically searched until 31 January 2019 to identify publication with (a) prospective study design; (b) T2D incidence; (c) gene-diet, gene-physical activity, and gene-weight loss intervention interaction; and (d) population who are healthy or prediabetic. Of 66 eligible publications, 28 reported significant interactions. A variety of different genetic variants and dietary factors were studied. Variants at TCF7L2 were most frequently investigated and showed interactions with fiber and whole grain on T2D incidence. Further gene-diet interactions were reported for, eg, a western dietary pattern with a T2D-GRS, fat and carbohydrate with IRS1 rs2943641, and heme iron with variants of HFE. Physical activity showed interaction with HNF1B, IRS1, PPAR gamma, ADRA2B, SLC2A2, and ABCC8 variants and weight loss interventions with ENPP1, PPAR gamma, ADIPOR2, ADRA2B, TNF alpha, and LIPC variants. However, most findings represent single study findings obtained in European ethnicities. Although some interactions have been reported, their conclusiveness is still low, as most findings were not yet replicated across multiple study populations.},
  language  = {en}
}
@article{GarciaRailaKoebnicketal.2006,
  author    = {Garcia, Ada Lizbeth and Raila, Jens and Koebnick, Corinna and Eulenberger, Klaus and Schweigert, Florian J.},
  title     = {Great apes show highly selective plasma carotenoids and have physiologically high plasma retinyl esters compared to humans},
  series = {American journal of physical anthropology},
  volume    = {131},
  journal   = {American journal of physical anthropology},
  number    = {2},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {0002-9483},
  doi       = {10.1002/ajpa.20428},
  pages     = {236 -- 242},
  year      = {2006},
  abstract  = {Great apes are the closest living relatives of humans. Physiological similarities between great apes and humans provide clues to identify which biological features in humans are primitive or derived from great apes. Vitamin A (VA) and carotenoid metabolism have been only partially studied in great apes, and comparisons between great apes and humans are not available. We aimed to investigate VA and carotenoid intake and plasma concentrations in great apes living in captivity, and to compare them to healthy humans. Dietary intakes of humans (n = 20) and, among the great apes, chimpanzees (n = 15) and orangutans (n = 5) were calculated. Plasma retinol (ROH), retinol-binding protein (RBP), retinyl esters, and major carotenoids were analyzed. The great ape diet was higher in VA than in humans, due to high intake of provitamin A carotenoids. Plasma ROH concentrations in great apes were similar to those in humans, but retinyl esters were higher in great apes than in humans. Differences in plasma carotenoid concentrations were observed between great apes and humans. Lutein was the main carotenoid in great apes, while P-carotene was the main carotenoid for humans. RBP concentrations did not differ between great apes and humans. The molar ratio of ROH to RBP was close to 1.0 in both great apes and humans. In conclusion, great apes show homeostatic ROH regulation, with high but physiological retinyl esters circulating in plasma. Furthermore, great apes show great selectivity in their plasmatic carotenoid concentration, which is not explained by dietary intake.},
  language  = {en}
}
@misc{BaylisKowalskiVoigtetal.2016,
  author    = {Baylis, Alastair M. M. and Kowalski, Gabriele Joanna and Voigt, Christian C. and Orben, Rachael A. and Trillmich, Fritz and Staniland, Iain J. and Hoffman, Joseph I.},
  title     = {Pup vibrissae stable isotopes reveal geographic differences in adult female southern sea lion habitat use during gestation},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {546},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-41184},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-411842},
  pages     = {11},
  year      = {2016},
  abstract  = {Individuals within populations often differ substantially in habitat use, the ecological consequences of which can be far reaching. Stable isotope analysis provides a convenient and often cost effective means of indirectly assessing the habitat use of individuals that can yield valuable insights into the spatiotemporal distribution of foraging specialisations within a population. Here we use the stable isotope ratios of southern sea lion (Otaria flavescens) pup vibrissae at the Falkland Islands, in the South Atlantic, as a proxy for adult female habitat use during gestation. A previous study found that adult females from one breeding colony (Big Shag Island) foraged in two discrete habitats, inshore (coastal) or offshore (outer Patagonian Shelf). However, as this species breeds at over 70 sites around the Falkland Islands, it is unclear if this pattern is representative of the Falkland Islands as a whole. In order to characterize habitat use, we therefore assayed carbon (delta C-13) and nitrogen (delta N-15) ratios from 65 southern sea lion pup vibrissae, sampled across 19 breeding colonies at the Falkland Islands. Model-based clustering of pup isotope ratios identified three distinct clusters, representing adult females that foraged inshore, offshore, and a cluster best described as intermediate. A significant difference was found in the use of inshore and offshore habitats between West and East Falkland and between the two colonies with the largest sample sizes, both of which are located in East Falkland. However, habitat use was unrelated to the proximity of breeding colonies to the Patagonian Shelf, a region associated with enhanced biological productivity. Our study thus points towards other factors, such as local oceanography and its influence on resource distribution, playing a prominent role in inshore and offshore habitat use.},
  language  = {en}
}
@misc{WotingBlaut2016,
  author    = {Woting, Anni and Blaut, Michael},
  title     = {The intestinal microbiota in metabolic disease},
  series = {Nutrients},
  journal   = {Nutrients},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407687},
  pages     = {19},
  year      = {2016},
  abstract  = {Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions.},
  language  = {en}
}
@phdthesis{Hudjetz2013,
  author    = {Hudjetz, Annekatrin},
  title     = {Modelllernen im Ern{\"a}hrungskontext : m{\"u}tterlicher und v{\"a}terlicher Einfluss auf die Ern{\"a}hrung adip{\"o}ser Kinder},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-72336},
  school      = {Universit{\"a}t Potsdam},
  year      = {2013},
  abstract  = {Adipositas ist eine chronische Erkrankung mit erheblichen Komorbidit{\"a}ten und Folgesch{\"a}den, die bereits im Kindes- und Jugendalter weit verbreitet ist. Unterschiedliche Faktoren sind an der {\"A}tiologie dieser St{\"o}rung beteiligt. Die Ern{\"a}hrung stellt dabei eine der Haupts{\"a}ulen dar, auf welche immer wieder Bezug genommen wird. Der Einfluss der Eltern auf die kindliche Ern{\"a}hrung spielt unbestritten eine zentrale Rolle - hinsichtlich genetischer Dispositionen, aber auch als Gestalter der Lebensumwelten und Vorbilder im Ern{\"a}hrungsbereich. Die vorliegende Arbeit hat zum Ziel, {\"U}bereinstimmungen elterlicher und kindlicher Ern{\"a}hrung zu untersuchen und dabei zu pr{\"u}fen, inwiefern Prozesse des Modelllernens f{\"u}r die Zusammenh{\"a}nge verantwortlich zeichnen. Grundlage ist die sozial-kognitive Theorie Albert Banduras mit dem Fokus auf seinen Ausf{\"u}hrungen zum Beobachtungs- oder Modelllernen. Die Zusammenh{\"a}nge elterlicher und kindlicher Ern{\"a}hrung wurden anhand einer Stichprobe 7 - 13-j{\"a}hriger adip{\"o}ser Kinder und ihrer Eltern in Beziehung gesetzt zu den Bedingungen des Modelllernens, die zuvor auch in anderen Studien gefunden worden waren. Eine hohe {\"A}hnlichkeit oder gute Beziehung zwischen Modell (Mutter bzw. Vater) und Lernendem (Kind) sollte demnach moderierend auf die St{\"a}rke des Zusammenhangs wirken. Aus Banduras Ausf{\"u}hrungen zu den Phasen des Modelllernens ergibt sich zudem ein dritter Aspekt, der in das Untersuchungsmodell einbezogen wurde. Die von Bandura postulierte Aneignungsphase setzt voraus, dass das zu lernende Verhalten auch beobachtet werden kann. Aus diesem Grund sollte die Analyse von Zusammenh{\"a}ngen im Verhalten nicht losgel{\"o}st von der Zeit betrachtet werden, die Modell und Beobachter miteinander verbringen bzw. verbracht haben. Zudem wurde die Wahrnehmung eines Elternteils als Vorbild beim Kind erfragt und als Moderator aufgenommen. In die Analysen eingeschlossen wurden vollst{\"a}ndige Mutter-Vater-Kind-Triaden. Im Querschnitt der Fragebogenerhebung waren die Daten von 171 M{\"a}dchen und 176 Jungen, in einem 7 Monate darauf folgenden L{\"a}ngsschnitt insgesamt 75 Triaden (davon 38 M{\"a}dchen) enthalten. Es zeigte sich ein positiver Zusammenhang zwischen der kindlichen und m{\"u}tterlichen Ern{\"a}hrung ebenso wie zwischen der kindlichen und v{\"a}terlichen Ern{\"a}hrung. Die {\"U}bereinstimmungen zwischen Mutter und Kind waren gr{\"o}ßer als zwischen Vater und Kind. {\"U}berwiegend best{\"a}tigt werden konnten der moderierende Einfluss der Beziehungsqualit{\"a}t und der Vorbildwahrnehmung auf die Zusammenh{\"a}nge elterlicher und kindlicher gesunder Ern{\"a}hrung und der Einfluss gemeinsam verbrachter Zeit vor allem in Bezug auf Vater-Kind-Zusammenh{\"a}nge problematischer Ern{\"a}hrung. Der v{\"a}terliche Einfluss, der sowohl in Studien als auch in pr{\"a}ventiven oder therapeutischen Angeboten oft noch vernachl{\"a}ssigt wird und in vorliegender Arbeit besondere bzw. gleichberechtigte Beachtung fand, zeigte sich durch den Einbezug moderierender Variablen verst{\"a}rkt. Eine Ansprache von M{\"u}ttern und V{\"a}tern gleichermaßen ist somit unbedingtes Ziel bei der Pr{\"a}vention und Therapie kindlicher Adipositas. Auch jenseits des Adipositaskontextes sollten Eltern f{\"u}r die Bedeutung elterlicher Vorbildwirkung sensibilisiert werden, um eine gesunde Ern{\"a}hrungsweise ihrer Kinder zu f{\"o}rdern.},
  language  = {de}
}