Einfluss einer Ernährungsintervention auf das Auftreten von Mikrokernen bei Insulinpflichtigen Typ II Diabetikern

Die Diabetes-Inzidenz steigt weltweit rapide an und durch multivariante Auslöser und diverse Folgeerkrankungen der Stoffwechselkrankheit stellt Diabetes Mellitus (DM) eine der größten Herausforderungen für die Gesundheitssysteme dar. DM kommt zu ca. 90% als Typ 2 Diabetes (DMT2) vor. Durch eine erhöhte Anfälligkeit auf oxidative DNA-Schäden ist auch das Krebsrisiko bei Diabetikern erhöht. Diese Arbeit versteht sich als ein Teil der DIAPLANT-Studie, welche den Einfluss gesunder Ernährung auf unterschiedliche metabolische Werte bei Patienten mit Typ 2 Diabetes (DMT2) untersucht. Der Schwerpunkt dieser Arbeit ist die Bewertung der Ernährungsintervention auf zellulärer Ebene anhand der Parameter des Cytokinesis Block Micronucleus Assay (CBMN-Assay) (Apoptosen, Necrosen, Micronuclei (MNi), Nucleplasmic Bridges (NPBs) und Nucleoplasmic Buds (NBUDs)) in den Lymphozyten. Die Studienpopulation wurde in unterschiedliche Gesundheitsgruppen (insulinpflichtige DMT2 (IDDM) (N = 41), nicht insulinpflichtige DMT2 (NIDDM) (N = 35), GESUND (N = 11) und Patienten mit gestörter Nüchternglucose (IFG) (N = 12)) eingeteilt. In dieser Arbeit wird die Gruppe der IDDM mit den anderen Gesundheitsgruppen verglichen. Der CBMN-Assay hat sich zu einer zuverlässigen Methode entwickelt, um DNA-Schäden und somit die Wahrscheinlichkeit einer Krebsentstehung zu bewerten. Ein erhöhtes Vorkommen an MNi ist unterschiedlichen Studien zufolge mit einem erhöhten Krebsrisiko assoziiert. Unterschiedliche Studien berichteten bereits von einer krebspräventiven Wirkung gesunder Ernährung. Einige Studien konnten DNA-stabilisierende Effekte nach der Einnahme von Folsäure und Vitamin B12 und antioxidativen Viatminen wie Vitamin E feststellen. Unter diesem Aspekt erhielt die Interventionsgruppe unserer Studie eine Ernährungsintervention aus 300 g Gemüse und 25 g Pflanzenöl. Beide mussten täglich über einen Zeitraum von 8 Wochen verzehrt werden. Am Anfang, am Ende der Intervention, nach 8 Wochen sowie nach 16 Wochen wurde die Studienpopulation auf die CBMN-Parameter und diverse Einflussfaktoren untersucht und die Interventionsgruppe mit der Informationsgruppe, die keine Lebensmittel erhielt, verglichen. Die Mikrokernhäufigkeit wurde durch die Ernährungsintervention nicht signifikant beeinflusst (MNi Interventionsgruppe alle Gesundheitsgruppen T0: 24,62 ± 10,28, T2: 25,93 ± 12,23, T3: 26,52 ± 11,02; IDDM T0: 26,55 ± 7,41, T2: 29,34 ± 11,47, T3: 28,77 ± 8,53), was auch den Erwartungen entspricht, da sich auch die Einflussfaktoren nicht signifikant geändert haben. Am deutlichsten zeigten sich die der Literatur entsprechenden Unterschiede der Geschlechter. Bei den Frauen war eine signifikant höhere MN-Frequenz zu erkennen als bei den Männern, welche jedoch mehr Apoptosen und Necrosen als die Frauen zeigten. Die Gruppe der IDDM zeigte keinen signifikanten Unterschied zu den Gesundheitsgruppen, was bedeutet, dass die Gemüse- und Ölintervention keinen Einfluss auf die Entstehung von MNi bei insulinpflichtigen DMT2 hat. Schlussendlich sind noch einige Studien auf diesem Gebiet nötig, da viele Fragen wie z.B. die nach den genauen Wirkmechanismen der MN-Entstehung und des Zellschutzes durch Mikronährstoffe bisweilen ungeklärt sind.The incidence of diabetes is rising rapidly worldwide and by multivariate trigger and various metabolic complications is Diabetes Mellitus (DM) a major challenge for the health systems. DM occurs in about 90% as Type 2 Diabetes (DMT2). By an increased susceptibility to oxidative DNA damage, cancer risk in diabetics is also increased. This work is one part of the DIAPLANT study, which examined the impact of a healthy diet with different metabolic biomarkers in Type 2 Diabetics (DMT2). The focus of this study is to assess the effects of a nutritional intervention at cellular level on the basis of the parameters of cytokinesis block micronucleus assay (CBMN assay) (apoptosis, necrosis, micronuclei (MNi), nucleoplasmic bridges (NPBs) and nucleoplasmic buds (NBUDs)) in lymphocytes. The study population was divided into different health groups (insulin dependent DMT2 (IDDM) (N = 41), non insulin dependent DMT2 (NIDDM) (N = 35), healthy (N = 11) and patients with an impaired fasting glucose (IFG) (N = 12)). In this work, the group of IDDM was compared to the other health groups. The CBMN assay has become a comprehensive method to assess DNA damage and thus to predict the likelihood of cancer. Different studies have already shown that a higher incidence of MNi is associated with an increased risk of cancer. Further cancer-preventive effects of healthy nutrition are evident. Some studies could show DNA-stabilizing effects after consumption of folic acid, vitamin B12 and antioxidant vitamins like vitamin E. Within this aspect, the intervention group of our study received a dietary intervention with 300 g of vegetables and 25 g of vegetable oil. At baseline and after the intervention of 8 weeks as well as after totally 16 weeks the study population was assessed for CBMN parameters and various confounding factors. The intervention group was compared with the information group which received no food-intervention. The MNi-frequency was not significantly affected by dietary intervention (MNi intervention group, all health groups T0: 24,62 ± 10,28, T2: 25,93 ± 12,23, T3: 26,52 ± 11,02; IDDM T0: 26,55 ± 7,41, T2: 29,34 ± 11,47, T3: 28,77 ± 8,53), which meets the expectations, since the other influencing factors showed no significant change. The results demonstrated most clearly the differences between the sexes, which is known from literature. Women had a higher MN-frequency than men, however, men showed more apoptotic and necrotic cells than women. The IDDM-group showed no significant difference to the healthy groups, which means that the treatment with vegetables and the oil has no influence on the development of MNi in insulin dependent DMT2. However, in order to draw final conclusions, more studies are needed in this area, as many open questions remain such as the mechanisms of MN-formation or cell protection by micronutrients

Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology

Gould E, Fraser H, Parker T, et al. Same data, different analysts: variation in effect sizes due to analytical decisions in ecology and evolutionary biology. 2023.Although variation in effect sizes and predicted values among studies of similar phenomena is inevitable, such variation far exceeds what might be produced by sampling error alone. One possible explanation for variation among results is differences among researchers in the decisions they make regarding statistical analyses. A growing array of studies has explored this analytical variability in different (mostly social science) fields, and has found substantial variability among results, despite analysts having the same data and research question. We implemented an analogous study in ecology and evolutionary biology, fields in which there have been no empirical exploration of the variation in effect sizes or model predictions generated by the analytical decisions of different researchers. We used two unpublished datasets, one from evolutionary ecology (blue tit, Cyanistes caeruleus, to compare sibling number and nestling growth) and one from conservation ecology (Eucalyptus, to compare grass cover and tree seedling recruitment), and the project leaders recruited 174 analyst teams, comprising 246 analysts, to investigate the answers to prespecified research questions. Analyses conducted by these teams yielded 141 usable effects for the blue tit dataset, and 85 usable effects for the Eucalyptus dataset. We found substantial heterogeneity among results for both datasets, although the patterns of variation differed between them. For the blue tit analyses, the average effect was convincingly negative, with less growth for nestlings living with more siblings, but there was near continuous variation in effect size from large negative effects to effects near zero, and even effects crossing the traditional threshold of statistical significance in the opposite direction. In contrast, the average relationship between grass cover and Eucalyptus seedling number was only slightly negative and not convincingly different from zero, and most effects ranged from weakly negative to weakly positive, with about a third of effects crossing the traditional threshold of significance in one direction or the other. However, there were also several striking outliers in the Eucalyptus dataset, with effects far from zero. For both datasets, we found substantial variation in the variable selection and random effects structures among analyses, as well as in the ratings of the analytical methods by peer reviewers, but we found no strong relationship between any of these and deviation from the meta-analytic mean. In other words, analyses with results that were far from the mean were no more or less likely to have dissimilar variable sets, use random effects in their models, or receive poor peer reviews than those analyses that found results that were close to the mean. The existence of substantial variability among analysis outcomes raises important questions about how ecologists and evolutionary biologists should interpret published results, and how they should conduct analyses in the future