@article{DanquahDobruckyFranketal.2015, author = {Danquah, Ina and Dobrucky, C. Lydia and Frank, Laura K. and Henze, Andrea and Amoako, Yaw A. and Bedu-Addo, George and Raila, Jens and Schulze, Matthias Bernd and Mockenhaupt, Frank P. and Schweigert, Florian J.}, title = {Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana}, series = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, volume = {102}, journal = {The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.}, number = {1}, publisher = {American Society for Nutrition, Inc.}, address = {Bethesda}, issn = {0002-9165}, doi = {10.3945/ajcn.114.101345}, pages = {207 -- 214}, year = {2015}, abstract = {Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension. Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard. Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol. Results: VAD (retinol <1.05 mu mol/L) was present in 10\% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95\% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72\%) and prealbumin (22\%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30\%; urinary albumin: 5\%) but not to inflammation. Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.}, language = {en} } @article{ChristakoudiTsilidisMulleretal.2020, author = {Christakoudi, Sofa and Tsilidis, Konstantinos K. and Muller, David C. and Freisling, Heinz and Weiderpass, Elisabete and Overvad, Kim and S{\"o}derberg, Stefan and H{\"a}ggstr{\"o}m, Christel and Pischon, Tobias and Dahm, Christina C. and Zhang, Jie and Tj{\o}nneland, Anne and Schulze, Matthias Bernd}, title = {A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, number = {1}, publisher = {Springer Nature}, address = {Berlin}, pages = {15}, year = {2020}, abstract = {Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39\% of the individuals within each BMI category, which had 22-55\% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.}, language = {en} } @article{MuehlenbruchKuxhausPencinaetal.2015, author = {M{\"u}hlenbruch, Kristin and Kuxhaus, Olga and Pencina, Michael J. and Boeing, Heiner and Liero, Hannelore and Schulze, Matthias Bernd}, title = {A confidence ellipse for the Net Reclassification Improvement}, series = {European journal of epidemiology}, volume = {30}, journal = {European journal of epidemiology}, number = {4}, publisher = {Springer}, address = {Dordrecht}, issn = {0393-2990}, doi = {10.1007/s10654-015-0001-1}, pages = {299 -- 304}, year = {2015}, abstract = {The Net Reclassification Improvement (NRI) has become a popular metric for evaluating improvement in disease prediction models through the past years. The concept is relatively straightforward but usage and interpretation has been different across studies. While no thresholds exist for evaluating the degree of improvement, many studies have relied solely on the significance of the NRI estimate. However, recent studies recommend that statistical testing with the NRI should be avoided. We propose using confidence ellipses around the estimated values of event and non-event NRIs which might provide the best measure of variability around the point estimates. Our developments are illustrated using practical examples from EPIC-Potsdam study.}, language = {en} } @article{MenzelLongreeAbrahametal.2022, author = {Menzel, Juliane and Longree, Alessa and Abraham, Klaus and Schulze, Matthias Bernd and Weikert, Cornelia}, title = {Dietary and plasma phospholipid profiles in vegans and omnivores-results from the RBVD study}, series = {Nutrients}, volume = {14}, journal = {Nutrients}, number = {14}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu14142900}, pages = {13}, year = {2022}, abstract = {Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional "Risks and Benefits of a Vegan Diet" (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64-111) in comparison to omnivores (median 104 g/day, IQR 88-143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.}, language = {en} } @misc{PerezCornagoCroweApplebyetal.2021, author = {Perez-Cornago, Aurora and Crowe, Francesca L. and Appleby, Paul N. and Bradbury, Kathryn E. and Wood, Angela M. and Jakobsen, Marianne Uhre and Johnson, Laura and Sacerdote, Carlotta and Steur, Marinka and Weiderpass, Elisabete and Wurtz, Anne Mette L. and Kuhn, Tilman and Katzke, Verena and Trichopoulou, Antonia and Karakatsani, Anna and La Vecchia, Carlo and Masala, Giovanna and Tumino, Rosario and Panico, Salvatore and Sluijs, Ivonne and Skeie, Guri and Imaz, Liher and Petrova, Dafina and Quiros, J. Ramon and Yohar, Sandra Milena Colorado and Jakszyn, Paula and Melander, Olle and Sonestedt, Emily and Andersson, Jonas and Wennberg, Maria and Aune, Dagfinn and Riboli, Elio and Schulze, Matthias Bernd and di Angelantonio, Emanuele and Wareham, Nicholas J. and Danesh, John and Forouhi, Nita G. and Butterworth, Adam S. and Key, Timothy J.}, title = {Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1}, issn = {1866-8372}, doi = {10.25932/publishup-56034}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-560340}, pages = {13}, year = {2021}, abstract = {Background: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. Results: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95\% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. Conclusions: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.}, language = {en} } @article{SchibornSchulze2022, author = {Schiborn, Catarina and Schulze, Matthias Bernd}, title = {Precision prognostics for the development of complications in diabetes}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-022-05731-4}, pages = {16}, year = {2022}, abstract = {Individuals with diabetes face higher risks for macro- and microvascular complications than their non-diabetic counterparts. The concept of precision medicine in diabetes aims to optimise treatment decisions for individual patients to reduce the risk of major diabetic complications, including cardiovascular outcomes, retinopathy, nephropathy, neuropathy and overall mortality. In this context, prognostic models can be used to estimate an individual's risk for relevant complications based on individual risk profiles. This review aims to place the concept of prediction modelling into the context of precision prognostics. As opposed to identification of diabetes subsets, the development of prediction models, including the selection of predictors based on their longitudinal association with the outcome of interest and their discriminatory ability, allows estimation of an individual's absolute risk of complications. As a consequence, such models provide information about potential patient subgroups and their treatment needs. This review provides insight into the methodological issues specifically related to the development and validation of prediction models for diabetes complications. We summarise existing prediction models for macro- and microvascular complications, commonly included predictors, and examples of available validation studies. The review also discusses the potential of non-classical risk markers and omics-based predictors. Finally, it gives insight into the requirements and challenges related to the clinical applications and implementation of developed predictions models to optimise medical decision making.}, language = {en} } @misc{Schulze2018, author = {Schulze, Matthias Bernd}, title = {Metabolic health in normal-weight and obese individuals}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {62}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {4}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-018-4787-8}, pages = {558 -- 566}, year = {2018}, abstract = {Cardiovascular complications are commonly associated with obesity. However, a subgroup of obese individuals may not be at an increased risk for cardiovascular complications; these individuals are said to have metabolically healthy obesity (MHO). In contrast, metabolically unhealthy individuals are at high risk of cardiovascular disease (CVD), irrespective of BMI; thus, this group can include individuals within the normal weight category (BMI 18.5-24.9kg/m(2)). This review provides a summary of prospective studies on MHO and metabolically unhealthy normal-weight (MUHNW) phenotypes. Notably, there is ongoing dispute surrounding the concept of MHO, including the lack of a uniform definition and the potentially transient nature of metabolic health status. This review highlights the relevance of alternative measures of body fatness, specifically measures of fat distribution, for determining MHO and MUHNW. It also highlights alternative approaches of risk stratification, which account for the continuum of risk in relation to CVD, which is observable for most risk factors. Moreover, studies evaluating the transition from metabolically healthy to unhealthy phenotypes and potential determinants for such conversions are discussed. Finally, the review proposes several strategies for the use of epidemiological research to further inform the current debate on metabolic health and its determination across different stages of body fatness.}, language = {en} } @article{WittenbecherKuxhausBoeingetal.2019, author = {Wittenbecher, Clemens and Kuxhaus, Olga and Boeing, Heiner and Stefan, Norbert and Schulze, Matthias Bernd}, title = {Associations of short stature and components of height with incidence of type 2 diabetes}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {62}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, number = {12}, publisher = {Springer}, address = {New York}, issn = {0012-186X}, doi = {10.1007/s00125-019-04978-8}, pages = {2211 -- 2221}, year = {2019}, abstract = {Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95\% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile.}, 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{EckelLiKuxhausetal.2018, author = {Eckel, Nathalie and Li, Yanping and Kuxhaus, Olga and Stefan, Norbert and Hu, Frank B. and Schulze, Matthias Bernd}, title = {Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study)}, series = {The lancet diabetes \& endocrinology}, volume = {6}, journal = {The lancet diabetes \& endocrinology}, number = {9}, publisher = {Elsevier}, address = {New York}, issn = {2213-8587}, doi = {10.1016/S2213-8587(18)30137-2}, pages = {714 -- 724}, year = {2018}, abstract = {Background Cardiovascular disease risk among individuals across different categories of BMI might depend on their metabolic health. It remains unclear to what extent metabolic health status changes over time and whether this affects cardiovascular disease risk. In this study, we aimed to examine the association between metabolic health and its change over time and cardiovascular disease risk across BMI categories. Findings During 2 127 391 person-years of follow-up with a median follow-up of 24 years, we documented 6306 cases of cardiovascular disease including 3304 myocardial infarction cases and 3080 strokes. Cardiovascular disease risk of women with metabolically healthy obesity was increased compared with women with metabolically healthy normal weight (HR 1.39, 95\% CI 1.15-1.68), but risk was considerably higher in women with metabolically unhealthy normal weight (2.43, 2.19-2.68), overweight (2.61, 2.36-2.89) and obesity (3.15, 2.83-3.50). The majority of metabolically healthy women converted to unhealthy phenotypes (2555 [84\%] of 3027 women with obesity, 22 215 [68\%] of 32 882 women with normal-weight after 20 years). Women who maintained metabolically healthy obesity during follow-up were still at a higher cardiovascular disease risk compared with women with stable healthy normal weight (HR 1.57, 1.03-2.38), yet this risk was lower than for initially metabolically healthy women who converted to an unhealthy phenotype (normal-weight 1.90, 1.66-2.17 vs obesity 2.74, 2.30-3.27). Particularly incident diabetes and hypertension increased the risk among women with initial metabolic health. Interpretation Even when metabolic health is maintained during long periods of time, obesity remains a risk factor for cardiovascular disease. However, risks are highest for metabolically unhealthy women across all BMI categories. A large proportion of metabolically healthy women converted to an unhealthy phenotype over time across all BMI categories, which is associated with an increased cardiovascular disease risk. Copyright (C) 2018 Elsevier Ltd. All rights reserved.}, language = {en} } @misc{GalbeteSchwingshacklSchwedhelmetal.2018, author = {Galbete, Cecilia and Schwingshackl, Lukas and Schwedhelm, Carolina and Boeing, Heiner and Schulze, Matthias Bernd}, title = {Evaluating Mediterranean diet and risk of chronic disease in cohort studies}, series = {European journal of epidemiology}, volume = {33}, journal = {European journal of epidemiology}, number = {10}, publisher = {Springer}, address = {Dordrecht}, issn = {0393-2990}, doi = {10.1007/s10654-018-0427-3}, pages = {909 -- 931}, year = {2018}, abstract = {Several meta-analyses have been published summarizing the associations of the Mediterranean diet (MedDiet) with chronic diseases. We evaluated the quality and credibility of evidence from these meta-analyses as well as characterized the different indices used to define MedDiet and re-calculated the associations with the different indices identified. We conducted an umbrella review of meta-analyses on cohort studies evaluating the association of the MedDiet with type 2 diabetes, cardiovascular disease, cancer and cognitive-related diseases. We used the AMSTAR (A MeaSurement Tool to Assess systematic Reviews) checklist to evaluate the methodological quality of the meta-analyses, and the NutriGrade scoring system to evaluate the credibility of evidence. We also identified different indices used to define MedDiet; tests for subgroup differences were performed to compare the associations with the different indices when at least 2 studies were available for different definitions. Fourteen publications were identified and within them 27 meta-analyses which were based on 70 primary studies. Almost all meta-analyses reported inverse associations between MedDiet and risk of chronic disease, but the credibility of evidence was rated low to moderate. Moreover, substantial heterogeneity was observed on the use of the indices assessing adherence to the MedDiet, but two indices were the most used ones [Trichopoulou MedDiet (tMedDiet) and alternative MedDiet (aMedDiet)]. Overall, we observed little difference in risk associations comparing different MedDiet indices in the subgroup meta-analyses. Future prospective cohort studies are advised to use more homogenous definitions of the MedDiet to improve the comparability across meta-analyses.}, language = {en} } @misc{SchulzeMartinezGonzalezFungetal.2018, author = {Schulze, Matthias Bernd and Martinez-Gonzalez, Miguel A. and Fung, Teresa T. and Lichtenstein, Alice H. and Forouhi, Nita G.}, title = {Food based dietary patterns and chronic disease prevention}, series = {BMJ-British medical journal}, volume = {361}, journal = {BMJ-British medical journal}, publisher = {BMJ Publishing Group}, address = {London}, issn = {1756-1833}, doi = {10.1136/bmj.k2396}, pages = {6}, year = {2018}, abstract = {Matthias B Schulze and colleagues discuss current knowledge on the associations between dietary patterns and cancer, coronary heart disease, stroke, and type 2 diabetes, focusing on areas of uncertainty and future research directions.}, language = {en} } @article{WeitkunatBishopWittmuessetal.2021, author = {Weitkunat, Karolin and Bishop, Christopher Allen and Wittm{\"u}ss, Maria and Machate, Tina and Schifelbein, Tina and Schulze, Matthias Bernd and Klaus, Susanne}, title = {Effect of microbial status on hepatic odd-chain fatty acids is diet-dependent}, series = {Nutrients / Molecular Diversity Preservation International (MDPI)}, volume = {13}, journal = {Nutrients / Molecular Diversity Preservation International (MDPI)}, number = {5}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu13051546}, pages = {15}, year = {2021}, abstract = {Odd-chain fatty acids (OCFA) are inversely associated with type-2-diabetes in epidemiological studies. They are considered as a biomarker for dairy intake because fermentation in ruminants yields high amounts of propionate, which is used as the primer for lipogenesis. Recently, we demonstrated endogenous OCFA synthesis from propionate in humans and mice, but how this is affected by microbial colonization is still unexplored. Here, we investigated the effect of increasing microbiota complexity on hepatic lipid metabolism and OCFA levels in different dietary settings. Germ-free (GF), gnotobiotic (SIH, simplified human microbiota) or conventional (CONV) C3H/HeOuJ-mice were fed a CHOW or high-fat diet with inulin (HFI) to induce microbial fermentation. We found that hepatic lipogenesis was increased with increasing microbiota complexity, independently of diet. In contrast, OCFA formation was affected by diet as well as microbiota. On CHOW, hepatic OCFA and intestinal gluconeogenesis decreased with increasing microbiota complexity (GF > SIH > CONV), while cecal propionate showed a negative correlation with hepatic OCFA. On HFI, OCFA levels were highest in SIH and positively correlated with cecal propionate. The propionate content in the CHOW diet was 10 times higher than that of HFI. We conclude that bacterial propionate production affects hepatic OCFA formation, unless this effect is masked by dietary propionate intake.}, language = {en} } @article{BishopSchulzeKlausetal.2020, author = {Bishop, Christopher Allen and Schulze, Matthias Bernd and Klaus, Susanne and Weitkunat, Karolin}, title = {The branched-chain amino acids valine and leucine have differential effects on hepatic lipid metabolism}, series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, volume = {34}, journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, number = {7}, publisher = {Wiley}, address = {Hoboken}, issn = {0892-6638}, doi = {10.1096/fj.202000195R}, pages = {9727 -- 9739}, year = {2020}, abstract = {Dairy intake, as a source of branched-chain amino acids (BCAA), has been linked to a lower incidence of type-2-diabetes and increased circulating odd-chain fatty acids (OCFA). To understand this connection, we aimed to investigate differences in BCAA metabolism of leucine and valine, a possible source of OCFA, and their role in hepatic metabolism. Male mice were fed a high-fat diet supplemented with leucine and valine for 1 week and phenotypically characterized with a focus on lipid metabolism. Mouse primary hepatocytes were treated with the BCAA or a Ppar alpha activator WY-14643 to systematically examine direct hepatic effects and their mechanisms. Here, we show that only valine supplementation was able to increase hepatic and circulating OCFA levels via two pathways; a PPAR alpha-dependent induction of alpha-oxidation and an increased supply of propionyl-CoA for de novo lipogenesis. Meanwhile, we were able to confirm leucine-mediated effects on the inhibition of food intake and transport of fatty acids, as well as induction of S6 ribosomal protein phosphorylation. Taken together, these data illustrate differential roles of the BCAA in lipid metabolism and provide preliminary evidence that exclusively valine contributes to the endogenous formation of OCFA which is important for a better understanding of these metabolites in metabolic health.}, language = {en} } @article{SchenkEichelmannSchulzeetal.2019, author = {Schenk, Matthew and Eichelmann, Fabian and Schulze, Matthias Bernd and Rudovich, Natalia and Pfeiffer, Andreas F. H. and di Giuseppe, Romina and B{\"o}ing, Heiner and Aleksandrova, Krasimira}, title = {Reproducibility of novel immune-inflammatory biomarkers over 4 months}, series = {Biomarkers in medicine}, volume = {13}, journal = {Biomarkers in medicine}, number = {8}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/bmm-2018-0351}, pages = {639 -- 648}, year = {2019}, abstract = {Aim: Assessment of the feasibility and reliability of immune-inflammatory biomarker measurements. Methods: The following biomarkers were assessed in 207 predominantly healthy participants at baseline and after 4 months: MMF, TGF-beta, suPAR and clusterin. Results: Intraclass correlation coefficients (95\% CIs) ranged from good for TGF-beta (0.75 [95\% CI: 0.33-0.90]) to excellent for MMF (0.81 [95\% CI: 0.64-0.90]), clusterin (0.83 [95\% CI: 0.78-0.87]) and suPAR (0.91 [95\% CI: 0.88-0.93]). Measurement of TGF-beta was challenged by the large number of values below the detection limit. Conclusion: Single measurements of suPAR, clusterin and MMF could serve as feasible and reliable biomarkers of immune-inflammatory pathways in biomedical research.}, language = {en} } @article{JannaschKroegerAgnolietal.2019, author = {Jannasch, Franziska and Kr{\"o}ger, Janine and Agnoli, Claudia and Barricarte, Aurelio and Boeing, Heiner and Cayssials, Val{\´e}rie and Colorado-Yohar, Sandra and Dahm, Christina C. and Dow, Courtney and Fagherazzi, Guy and Franks, Paul W. and Freisling, Heinz and Gunter, Marc J. and Kerrison, Nicola D. and Key, Timothy J. and Khaw, Kay-Tee and K{\"u}hn, Tilman and Kyro, Cecilie and Mancini, Francesca Romana and Mokoroa, Olatz and Nilsson, Peter and Overvad, Kim and Palli, Domenico and Panico, Salvatore and Quiros Garcia, Jose Ramon and Rolandsson, Olov and Sacerdote, Carlotta and Sanchez, Maria-Jose and Sahrai, Mohammad Sediq and Sch{\"u}bel, Ruth and Sluijs, Ivonne and Spijkerman, Annemieke M. W. and Tjonneland, Anne and Tong, Tammy Y. N. and Tumino, Rosario and Riboli, Elio and Langenberg, Claudia and Sharp, Stephen J. and Forouhi, Nita G. and Schulze, Matthias Bernd and Wareham, Nicholas J.}, title = {Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations}, series = {The Journal of Nutrition}, volume = {149}, journal = {The Journal of Nutrition}, number = {6}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0022-3166}, doi = {10.1093/jn/nxz031}, pages = {1047 -- 1055}, year = {2019}, abstract = {Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95\% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95\% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95\% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.}, language = {en} } @article{PerezCornagoCroweApplebyetal.2021, author = {Perez-Cornago, Aurora and Crowe, Francesca L. and Appleby, Paul N. and Bradbury, Kathryn E. and Wood, Angela M. and Jakobsen, Marianne Uhre and Johnson, Laura and Sacerdote, Carlotta and Steur, Marinka and Weiderpass, Elisabete and Wurtz, Anne Mette L. and Kuhn, Tilman and Katzke, Verena and Trichopoulou, Antonia and Karakatsani, Anna and La Vecchia, Carlo and Masala, Giovanna and Tumino, Rosario and Panico, Salvatore and Sluijs, Ivonne and Skeie, Guri and Imaz, Liher and Petrova, Dafina and Quiros, J. Ramon and Yohar, Sandra Milena Colorado and Jakszyn, Paula and Melander, Olle and Sonestedt, Emily and Andersson, Jonas and Wennberg, Maria and Aune, Dagfinn and Riboli, Elio and Schulze, Matthias Bernd and di Angelantonio, Emanuele and Wareham, Nicholas J. and Danesh, John and Forouhi, Nita G. and Butterworth, Adam S. and Key, Timothy J.}, title = {Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort}, series = {International journal of epidemiology}, volume = {50}, journal = {International journal of epidemiology}, number = {1}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0300-5771}, doi = {10.1093/ije/dyaa155}, pages = {212 -- 222}, year = {2021}, abstract = {Background: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD. Results: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95\% confidence interval (CI): 0.90-0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95-1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82-0.98, Ptrend = 0.020), total fibre (per 10 g/day 0.91, 0.85-0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91-0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95-1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk. Conclusions: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.}, language = {en} } @misc{ChristakoudiTsilidisMulleretal.2020, author = {Christakoudi, Sofa and Tsilidis, Konstantinos K. and Muller, David C. and Freisling, Heinz and Weiderpass, Elisabete and Overvad, Kim and S{\"o}derberg, Stefan and H{\"a}ggstr{\"o}m, Christel and Pischon, Tobias and Dahm, Christina C. and Zhang, Jie and Tj{\o}nneland, Anne and Schulze, Matthias Bernd}, title = {A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {1}, issn = {1866-8372}, doi = {10.25932/publishup-52582}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-525827}, pages = {17}, year = {2020}, abstract = {Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39\% of the individuals within each BMI category, which had 22-55\% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.}, language = {en} } @article{JannaschNickelSchulze2021, author = {Jannasch, Franziska and Nickel, Daniela and Schulze, Matthias Bernd}, title = {The reliability and relative validity of predefined dietary patterns were higher than that of exploratory dietary patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam population}, series = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society}, volume = {125}, journal = {British journal of nutrition : BJN : an international journal of nutritional science / published on behalf of The Nutrition Society}, number = {11}, publisher = {Cambridge University Press}, address = {Cambridge}, issn = {1475-2662}, doi = {10.1017/S0007114520003517}, pages = {1270 -- 1280}, year = {2021}, abstract = {The aim of this study was to assess the ability of the FFQ to describe reliable and valid dietary pattern (DP) scores. In a total of 134 participants of the European Prospective Investigation into Cancer and Nutrition-Potsdam study aged 35-67 years, the FFQ was applied twice (baseline and after 1 year) to assess its reliability. Between November 1995 and March 1997, twelve 24-h dietary recalls (24HDR) as reference instrument were applied to assess the validity of the FFQ. Exploratory DP were derived by principal component analyses. Investigated predefined DP were the Alternative Healthy Eating Index (AHEI) and two Mediterranean diet indices. From dietary data of each FFQ, two exploratory DP were retained, but differed in highly loading food groups, resulting in moderate correlations (r 0 center dot 45-0 center dot 58). The predefined indices showed higher correlations between the FFQ (r(AHEI) 0 center dot 62, r(Mediterranean Diet Pyramid Index (MedPyr)) 0 center dot 62 and r(traditional Mediterranean Diet Score (tMDS)) 0 center dot 51). From 24HDR dietary data, one exploratory DP retained differed in composition to the first FFQ-based DP, but showed similarities to the second DP, reflected by a good correlation (r 0 center dot 70). The predefined DP correlated moderately (r 0 center dot 40-0 center dot 60). To conclude, long-term analyses on exploratory DP should be interpreted with caution, due to only moderate reliability. The validity differed extensively for the two exploratory DP. The investigated predefined DP showed a better reliability and a moderate validity, comparable to other studies. Within the two Mediterranean diet indices, the MedPyr performed better than the tMDs in this middle-aged, semi-urban German study population.}, language = {en} } @article{WittenbecherOuniKuxhausetal.2019, author = {Wittenbecher, Clemens and Ouni, Meriem and Kuxhaus, Olga and J{\"a}hnert, Markus and Gottmann, Pascal and Teichmann, Andrea and Meidtner, Karina and Kriebel, Jennifer and Grallert, Harald and Pischon, Tobias and Boeing, Heiner and Schulze, Matthias Bernd and Sch{\"u}rmann, Annette}, title = {Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {68}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {1}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, doi = {10.2337/db18-0620}, pages = {188 -- 197}, year = {2019}, abstract = {Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk.}, language = {en} }