TY  - JOUR
A1  - Allan, Eric
A1  - Bossdorf, Oliver
A1  - Dormann, Carsten F.
A1  - Prati, Daniel
A1  - Gossner, Martin M.
A1  - Tscharntke, Teja
A1  - Blüthgen, Nico
A1  - Bellach, Michaela
A1  - Birkhofer, Klaus
A1  - Boch, Steffen
A1  - Böhm, Stefan
A1  - Börschig, Carmen
A1  - Chatzinotas, Antonis
A1  - Christ, Sabina
A1  - Daniel, Rolf
A1  - Diekötter, Tim
A1  - Fischer, Christiane
A1  - Friedl, Thomas
A1  - Glaser, Karin
A1  - Hallmann, Christine
A1  - Hodac, Ladislav
A1  - Hölzel, Norbert
A1  - Jung, Kirsten
A1  - Klein, Alexandra-Maria
A1  - Klaus, Valentin H.
A1  - Kleinebecker, Till
A1  - Krauss, Jochen
A1  - Lange, Markus
A1  - Morris, E. Kathryn
A1  - Müller, Jörg
A1  - Nacke, Heiko
A1  - Pasalic, Esther
A1  - Rillig, Matthias C.
A1  - Rothenwoehrer, Christoph
A1  - Schally, Peter
A1  - Scherber, Christoph
A1  - Schulze, Waltraud X.
A1  - Socher, Stephanie A.
A1  - Steckel, Juliane
A1  - Steffan-Dewenter, Ingolf
A1  - Türke, Manfred
A1  - Weiner, Christiane N.
A1  - Werner, Michael
A1  - Westphal, Catrin
A1  - Wolters, Volkmar
A1  - Wubet, Tesfaye
A1  - Gockel, Sonja
A1  - Gorke, Martin
A1  - Hemp, Andreas
A1  - Renner, Swen C.
A1  - Schöning, Ingo
A1  - Pfeiffer, Simone
A1  - König-Ries, Birgitta
A1  - Buscot, Francois
A1  - Linsenmair, Karl Eduard
A1  - Schulze, Ernst-Detlef
A1  - Weisser, Wolfgang W.
A1  - Fischer, Markus
T1  - Interannual variation in land-use intensity enhances grassland multidiversity
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
KW  - biodiversity loss
KW  - agricultural grasslands
KW  - Biodiversity Exploratories
Y1  - 2014
U6  - https://doi.org/10.1073/pnas.1312213111
SN  - 0027-8424
VL  - 111
IS  - 1
SP  - 308
EP  - 313
PB  - National Acad. of Sciences
CY  - Washington
ER  - 
TY  - JOUR
A1  - Allan, Eric
A1  - Weisser, Wolfgang W.
A1  - Fischer, Markus
A1  - Schulze, Ernst-Detlef
A1  - Weigelt, Alexandra
A1  - Roscher, Christiane
A1  - Baade, Jussi
A1  - Barnard, Romain L.
A1  - Bessler, Holger
A1  - Buchmann, Nina
A1  - Ebeling, Anne
A1  - Eisenhauer, Nico
A1  - Engels, Christof
A1  - Fergus, Alexander J. F.
A1  - Gleixner, Gerd
A1  - Gubsch, Marlen
A1  - Halle, Stefan
A1  - Klein, Alexandra-Maria
A1  - Kertscher, Ilona
A1  - Kuu, Annely
A1  - Lange, Markus
A1  - Le Roux, Xavier
A1  - Meyer, Sebastian T.
A1  - Migunova, Varvara D.
A1  - Milcu, Alexandru
A1  - Niklaus, Pascal A.
A1  - Oelmann, Yvonne
A1  - Pasalic, Esther
A1  - Petermann, Jana S.
A1  - Poly, Franck
A1  - Rottstock, Tanja
A1  - Sabais, Alexander C. W.
A1  - Scherber, Christoph
A1  - Scherer-Lorenzen, Michael
A1  - Scheu, Stefan
A1  - Steinbeiss, Sibylle
A1  - Schwichtenberg, Guido
A1  - Temperton, Vicky
A1  - Tscharntke, Teja
A1  - Voigt, Winfried
A1  - Wilcke, Wolfgang
A1  - Wirth, Christian
A1  - Schmid, Bernhard
T1  - A comparison of the strength of biodiversity effects across multiple functions
JF  - Oecologia
N2  - In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination.
KW  - Bottom-up effects
KW  - Carbon cycling
KW  - Ecological synthesis
KW  - Ecosystem processes
KW  - Grasslands
KW  - Jena experiment
KW  - Nitrogen cycling
Y1  - 2013
U6  - https://doi.org/10.1007/s00442-012-2589-0
SN  - 0029-8549
VL  - 173
IS  - 1
SP  - 223
EP  - 237
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Andres, Dorothee
A1  - Gohlke, Ulrich
A1  - Bröker, Nina Kristin
A1  - Schulze, Stefan
A1  - Rabsch, Wolfgang
A1  - Heinemann, Udo
A1  - Barbirz, Stefanie
A1  - Seckler, Robert
T1  - An essential serotype recognition pocket on phage P22 tailspike protein forces Salmonella enterica serovar Paratyphi A O-antigen fragments to bind as nonsolution conformers
JF  - Glycobiology
N2  - Bacteriophage P22 recognizes O-antigen polysaccharides of Salmonella enterica subsp. enterica (S.) with its tailspike protein (TSP). In the serovars S. Typhimurium, S. Enteritidis, and S. Paratyphi A, the tetrasaccharide repeat units of the respective O-antigens consist of an identical main chain trisaccharide but different 3,6-dideoxyhexose substituents. Here, the epimers abequose, tyvelose and paratose determine the specific serotype. P22 TSP recognizes O-antigen octasaccharides in an extended binding site with a single 3,6-dideoxyhexose binding pocket. We have isolated S. Paratyphi A octasaccharides which were not available previously and determined the crystal structure of their complex with P22 TSP. We discuss our data together with crystal structures of complexes with S. Typhimurium and S. Enteritidis octasaccharides determined earlier. Isothermal titration calorimetry showed that S. Paratyphi A octasaccharide binds P22 TSP less tightly, with a difference in binding free energy of similar to 7 kJ mol(-1) at 20 degrees C compared with S. Typhimurium and S. Enteritidis octasaccharides. Individual protein-carbohydrate contacts were probed by amino acid replacements showing that the dideoxyhexose pocket contributes to binding of all three serotypes. However, S. Paratyphi A octasaccharides bind in a conformation with an energetically unfavorable phi/epsilon glycosidic bond angle combination. In contrast, octasaccharides from the other serotypes bind as solution-like conformers. Two water molecules are conserved in all P22 TSP complexes with octasaccharides of different serotypes. They line the dideoxyhexose binding pocket and force the S. Paratyphi A octasaccharides to bind as nonsolution conformers. This emphasizes the role of solvent as part of carbohydrate binding sites.
KW  - bacterial O-antigen
KW  - carbohydrate interaction
KW  - paratose
KW  - structural thermodynamics
KW  - tailspike protein
Y1  - 2013
U6  - https://doi.org/10.1093/glycob/cws224
SN  - 0959-6658
VL  - 23
IS  - 4
SP  - 486
EP  - 494
PB  - Oxford Univ. Press
CY  - Cary
ER  - 
TY  - JOUR
A1  - Birkhofer, Klaus
A1  - Schöning, Ingo
A1  - Alt, Fabian
A1  - Herold, Nadine
A1  - Klarner, Bernhard
A1  - Maraun, Mark
A1  - Marhan, Sven
A1  - Oelmann, Yvonne
A1  - Wubet, Tesfaye
A1  - Yurkov, Andrey
A1  - Begerow, Dominik
A1  - Berner, Doreen
A1  - Buscot, Francois
A1  - Daniel, Rolf
A1  - Diekötter, Tim
A1  - Ehnes, Roswitha B.
A1  - Erdmann, Georgia
A1  - Fischer, Christiane
A1  - Fösel, Baerbel
A1  - Groh, Janine
A1  - Gutknecht, Jessica
A1  - Kandeler, Ellen
A1  - Lang, Christa
A1  - Lohaus, Gertrud
A1  - Meyer, Annabel
A1  - Nacke, Heiko
A1  - Näther, Astrid
A1  - Overmann, Jörg
A1  - Polle, Andrea
A1  - Pollierer, Melanie M.
A1  - Scheu, Stefan
A1  - Schloter, Michael
A1  - Schulze, Ernst-Detlef
A1  - Schulze, Waltraud X.
A1  - Weinert, Jan
A1  - Weisser, Wolfgang W.
A1  - Wolters, Volkmar
A1  - Schrumpf, Marion
T1  - General relationships between abiotic soil properties and soil biota across spatial scales and different land-use types
JF  - PLoS one
N2  - Very few principles have been unraveled that explain the relationship between soil properties and soil biota across large spatial scales and different land-use types. Here, we seek these general relationships using data from 52 differently managed grassland and forest soils in three study regions spanning a latitudinal gradient in Germany. We hypothesize that, after extraction of variation that is explained by location and land-use type, soil properties still explain significant proportions of variation in the abundance and diversity of soil biota. If the relationships between predictors and soil organisms were analyzed individually for each predictor group, soil properties explained the highest amount of variation in soil biota abundance and diversity, followed by land-use type and sampling location. After extraction of variation that originated from location or land-use, abiotic soil properties explained significant amounts of variation in fungal, meso-and macrofauna, but not in yeast or bacterial biomass or diversity. Nitrate or nitrogen concentration and fungal biomass were positively related, but nitrate concentration was negatively related to the abundances of Collembola and mites and to the myriapod species richness across a range of forest and grassland soils. The species richness of earthworms was positively correlated with clay content of soils independent of sample location and land-use type. Our study indicates that after accounting for heterogeneity resulting from large scale differences among sampling locations and land-use types, soil properties still explain significant proportions of variation in fungal and soil fauna abundance or diversity. However, soil biota was also related to processes that act at larger spatial scales and bacteria or soil yeasts only showed weak relationships to soil properties. We therefore argue that more general relationships between soil properties and soil biota can only be derived from future studies that consider larger spatial scales and different land-use types.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0043292
SN  - 1932-6203
VL  - 7
IS  - 8
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Birukov, Anna
A1  - Polemiti, Elli
A1  - Jaeger, Susanne
A1  - Stefan, Norbert
A1  - Schulze, Matthias Bernd
T1  - Fetuin-A and risk of diabetes-related vascular complications
BT  - a prospective study
JF  - Cardiovascular diabetology
N2  - Background
Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes.
It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. 
We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. 

Methods 
Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years).
Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. 

Results 
In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). 

Conclusions 
Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.
KW  - Fetuin-A
KW  - biomarkers
KW  - epidemiology
KW  - Type 2 diabetes
KW  - vascular disease;
KW  - vascular calcification
KW  - microvascular complications
Y1  - 2022
U6  - https://doi.org/10.1186/s12933-021-01439-8
SN  - 1475-2840
VL  - 21
IS  - 1
PB  - BMC
CY  - London
ER  - 
TY  - JOUR
A1  - Christakoudi, Sofa
A1  - Tsilidis, Konstantinos K.
A1  - Muller, David C.
A1  - Freisling, Heinz
A1  - Weiderpass, Elisabete
A1  - Overvad, Kim
A1  - Söderberg, Stefan
A1  - Häggström, Christel
A1  - Pischon, Tobias
A1  - Dahm, Christina C.
A1  - Zhang, Jie
A1  - Tjønneland, Anne
A1  - Schulze, Matthias Bernd
T1  - A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort
JF  - Scientific Reports
N2  - 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.
KW  - all-cause mortality
KW  - anthropometric measures
KW  - mass index
KW  - overweight
KW  - cancer
KW  - prediction
KW  - adiposity
KW  - size
Y1  - 2020
VL  - 10
IS  - 1
PB  - Springer Nature
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Eckel, Nathalie
A1  - Li, Yanping
A1  - Kuxhaus, Olga
A1  - Stefan, Norbert
A1  - Hu, Frank B.
A1  - Schulze, Matthias Bernd
T1  - Transition from metabolic healthy to unhealthy phenotypes and association with cardiovascular disease risk across BMI categories in 90 257 women (the Nurses' Health Study)
BT  - 30 year follow-up from a prospective cohort study
JF  - The lancet diabetes & endocrinology
N2  - 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.
Y1  - 2018
U6  - https://doi.org/10.1016/S2213-8587(18)30137-2
SN  - 2213-8587
VL  - 6
IS  - 9
SP  - 714
EP  - 724
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Heinze, Eric
A1  - Boch, Steffen
A1  - Fischer, Markus
A1  - Hessenmöller, Dominik
A1  - Klenk, Bernd
A1  - Müller, Jörg
A1  - Prati, Daniel
A1  - Schulze, Ernst-Detlef
A1  - Seele, Carolin
A1  - Socher, Stephanie
A1  - Halle, Stefan
T1  - Habitat use of large ungulates in northeastern Germany in relation to forest management
JF  - Forest ecology and management
N2  - Estimating large herbivore density has been a major area of research in recent decades. Previous studies monitoring ungulate density, however, focused mostly on determining animal abundance, and did not interpret animal distribution in relation to habitat parameters. We surveyed large ungulates in the Biodiversity Exploratory Schorfheide-Chorin using faecal pellet group counts. This allowed us to explore the link between relative ungulate abundance, habitat use, and browsing damage on trees in a region with several types of forest, including unharvested and age-class beech forests, as well as age-class pine forests. Our results demonstrate that roe deer and fallow deer relative abundance is negatively correlated with large tree cover, and positively correlated with the cover of small shrubs (Rubus spec., Vaccinium spec.), and winter food supply. Habitat use of roe deer and fallow deer, as estimated by counting faecal pellet groups, revealed a preference for mature pine forests, and avoidance of deciduous forests. This differential habitat use is explained by different distributions of high quality food resources during winter. The response of deer to understory cover differed between roe deer and fallow deer at high cover percentages. The amount of browsing damage we observed on coniferous trees was not consistent with the relative deer abundance. Browsing damage was consistently higher on most deciduous trees, except for beech saplings which sustained less damage when roe deer density was low. Because roe deer is a highly selective feeder, it was reported to affect tree diversity by feeding only on trees with high nutritional value. Consequently, we propose that managing the number of all deer species by hunting is necessary to allow successful forest regeneration. Such an adjustment to deer numbers would need to account for both current tree diversity and alternative food resources. Our findings may be applicable to other forest landscapes in northeastern Germany including mature pine stands and differently harvested deciduous forests.
KW  - Large ungulates
KW  - Faecal pellet group count
KW  - Forest management
KW  - Browsing damage
Y1  - 2011
U6  - https://doi.org/10.1016/j.foreco.2010.10.022
SN  - 0378-1127
VL  - 261
IS  - 2
SP  - 288
EP  - 296
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Keller, Johannes
A1  - Catala-Lehnen, Philip
A1  - Huebner, Antje K.
A1  - Jeschke, Anke
A1  - Heckt, Timo
A1  - Lueth, Anja
A1  - Krause, Matthias
A1  - Koehne, Till
A1  - Albers, Joachim
A1  - Schulze, Jochen
A1  - Schilling, Sarah
A1  - Haberland, Michael
A1  - Denninger, Hannah
A1  - Neven, Mona
A1  - Hermans-Borgmeyer, Irm
A1  - Streichert, Thomas
A1  - Breer, Stefan
A1  - Barvencik, Florian
A1  - Levkau, Bodo
A1  - Rathkolb, Birgit
A1  - Wolf, Eckhard
A1  - Calzada-Wack, Julia
A1  - Neff, Frauke
A1  - Gailus-Durner, Valerie
A1  - Fuchs, Helmut
A1  - de Angelis, Martin Hrabe
A1  - Klutmann, Susanne
A1  - Tsourdi, Elena
A1  - Hofbauer, Lorenz C.
A1  - Kleuser, Burkhard
A1  - Chun, Jerold
A1  - Schinke, Thorsten
A1  - Amling, Michael
T1  - Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts
JF  - Nature Communications
N2  - The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signalling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P(3). Finally, pharmacologic treatment with the nonselective S1P receptor agonist FTY720 causes increased bone formation in wild-type, but not in S1P(3)-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.
Y1  - 2014
U6  - https://doi.org/10.1038/ncomms6215
SN  - 2041-1723
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Kroeger, Janine
A1  - Meidtner, Karina
A1  - Stefan, Norbert
A1  - Guevara, Marcela
A1  - Kerrison, Nicola D.
A1  - Ardanaz, Eva
A1  - Aune, Dagfinn
A1  - Boeing, Heiner
A1  - Dorronsoro, Miren
A1  - Dow, Courtney
A1  - Fagherazzi, Guy
A1  - Franks, Paul W.
A1  - Freisling, Heinz
A1  - Gunter, Marc J.
A1  - Maria Huerta, Jose
A1  - Kaaks, Rudolf
A1  - Key, Timothy J.
A1  - Khaw, Kay Tee
A1  - Krogh, Vittorio
A1  - Kuehn, Tilman
A1  - Mancini, Francesca Romana
A1  - Mattiello, Amalia
A1  - Nilsson, Peter M.
A1  - Olsen, Anja
A1  - Overvad, Kim
A1  - Palli, Domenico
A1  - Ramon Quiros, J.
A1  - Rolandsson, Olov
A1  - Sacerdote, Carlotta
A1  - Sala, Nuria
A1  - Salamanca-Fernandez, Elena
A1  - Sluijs, Ivonne
A1  - Spijkerman, Annemieke M. W.
A1  - Tjonneland, Anne
A1  - Tsilidis, Konstantinos K.
A1  - Tumino, Rosario
A1  - van der Schouw, Yvonne T.
A1  - Forouhi, Nita G.
A1  - Sharp, Stephen J.
A1  - Langenberg, Claudia
A1  - Riboli, Elio
A1  - Schulze, Matthias Bernd
A1  - Wareham, Nicholas J.
T1  - Circulating Fetuin-A and Risk of Type 2 Diabetes
BT  - a mendelian randomization analysis
JF  - Diabetes : a journal of the American Diabetes Association
N2  - Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
Y1  - 2018
U6  - https://doi.org/10.2337/db17-1268
SN  - 0012-1797
SN  - 1939-327X
VL  - 67
IS  - 6
SP  - 1200
EP  - 1205
PB  - American Diabetes Association
CY  - Alexandria
ER  -