@article{WittenbecherCuadratJohnstonetal.2022,
  author    = {Wittenbecher, Clemens and Cuadrat, Rafael and Johnston, Luke and Eichelmann, Fabian and J{\"a}ger, Susanne and Kuxhaus, Olga and Prada, Marcela and Del Greco, Fabiola M. and Hicks, Andrew A. and Hoffman, Per and Krumsiek, Jan and Hu, Frank B. and Schulze, Matthias B.},
  title     = {Dihydroceramide- and ceramide-profiling provides insights into human cardiometabolic disease etiology},
  series = {Nature communications},
  volume    = {13},
  journal   = {Nature communications},
  publisher = {Nature Research},
  address   = {Berlin},
  issn      = {2041-1723},
  doi       = {10.1038/s41467-022-28496-1},
  pages     = {13},
  year      = {2022},
  abstract  = {Metabolic alterations precede cardiometabolic disease onset. Here we present ceramide- and dihydroceramide-profiling data from a nested case-cohort (type 2 diabetes [T2D, n = 775]; cardiovascular disease [CVD, n = 551]; random subcohort [n = 1137]) in the prospective EPIC-Potsdam study. We apply the novel NetCoupler-algorithm to link a data-driven (dihydro)ceramide network to T2D and CVD risk. Controlling for confounding by other (dihydro)ceramides, ceramides C18:0 and C22:0 and dihydroceramides C20:0 and C22:2 are associated with higher and ceramide C20:0 and dihydroceramide C26:1 with lower T2D risk. Ceramide C16:0 and dihydroceramide C22:2 are associated with higher CVD risk. Genome-wide association studies and Mendelian randomization analyses support a role of ceramide C22:0 in T2D etiology. Our results also suggest that (dh)ceramides partly mediate the putative adverse effect of high red meat consumption and benefits of coffee consumption on T2D risk. Thus, (dihydro)ceramides may play a critical role in linking genetic predisposition and dietary habits to cardiometabolic disease risk.},
  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}
}