TY - GEN A1 - Mühlenbruch, Kristin A1 - Kuxhaus, Olga A1 - Pencina, Michael J. A1 - Boeing, Heiner A1 - Liero, Hannelore A1 - Schulze, Matthias Bernd T1 - A confidence ellipse for the Net Reclassification Improvement T2 - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe N2 - 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. KW - risk assessment KW - risk model KW - model comparison KW - reclassification KW - confidence intervals Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427371 SN - 1866-8372 IS - 825 SP - 299 EP - 304 ER - TY - JOUR A1 - Mühlenbruch, Kristin A1 - Kuxhaus, Olga A1 - Pencina, Michael J. A1 - Boeing, Heiner A1 - Liero, Hannelore A1 - Schulze, Matthias Bernd T1 - A confidence ellipse for the Net Reclassification Improvement JF - European journal of epidemiology N2 - 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. KW - Risk assessment KW - Risk model KW - Model comparison KW - Reclassification KW - Confidence intervals Y1 - 2015 U6 - https://doi.org/10.1007/s10654-015-0001-1 SN - 0393-2990 SN - 1573-7284 VL - 30 IS - 4 SP - 299 EP - 304 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Kuxhaus, Olga A1 - Boeing, Heiner A1 - Stefan, Norbert A1 - Schulze, Matthias Bernd T1 - Associations of short stature and components of height with incidence of type 2 diabetes BT - mediating effects of cardiometabolic risk factors JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - 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. KW - Adult height KW - Blood pressure KW - Diabetes incidence KW - Leg length KW - Liver fat KW - Short stature KW - Trunk length Y1 - 2019 U6 - https://doi.org/10.1007/s00125-019-04978-8 SN - 0012-186X SN - 1432-0428 VL - 62 IS - 12 SP - 2211 EP - 2221 PB - Springer CY - New York ER - TY - JOUR A1 - Eichelmann, Fabian A1 - Sellem, Laury A1 - Wittenbecher, Clemens A1 - Jäger, Susanne A1 - Kuxhaus, Olga A1 - Prada, Marcela A1 - Cuadrat, Rafael A1 - Jackson, Kim G. A1 - Lovegrove, Julie A. A1 - Schulze, Matthias Bernd T1 - Deep lipidomics in human plasma: cardiometabolic disease risk and effect of dietary fat modulation JF - Circulation N2 - Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95% CI, 0.4-0.7) SD units. Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention. KW - cardiovascular diseases KW - cholesterol KW - diabetes mellitus KW - type 2 KW - diet KW - food KW - and nutrition KW - epidemiology KW - lipids Y1 - 2022 U6 - https://doi.org/10.1161/CIRCULATIONAHA.121.056805 SN - 0009-7322 SN - 1524-4539 VL - 146 IS - 1 SP - 21 EP - 35 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Ouni, Meriem A1 - Kuxhaus, Olga A1 - Jähnert, Markus A1 - Gottmann, Pascal A1 - Teichmann, Andrea A1 - Meidtner, Karina A1 - Kriebel, Jennifer A1 - Grallert, Harald A1 - Pischon, Tobias A1 - Boeing, Heiner A1 - Schulze, Matthias Bernd A1 - Schürmann, Annette T1 - Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes JF - Diabetes : a journal of the American Diabetes Association N2 - 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. Y1 - 2019 U6 - https://doi.org/10.2337/db18-0620 SN - 0012-1797 SN - 1939-327X VL - 68 IS - 1 SP - 188 EP - 197 PB - American Diabetes Association CY - Alexandria ER - TY - BOOK A1 - Kuxhaus, Olga T1 - Parametrische Schätzung von elliptischen Copulafunktionen T3 - Preprint / Universität Potsdam, Institut für Mathematik, Mathematische Statistik un Y1 - 2010 SN - 1613-3307 PB - Univ. CY - Potsdam ER - TY - INPR A1 - Kuxhaus, Olga T1 - Parametrische Schätzungen von elliptischen Copulafunktionen N2 - Aus dem Inhalt: Inhaltsverzeichnis Abbildungsverzeichnis Tabellenverzeichnis 1 Einleitung und Motivation 2 Multivariate Copulafunktionen 2.1 Einleitung 2.2 Satz von Sklar 2.3 Eigenschaften von Copulafunktionen 3 Abhängigkeitskonzepte 3.1 Lineare Korrelation 3.2 Copulabasierte Abhängigkeitsmaße 3.2.1 Konkordanz 3.2.2 Kendall’s und Spearman’s 3.2.3 Asymptotische Randabhängigkeit 4 Elliptische Copulaklasse 4.1 Sphärische und elliptische Verteilungen 4.2 Normal-Copula 4.3 t-Copula 5 Parametrische Schätzverfahren 5.1 Maximum-Likelihood-Methode 5.1.1 ExakteMaximum-Likelihood-Methode 5.1.2 2-stufige parametrische Maximum-Likelihood-Methode 5.1.3 2-stufige semiparametrische Maximum-Likelihood-Methode 5.2 Momentenmethode 5.3 Kendall’s -Momentenmethode 6 Parameterschätzungen für Normal- und t-Copula 6.1 Normal-Copula 6.1.1 Maximum-Likelihood-Methode 6.1.2 Momentenmethode 6.1.3 Kendall’s Momentenmethode 6.1.4 Spearman’s Momentenmethode 6.2 t-Copula 6.2.1 Verfahren 1 (exakte ML-Methode) 6.2.2 Verfahren 2 (2-stufige rekursive ML-Methode) 6.2.3 Verfahren 3 (2-stufige KM-ML-Methode) 6.2.4 Verfahren 4 (3-stufige M-ML-Methode) 7 Simulationen 7.1 Grundlagen 7.2 Parametrischer Fall 7.3 Nichtparametrischer Fall 7.4 Fazit A Programmausschnitt Literaturverzeichnis T3 - Mathematische Statistik und Wahrscheinlichkeitstheorie : Preprint - 2010, 09 Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-51681 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 -