TY - JOUR A1 - Mühlenbruch, Kristin A1 - Zhuo, Xiaohui A1 - Bardenheier, Barbara A1 - Shao, Hui A1 - Laxy, Michael A1 - Icks, Andrea A1 - Zhang, Ping A1 - Gregg, Edward W. A1 - Schulze, Matthias Bernd T1 - Selecting the optimal risk threshold of diabetes risk scores to identify high-risk individuals for diabetes prevention BT - a cost-effectiveness analysis JF - Acta Diabetologica N2 - Aims: Although risk scores to predict type 2 diabetes exist, cost-effectiveness of risk thresholds to target prevention interventions are unknown. We applied cost-effectiveness analysis to identify optimal thresholds of predicted risk to target a low-cost community-based intervention in the USA. Methods: We used a validated Markov-based type 2 diabetes simulation model to evaluate the lifetime cost-effectiveness of alternative thresholds of diabetes risk. Population characteristics for the model were obtained from NHANES 2001-2004 and incidence rates and performance of two noninvasive diabetes risk scores (German diabetes risk score, GDRS, and ARIC 2009 score) were determined in the ARIC and Cardiovascular Health Study (CHS). Incremental cost-effectiveness ratios (ICERs) were calculated for increasing risk score thresholds. Two scenarios were assumed: 1-stage (risk score only) and 2-stage (risk score plus fasting plasma glucose (FPG) test (threshold 100 mg/dl) in the high-risk group). Results: In ARIC and CHS combined, the area under the receiver operating characteristic curve for the GDRS and the ARIC 2009 score were 0.691 (0.677-0.704) and 0.720 (0.707-0.732), respectively. The optimal threshold of predicted diabetes risk (ICER < $50,000/QALY gained in case of intervention in those above the threshold) was 7% for the GDRS and 9% for the ARIC 2009 score. In the 2-stage scenario, ICERs for all cutoffs >= 5% were below $50,000/QALY gained. Conclusions: Intervening in those with >= 7% diabetes risk based on the GDRS or >= 9% on the ARIC 2009 score would be cost-effective. A risk score threshold >= 5% together with elevated FPG would also allow targeting interventions cost-effectively. KW - diabetes mellitus KW - type 2 KW - cost-effectiveness analysis KW - lifestyle risk reduction KW - clinical prediction rule Y1 - 2019 U6 - https://doi.org/10.1007/s00592-019-01451-1 SN - 0001-5563 SN - 0940-5429 SN - 1432-5233 VL - 57 IS - 4 SP - 447 EP - 454 PB - Springer CY - Mailand 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 - Dietrich, Stefan A1 - Jacobs, Simone A1 - Zheng, Ju-Sheng A1 - Meidtner, Karina A1 - Schwingshackl, Lukas A1 - Schulze, Matthias Bernd T1 - Gene-lifestyle interaction on risk of type 2 diabetes BT - A systematic review JF - Obesity reviews : an official journal of the International Association for the Study of Obesity N2 - 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. KW - diet KW - gene-lifestyle interaction KW - incident type 2 diabetes KW - physical activity KW - weight loss intervention Y1 - 2019 U6 - https://doi.org/10.1111/obr.12921 SN - 1467-7881 SN - 1467-789X VL - 20 IS - 11 SP - 1557 EP - 1571 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Schenk, Matthew A1 - Eichelmann, Fabian A1 - Schulze, Matthias Bernd A1 - Rudovich, Natalia A1 - Pfeiffer, Andreas F. H. A1 - di Giuseppe, Romina A1 - Böing, Heiner A1 - Aleksandrova, Krasimira T1 - Reproducibility of novel immune-inflammatory biomarkers over 4 months BT - an analysis with repeated measures design JF - Biomarkers in medicine N2 - 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. KW - clusterin KW - immune-inflammatory biomarkers KW - MMF KW - repeated measures design KW - reproducibility KW - suPAR KW - TGF-beta Y1 - 2019 U6 - https://doi.org/10.2217/bmm-2018-0351 SN - 1752-0363 SN - 1752-0371 VL - 13 IS - 8 SP - 639 EP - 648 PB - Future Medicine CY - London ER - TY - JOUR A1 - Jannasch, Franziska A1 - Kröger, Janine A1 - Agnoli, Claudia A1 - Barricarte, Aurelio A1 - Boeing, Heiner A1 - Cayssials, Valérie A1 - Colorado-Yohar, Sandra A1 - Dahm, Christina C. A1 - Dow, Courtney A1 - Fagherazzi, Guy A1 - Franks, Paul W. A1 - Freisling, Heinz A1 - Gunter, Marc J. A1 - Kerrison, Nicola D. A1 - Key, Timothy J. A1 - Khaw, Kay-Tee A1 - Kühn, Tilman A1 - Kyro, Cecilie A1 - Mancini, Francesca Romana A1 - Mokoroa, Olatz A1 - Nilsson, Peter A1 - Overvad, Kim A1 - Palli, Domenico A1 - Panico, Salvatore A1 - Quiros Garcia, Jose Ramon A1 - Rolandsson, Olov A1 - Sacerdote, Carlotta A1 - Sanchez, Maria-Jose A1 - Sahrai, Mohammad Sediq A1 - Schübel, Ruth A1 - Sluijs, Ivonne A1 - Spijkerman, Annemieke M. W. A1 - Tjonneland, Anne A1 - Tong, Tammy Y. N. A1 - Tumino, Rosario A1 - Riboli, Elio A1 - Langenberg, Claudia A1 - Sharp, Stephen J. A1 - Forouhi, Nita G. A1 - Schulze, Matthias Bernd A1 - Wareham, Nicholas J. T1 - Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations JF - The Journal of Nutrition N2 - 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. KW - dietary patterns KW - principal component analysis KW - diet-disease association KW - type 2 diabetes mellitus KW - replication KW - meta-analysis Y1 - 2019 U6 - https://doi.org/10.1093/jn/nxz031 SN - 0022-3166 SN - 1541-6100 VL - 149 IS - 6 SP - 1047 EP - 1055 PB - Oxford Univ. Press CY - Oxford 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 - JOUR A1 - Eichelmann, Fabian A1 - Schulze, Matthias Bernd A1 - Wittenbecher, Clemens A1 - Menzel, Juliane A1 - Weikert, Cornelia A1 - di Giuseppe, Romina A1 - Biemann, Ronald A1 - Isermann, Berend A1 - Fritsche, Andreas A1 - Boeing, Heiner A1 - Aleksandrova, Krasimira T1 - Association of Chemerin Plasma Concentration With Risk of Colorectal Cancer JF - JAMA network open N2 - IMPORTANCE Inflammatory processes have been suggested to have an important role in colorectal cancer (CRC) etiology. Chemerin is a recently discovered inflammatory biomarker thought to exert chemotactic, adipogenic, and angiogenic functions. However, its potential link with CRC has not been sufficiently explored. OBJECTIVE To evaluate the prospective association of circulating plasma chemerin concentrations with incident CRC. DESIGN, SETTING, AND PARTICIPANTS Prospective case-cohort study based on 27 548 initially healthy participants from the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam cohort who were followed for up to 16 years. Baseline study information and samples were collected between August 23, 1994, and September 25, 1998. Recruitment was according to random registry sampling from the geographical area of Potsdam, Germany, and surrounding municipalities. The last date of study follow-up was May 10, 2010. Statistical analysis was conducted in 2018. MAIN OUTCOMES AND MEASURES Incident CRC, colon cancer, and rectal cancer. Baseline chemerin plasma concentrations were measured by enzyme-linked immunosorbent assay. CONCLUSIONS AND RELEVANCE This study found that the association between chemerin concentration and the risk of incident CRC was linear and independent of established CRC risk factors. Further studies are warranted to evaluate chemerin as a novel immune-inflammatory agent in colorectal carcinogenesis. Y1 - 2019 U6 - https://doi.org/10.1001/jamanetworkopen.2019.0896 SN - 2574-3805 VL - 2 IS - 3 PB - American Veterinary Medical Association CY - Chicago ER - TY - JOUR A1 - Willmann, Caroline A1 - Heni, Martin A1 - Linder, Katarzyna A1 - Wagner, Robert A1 - Stefan, Norbert A1 - Machann, Jürgen A1 - Schulze, Matthias Bernd A1 - Joost, Hans-Georg A1 - Haring, Hans-Ulrich A1 - Fritsche, Andreas T1 - Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content BT - a randomized and controlled dietary intervention study JF - The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc. N2 - Background: Epidemiological studies suggest that an increased red meat intake is associated with a higher risk of type 2 diabetes, whereas an increased fiber intake is associated with a lower risk. Objectives: We conducted an intervention study to investigate the effects of these nutritional factors on glucose and lipid metabolism, body-fat distribution, and liver fat content in subjects at increased risk of type 2 diabetes. Methods: This prospective, randomized, and controlled dietary intervention study was performed over 6 mo. All groups decreased their daily caloric intake by 400 kcal. The "control" group (N = 40) only had this requirement. The "no red meat" group (N = 48) in addition aimed to avoid the intake of red meat, and the "fiber" group (N = 44) increased intake of fibers to 40 g/d. Anthropometric parameters and frequently sampled oral glucose tolerance tests were performed before and after intervention. Body-fat mass and distribution, liver fat, and liver iron content were assessed by MRI and single voxel proton magnetic resonance spectroscopy. Results: Participants in all groups lost weight (mean 3.3 +/- 0.5 kg, P < 0.0001). Glucose tolerance and insulin sensitivity improved (P < 0.001), and body and visceral fat mass decreased in all groups (P < 0.001). These changes did not differ between groups. Liver fat content decreased significantly (P < 0.001) with no differences between the groups. The decrease in liver fat correlated with the decrease in ferritin during intervention (r(2) = 0.08, P = 0.0021). This association was confirmed in an independent lifestyle intervention study (Tuebingen Lifestyle Intervention Program, N = 229, P = 0.0084). Conclusions: Our data indicate that caloric restriction leads to a marked improvement in glucose metabolism and body-fat composition, including liver-fat content. The marked reduction in liver fat might be mediated via changes in ferritin levels. In the context of caloric restriction, there seems to be no additional beneficial impact of reduced red meat intake and increased fiber intake on the improvement in cardiometabolic risk parameters. This trial was registered at clinicaltrials.gov as NCT03231839. KW - type 2 diabetes KW - prevention KW - randomized controlled intervention study KW - nutritional factors KW - fiber KW - red meat Y1 - 2019 U6 - https://doi.org/10.1093/ajcn/nqy307 SN - 0002-9165 SN - 1938-3207 VL - 109 IS - 2 SP - 288 EP - 296 PB - Oxford Univ. Press CY - Oxford ER -