TY - JOUR A1 - Garcia, A. L. A1 - Steiniger, J. A1 - Reich, S. C. A1 - Weickert, M. O. A1 - Harsch, I. A1 - Machowetz, A. A1 - Mohlig, M. A1 - Spranger, Joachim A1 - Rudovich, N. N. A1 - Meuser, F. A1 - Doerfer, J. A1 - Katz, N. A1 - Speth, M. A1 - Zunft, Hans-Joachim Franz A1 - Pfeiffer, Andreas F. H. A1 - Koebnick, Corinna T1 - Arabinoxylan fibre consumption improved glucose metabolism, but did not affect serum adipokines in subjects with impaired glucose tolerance JF - Hormone and metabolic research N2 - The consumption of arabinoxylan, a soluble fibre fraction, has been shown to improve glycemic control in type 2 diabetic subjects. Soluble dietary fibre may modulate gastrointestinal or adipose tissue hormones regulating food intake. The present study investigated the effects of arabinoxylan consumption on serum glucose, insulin, lipids, leptin, adiponectin and resistin in subjects with impaired glucose tolerance. In a randomized, single-blind, controlled, crossover intervention trial, 11 adults consumed white bread rolls as either placebo or supplemented with 15g arabinoxylan for 6 weeks with a 6-week washout period. Fasting serum glucose, insulin, triglycerides, unesterified fatty acids, apolipoprotein A1 and B, adiponectin, resistin and leptin were assessed before and after intervention. Fasting serum glucose, serum triglycerides and apolipoprotein A-1 were significantly lower during arabinoxylan consumption compared to placebo (p = 0.029, p = 0.047; p = 0.029, respectively). No effects of arabinoxylan were observed for insulin, adiponectin, leptin and resistin as well as for apolipoprotein B, and unesterified fatty acids. In conclusion, the consumption of AX in subjects with impaired glucose tolerance improved fasting serum glucose, and triglycerides. However, this beneficial effect was not accompanied by changes in fasting adipokine concentrations. KW - dietary fibre KW - arabinoxylan KW - adiponectin KW - resistin KW - leptin Y1 - 2006 U6 - https://doi.org/10.1055/s-2006-955089 SN - 0018-5043 VL - 38 IS - 2 SP - 761 EP - 766 PB - Thieme CY - Stuttgart ER - TY - GEN A1 - Hische, Manuela A1 - Larhlimi, Abdelhalim A1 - Schwarz, Franziska A1 - Fischer-Rosinský, Antje A1 - Bobbert, Thomas A1 - Assmann, Anke A1 - Catchpole, Gareth S. A1 - Pfeiffer, Andreas F. H. A1 - Willmitzer, Lothar A1 - Selbig, Joachim A1 - Spranger, Joachim T1 - A distinct metabolic signature predictsdevelopment of fasting plasma glucose T2 - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe N2 - Background High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 850 KW - prediction KW - fasting glucose KW - type 2 diabetes KW - metabolomics KW - plasma KW - random forest KW - metabolite KW - regression KW - biomarker Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427400 SN - 1866-8372 IS - 850 ER - TY - JOUR A1 - Hische, Manuela A1 - Luis-Dominguez, Olga A1 - Pfeiffer, Andreas F. H. A1 - Schwarz, Peter E. A1 - Selbig, Joachim A1 - Spranger, Joachim T1 - Decision trees as a simple-to-use and reliable tool to identify individuals with impaired glucose metabolism or type 2 diabetes mellitus N2 - Objective: The prevalence of unknown impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or type 2 diabetes mellitus (T2DM) is high. Numerous studies demonstrated that IFG, IGT, or T2DM are associated with increased cardiovascular risk, therefore an improved identification strategy would be desirable. The objective of this study was to create a simple and reliable tool to identify individuals with impaired glucose metabolism (IGM). Design and methods: A cohort of 1737 individuals (1055 controls, 682 with previously unknown IGM) was screened by 75 g oral glucose tolerance test (OGTT). Supervised machine learning was used to automatically generate decision trees to identify individuals with IGM. To evaluate the accuracy of identification, a tenfold cross-validation was performed. Resulting trees were subsequently re-evaluated in a second, independent cohort of 1998 individuals (1253 controls, 745 unknown IGM). Results: A clinical decision tree included age and systolic blood pressure (sensitivity 89.3%, specificity 37.4%, and positive predictive value (PPV) 48.0%), while a tree based on clinical and laboratory data included fasting glucose and systolic blood pressure (sensitivity 89.7%, specificity 54.6%, and PPV 56.2%). The inclusion of additional parameters did not improve test quality. The external validation approach confirmed the presented decision trees. Conclusion: We proposed a simple tool to identify individuals with existing IGM. From a practical perspective, fasting blood glucose and blood pressure measurements should be regularly measured in all individuals presenting in outpatient clinics. An OGTT appears to be useful only if the subjects are older than 48 years or show abnormalities in fasting glucose or blood pressure. Y1 - 2010 UR - http://www.eje-online.org/ U6 - https://doi.org/10.1530/Eje-10-0649 SN - 0804-4643 ER - TY - JOUR A1 - Moehlig, M. A1 - Floeter, A. A1 - Spranger, Joachim A1 - Weickert, Martin O. A1 - Schill, T. A1 - Schloesser, H. W. A1 - Brabant, G. A1 - Pfeiffer, Andreas F. H. A1 - Selbig, Joachim A1 - Schoefl, C. T1 - Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose < 6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >= 7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100% sensitivity, 74% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100% sensitivity, 57% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100% sensitivity, 29% specificity to detect IGM). The validity of both trees was tested by a leave-10%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced. KW - decision tree KW - HOMA KW - impaired glucose tolerance KW - insulin KW - insulin resistance KW - polycystic ovary syndrome KW - proinsulin KW - type 2 diabetes mellitus Y1 - 2006 U6 - https://doi.org/10.1007/s00125-006-0395-0 SN - 0012-186X VL - 49 SP - 2572 EP - 2579 PB - Springer CY - Berlin ER - TY - JOUR A1 - Frey, Simone K. A1 - Spranger, Joachim A1 - Henze, Andrea A1 - Pfeiffer, Andreas F. H. A1 - Schweigert, Florian J. A1 - Raila, Jens T1 - Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus N2 - Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction. Y1 - 2009 UR - http://www.sciencedirect.com/science/journal/00260495 U6 - https://doi.org/10.1016/j.metabol.2009.05.003 SN - 0026-0495 ER - TY - JOUR A1 - Bobbert, Thomas A1 - Raila, Jens A1 - Schwarz, Franziska A1 - Mai, Knut A1 - Henze, Andrea A1 - Pfeiffer, Andreas F. H. A1 - Schweigert, Florian J. A1 - Spranger, Joachim T1 - Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness N2 - Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/00219150 U6 - https://doi.org/10.1016/j.atherosclerosis.2010.07.063 SN - 0021-9150 ER - TY - JOUR A1 - Henze, Andrea A1 - Frey, Simone K. A1 - Raila, Jens A1 - Scholze, Alexandra A1 - Spranger, Joachim A1 - Weickert, Martin O. A1 - Tepel, Martin A1 - Zidek, Walter A1 - Schweigert, Florian J. T1 - Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters N2 - Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/0006291X U6 - https://doi.org/10.1016/j.bbrc.2010.01.082 SN - 0006-291X ER -