Search Results

You are looking at 1 - 10 of 11 items for

  • Author: Matthias Blüher x
Clear All Modify Search
Free access

Matthias Blüher

Obesity has become one of the major public health concerns of the past decades, because it is a key risk factor for type 2 diabetes, cardiovascular diseases, dyslipidemia, hypertension, and certain types of cancer, which may lead to increased mortality. Both treatment of obesity and prevention of obesity-related diseases are frequently not successful. Moreover, a subgroup of individuals with obesity does not seem to be at an increased risk for metabolic complications of obesity. In this literature, this obesity subphenotype is therefore referred to as metabolically healthy obesity (MHO). Importantly, individuals with MHO do not significantly improve their cardio-metabolic risk upon weight loss interventions and may therefore not benefit to the same extent as obese patients with metabolic comorbidities from early lifestyle, bariatric surgery, or pharmacological interventions. However, it can be debated whether MHO individuals are really healthy, especially since there is no general agreement on accepted criteria to define MHO. In addition, overall health of MHO individuals may be significantly impaired by several psycho-social factors, psychosomatic comorbidities, low fitness level, osteoarthritis, chronic pain, diseases of the respiratory system, the skin, and others. There are still open questions about predictors, biological determinants, and the mechanisms underlying MHO and whether MHO represents a transient phenotype changing with aging and behavioral and environmental factors. In this review, the prevalence, potential biological mechanisms, and the clinical relevance of MHO are discussed.

Free access

Susan Kralisch, Matthias Bluher, Anke Tonjes, Ulrike Lossner, Ralf Paschke, Michael Stumvoll and Mathias Fasshauer

Objective: Tissue inhibitor of metalloproteinase (TIMP)-1 is upregulated in fat of obese rodents and promotes adipose tissue development in these animals. However, it is unclear whether TIMP-1 independently predicts adiposity in humans and whether serum levels are increased in s.c. and visceral obesity.

Design: Twenty-four lean, 16 s.c. obese, and 20 visceral obese subjects were studied.

Methods: Plasma TIMP-1 concentrations were quantified using ELISAs and correlated to clinical parameters.

Results: Plasma TIMP-1 levels were significantly different between lean (156 ± 42 μg/l), s.c. obese (186 ± 52 μg/l), and visceral obese (198 ± 42 μg/l) subjects (P < 0.01). Furthermore, TIMP-1 correlated positively with body mass index (BMI), waist-to-hip ratio (WHR), % body fat, fasting insulin, free fatty acids, cholesterol, leptin, interleukin-6, and negatively with adiponectin (P < 0.05). Moreover, TIMP-1 serum levels predicted % body fat but not WHR independent of age, sex, and plasma insulin.

Conclusions: We demonstrate that increased TIMP-1 serum levels are found with increased adiposity in humans.

Free access

Christian Herder, Julia M Kannenberg, Corinna Niersmann, Cornelia Huth, Maren Carstensen-Kirberg, Clemens Wittenbecher, Matthias Schulze, Matthias Blüher, Wolfgang Rathmann, Annette Peters, Michael Roden, Christa Meisinger and Barbara Thorand

Objective

Cross-sectional studies found that higher levels of the novel adipokine omentin-1 were associated with higher adiponectin and lower levels of risk factors for type 2 diabetes, but its relevance for incident type 2 diabetes is currently not understood. Therefore this study investigated whether serum omentin-1 was associated with changes in glycaemia and incident type 2 diabetes independently of adiponectin.

Design and methods

The study was based on participants aged 62–81 years from the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4/FF4 cohort. Associations of baseline serum levels of omentin-1 and adiponectin with changes in glycaemia were assessed in 471 non-diabetic participants, and associations between both adipokines and incident type 2 diabetes were assessed in 76 cases and 430 non-cases (follow-up time 6.5 years). Multivariable linear and logistic regression models were adjusted for multiple potential confounders.

Results

Higher serum levels of omentin-1 were associated with increases in fasting glucose, 2-h glucose and HbA1c (all P < 0.001) and with incident type 2 diabetes (adjusted odds ratio (OR) (95% CI): 1.40 (1.03; 1.90) per s.d. of log2-transformed omentin-1; P = 0.032). These associations were independent from adiponectin levels, which showed associations with changes in glycaemia and risk of type 2 diabetes in the opposite direction. We found no statistically significant interactions of omentin-1 with adiponectin or sex in the association with incident type 2 diabetes (all P > 0.1).

Conclusions

Systemic levels of omentin-1 were positively associated with increases in glycaemia and incident type 2 diabetes in this older population. These associations were independent of potential confounders including adiponectin.

Free access

Andreas Oberbach, Anke Tönjes, Nora Klöting, Mathias Fasshauer, Jürgen Kratzsch, Martin W Busse, Ralf Paschke, Michael Stumvoll and Matthias Blüher

Objective: Subclinical chronic inflammation could be a unifying factor linking type 2 diabetes (T2D) and atherosclerosis. The beneficial effects of physical activity on a reduced risk of coronary heart disease could at least in part be mediated by improved markers of inflammation.

Research design and methods: The aim of this study was to determine the effect of 4 weeks of physical training on plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP), adiponectin and IL-10 in 60 individuals with normal glucose tolerance, impaired glucose tolerance (IGT) or T2D.

Results: In patients with IGT and T2D, significant improvement in body fat, fitness level, glucose metabolism and insulin sensitivity after 4 weeks of physical training was associated with significantly improved plasma concentrations of adiponectin and CRP, but not IL-6. Regression analysis demonstrated only for the anti-inflammatory parameters adiponectin and IL-10 a significant relationship with the decrease in fasting plasma glucose, whereas changes in IL-6 and CRP were not significantly related to changes in fasting plasma glucose, body fat, maximal oxygen uptake, or insulin sensitivity. In a multivariate linear regression analysis, only changes in circulating adiponectin, fasting plasma glucose and percentage body fat were determinants of changes in insulin sensitivity.

Conclusions: Physical training was associated with a near normalization of adiponectin and CRP plasma concentrations in subjects with IGT and T2D. Increased insulin sensitivity after training was most strongly related to changes in adiponectin plasma concentrations, in fasting plasma glucose and percentage body fat, whereas changes in IL-6, IL-10 and CRP plasma concentrations did not significantly contribute to improved insulin sensitivity.

Free access

Andreas Oberbach, Stefanie Lehmann, Katharina Kirsch, Joanna Krist, Melanie Sonnabend, Axel Linke, Anke Tönjes, Michael Stumvoll, Matthias Blüher and Peter Kovacs

Objective

Exercise training has been shown to have anti-inflammatory effects in patients with type 2 diabetes. Changes in interleukin-6 (IL-6) serum concentrations in response to training could contribute to these beneficial effects. However, there are heterogeneous data on whether circulating IL-6 is altered by exercise training. We therefore hypothesize that genetic factors modify the individual changes in IL-6 levels after long-term training.

Research design and methods

The −174G/C variant in the IL-6 gene was genotyped in 60 subjects with impaired glucose tolerance. For a 12-month interventional study, patients were randomized into three groups: a control group (n=16) was compared with one group, which underwent a standardized training program (n=24) and another group, which was treated with 4 mg rosiglitazone once daily (n=20). At baseline, after 1, 6, and 12 months, we measured anthropometric parameters and serum concentration of IL-6 and, at baseline and after 12 months, we determined glucose tolerance and fitness level.

Results

Only in subjects carrying the SNP −174C allele did long-term exercise training result in significantly reduced IL-6 serum concentrations. Multivariate linear regression analysis identified the IL-6 genotype as a significant predictor of changes in IL-6 serum concentrations independent of age, gender and improvement in body mass index, hemoglobin (Hb)A1c, and fitness level in response to training.

Conclusions

Genetic variants in the IL-6 gene significantly modify changes in IL-6 serum concentrations in response to long-term exercise training programs. Our data suggest that genetic factors are important determinants for the individual response to anti-inflammatory effects of exercise training.

Free access

Thomas Ebert, Susan Kralisch, Ulrike Wurst, Ulrike Lössner, Jürgen Kratzsch, Matthias Blüher, Michael Stumvoll, Anke Tönjes and Mathias Fasshauer

Objective

Betatrophin has recently been introduced as a novel adipokine/hepatokine, which promotes pancreatic β cell proliferation and improves glucose tolerance in several mouse models of insulin resistance. However, regulation of betatrophin in gestational diabetes mellitus (GDM), as well as its association with markers of obesity, such as glucose and lipid metabolism, inflammation, and renal function, have not been elucidated.

Design and methods

Circulating betatrophin was quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by ELISA. In a subset of the study population comprising of 85 patients (41 previous controls, 44 previous women with GDM), postpartum betatrophin levels were measured in a follow-up study.

Results

Median (interquartile range) serum betatrophin levels were higher in women with GDM (1.79 (0.53) μg/l) as compared to non-diabetic pregnant controls (1.58 (0.44) μg/l) (P=0.002). In multivariate analysis, GDM status was an independent and positive predictor of circulating betatrophin (P=0.001). Furthermore, betatrophin levels were significantly higher during gestation (1.70 (0.53) μg/l) as compared to postpartum levels (1.55 (0.66) μg/l) (P=0.028). Moreover, postpartum irisin remained a positive and independent predictor of postpartum betatrophin concentrations.

Conclusions

Women with GDM have significantly higher betatrophin levels as compared to healthy pregnant controls and GDM status positively predicts circulating betatrophin. Furthermore, postpartum levels are significantly lower as compared to betatrophin concentrations during pregnancy. Moreover, irisin is a significant predictor of postpartum betatrophin levels.

Free access

Karen Ruschke, Lauren Fishbein, Arne Dietrich, Nora Klöting, Anke Tönjes, Andreas Oberbach, Mathias Fasshauer, Jost Jenkner, Michael R Schön, Michael Stumvoll, Matthias Blüher and Christos S Mantzoros

Objective

Obesity and type 2 diabetes (T2D) are reaching epidemic proportions in Western societies, and they contribute to substantial morbidity and mortality. The peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1α (PGC-1α) system plays an important role in the regulation of efficient energy utilization and oxidative phosphorylation, both of which are decreased in obesity and insulin resistance.

Design and methods

We measured the metabolic parameters and the expression of PPARγ and PGC-1α mRNA using quantitative real-time PCR in omental and subcutaneous (SC) adipose tissues in an observational study of 153 individuals as well as in SC fat and skeletal muscle in an interventional study of 60 subjects (20 each with normal glucose tolerance, impaired glucose tolerance, and T2D) before and after intensive physical training for 4 weeks.

Results

PPARγ and PGC-1α mRNA expression in both fat depots as well as in skeletal muscle is associated with markers of insulin resistance and cardiovascular risk. PGC-1α mRNA expression is significantly higher in SC fat than in omental fat, whereas PPARγ mRNA expression is not significantly different between these fat depots. Skeletal muscle and SC fat PPARγ and PGC-1α mRNA expression increased significantly in response to physical training.

Conclusions

Gene expression of PPARγ and PGC-1α in human adipose tissue is related to markers of insulin resistance and cardiovascular risk. Increased muscle and adipose tissue PPARγ and PGC-1α expression in response to physical training may mediate the beneficial effects of exercise on insulin sensitivity.

Free access

Mathias Fasshauer, Theresa Waldeyer, Jeannette Seeger, Susanne Schrey, Thomas Ebert, Jürgen Kratzsch, Ulrike Lössner, Matthias Blüher, Michael Stumvoll, Renaldo Faber and Holger Stepan

Objective

Preeclampsia (PE) is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, a paradoxical upregulation of the insulin-sensitizing and anti-atherogenic adipokine adiponectin has been shown in PE. Furthermore, high-molecular-weight (HMW) adiponectin has been suggested as the biologically active form of this adipokine.

Design and methods

HMW adiponectin and total adiponectin serum concentrations were quantified by ELISA in PE (n=16) patients and pregnant control women without PE (n=20). Furthermore, HMW adiponectin and total adiponectin were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation.

Results

Median maternal HMW adiponectin and total adiponectin levels were significantly and independently upregulated almost twofold in PE when compared with controls. HMW adiponectin and total adiponectin correlated positively with creatinine and negatively with fasting insulin in univariate and multivariate analyses.

Conclusions

We show that maternal HMW adiponectin and total adiponectin serum concentrations are significantly increased in PE and are positively associated with markers of insulin sensitivity and renal dysfunction. Adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in PE.

Free access

Susan Kralisch, Holger Stepan, Jürgen Kratzsch, Michael Verlohren, Hans-Joachim Verlohren, Kathrin Drynda, Ulrike Lössner, Matthias Blüher, Michael Stumvoll and Mathias Fasshauer

Objective

Adipocyte fatty acid binding protein (AFABP) was recently introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In the current study, we investigated serum concentrations of AFABP in patients with gestational diabetes mellitus (GDM) as compared with healthy pregnant controls matched for gestational age and fasting insulin.

Design and methods

AFABP was determined by ELISA in controls (n=80) and GDM patients (n=40) and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation, in both groups.

Results

Median serum AFABP concentrations were significantly elevated in subjects with GDM (22.9 μg/l) as compared with healthy pregnant controls (18.3 μg/l; P<0.05). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis (P<0.05). In addition, markers of adiposity (body mass index, serum leptin), triglycerides and serum creatinine were independently associated with circulating AFABP (P<0.05).

Conclusions

Maternal AFABP concentrations are significantly increased in GDM. The adipokine might contribute to the increased metabolic and cardiovascular risk of the disease.

Free access

Thomas Ebert, Denise Focke, David Petroff, Ulrike Wurst, Judit Richter, Anette Bachmann, Ulrike Lössner, Susan Kralisch, Jürgen Kratzsch, Joachim Beige, Ingolf Bast, Matthias Anders, Matthias Blüher, Michael Stumvoll and Mathias Fasshauer

Objective

Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied.

Design and methods

Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD).

Results

Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis.

Conclusions

We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.