K Müssig

Heinrich-Heine-Universität Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (164)362.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory processes are involved in the progression of insulin resistance and β-cell dysfunction in individuals with prediabetes and contribute to the development of diabetes. We hypothesized that higher levels of biomarkers of low-grade inflammation are associated with the early progression of recently diagnosed diabetes. Within the prospective German Diabetes Study, patients with recently diagnosed type 1 (n = 42) and type 2 (n = 94) diabetes underwent detailed metabolic characterization within the first year after diagnosis and 2 years thereafter. Associations between changes in markers of low-grade inflammation with changes in glycemic control, β-cell function, and glucose disappearance rate were assessed using multivariable linear regression analysis. Associations were adjusted for age, sex, BMI, smoking status, and 2-year changes in BMI, smoking status, and glucose-lowering medication. Patients with type 1 and type 2 diabetes exhibited good glucometabolic control at baseline (mean HbA1c 7.08 ± 1.58% [54 ± 17 mmol/mol] and 6.43 ± 0.98% [47 ± 11 mmol/mol], respectively) and 2 years thereafter (mean HbA1c 7.03 ± 1.20% (53 ± 13 mmol/mol) and 6.62 ± 1.14% (49 ± 13), respectively). Two-year increases of high-sensitivity C-reactive protein, soluble E-selectin (sE-selectin), and soluble intercellular adhesion molecule-1 in type 2 diabetes and of IL-18 in type 1 diabetes were associated with 2-year increases of HbA1c. Additionally, 2-year increases of sE-selectin were associated with 2-year decreases of prehepatic β-cell function in type 2 diabetes (all P < 0.05). These data indicate that with the clinical onset of diabetes, low-grade inflammation relates to worsening of glycemia and that endothelial activation may contribute to decreasing β-cell function. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
    Diabetes care 07/2015; DOI:10.2337/dc15-0169 · 8.57 Impact Factor
  • Karsten Müssig · Julia Szendrödi · Michael Roden
    Diabetes aktuell 05/2015; 13(02):68-70. DOI:10.1055/s-0035-1552947
  • Diabetologie und Stoffwechsel 04/2015; 10(S 01). DOI:10.1055/s-0035-1549771 · 0.31 Impact Factor
  • Diabetologie und Stoffwechsel 04/2015; 10(S 01). DOI:10.1055/s-0035-1549742 · 0.31 Impact Factor
  • I Ratjen · K S Weber · M Roden · M-E Herrmann · K Müssig
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    ABSTRACT: Aims: The number of patients with type 1 diabetes mellitus who are actively participating in competitive sports is increasing. Here, we aimed to assess individual experiences of competitive athletes with type 1 diabetes and to compare these experiences with current recommendations. Methods: A survey of 20 competitive athletes with type 1 diabetes, categorized as endurance (n=10) and non-endurance (n=10) athletes, was performed. Results: Endurance and non-endurance athletes did not differ in gender distribution, age, body mass index, and known diabetes duration. Self-reported target blood glucose values prior to exercise were lower in non-endurance than in endurance athletes (195±34 vs. 137±28 mg/dl, P=0.001). The majority of all athletes experienced activity-induced hypo- and hyperglycemic events, independently of exercise type. However, endurance athletes used additional carbohydrate units to prevent activity-induced hypoglycemic events more frequently without monitoring their blood glucose levels than non-endurance athletes (50% vs. 0%, P=0.01). The reduction of the insulin dose on training and competition days compared to days without exercise was similar for endurance and non-endurance athletes. Conclusion: These results point to a very individual adaption of the athlete's therapy during training and competition. However, there are distinct differences in diabetes management between endurance and non-endurance athletes. © Georg Thieme Verlag KG Stuttgart · New York.
    Experimental and Clinical Endocrinology & Diabetes 04/2015; 123(07). DOI:10.1055/s-0035-1545344 · 1.76 Impact Factor
  • Experimental and Clinical Endocrinology & Diabetes 03/2015; 122(03). DOI:10.1055/s-0035-1547773 · 1.76 Impact Factor
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    ABSTRACT: This study aimed to perform a comprehensive analysis of interlobular, intralobular and parenchymal pancreatic fat in order to assess their respective effects on beta cell function. Fifty-six participants (normal glucose tolerance [NGT] (n = 28), impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) (n = 14) and patients with type 2 diabetes (n = 14)) underwent a frequent-sampling OGTT and non-invasive magnetic resonance imaging (MRI; whole-body and pancreatic) and proton magnetic resonance spectroscopy ((1)H-MRS; liver and pancreatic fat). Total pancreatic fat was assessed by a standard 2 cm(3) (1)H-MRS method, intralobular fat by 1 cm(3) (1)H-MRS that avoided interlobular fat within modified DIXON (mDIXON) water images, and parenchymal fat by a validated mDIXON-MRI fat-fraction method. Comparison of (1)H-MRS techniques revealed an inhomogeneous distribution of interlobular and intralobular adipose tissue, which increased with decreasing glucose tolerance. mDIXON-MRI measurements provided evidence against uniform steatosis, revealing regions of parenchymal tissue void of lipid accumulation in all participants. Total (r = 0.385, p < 0.01) and intralobular pancreas adipose tissue infiltration (r = 0.310, p < 0.05) positively associated with age, but not with fasting or 2 h glucose levels, BMI or visceral fat content (all p > 0.5). Furthermore, no associations were found between total and intralobular pancreatic adipose tissue infiltration and insulin secretion or beta cell function within NGT, IFG/IGT or patients with type 2 diabetes (all p > 0.2). The pancreas does not appear to be another target organ for abnormal endocrine function because of ectopic parenchymal fat storage. No relationship was found between pancreatic adipose tissue infiltration and beta cell function, regardless of glucose tolerance status.
    Diabetologia 03/2015; 58(7). DOI:10.1007/s00125-015-3544-5 · 6.88 Impact Factor
  • Thomas Leyhe · Karsten Müssig
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    ABSTRACT: Hashimoto’s thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced grey matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto’s encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in-vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in-vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits.
    Brain Behavior and Immunity 10/2014; 41(14). DOI:10.1016/j.bbi.2014.03.008 · 6.13 Impact Factor
  • Katharina Weber · Michael Roden · Karsten Müssig
    Diabetes aktuell 07/2014; 12(04):164-170. DOI:10.1055/s-0034-1387172
  • Franziska Schwarz · Karsten Müssig
    Diabetologie und Stoffwechsel 07/2014; 9(03):141-142. DOI:10.1055/s-0033-1362659 · 0.31 Impact Factor
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    ABSTRACT: Objectif Une TEP au 68Ga-DOTATOC permet l’exploration par imagerie et l’évaluation quantitative de l’expression des récepteurs de la somatostatine dans les tumeurs neuro-endocrines (TNE). Ce travail visait à étudier si la TEP-TDM au 68Ga-DOTATOC avant traitement a une valeur prédictive de la réponse à la radiothérapie interne vectorisée (RIV). Patients et méthodes Quarante patients présentant une TNE de stade avancé ont reçu une dose fixe de 90Y-DOTATOC (5550 ou 3700 MBq). Avant la RIV, chaque patient a bénéficié d’une TEP-TDM au 68Ga-DOTATOC. Les résultats à trois mois ont été évalués par exploration scanographique, dosage de marqueurs tumoraux et appréciation de l’évolution clinique, puis corrélés à la fixation du 68Ga-DOTATOC (SUVmax) et à la fixation estimée du 90Y-DOTATOC dans les manifestations tumorales (MBq/g). Nous avons construit des courbes ROC et comparé deux à deux les ASC (aires sous la courbe) ; les variables continues étaient la fixation avant RIV du 68Ga-DOTATOC, la fixation estimée du 90Y-DOTATOC, l’activité thérapeutique seule et l’activité rapportée au poids ; la réponse ou l’absence de réponse constituait la variable de classification. Résultats En nous basant sur des critères conventionnels (réduction du volume tumoral, diminution des marqueurs tumoraux, amélioration ou stabilisation clinique), nous avons identifié 20 patients répondeurs et 16 patients non répondeurs ; pour quatre patients, les résultats étaient équivoques. Nous avons choisi une SUV > 17,9 comme seuil de résultat favorable ; la TEP était un indicateur prédictif de la réponse au traitement chez tous les patients répondeurs et chez 15 patients non répondeurs sur 16. Les quatre patients aux résultats équivoques avaient une SUV ≤ 17,9 ; ils ont rapidement présenté une progression tumorale. Avec une fixation tumorale estimée du 90Y-DOTATOC > 1,26 MBq/g comme seuil prédictif de réponse au traitement, 19 patients répondeurs sur 20 et 14 non-répondeurs sur 16 ont pu être identifiés avec exactitude. Chez tous les patients aux résultats équivoques, la fixation estimée du 90Y-DOTATOC était inférieure à 1,26 MBq/g. Conclusion La fixation tumorale du 68Ga-DOTATOC avant RIV, ainsi que la fixation estimée du 90Y-DOTATOC, sont étroitement associées aux résultats ultérieurs de la RIV. Les valeurs seuil choisies doivent être confirmées par des études prospectives et pourraient ensuite justifier des posologies individuelles et la sélection de patients ayant une probabilité élevée de réponse positive.
    03/2014; 95(3):292–303. DOI:10.1016/j.jradio.2013.01.018
  • Sabine Kahl · Michael Roden · Klaus Moerike · Karsten Muessig
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    ABSTRACT: History and admission findings: We report on a 48-year-old female patient with recently developed severe hypertriglyceridemia. Medical history was remarkable for breast cancer with breast-preserving surgery and chemoradiotherapy. The patient has been treated with 20 mg tamoxifen per day for three months. Investigations: Laboratory results showed hypertriglyeridemia, hypercholesterolemia and lowered HDL-cholesterol. Diagnosis, treatment and course: Findings were consistent with a drug-induced hypertriglyceridemia caused by anti-estrogenic therapy with tamoxifen. After consulting the patient's gynaecologist, we discontinued tamoxifen treatment. Thereupon, triglyceride levels fell consistently. There were no signs of pancreatitis, serum amylase and lipase were in the normal range. Conclusions: Patients with pre-diagnosed metabolic disorders, especially dyslipidemia and type 2 diabetes, should undergo regular controls of serum triglycerides during tamoxifen treatment. Also, one should keep in mind that a subacute, severe rise in serum triglyceride levels may be caused, in rare cases, by tamoxifen treatment.
    DMW - Deutsche Medizinische Wochenschrift 11/2013; 138(47):2410. DOI:10.1055/s-0033-1349600 · 0.55 Impact Factor
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    ABSTRACT: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy (PRRT). Forty patients with advanced stage NET were treated with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y-DOTATOC and treatment activity alone and in relation to body weight as continuous variables, and response/no response as classification variable. According to conventional criteria (tumor shrinkage, decrease of tumor markers, improved or stable clinical condition), 20 patients were classified as responders, 16 as non-responders and in four patients findings were equivocal. Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to predict treatment response of all responders and 15 out of 16 non-responders. All four patients with equivocal findings showed SUV less than or equal to 17.9 and soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor manifestations using a cut-off more than 1.26MBq/g as predictor of response was able to correctly classify 19 out of 20 responders, and 14 out of 16 non-responders. In all patients with equivocal findings, the assumed uptake of (90)Y-DOTATOC was below 1.26MBq/g. Pre-therapeutic (68)Ga-DOTATOC tumor uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with the results of subsequent PRRT. The defined cut-off values should be confirmed by prospective studies and may then provide the rationale for individual dosing and selecting patients with high likelihood of favorable treatment outcome.
    09/2013; 95(3). DOI:10.1016/j.diii.2013.07.006
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    ABSTRACT: History and admission findings: We report on a 44-year-old patient with type 1 diabetes who suffered from vomiting and diarrhoea for 10 days as well as episodes of recurrent hypoglycaemia with reduced insulin requirements. Medical history was remarkable for nasopharyngeal carcinoma that had been treated by radiation and chemotherapy five years earlier. Investigations: Laboratory results showed hyponatraemia, reduced free thyroxine with normal thyroid- stimulating hormone and diminished morning serum cortisol levels. Short synacthen test revealed inadequate stimulation of cortisol. Corticotropin-releasing hormone test showed a subnormal stimulation of cortisol with a strong increase of adrenocorticotropin. Besides, testosterone, luteinizing hormone and insulin- like growth factor-1 levels were reduced. The growth hormone-releasing hormone-arginine test revealed complete growth hormone deficiency. A MRI of the sella revealed no abnormalities in hypothalamus and pituitary gland. Diagnosis, treatment and course: Findings were consistent with panhypopituitarism following radiotherapy for nasopharyngeal carcinoma. A replacement therapy was started comprising hydrocortisone, L-thyroxine and testosterone. Accordingly, symptomatology improved. Conclusions: Obscure recurrent hypoglycaemia requires endocrinological tests to clarify possible underlying hypocortisolism.
    DMW - Deutsche Medizinische Wochenschrift 07/2013; 138(28/29):1470. DOI:10.1055/s-0033-1343305 · 0.55 Impact Factor
  • S Nowak · M Scheer · B Nowotny · K Müssig · M Roden · D Ziegler
    Diabetologie und Stoffwechsel 04/2013; 8(S 01). DOI:10.1055/s-0033-1341871 · 0.31 Impact Factor
  • F. Schwarz · M. Roden · K. Müssig
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    ABSTRACT: Die diabetische Dyslipidämie stellt bei Menschen mit Typ-2-Diabetes einen wichtigen kardiovaskulären Risikofaktor dar. Verantwortlich für die Veränderungen im Lipidstoffwechsel ist insbesondere die Insulinresistenz, die die exzessive Bildung von großen, triglyzeridreichen Very-low-density-Lipoprotein(VLDL)-1-Partikeln und somit die Hypertriglyzeridämie begünstigt. Die erhöhten VLDL-Plasma-Spiegel entstehen zum einem durch vermehrte Produktion infolge des gesteigerten Zuflusses freier Fettsäuren zur Leber und zum anderen durch verminderten Abbau infolge von Insulinresistenz und niedrigem Adiponektinplasmaspiegel. Eine Ansammlung triglyzeridreicher Lipoproteine führt zur vermehrten Anzahl kleiner, dichter Low-density Lipoproteins („small-dense-LDL“, sdLDL) und verringerter Konzentration der Cholesterin rücktransportierenden High-density-Lipoprotein(HDL)-Partikel. Durch das Cholesterinestertransferprotein (CETP) wird der Austausch von Triglyzeriden der VLDL oder Chylomikronen gegen Cholesterinester der LDL- bzw. HDL-Partikel vermittelt. Durch Hydrolyse der triglyzeridreichen LDL bzw. HDL entsteht schließlich die atherogene Komposition aus sdLDL und kleineren, dysfunktionalen HDL-Partikeln, die rasch abgebaut werden.
    Der Diabetologe 11/2012; 8(7):550-555. DOI:10.1007/s11428-012-0888-z · 0.06 Impact Factor
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    ABSTRACT: Purpose: Though increased thyroid perfusion assessed by colour-coded Doppler ultrasound (CDUS) is characteristic of Graves' disease (GD), sometimes perfusion assessment by CDUS is not possible. In these cases, arterial spin labelling (ASL), a novel magnetic resonance imaging (MRI) technique allowing non-invasive thyroid perfusion quantification, may have additional diagnostic value. We aimed to evaluate the potential of ASL-MRI for assessment of increased blood perfusion in patients with GD compared to CDUS.Materials and Methods: Thyroid perfusion was measured by CDUS (volume flow rate calculated from pulsed wave Doppler signals and vessel diameter) and ASL-MRI at 1.5 T in 7 patients with GD and 10 healthy controls.Results: In patients with GD, average perfusion in both thyroid lobes was markedly increased compared to controls. Both techniques applied for volume related perfusion as well as absolute volume flow in thyroid feeding vessels provided similar results (all p = 0.0008). Using a cut-off value of 22 ml/min for the volume flow rate assessed by CDUS in the four feeding vessels allowed discrimination between patients with GD and controls in all cases. After adjusting thyroid perfusion for the differences in organ volume, both CDUS and ASL revealed also complete discrimination between health and disease. Conclusion: Thyroid perfusion measurement by ASL-MRI reliably discriminate GD from normal thyroid glands. In patients in whom thyroid arteries cannot be depicted by CDUS for technical or anatomical reasons, ASL-MRI may have additional diagnostic value.
    RöFo - Fortschritte auf dem Gebiet der R 10/2012; 184(12). DOI:10.1055/s-0032-1325342 · 1.96 Impact Factor
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    ABSTRACT: Hashimoto's thyroiditis (HT) can casually co-occur with an encephalopathy associated with autoimmune thyroid disease. Recently we found an increased occurrence of weaknesses in sustained attention and response inhibition in a subgroup of euthyroid patients with HT as obtained by the d2 attention test. Previous studies in healthy subjects and patients with brain lesions demonstrated a pivotal role for the left inferior frontal gyrus (LIFG) in these skills. Therefore, we studied the association between the performance in the d2 test and grey matter (GM) density of the LIFG in 13 euthyroid patients with HT compared to a control group of 12 euthyroid patients with other thyroid diseases. A significant correlation between GM density and d2 test total score was detected for the opercular part of the LIFG in patients with HT (p<0.001), but not in the control group (p=0.94). Regression in patients with HT was significantly stronger than in the control group (p=0.02). Moreover, GM density was significantly reduced when comparing HT patients with control patients that scored in the lower third during d2 attention testing (p<0.05). It can be concluded that in HT performance in the d2 test correlated with GM density of the LIFG. Particularly low achievement was associated with reduced GM density of this brain region suggesting an influence of autoimmune processes on the frontal cortex in this disease. This could be due to not yet known antibodies affecting brain morphology or an influence of thyroid antibodies themselves.
    Brain Behavior and Immunity 09/2012; 27(1). DOI:10.1016/j.bbi.2012.09.007 · 6.13 Impact Factor
  • Alzheimer's and Dementia 07/2012; 8(4):P505. DOI:10.1016/j.jalz.2012.05.1372 · 17.47 Impact Factor
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    ABSTRACT: Previous studies suggest impairments of physical, mental, and psychic well-being in patients with Hashimoto's thyroiditis (HT), but these impairments have been shown to be independent of thyroid dysfunction. In 64 euthyroid patients with HT, symptomatic distress was assessed with the Symptom Checklist-90-Revised (SCL-90-R), a 90-item multidimensional self-report symptom inventory using a 5-point rating scale. In a subgroup of patients, endocrine testing 3 years prior to the current investigation was available. Anti-thyroid peroxidase antibodies (TPO-Abs) were associated with the three SCL-90-R global indices Global Severity Index (GSI), Positive Symptom Distress Index (PSDI), and Positive Symptom Total (PST) as well as with somatization and obsessive-compulsive symptoms after adjustment for age, gender, and thyroid function as assessed by TSH levels (all p<0.05). HT patients positive for TPO-Abs showed poorer results in the three SCL-90-R global indices as well as in the three domains: somatization, obsessive-compulsive symptoms, and depression (all p≤0.02), though the aforementioned associations did not withstand sequential Bonferroni correction for multiple testing. In contrast, TPO-Abs positivity, defined as TPO-Abs >100 IU/l, significantly predicted poorer psychosocial well-being in all of the three SCL-90-R global indices after three years, even after correction (all p≤0.02). In conclusion, high TPO-Abs are associated with poor physical and psychological well-being and appear to predict future health perception in HT patients.
    Brain Behavior and Immunity 01/2012; 26(4):559-63. DOI:10.1016/j.bbi.2012.01.006 · 6.13 Impact Factor

Publication Stats

829 Citations
362.04 Total Impact Points


  • 2012–2015
    • Heinrich-Heine-Universität Düsseldorf
      • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany
    • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2014
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2004–2012
    • University of Tuebingen
      • • Department of Internal Medicine
      • • Department of Ethnology
      Tübingen, Baden-Württemberg, Germany
  • 2010
    • Group Florence Nightingale Hastaneleri
      İstanbul, Istanbul, Turkey
  • 2005–2010
    • Universitätsklinikum Tübingen
      • • Internal Medicine IV - Endocrinology and diabetology, angiology, nephrology and clinical chemistry
      • • Department of Medicine
      Tübingen, Baden-Württemberg, Germany