K Müssig

Universitätsklinikum Düsseldorf, Düsseldorf, North Rhine-Westphalia, Germany

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Publications (151)334.93 Total impact

  • 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; 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. 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
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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
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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 · 0.65 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 · 2.76 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. DOI:10.1016/j.bbi.2012.09.007 · 5.61 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 · 5.61 Impact Factor
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    ABSTRACT: Although the prognosis of differentiated thyroid carcinoma (DTC) is excellent, with 10-year survival rates of about 90%, about one-third of patients experiences recurrent disease. We aimed to identify novel histological prognostic factors to optimize treatment and follow-up of patients at risks. Retrospective analysis of patients diagnosed from January 1990 to March 2004. A total of 93 patients diagnosed with DTC of which 67 with papillary and 26 with follicular histology. Analysis of immunohistochemical expression of somatostatin receptor (sst) subtypes 1-5, glucose transporter-1 (GLUT-1), receptor tyrosine kinase c-KIT, oestrogen and progesterone receptors, and proliferation marker Ki-67 and correlation with the patients' clinical outcome. DTC showed immunohistochemical expression of GLUT-1, C-KIT and progesterone receptor in a high percentage of cases (range: 57-80%). In contrast, the oestrogen receptor as well as the sst subtypes 1-5 was less frequently detected (range: 15-29%). Mean staining of the proliferation marker Ki-67 was 6% positive cells (range 0-20%). Ki-67 expression was significantly associated with tumour staging (ρ = 0·2076, P = 0·0459), whereas the other histopathological markers were not associated with gender, age, tumour entity, or tumour classification. Tumour staging and expression of Ki-67, oestrogen receptor and sst2, but of none of the other histopathological factors, independently predicted the clinical outcome 5 years after definitive treatment (P < 0·0001, P < 0·0001, P = 0·0004 and P = 0·0206, respectively). In patients with DTC, Ki-67 expression associates with tumour staging and clinical outcome.
    Clinical Endocrinology 01/2012; 77(1):139-45. DOI:10.1111/j.1365-2265.2012.04343.x · 3.35 Impact Factor
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    ABSTRACT: A 51-year-old woman was admitted from a mental institution for evaluation of hypercalcemia. She was treated with lithium for a bipolar disorder since 25 years. She complained of polydypsia and polyuria. The physical examination findings were unremarkable up to manic symptoms. Laboratory values showed elevated serum calcium and parathormone. Serum phosporus was within the normal range. Neck ultrasound revealed a goiter with one nodule in the right thyroid lobe and a suspected enlarged lower left parathyroid gland. The sesta-MIBI-scan failed to detect an adenoma. In light of long-term treatment with lithium and negative MIBI-scan, lithium-associated- hyperparathyreoidism (LAH) was suspected. The patient refused further preoperative imaging studies, such as c-11 methionine positron emission tomography and thyroid scan. Until surgery after stabilization of the psychiatric condition, treatment with the calcimimetic cinacalcet was initiated. Long-term lithium therapy is frequently associated with LAH. The criteria of diagnosis and therapy are similar to those of primary hyperparathyroidism. Lithium alters the set-point of the calcium-sensing-receptor and results in elevation of parathormone und hyperplasia of the parathyroid glands. Patient with LAH have a higher prevalence of multiglandular disease compared with sporadic hyperparathyreoidism. Thus, the preoperative localization is challenging. After surgery recurrent or resistant disease is more frequent. The calcimimetic cinacalcet is a potential alternative for patients who have contraindications to surgery, refuse surgery, or experience recurrent disease after surgery.
    DMW - Deutsche Medizinische Wochenschrift 12/2011; 136(50):2621. DOI:10.1055/s-0031-1292848 · 0.65 Impact Factor
  • RöFo - Fortschritte auf dem Gebiet der R 11/2011; 183(11):995-1000. · 2.76 Impact Factor
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    ABSTRACT: A 48-year-old patient presented with an insufficient control of his diabetes mellitus which was known since 3 years. The antidiabetic medication comprised metformin and exenatide. Physical examination revealed, beside elevated blood pressure, abdominal purple striae. Endocrine testing was consistent with ectopic Cushing's syndrome. Abdominal CT showed a 5 cm measuring, inhomogeneous, contrast-enhanced mass in the right suprarenal area which was positive on iodine-131 MIBG SPECT. Furthermore, urinary catecholamines were markedly increased. Diagnosis of an ACTH-producing pheochromocytoma was made and an open adrenalectomy was performed. Histology confirmed a pheochromocytoma with potential aggressive clinical behaviour according to the Pheocromocytoma of the Adrenal gland Scaled Score. 6 months after the intervention, glucose control was significantly improved with an HbA1c of 5.5%. An ACTH-producing pheochromocytoma is a very rare cause of deterioration of glucose control. However, in presence of typical clinical findings an endocrine work-up is warranted.
    DMW - Deutsche Medizinische Wochenschrift 10/2011; 136(43):2196. DOI:10.1055/s-0031-1289124 · 0.65 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 07/2011; 136(28-29):1476. DOI:10.1055/s-0030-1247626 · 0.65 Impact Factor
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    ABSTRACT: Although pituitary adenomas are common, pituitary carcinoma is a very rare condition. We report on a 48-yr-old male presenting with pituitary carcinoma with malignant growth from the beginning and a fulminant clinical course and give an overview of the previously reported cases, paying special attention to clinical and histological parameters that may predict the clinical course. We performed a MEDLINE search for previously published cases of pituitary carcinoma and analyzed the clinical, laboratory, and radiological findings. Ki-67 index and the number of metastatic diseases found on postmortem examination were significantly increased in patients with no treatment response compared to those with some treatment response (P = 0.03 and P = 0.02, respectively). In contrast, time to occurrence of metastatic disease and time to death were significantly shortened in patients with no treatment response (P = 0.01 and P = 0.02, respectively). No differences were found between the two groups for gender distribution, tumor size, mitotic activity assessed as the number of mitotic figures per 10 high-power fields, and number of locations of metastatic disease. Frequently relapsing, invasive adenoma should raise a suspicion of a malignant disease. Clinically only the presence of metastases is a criterion of malignancy. A high Ki-67 index in the pituitary carcinoma and early manifestation of metastatic disease appear to predict rapid disease progression.
    The Journal of Clinical Endocrinology and Metabolism 06/2011; 96(9):2665-9. DOI:10.1210/jc.2011-1166 · 6.31 Impact Factor
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    ABSTRACT: Pancreatic neuroendocrine tumours (PNET) are rare entities with an annual incidence of < 100,000. About 1 - 2 % of pancreatic neoplasias are neuroendocrine tumours. About one third of these tumours secrete biologically active substances that lead to development of specific clinical syndromes. PNET may occur sporadically or in association with hereditary syndromes, such as multiple endocrine neoplasia type 1 (MEN1). Among the functional PNET, insulinomas and gastrinomas are the most common entities. In contrast, vasoactive intetinale peptide (VIP)-secreting tumours, glucagonomas, serotonin-secreting carcinoid tumors, and tumours with secretion of ectopic hormones, such as calcitonin, are extremely rare. Once diagnosis has been established on the basis of clinical and laboratory findings, localization of the source of pathologic hormone secretion is warranted. Imaging methods frequently used for localization of PNET comprise anatomical imaging modalities, computed tomography, and magnetic resonance imaging, endoscopic ultrasound, selective arterial catheterization with hepatic venous sampling, DTPA-octreotid scintigraphy and DOTA-D-Phe(1)-Tyr(3)-octreotid positron emission tomography. Therapy is based on the specific tumour entity and the extent of the disease. In the majority of patients, even in the case of malignant disease, a surgical approach is warranted, eventually combined with a medical treatment.
    DMW - Deutsche Medizinische Wochenschrift 06/2011; 136(24):1319-30. DOI:10.1055/s-0031-1280554 · 0.65 Impact Factor
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    ABSTRACT: The functional knockout of the calcium-sensitive, nonselective cation channel TRPM5 alters glucose-induced insulin secretion and glucose tolerance. We hypothesized that genetic variation in the TRPM5 gene may contribute to prediabetic phenotypes, including pancreatic β-cell dysfunction. We genotyped 1798 white subjects at increased type 2 diabetes mellitus risk for 9 TRPM5 single nucleotide polymorphisms (namely, rs2301696, rs800344, rs800345, rs800347, rs800348, rs2074234, rs2301698, rs886277, and rs2301699) and also performed correlational analyses with metabolic traits. An oral glucose tolerance test (OGTT) was conducted on all subjects, and a subset (n = 525) additionally underwent a hyperinsulinemic-euglycemic clamp. The 9 chosen single nucleotide polymorphisms cover 100% of the common genetic variation (minor allele frequency ≥0.05) within the TRPM5 locus (D' = 1.0; r² ≥ 0.8). Rs800344, rs800345, and rs2301699 were significantly associated with area under the curve (AUC) glucose during the OGTT in the additive and dominant models after adjustment for sex, age, and body mass index (all Ps ≤ .0025). Furthermore, rs800344 was significantly associated with 2-hour glucose in the dominant model (P = .0009). After stratification for sex, rs2301699 was significantly associated with the ratio of AUC insulin 0 to 30 minutes to AUC glucose 0 to 30 minutes in women (P = .0097), but not in men (P = .3), in the dominant model. Female minor allele carriers of rs2301699 showed significantly lower glucagon-like peptide-1 levels at 30 minutes during the OGTT compared with major allele homozygotes (P = .0124), whereas in male subjects, no significant differences were found (P = .3). In our German population, the common TRPM5 variants are likely to be associated with prediabetic phenotypes; and this may in turn contribute to the development of type 2 diabetes mellitus.
    Metabolism: clinical and experimental 04/2011; 60(9):1325-33. DOI:10.1016/j.metabol.2011.02.002 · 3.61 Impact Factor
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    ABSTRACT: To give an overview on the relationship between diabetes mellitus and increased cancer risk. We identified studies evaluating the association between diabetes mellitus, its treatment with insulin and insulin analogues and malignancies, paying special attention to studies on in vitro and in vivo effects of the long-acting analogue insulin glargine. Even although the pathophysiological mechanisms underlying the relationship between elevated cancer risk and Type 2 diabetes mellitus are not completely understood, hyperinsulinaemia in the presence of insulin resistance appears to be a key factor. Because of the mitogenic actions of insulin at high concentrations, hyperinsulinaemia may favour tumorigenesis. In line with this, an insulin-based therapy is associated with an increased cancer risk, whereas an insulin-sensitizing treatment results in a cancer risk reduction. Furthermore, alterations of the insulin receptor profile on tumour cells may contribute to an enhanced susceptibility towards insulin. Studies on the analogue insulin glargine have been controversial. In vitro data pointed to an elevated mitogenicity of insulin glargine, whereas in vivo data did not confirm cancerogenous effects. Moreover, recently published clinical studies on the association of insulin glargine (Lantus®) and cancer suggest that treatment with insulin glargine is not associated with increased cancer risk. The relationship between elevated cancer risk and Type 2 diabetes mellitus has been shown by numerous epidemiological studies, with endogenous and exogenous hyperinsulinaemia in the presence of insulin resistance as potential underlying pathophysiological mechanisms. Recent clinical studies do not support an increased cancer risk in patients treated with insulin glargine.
    Diabetic Medicine 03/2011; 28(3):276-86. DOI:10.1111/j.1464-5491.2010.03132.x · 3.24 Impact Factor
  • DMW - Deutsche Medizinische Wochenschrift 02/2011; 136(8):369-70. DOI:10.1055/s-0031-1272557 · 0.65 Impact Factor

Publication Stats

762 Citations
334.93 Total Impact Points


  • 2014
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2013–2014
    • Heinrich-Heine-Universität Düsseldorf
      • German Diabetes Center
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2005–2012
    • Universitätsklinikum Tübingen
      • • Internal Medicine IV - Endocrinology and diabetology, angiology, nephrology and clinical chemistry
      • • Department of Medicine
      Tübingen, Baden-Württemberg, 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