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Biomedical subjects

M Schütt

Publications and source records attributed to M Schütt.

At least 19 recordsLinked to original sources
PubMed2006

Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria.

Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,on intensified (>or=4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day,p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit ofSMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.insulin therapy and center difference, the SMBG frequency was associated with better metabolic control (HbA1c-reduction of0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients Blood glucose measurements are generally accepted components of a modern diabetes self-management. The value of self-monitoring of blood glucose (SMBG) is, however, discussed controversially and only a few studies addressed the efficacy of SMBG under real-life conditions so far. In order to investigate whether the frequency of SMBG is related to long-term metabolic control, data from the DPV-Wiss-database, a standardized,prospective, computer-based documentation of diabetes care and outcome, were analyzed for patients with type 1(n = 19,491) and type 2 (n = 5,009) diabetes from 191 centers in Germany and Austria. Local HbA1c reference ranges were mathematically adjusted to the DCCT reference. For each patient, data from the most recent year of diabetes care were used. On average,patients with type 1 diabetes performed 4.4 blood glucose measurements/day. Corrected for age, gender, diabetes duration,insulin therapy and center difference, the SMBG frequency wasassociated with better metabolic control (HbA1c-reduction of 0.26% for one additional SMBG/day, p < 0.0001). HbA1c-reduction with higher frequency of SMBG was more pronounced in patients on intensified (>or= 4 daily injections or CSII) therapy (HbA1c reduction of 0.32% for one additional SMBG/day) compared to patients on conventional (1-3 daily injections) therapy(HbA1c-reduction of 0.16% for one additional SMBG/day). In 2,021 patients with insulin-treated type 2 diabetes (2.7 measurements/day), more frequent SMBG was associated with better metabolic control (HbA1c-reduction of 0.16% for one additionalSMBG/day, p < 0.0001), while in 2,988 patients on OAD or diet alone (2.0 measurements/day), more frequent blood glucose measurements were associated with higher HbA1c-levels(HbA1c-increase of 0.14% for one additional SMBG/day, p < 0.0001). These data indicate that more frequent SMBG are associated with better metabolic control in both, patients with type 1 and insulin-treated type 2 diabetes. Since no benefit of SMBG on metabolic control was found in patients with type 2 diabetes on OAD or diet alone, SMBG should primarily be recommended for those patients with suboptimal metabolic control whereas the benefit of SHBG in non-insulin-treated patients with adequate HbA1c-levels remains uncertain.

Austria↗
PubMed2004

[Structured concept for the establishment of a broad and ambulatory care of patients with type 2 diabetes: one-year evaluation of a regional teaching organization].

BACKGROUND: The increasing prevalence of diabetes mellitus and its long-term complications are associated with an expanding social medical problem. In order to originate an established teaching and training program on a physician-based level in short time, three specialist diabetes centers from Lübeck transferred their concept to a diabetes organization based on 17 physicians who had only rarely undertaken any diabetes teaching before. We investigated the achievement and effectiveness of this concept in a prospective multicenter evaluation one year after the patients had received structured diabetes teaching by the organization. PATIENTS AND METHODS: Physicians and their teaching staff were trained by the specialists from the diabetes centers according to an official agreement. Patients were treated by each practice, while the diabetes teaching was done centrally by the organization through a diabetes assistant/dietician based on a modified official diabetes teaching and training program (ZI-program). 230 of 250 patients (120 male, 110 female) were reinvestigated one year after they had received the teaching. The group consisted of 179 non-insulin-treated (NIB; 94 via physicians, 85 via specialists) and 51 insulin-treated (IB; 19 via physicians, 32 via specialists) participants. RESULTS: The average age of NIB was 60.4+/-9.8 years, while IBs were 68.8+/-7.3 years old. HbA (1c) values were reduced in both groups, NIB and IB, by approximately 1% (NIB: 7.59+/-1.97% to 6.59+/-1.84%; IB: 8.47+/-1.35% to 7,36+/-1,38 %; p < 0,001). In the NIB-group the BMI was reduced by 0,64+/-0,14 kg x m (-2), whereas it was increased in the IB-group by 0.33+/-0.24 kg x m(-2) (NIB: 30.55+/-0.40 to 29.91+/-0.39 kg x m(-2), p < 0.001; IB: 28.83+/-0.74 to 29.16+/-0.75 kg x m(-2), p = 0.82). CONCLUSION: The transfer of established teaching and training concepts of specialist diabetes centers to a newly founded, physician-based diabetes organization resulted in a broad, effective and long-lasting medical care of patients with type 2 diabetics treated without or with insulin. The results are superior to those of other evaluations based on diabetes training ZI-programs.

Aged↗
PubMed2004

[Prevalence of hantavirus infections in Germany].

Hantaviruses belong to the group of "emerging" viruses. Pathogenic European hantaviruses can cause a human disease designated "hemorrhagic fever with renal syndrome" of varying severity. In general, diagnostics of hantavirus infections are based on immunofluorescence assays using virus-infected cells or enzyme immunoassays and Western blot tests using recombinant nucleocapsid proteins. For highly sensitive detection of hantavirus-specific antibodies in the enzyme immunoassay, a homologous hantavirus nucleocapsid protein is needed as a diagnostic antigen. Serological typing of hantavirus infections can be obtained by neutralization assays, which in certain cases require the use of late convalescent sera. The seroprevalence in the normal German population is about 1%. In professionally exposed risk groups, e. g., forest workers, a seroprevalence higher than that in the normal population was observed. Endemic regions for hantavirus infections are located mainly in Baden-Württemberg. In the years 2001-2003 an annual number of about 200 clinically apparent hantavirus infections were registered in Germany. Neutralization assays detected almost exclusively human infections caused by Puumala and Dobrava viruses, only very rarely by Tula virus. Until this day in Germany mainly mild to moderate courses of human hantavirus infections have been documented. Besides infections caused by "German" hantaviruses, up to 10% of the clinically apparent hantavirus infections registered annually in Germany are caused by infections imported from other countries, mainly from Europe. So far only very limited molecular genetic data about the circulating hantaviruses in Germany are available. Additional investigations are needed to get a more precise picture about the distribution of hantaviruses in Germany and to calculate the resulting risk for the human population.

Communicable Disease Control↗
PubMed2004

Long-term effects of HIV-1 protease inhibitors on insulin secretion and insulin signaling in INS-1 beta cells.

The mechanism by which chronic treatment with HIV (human immunodeficiency virus)-1 protease inhibitors leads to a deterioration of glucose metabolism appears to involve insulin resistance, and may also involve impaired insulin secretion. Here we investigated the long-term effects of HIV-1 protease inhibitors on glucose-stimulated insulin secretion from beta cells and explored whether altered insulin secretion might be related to altered insulin signaling. INS-1 cells were incubated for 48 h with different concentrations of amprenavir, indinavir, nelfinavir, ritonavir or saquinavir, stimulated with 20 mM d-glucose, and insulin determined in the supernatant. To evaluate insulin signaling, cells were stimulated with 100 nM insulin for 2 min, and insulin-receptor substrate (IRS)-1, -2 and Akt phosphorylation determined. Incubation for 48 h with ritonavir, nelfinavir and saquinavir resulted in impaired glucose-induced insulin secretion at 2.5, 5 and 5 microM respectively, whereas amprenavir or indinavir had no effects even at 20 and 100 microM respectively. The impaired insulin secretion by ritonavir, nelfinavir and saquinavir was associated with decreased insulin-stimulated IRS-2 phosphorylation, and, for nelfinavir and saquinavir, with decreased insulin-stimulated IRS-1 and Thr308-Akt phosphorylation. No such effects on signaling were observed with amprenavir or indinavir. In conclusion, certain HIV-1 protease inhibitors, such as ritonavir, nelfinavir and saquinavir, not only induce peripheral insulin resistance, but also impair glucose-stimulated insulin secretion from beta cells. With respect to the long-term effect on beta-cell function there appear to be differences between the protease inhibitors that may be clinically relevant. Finally, these effects on insulin secretion after a 48 h incubation with protease inhibitor were associated with a reduction of the insulin-stimulated phosphorylation of insulin signaling parameters, particularly IRS-2, suggesting that protease inhibitor-induced alterations in the insulin signaling pathway may contribute to the impaired beta-cell function.

Carbamates↗
PubMed2004

Life-threatening Dobrava hantavirus infection with unusually extended pulmonary involvement.

In Europe, hantavirus infections usually present as hemorrhagic fever with renal syndrome and its mild form nephropathia epidemica, while clinical cases with severe pulmonary affections are extremely rare and appear to be confined to infections by New World hanta viruses in the Americas. We report on a female patient from Northern Germany, who suffered primarily from severe acute respiratory distress syndrome-like pulmonary failure due to Dobrava hantavirus infection that was complicated by acute renal insufficiency.

Female↗
PubMed2003

The HIV protease inhibitor indinavir impairs glycogen synthesis in HepG2 hepatoma cells.

HIV protease inhibitor treatment is associated with insulin resistance. We have recently demonstrated that the HIV protease inhibitor indinavir influences initial insulin signaling steps in HepG2 cells. Here we investigated in the same cell model whether indinavir alters insulin-stimulated glycogen synthesis. Since an altered phosphotyrosine phosphatase activity could represent a mechanism by which insulin signaling is influenced, we also assessed potential indinavir effects on protein tyrosine phosphatase activity directed against tyrosine phosphorylated insulin receptor substrate-1. HepG2 cells were incubated for 48 h without or with indinavir (100 micro mol/l). Subsequently, the insulin-stimulated incorporation of 14C-glucose into glycogen was measured. In indinavir-treated cells the insulin effect on glycogen synthesis was reduced by 30 +/- 4.5 %. Dephosphorylation of immobilized tyrosine-phosphorylated insulin-receptor substrate-1 by the cell extracts was determined using a microwell plate-based method, and indinavir treatment did not alter this dephosphorylation. In conclusion, our data suggest that indinavir affects insulin-stimulation of glycogen synthesis in liver cells, and this may be related to the previously observed alterations in insulin signaling. Direct effects of indinavir on the GLUT4 transport system, that have been suggested from data in other cell systems, are unlikely in HepG2 cells that express no or almost no GLUT4 transport system. Finally, our data do not support the hypothesis that indinavir alters insulin signaling by influencing protein tyrosine phosphatase activity directed against insulin receptor substrate-1.

Carcinoma, Hepatocellular↗
PubMed2001

[Recurrent hypoglycemia caused by malignant insulinoma: chemoembolization as a therapeutic option].

HISTORY AND CLINICAL FINDINGS: A 73-year-old previously healthy woman presented with recurrent weakness, vertigo and perioral paresthesia of 3 months' duration. Physical examination on admission was unremarkable and revealed a patient in good condition. INVESTIGATIONS: Recurrent episodes of fasting hypoglycemia let us to proceed with a fasting test. The test was stopped after 24 hours when the patient became presyncopal and was found to have a blood sugar value of 2.2 mmol/l (accompanied by inadequately increased values for proinsulin, insulin and C-peptide). Ultrasound and computertomography of the abdomen showed a huge inhomogeneous mass in the tail of pancreas and multiple lesions in the liver, respectively. Core needle biopsies revealed typical histopathological findings of a neuroendocrine carcinoma. TREATMENT AND COURSE: Eight cycles of chemotherapy were given using streptozotocin/doxorubicin for three cycles and streptozotocin/5-fluorouracil for the remaining therapy over a period of 16 months resulting in a reduction in size of liver metastases and improvement of symptoms. Following 6 months without any therapy new episodes of severe hypoglycemia and progression of the liver metastases occurred. Despite seven further cycles of chemotherapy and additional treatment with diazoxide/octreotide the patient remained hypoglycemic and continuous glucose infusions became necessary. Therefore, chemoembolization of the liver with streptozotocin/5-fluorouracil and lipiodol-emulsion was performed. This resulted in a significant improvement of symptoms and the patient could subsequently be discharged. The patient died 4 months later. CONCLUSION: Chemoembolization is an effective possibility in the palliative treatment of advanced malignant insulinoma.

Aged↗
PubMed2001

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species.

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381-935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans.

Adolescent↗
PubMed2001

Clinical characterization of Dobrava hantavirus infections in Germany.

There is increasing evidence that Dobrava (DOBV) but not Hantaan (HTNV) hantavirus is a hemorrhagic fever with renal syndrome (HFRS) causing agent in Central Europe. However, only single clinical cases of HFRS due to acute DOBV infection have been described so far. We report on three male patients from a non-endemic hantavirus focus in Northern Germany who suffered from mild to moderate HFRS strongly resembling nephropathia epidemica. Serotyping by detection of hantavirus species-specific neutralizing antibodies revealed acute infections by the HTNV-related hantavirus DOBV in all three cases. Since DOBV infections in the Balkans frequently present as severe HFRS, our cases suggest that Central-European DOBV infections have a different, less severe clinical outcome. These differences in DOBV virulence towards humans might be due to the existence of different genetic lineages of DOBV.

Acute Disease↗
PubMed2000

The HIV-1 protease inhibitor indinavir impairs insulin signalling in HepG2 hepatoma cells.

AIMS/HYPOTHESIS: Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling. METHODS: We incubated HepG2 cells for 48 h without or with indinavir (100 micromol/l). Subsequently 125I-insulin binding to the cells and the effects of insulin stimulation on insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-Thr308-phosphorylation were measured. RESULTS: In cells not exposed to indinavir, insulin (100 nmol/l) led to rapid increases of insulin-receptor substrate-1-phosphorylation, association of phosphatidylinositol 3-kinase with insulin-receptor substrate-1 and Akt-phosphorylation during the first 75 s, followed by subsequent decreases. In indinavir-treated cells, these insulin-stimulated increases during the first 75 s were reduced by 30-60% and this was not associated with alterations in cell number or viability, insulin binding to the cells or cellular insulin-receptor substrate-1-content. CONCLUSION/INTERPRETATION: Effects of indinavir on initial insulin signalling could cause, or contribute to, the metabolic effects of human immunodeficiency virus-1 protease inhibitors.

Carcinoma, Hepatocellular↗
PubMed2000

Coexistence of factor V Leiden and primary antiphospholipid syndrome: a patient with recurrent myocardial infarctions and thrombocytopenia.

Increased thrombin generation associated with resistance to activated protein C makes the latter a likely candidate for an increased risk of acute coronary events. Activated protein C resistance (factor V Leiden) on its own, however, appears to have no significant effect in this regard. We describe a case of recurrent myocardial infarction caused by coronary thrombosis in a patient with persistent thrombocytopenia who was found to have a coexistence of heterozygous factor V Leiden and primary antiphospholipid syndrome. Since both thrombophilic disorders interfere with the protein C anticoagulant system, the simultaneous existence of inherited and acquired resistance against activated protein C could account for an increased thrombophilia with manifestation in the coronary arteries. This case suggests that evaluation of patients who present with recurrent acute coronary events should also consider these coagulation defects.

Activated Protein C Resistance↗
PubMed2000

Functional characteristics of insulin receptors with a Thr-->Ser1200 mutation overexpressed in Chinese hamster ovary cells.

OBJECTIVE: To investigate the functional properties of insulin receptors with a Thr-->Ser(1200)-mutation that is associated with severe insulin resistance in humans. DESIGN AND METHODS: The effect of in situ insulin-stimulation on insulin receptor kinase activity was studied in Chinese hamster ovary cells with overexpressed human Ser(1200)-mutated, non-mutated, and ATP-binding site-mutated (Lys-->Arg(1030)) receptors using a microwell-based assay that only detects human (and not hamster) insulin receptors. Moreover, the fraction of anti-phosphotyrosine antibody-binding receptors following in situ stimulation was separated, and autophosphorylation and kinase activity resulting from in situ and/or in vitro activation evaluated in this fraction. RESULTS: Although insulin-stimulated kinase activity of human-specific anti-insulin receptor antibody-binding receptors in cells with Ser(1200)-mutated insulin receptors represented only 3.3% of that reached in cells with non-mutated receptors, a clear insulin-induced increase in kinase activity was observed (3.4-fold; P<0.05). This increase was associated with a 2.3+/-0.6% (P<0.05) increase in anti-phosphotyrosine-binding receptors with a kinase activity representing 43+/-8% of that found in activated non-mutated receptors. In vitro autophosphorylation and kinase activation proceeded much more slowly in Ser(1200)-mutated receptors (t(1/2)): 100 min) compared with non-mutated receptors (t(1/2)): 1 min) and were inhibitable by lower alkaline phosphatase concentrations (EC(50): 3 U/ml and 70 U/ml respectively). No activation of insulin receptor kinase was observed with Arg(1030)-mutated receptors. CONCLUSIONS: Overexpressed Ser(1200)-mutated human insulin receptors possess insulin-stimulated kinase activity and can be activated in situ and in vitro. They are characterized by a markedly slower autophosphorylation reaction, which, in a phosphatase-containing environment, results in a small fraction of phosphorylated and activated receptors.

Alkaline Phosphatase↗
PubMed2000

Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia.

Recent studies suggest that high glucose concentrations impair insulin receptor phosphorylation and kinase activation in certain cell models. To examine whether such an effect of glucose can also be demonstrated in vivo, insulin receptor kinase activation was studied in erythrocytes from 11 patients with non-insulin-dependent diabetes (NIDDM), before and after reduction of hyperglycemia (from 14.6+/-1.6 to 6.6+/-0.5 mmol/l fasting plasma glucose within 8.6+/-0.6 days). For the measurement of receptor kinase activation, cells were incubated with insulin (0-400 nmol/l), solubilized and insulin receptors immobilized to microwells coated with anti-insulin receptor antibody. Kinase activity towards insulin receptor substrate-1 and insulin binding were then measured in these wells. Kinase activities (expressed as amol phosphate transferred per min and per fmol insulin binding activity) were similar before (2.4+/-0.4 and 32.2+/-2.0 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) and after improvement of metabolic control (2.4+/-0.5 and 32.0+/-2.3 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). Moreover, activities were also similar in 22 hyperglycemic patients with NIDDM (2.1+/-0.3 and 35.1+/-1.4 amol/min per fmol with 0 and 400 nmol/l insulin, respectively) compared with those in 21 non-diabetic control individuals (2.1+/-0.3 and 34.2+/-1.2 amol/min per fmol with 0 and 400 nmol/l insulin, respectively). We conclude that insulin activation of erythrocyte insulin receptor kinase is not impaired in NIDDM and is not influenced by hyperglycemia.

Blood Glucose↗
PubMed1998

Familial coexistence of primary antiphospholipid syndrome and factor VLeiden.

The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder in which thromboembolism and thrombocytopenia occur. The antiphospholipid antibodies in these patients may cause acquired activated protein C resistance, whereas hereditary activated protein C resistance results from a common single point mutation in coagulation factor V (factor VLeiden). In a family of 11 members with 4 normal subjects, autoimmune thrombocytopenia was documented in 6 patients. Three out of these were found to have thrombocytopenia associated with primary APS. In addition, these 3 subjects were also heterozygous for the factor VLeiden. Only in this group of individuals did life threatening thromboembolic complications occur, while other thrombocytopenic family members showed no thrombotic manifestations. Genetic studies revealed no linkage between APS and HLA class II alleles. Taken together, we present a family with autoimmune thrombocytopenia, which is associated with primary APS in at least 50% of thrombocytopenic individuals. The coexistence of both APS and factor VLeiden in thrombocytopenic subjects, led to an increased number of thrombotic events, suggesting a critical role of combined acquired and hereditary activated protein C resistance in the development of thrombosis in this family. Since no association between APS and specific HLA groups was found, other underlying risk factors for the development of APS must be considered.

Adolescent↗