55 results on '"Georg Lübben"'
Search Results
2. Successful switch from insulin therapy to treatment with pioglitazone in type 2 diabetes patients with residual β-cell function: results from the PioSwitch Study
- Author
-
M. Borchert, A. Pfützner, Thomas Schöndorf, E. Karagiannis, C. Hohberg, Thomas Forst, and Georg Lübben
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Pilot Projects ,Type 2 diabetes ,Gastroenterology ,Body Mass Index ,Endocrinology ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Prospective Studies ,Aged ,Pioglitazone ,Adiponectin ,business.industry ,Middle Aged ,medicine.disease ,Glimepiride ,Sulfonylurea Compounds ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,Thiazolidinediones ,business ,Body mass index ,Biomarkers ,medicine.drug - Abstract
AIM Insulin treatment is considered to be the final option for patients with progressive type 2 diabetes. This study investigated, whether reconverting type 2 patients from insulin treatment to oral treatment using pioglitazone is possible without deterioration of blood glucose control. METHODS The PioSwitch study was a prospective, open label, proof of concept study. Thiazolidinedione-naive patients with residual beta-cell function were switched from an existing insulin therapy to treatment with pioglitazone and glimepiride for 6 months. Efficacy was assessed by laboratory parameters and scores for evaluation of metabolic control, beta-cell function, insulin resistance and cardiovascular risk. RESULTS In total, 98 patients [66 men, 32 women, age (mean +/- s.d.): 59 +/- 9 years; disease duration: 5.6 +/- 3.6 years; Hemoglobin A1c (HbA1c): 6.9 +/- 0.8%; body mass index (BMI): 33.9 +/- 5.2 kg/m(2), initial daily insulin therapy dose: 0.36 +/- 0.3 U/kg body weight] out of 117 screened patients were treated. During the observation period, 23 patients were prematurely terminated because of an increase in HbA1c from baseline > 0.5% or other reasons. In 75 patients (76%), no deterioration of glucose metabolism occurred and additional improvements were seen in the majority of the observation parameters [baseline vs. endpoint; HbA1c: 6.79 +/- 0.74%/6.66 +/- 0.69% (p < 0.05), glucose: 6.4 +/- 1.5/5.2 +/- 1.4 mmol/l (p < 0.001), adiponectin: 7 +/- 3 mg/l/17 +/- 8 mg/l (p < 0.001), C-peptide: 987 +/- 493/1756 +/- 789 (p < 0.001), sensitivity index derived from the intravenous glucose tolerance test (SI(ivGTT)): 1.21 +/- 0.85/1.49 +/- 0.95 (p < 0.05), hsCRP: 3.3 +/- 2.4/2.6 +/- 2.4 mg/l (p < 0.01), macrophage chemo-attractant protein 1 (MCP1): 487 +/- 246/382 +/- 295 ng/l (p < 0.05)]. BMI increased from 33.8 +/- 5.1 to 34.4 +/- 5.3 kg/m(2) (p < 0.001). CONCLUSIONS The switch from insulin therapy resulting in a moderately HbA1c level, to oral treatment with pioglitazone was successful in a majority of patients with sufficient residual beta-cell function. It allows a simple and less expensive therapy with a better cardiovascular risk marker profile.
- Published
- 2009
3. Changes in Insulin Resistance and Cardiovascular Risk Induced by PPARγ Activation have no Impact on RBP4 Plasma Concentrations in Nondiabetic Patients
- Author
-
A. Pfützner, Georg Lübben, B. Wilhelm, E. Karagiannis, Markolf Hanefeld, Peter H. Kann, Thomas Schöndorf, and Thomas Forst
- Subjects
Simvastatin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Placebo ,Biochemistry ,Cardiovascular Physiological Phenomena ,Endocrinology ,Insulin resistance ,Double-Blind Method ,Reference Values ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Retinol binding protein 4 ,Pioglitazone ,Adiponectin ,biology ,business.industry ,Biochemistry (medical) ,General Medicine ,medicine.disease ,Impaired fasting glucose ,PPAR gamma ,Gene Expression Regulation ,Cardiovascular Diseases ,biology.protein ,Thiazolidinediones ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Insulin Resistance ,Metabolic syndrome ,business ,Retinol-Binding Proteins, Plasma ,medicine.drug - Abstract
Retinol binding protein 4 (RBP4) has recently been suggested as a good biomarker for insulin resistance and the metabolic syndrome. With this study, we wanted to investigate the effect of pioglitazone (PIO) and simvastatin (SIMVA) on insulin resistance and RBP4 plasma concentrations in nondiabetic patients with metabolic syndrome and increased risk for cardiovascular complications. The prospective, parallel, randomized, double-blind clinical trial was performed with 125 nondiabetic patients with increased cardiovascular risk (78 females, 47 males, age (mean+/-STD): 58.6+/-7.8 years, BMI: 30.8+/-4.2 kg/m (2)). They were randomized to either receive PIO (45 mg)+placebo, SIMVA (40 mg)+placebo, or PIO+SIMVA for 3 months. Key outcome measures were the HOMA (IR)-Score, an oral glucose tolerance test, adiponectin, hsCRP, and RBP4 at baseline and endpoint. No correlation could be detected between the HOMA (IR) values or the impaired fasting glucose tolerance status and RBP-4. Treatment with PIO alone or in combination with SIMVA resulted in a significant improvement of the HOMA (IR)-Score and the adiponectin values, while no change in HOMA (IR) and a decrease in adiponectin (p
- Published
- 2009
4. Effects of pioglitazone and/or simvastatin on low density lipoprotein subfractions in non-diabetic patients with high cardiovascular risk: A sub-analysis from the PIOSTAT study
- Author
-
Thomas Forst, Jens Pietzsch, Georg Lübben, Andreas Pfützner, E. Karagiannis, Jürgen Müller, Markolf Hanefeld, and W. Leonhardt
- Subjects
Adult ,Male ,Simvastatin ,medicine.medical_specialty ,Cohort Studies ,chemistry.chemical_compound ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Triglycerides ,Aged ,Pioglitazone ,biology ,Triglyceride ,business.industry ,Cholesterol ,Middle Aged ,medicine.disease ,Lipoproteins, LDL ,Treatment Outcome ,Endocrinology ,chemistry ,Cardiovascular Diseases ,Low-density lipoprotein ,HMG-CoA reductase ,biology.protein ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Lipoprotein - Abstract
Background We analyzed the efficacy and possible synergistic actions of pioglitazone and simvastatin monotherapy versus their combination on LDL subfractions from a subpopulation from the PIOSTAT three-arm randomized controlled trial. PPARγ agonists, such as pioglitazone, improve insulin sensitivity and glycemic control and appear to lower the concentration of atherogenic small dense LDL particles. Insulin resistance frequently occurs in non-diabetic patients with cardiovascular disease. Statins, such as simvastatin, reduce cardiovascular events by lowering LDL-C. So far, only scarce information exists for comparative efficacy and possible synergistic effects of combination therapy on LDL subfractions, cholesterol particle load, and particle number of atherogenic small dense LDL. Methods 125 non-diabetic patients with high cardiovascular risk were randomized to therapy with pioglitazone 45 mg/day, simvastatin 40 mg/day, or the combination of both, for 12 weeks. In the present sub-study, LDL subfractions from 88 patients were separated by very-fast ultracentrifugation. Results Simvastatin monotherapy significantly reduced cholesterol and triglyceride concentrations in IDL, LDL1, and LDL2. The lipid concentrations and lipid loads in LDL3 remained unchanged. By contrast, treatment with pioglitazone reduced the cholesterol concentration in LDL3 (density 1.040–1.066 kg/l) from 0.38 to 0.31 mmol/l ( p = 0.0004) and of the cholesterol load per particle from 1058 to 934 mol/mol ( p = 0.0149). Even greater reductions of cholesterol in LDL3 were observed with the combination of pioglitazone and simvastatin: from 0.38 to 0.29 mmol/l ( p = 0.0006) and from 1021 to 903 mol/mol ( p = 0.0011), respectively. In addition, combination therapy reduced the particle number of LDL3 from 356 to 316 nmol/l ( p = 0.0074). Conclusions Simvastatin preferentially lowered LDL1 and LDL2 subfractions, whereas pioglitazone reduced LDL3 cholesterol and cholesterol load. In addition, the combination reduced the LDL3 particle number. Thus, our data suggest a synergistic action of pioglitazone and simvastatin on atherogenicity of small dense LDL particles.
- Published
- 2008
5. Pioglitazon vermindert das kardiovaskuläre Risiko bei Typ-2-Diabetespatienten
- Author
-
E. Karagiannis, J. Merke, M. Dietlein, C. Hofmann, A. Grünerbel, C. Franzen, R. A. Bierwirth, and Georg Lübben
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,medicine ,business - Abstract
Typ-2-Diabetiker haben ein erhohtes Risiko kardiovaskularer Erkrankungen. Glitazone wie Pioglitazon verbessern nicht nur metabolische Parameter, sondern reduzieren auch die Intima-Media-Dicke (IMT) der A. carotis. Dieser Parameter gilt als Pradiktor fur das kardiovaskulare Risiko. Untersucht wurde der Effekt von Pioglitazon auf die IMT in einer offenen, nichtinterventionellen Beobachtungsstudie in hausarztlichen Praxen bei 1426 Patienten. Der HbA1c ging nach etwa 26 Wochen im Mittel von 7,7% auf 6,7% zuruck (p
- Published
- 2008
6. Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease
- Author
-
W. Dänschel, Andreas Pfützner, Gerhard Dikta, M. Morcos, Georg Lübben, E. Karagiannis, Thomas Forst, M. Drexler, C. Hohberg, Thomas Schöndorf, and M. Borchert
- Subjects
Blood Glucose ,Male ,Vasculitis ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Placebo-controlled study ,Inflammation ,Coronary Artery Disease ,Type 2 diabetes ,Gastroenterology ,Placebos ,Coronary artery disease ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Hypoglycemic Agents ,Aged ,Pioglitazone ,business.industry ,Vascular disease ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,C-Reactive Protein ,Endocrinology ,Diabetes Mellitus, Type 2 ,Matrix Metalloproteinase 9 ,Female ,Thiazolidinediones ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,medicine.drug - Abstract
We investigated MMP-9 levels and inflammatory markers during pioglitazone treatment in type 2 diabetic patients with cardiovascular disease. In this randomized multicenter, double blinded, placebo controlled study, 92 type 2 diabetic patients with angiographically proven CHD were randomly assigned to pioglitazone or placebo treatment. At baseline and during a 28 days observational period MMP-9, MCP1, hsCRP, IL-6, sCD40, and P-selectin were monitored. During Pioglitazone treatment, a 12% reduction in MMP-9 and a 18% reduction in hsCRP levels (p < 0.05, respectively) could be observed already after 3 days. MCP-1 levels were reduced by 14% after 10 days of treatment (p < 0.0001). At the end of the study, these parameters were significantly lower in the pioglitazone group as compared to the placebo group (MMP-9: 392 ± 286 versus 427 ± 166 ng/ml; hsCRP: 1.9 ± 1.7 versus 3.1 ± 2.3 ng/L; MCP-1: 413 ± 115 versus 471 ± 146 pg/ml; p < 0.05, respectively). sCD40 levels decreased by 32.5% (p < 0.05) and P-selectin decreased by 3.2% (p = 0.053) in the pioglitazone group. No change could be found with regard to the other study endpoints. No changes in these parameters could be observed during placebo treatment. Even before effects on glucose metabolism could be obtained, pioglitazone exerts immediate effects on plasma markers of plaque vulnerability and inflammation.
- Published
- 2008
7. Pioglitazone Improves Metabolic Markers in Patients with Type 2 Diabetes Independently from Physical Activities: Results from the IRIS III Study
- Author
-
E. Karagiannis, Thomas Schöndorf, Thomas Forst, Werner Roth, Andreas Pfützner, and Georg Lübben
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Physical exercise ,Original Articles ,Type 2 diabetes ,medicine.disease ,Gastroenterology ,Insulin resistance ,Blood pressure ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,business ,Lipid profile ,Pioglitazone ,Glycemic ,medicine.drug - Abstract
AIM Pioglitazone is an established peroxisome proliferator-activated receptor gamma agonist for the treatment of insulin resistance in patients with type 2 diabetes mellitus. This analysis of the observational IRIS III study was performed to evaluate the effects of pioglitazone treatment in relation to the degree of physical exercise activities in a large patient population under daily life conditions. METHODS A total of 1298 patients out of 2092 enrolled into the IRIS III study who had provided information about their exercise level could be included in the final analysis (622 female, 676 male; age: 63.1 +/- 10.4 years, diabetes duration: 6.6 +/- 5.0 years, mean +/- SD). All patients were glitazone naive prior to study entry. They received pioglitazone in addition to their previous oral antidiabetic treatment. The patients were stratified according to their physical activity level (never, sometimes, and regularly). Data were evaluated at baseline and after 20 +/- 2 weeks of treatment. Observation parameters were fasting blood glucose, lipids, and blood pressure. Hemoglobin A1c (HbA1c) was determined in a central laboratory, and insulin sensitivity was assessed by the IRIS II score. RESULTS Glycemic control, blood pressure, and the lipid profile improved independently from the degree of physical activity (e.g., no exercise vs frequent exercise: DeltaHbA1c: -0.89 +/- 1.2% vs -0.72 +/- 1.1%, not significant). A positive impact of exercise on insulin resistance could be observed at baseline, which, however, was further decreased by pioglitazone treatment [IRIS II score (baseline/end point): no exercise vs frequent exercise: 74.0 +/- 15.9/62.5 +/- 20.2 vs 66.7 +/- 19.0/58.0 +/- 21.8, p < 0.001/not significant]. CONCLUSIONS These observational results, obtained from a nonselected patient population under daily routine conditions, confirm that the benefits of pioglitazone treatment on glycemic control, lipid metabolism, and blood pressure are independent from physical activity. Exercise has a positive influence on insulin sensitivity, but pioglitazone shows additional favorable effects and is, therefore, recommended for use independently from the activity level of the patients.
- Published
- 2008
8. Die Relaxinexpression korreliert mit Änderungen der Fibrinogenspiegel bei Patientinnen mit Typ-2-Diabetes unter oraler antidiabetischer Therapie
- Author
-
F. P. Armbruster, A. Pfützner, T. Forst, Georg Lübben, M. Breidenbach, Thomas Schöndorf, M. Borchert, and C. Hohberg
- Subjects
Maternity and Midwifery ,Obstetrics and Gynecology - Published
- 2007
9. Effect of simvastatin and/or pioglitazone on insulin resistance, insulin secretion, adiponectin, and proinsulin levels in nondiabetic patients at cardiovascular risk—the PIOSTAT Study
- Author
-
Thomas Forst, Carsta Koehler, E. Karagiannis, Markolf Hanefeld, Georg Lübben, Nikolaus Marx, Marc Weber, C. Hohberg, Werner Baurecht, and Andreas Pfützner
- Subjects
Simvastatin ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Population ,Endocrinology ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Internal medicine ,Insulin Secretion ,Humans ,Hypoglycemic Agents ,Insulin ,Medicine ,Prospective Studies ,education ,Proinsulin ,education.field_of_study ,Pioglitazone ,Adiponectin ,business.industry ,nutritional and metabolic diseases ,Glucose Tolerance Test ,medicine.disease ,Postprandial ,Cardiovascular Diseases ,Thiazolidinediones ,Insulin Resistance ,business ,medicine.drug - Abstract
We investigated the effect of pioglitazone in comparison with and in combination with simvastatin on insulin resistance, plasma adiponectin, postprandial plasma glucose, insulin, and intact proinsulin levels in a nondiabetic population at cardiovascular risk. One hundred twenty-five nondiabetic patients at cardiovascular risk were randomized to pioglitazone (PIO), pioglitazone and simvastatin (PIO/SIM), or simvastatin (SIM) treatments. Blood samples were taken for the measurement of adiponectin and lipid levels. In addition, an oral glucose load with the measurements of glucose, insulin, and intact proinsulin levels was performed. Adiponectin levels increased from 14.0 ± 8.2 to 27.6 ± 14.5 μg/mL (P < .0001) during PIO treatment and from 11.7 ± 10.0 to 26.7 ± 15.7 μg/mL (P < .0001) during PIO/SIM treatment. A decrease in adiponectin levels from 15.5 ± 12.7 to 11.6 ± 7.0 μg/mL (P < .05) was observed during SIM treatment. Although fasting intact proinsulin levels remained unchanged, the increase in postprandial intact proinsulin levels could be reduced from 29.5 ± 21.4 to 22.1 ± 17.5 pmol/L (P < .01) during PIO treatment and from 24.3 ± 27.4 to 21.1 ± 16.5 mmol/L (P < .05) during PIO/SIM treatment. Lipid parameters improved during SIM treatment but not during PIO treatment. Combined treatment with PIO/SIM was superior in improving overall cardiovascular risk profile than every single drug.
- Published
- 2007
10. Anti-Inflammatory Effects of Pioglitazone and/or Simvastatin in High Cardiovascular Risk Patients With Elevated High Sensitivity C-Reactive Protein
- Author
-
Ulf Stier, Georg Lübben, Markolf Hanefeld, Werner Baurecht, E. Karagiannis, Nikolaus Marx, Thomas Forst, and Andreas Pfützner
- Subjects
medicine.medical_specialty ,biology ,business.industry ,C-reactive protein ,Type 2 diabetes ,medicine.disease ,Placebo ,Endocrinology ,Insulin resistance ,Simvastatin ,Internal medicine ,medicine ,biology.protein ,Metabolic syndrome ,Cardiology and Cardiovascular Medicine ,business ,Plasminogen activator ,Pioglitazone ,medicine.drug - Abstract
Objectives The purpose of this study was to test the safety and efficacy of pioglitazone and simvastatin in combination versus each drug individually in non-diabetic subjects with cardiovascular disease (CVD) and elevated high-sensitivity C-reactive protein (hs-CRP) levels. Background Low-grade inflammation is a pathogenic factor for atherosclerosis. High-sensitivity CRP, matrix metalloproteinase (MMP)-9, and plasminogen activator inhibitor (PAI)-1 are markers of inflammation. Statins and peroxisome proliferator-activated receptor (PPAR)-γ agonists lower inflammatory markers and reduce CVD in type 2 diabetes. Methods In a 12-week, prospective, double-blind trial, 125 subjects were randomized to simvastatin or pioglitazone plus placebo or a simvastatin/pioglitazone combination. We tested changes in hs-CRP by analysis of covariance. A subgroup analysis was performed in patients with and without the metabolic syndrome (MetS). The correlation between changes in hs-CRP and homeostasis model assessment (HOMA; a measure of insulin resistance) was calculated with the Spearman’s rank test. Results At baseline, there were no significant between-group differences. At 12 weeks, pioglitazone and simvastatin monotherapies significantly reduced hs-CRP (3.64 ± 2.42 mg/l to 2.48 ± 1.77 mg/l and 3.26 ± 2.02 mg/l to 2.81 ± 2.11 mg/l) and the combination regimen had an additive effect (from 3.49 ± 1.97 mg/l to 2.06 ± 1.42 mg/l, p Conclusions Pioglitazone, probably by reducing insulin resistance, has additive anti-inflammatory effects to simvastatin in non-diabetic subjects with CVD and high hs-CRP.
- Published
- 2007
11. IRIS II Study: Intact Proinsulin Is Confirmed as a Highly Specific Indicator for Insulin Resistance in a Large Cross-Sectional Study Design
- Author
-
Matthias R. Langenfeld, Georg Lübben, Thomas Konrad, Eberhard Standl, Thomas Forst, Jan Schulze, Hermann-Josef Strotmann, C. Hohberg, and Andreas Pfützner
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Health Status ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Endocrinology ,Insulin resistance ,Surveys and Questionnaires ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Vascular Diseases ,Aged ,Macrovascular disease ,Morning ,Proinsulin ,Glycated Hemoglobin ,business.industry ,Middle Aged ,medicine.disease ,Medical Laboratory Technology ,Cross-Sectional Studies ,Female ,Hemoglobin ,Insulin Resistance ,business ,Body mass index ,Biomarkers - Abstract
The cross-sectional IRIS-II study tried to assess the prevalence of insulin resistance and macrovascular disease in orally treated patients with Type 2 diabetes.In total, 4,270 patients were enrolled into the study (2,146 male, 2,124 female; mean +/- SD age 63.9 +/- 11.1 years; body mass index 30.1 +/- 5.5 kg/m2; duration of disease 5.4 +/- 5.6 years; hemoglobin A1c 6.8 +/- 1.3%). The study consisted of a single morning visit with completion of a standardized questionnaire and collection of a fasting blood sample.The mean intact proinsulin value was 11.4 +/- 12.4 pmol/L (normal range10 pmol/L). Homeostasis model assessment resulted in 1,147 insulin-sensitive patients (26.9%) and 3,123 patients (73.1%) with insulin resistance. Of the latter patients 1,465 (34.3% of all patients) had also elevated intact proinsulin values, while 1,658 (38.8%) had no proinsulin elevation. In contrast, 1,042 (24.4%) of the insulin-sensitive patients had normal intact proinsulin, and only 105 (2.4%) had elevated intact proinsulin concentrations (chi2 test P0.0001). A specificity of 93.2% (sensitivity 46.9%) was calculated for elevated intact proinsulin as an indirect marker for insulin resistance. Of the 1,451 patients treated with sulfonylurea 52% had elevated intact proinsulin values and increased prevalence of cardiovascular complications (odds ratio 1.45).Type 2 patients with elevated fasting intact proinsulin values can be regarded as being insulin resistant. The results confirm that fasting intact proinsulin is a suitable measure for beta-cell dysfunction and insulin resistance in type 2 diabetes and may be used to support therapeutic decisions.
- Published
- 2005
12. Improvement of Cardiovascular Risk Markers by Pioglitazone Is Independent From Glycemic Control
- Author
-
Matthias R.W. Langenfeld, Thomas Forst, Georg Lübben, Thomas Konrad, Andreas Pfützner, Daniel Walcher, and Nikolaus Marx
- Subjects
medicine.medical_specialty ,Adiponectin ,biology ,business.industry ,Insulin ,medicine.medical_treatment ,C-reactive protein ,Type 2 diabetes ,medicine.disease ,Fibrinogen ,Glimepiride ,Endocrinology ,Diabetes mellitus ,Internal medicine ,medicine ,biology.protein ,business ,Cardiology and Cardiovascular Medicine ,Pioglitazone ,medicine.drug - Abstract
Objectives This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. Background Type 2 diabetes is associated with increased cardiovascular risk. Methods A total of 192 patients were enrolled into a six-month, prospective, open-label, controlled clinical study. They were randomized to receive either pioglitazone (45 mg) or glimepiride (1 to 6 mg, with the intent to optimize therapy). Biochemical and clinical markers to assess therapeutic effects included HbA1c, fasting glucose, insulin, adiponectin, lipids, high-sensitivity C-reactive protein (hsCRP), intracellular adhesion molecule, vascular cell adhesion molecule, vascular endothelial growth factor, fibrinogen, von Willebrand factor, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, and carotid intima-media thickness (IMT). Results The study was completed by 173 patients (66 female, 107 male; age [± SD]: 63 ± 8 years; disease duration: 7.2 ± 7.2 years; HbA1c: 7.5 ± 0.9%; pioglitazone arm: 89 patients). A comparable reduction in HbA1c was seen in both groups (p Conclusions This prospective study gives evidence of an anti-inflammatory and antiatherogenic effect of pioglitazone versus glimepiride. This effect is independent from blood glucose control and may be attributed to peroxisome proliferator-activated receptor gamma activation.
- Published
- 2005
- Full Text
- View/download PDF
13. Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus
- Author
-
C. Hohberg, T. Konrad, C. Sachara, Matthias R.W. Langenfeld, Andreas Pfützner, Peter H. Kann, S. Füllert, T. Forst, and Georg Lübben
- Subjects
Male ,medicine.medical_specialty ,Urology ,Type 2 diabetes ,Insulin resistance ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,Humans ,Hypoglycemic Agents ,Medicine ,Stroke ,Aged ,Pioglitazone ,business.industry ,Type 2 Diabetes Mellitus ,Middle Aged ,Prognosis ,medicine.disease ,Glimepiride ,Carotid Arteries ,Treatment Outcome ,Endocrinology ,Diabetes Mellitus, Type 2 ,Intima-media thickness ,Cardiovascular Diseases ,Hyperglycemia ,Female ,Thiazolidinediones ,Insulin Resistance ,Tunica Intima ,Tunica Media ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
Background— Patients with type 2 diabetes mellitus are at high risk of cardiovascular disease. Carotid intima-media thickness (IMT) is a strong predictor of myocardial infarction and stroke. Methods and Results— We compared the effects of pioglitazone-based therapy (45 mg/d) and glimepiride-based treatment (2.7±1.6 mg/d) for 12 and 24 weeks on metabolic control (HbA 1c ), insulin resistance (homeostasis model assessment), and carotid IMT (B-mode ultrasonography) in a randomized controlled study in 173 orally treated patients with type 2 diabetes (66 women, 107 men; mean±SD age, 62.6±7.9 years; body mass index, 31.8±4.6 kg/m 2 ; HbA 1c , 7.5±0.9%). Treatment was generally well tolerated in both groups. Despite similar improvements in metabolic control (HbA 1c ) after 24 weeks (−0.8±0.9% [pioglitazone] versus −0.6±0.8% [glimepiride]; P =NS), carotid IMT was reduced only in the pioglitazone group after 12 weeks (−0.033±0.052 versus −0.002±0.047 mm [glimepiride]; P P P r =0.29, P r =0.03, P =0.68). Conclusions— We found a substantial regression of carotid IMT, independent of improved glycemic control, after 12 and 24 weeks of pioglitazone treatment. This finding may have important prognostic implications for patients with type 2 diabetes mellitus.
- Published
- 2005
14. A comparison of the effects of thiazolidinediones and metformin on metabolic control in patients with type 2 diabetes mellitus
- Author
-
Jochen Seufert, Karin Dietrich, Peter C. Bates, and Georg Lübben
- Subjects
Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,Glucose uptake ,Type 2 diabetes ,In Vitro Techniques ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Pharmacology ,business.industry ,Insulin ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,medicine.disease ,Metformin ,Treatment Outcome ,Endocrinology ,Diabetes Mellitus, Type 2 ,Liver ,Metabolic control analysis ,Thiazolidinediones ,Insulin Resistance ,business ,medicine.drug - Abstract
Background: Type 2 diabetes mellitus is a condition characterized by impaired insulin secretion and resistance to insulin-mediated glucose uptake and utilization. A number of oral antidiabetic medication are available for its treatment, including metformin and the thiazolidinediones (TZDs). The TZDs have been shown to improve insulin resistance, and it has been suggested that metformin has similar effects. Although both types of agents improve glycemic control, their mechanisms of action and effects on metabolic processes differ. Objective: The goal of this review was to compare the effects of TZDs and metformin on metabolic control in patients with type 2 diabetes. Methods: A search of MEDLINE to March 2004 using the terms metformin and biguanides , and thiazolidinediones and glitazones was conducted to identify preclinical and clinical studies focusing on the mechanisms of action and comparative effects of TZDs and metformin. Also searched were published abstracts from recent major diabetes and endocrinology conferences. Results: In the studies reviewed, both TZDs and metformin demonstrated the ability to improve glycemic control, although long-term monotherapy with TZDs appeared to be more effective than metformin. There continues to be debate abouth whether metformin is more effective than TZDs in terms of inhibition of hepatic glucose production. However, various studies have found TZDs to be more effective in promoting an increase in whole-body insulin sensitivity. With respect to lipid metabolism, patients who received TZDs had a greater reduction in concentrations of both plasma triglycerides and free fatty acids. Metformin was more effective in promoting weight loss in patients with type 2 diabetes, although TZDs may decrease visceral fat levels. Treatment with either metformin or TZDs was associated with a reduction in the risk of cardiovascular disease, although the mechanisms by which they accomplished this seem to differ. Conclusions: The evidence suggests that the predominant effect of metformin is inhibition of hepatic glucose production, whereas the primary effects of TZDs is reduction of insulin resistance and promotion of peripheral glucose uptake. TZDs appear to have more positive effects on other metabolic processes and to be associated with greater improvements in cardiovascular risk factors compared with metformin.
- Published
- 2004
15. Analysis of the Relationship Between the Pro12Ala Variant in the PPAR-γ2 Gene and the Response Rate to Therapy With Pioglitazone in Patients With Type 2 Diabetes
- Author
-
Matthias Blüher, Georg Lübben, and Ralf Paschke
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Genotype ,Proline ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Receptors, Cytoplasmic and Nuclear ,Peroxisome proliferator-activated receptor ,Type 2 diabetes ,law.invention ,Efficacy ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Thiazolidinedione ,Aged ,Glycated Hemoglobin ,Advanced and Specialized Nursing ,chemistry.chemical_classification ,Alanine ,Pioglitazone ,business.industry ,Middle Aged ,medicine.disease ,Thiazoles ,Treatment Outcome ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Female ,Thiazolidinediones ,business ,Pharmacogenetics ,Transcription Factors ,medicine.drug - Abstract
OBJECTIVE—To investigate the influence of peroxisome proliferator-activated receptor-γ (PPAR-γ) gene variants on the response rate to therapy with the thiazolidinedione (TZD) pioglitazone, because in vitro studies have suggested that genetic variants of the PPAR-γ gene may influence the drug efficacy of TZD. RESEARCH DESIGN AND METHODS—A total of 131 patients were treated in an open-label, randomized, multicenter study with pioglitazone (45 mg o.d.) during a course of ≥26 weeks. Response to the pioglitazone therapy was defined by either a >20% decrease in fasting plasma glucose or a >15% decrease in HbA1c values after 26 weeks of pioglitazone treatment. We evaluated the association between the PPAR-γ genotype and the response rate to pioglitazone treatment. RESULTS—The Pro12Ala and the Pro12Pro variants in the PPAR-γ gene are not associated with the response rate to pioglitazone treatment in patients with type 2 diabetes. However, we identified initial fasting plasma glucose level >11.0 mmol/l, HbA1c value >9.0%, BMI >32 kg/m2, and fasting C-peptide concentrations at baseline >2.5 pmol/l as predominant confounding factors for the responder frequency to pioglitazone treatment. CONCLUSIONS—The Pro12Ala variant in the PPAR-γ gene does not affect the therapy efficacy of pioglitazone, suggesting that the drug-treatment response is independent from pharmacogenetic effects between PPAR-γ and its ligand pioglitazone. Whether the Ala12Ala genotype plays a role in the response rate to TZD therapy remains to be determined.
- Published
- 2003
16. Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease
- Author
-
Thomas Forst, Elisabeth Pfützner-Riehn, E. Karagiannis, Michael Morcos, Georg Lübben, Marc Weber, Alexander Weise, and Andreas Pfützner
- Subjects
medicine.medical_specialty ,Article Subject ,business.industry ,Type 2 Diabetes Mellitus ,Type 2 diabetes ,medicine.disease ,Bioinformatics ,Placebo ,Gastroenterology ,Peripheral blood mononuclear cell ,Metformin ,Proinflammatory cytokine ,lcsh:Biology (General) ,Internal medicine ,Drug Discovery ,Clinical Study ,Medicine ,Biomarker (medicine) ,Pharmacology (medical) ,business ,Pioglitazone ,lcsh:QH301-705.5 ,medicine.drug - Abstract
Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers).Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD):66±7 yrs, disease duration:6.6±9.6 yrs, HbA1c:6.7±0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: −19%/placebo: +6%, RelA: −20%/+2%, MMP−9: −36%/+9%, TNFα: −10%/+14%,P<0.05between groups in all cases).Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control.
- Published
- 2011
- Full Text
- View/download PDF
17. Increased prevalence of cardiovascular disease and risk biomarkers in patients with unknown type 2 diabetes visiting cardiology specialists: results from the DIASPORA study
- Author
-
Andreas Pfützner, Georg Lübben, E. Karagiannis, Thomas Forst, Erland Erdmann, and Thomas Schöndorf
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Cardiology ,Coronary Disease ,Disease ,Type 2 diabetes ,Comorbidity ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Germany ,Internal Medicine ,medicine ,Prevalence ,Glucose homeostasis ,Humans ,Aged ,medicine.diagnostic_test ,business.industry ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Cohort ,Biomarker (medicine) ,Blood sugar regulation ,Female ,Cardiology and Cardiovascular Medicine ,Lipid profile ,business - Abstract
Background: Patients with diabetes mellitus and IGT have a high risk for cardiovascular events. It is tempting to speculate that these patients are often first seen by cardiologists. Design: This cross-sectional study investigates the diabetes prevalence in cardiology care units and the correlated metabolic conditions as assessed by several circulating biomarkers. Methods: Patients aged 55 or older with suspected or overt coronary heart disease were eligible for trial participation. Fasting blood samples were drawn from patients to determine HOMA score, glycaemic and lipid profile, and several risk biomarkers. An OGTT was performed in patients without known diabetes. Results: We enrolled 530 patients (181 male, 349 female, mean age, 68±7 years) in this study from 22 German cardiology centres; 156 patients (29.4%) had known diabetes and OGTT revealed that 184 patients (34.7%) had no diabetes, 106 patients (20.0%) had IGT or IFG and 84 patients (15.9%) were newly diagnosed with diabetes. Increased cardiovascular risk as reflected by increased hsCRP, ICAM and MMP-9 values was observed in diabetes patients. A higher cardiovascular biomarkers risk profile was seen in the IGT/IFG cohort. Conclusions:This study confirms the observation that one third of patients of a cardiologic care unit suffer from impaired glucose regulation. Furthermore, the cardiology patients with previously unknown glucose homeostasis abnormalities had a higher prevalence of macrovacular disease and an impaired biomarker risk profile. This study underlines the importance of joint treatment efforts by cardiologists in concert with diabetologists for treatment of this patient group at high risk for cardiovascular events.
- Published
- 2010
18. The IRIS V study: pioglitazone improves systemic chronic inflammation in patients with type 2 diabetes under daily routine conditions
- Author
-
Thomas Forst, E. Karagiannis, Thomas Schöndorf, Martin Grabellus, Andreas Pfützner, Georg Lübben, Manja Flannery, and Werner Roth
- Subjects
Agonist ,Male ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Blood Pressure ,Type 2 diabetes ,Gastroenterology ,Body Mass Index ,Endocrinology ,Internal medicine ,Diabetes mellitus ,Medicine ,Humans ,Hypoglycemic Agents ,Aged ,Glycated Hemoglobin ,Inflammation ,Pioglitazone ,business.industry ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,PPAR gamma ,Medical Laboratory Technology ,Diabetes Mellitus, Type 2 ,Chronic Disease ,Biomarker (medicine) ,Female ,Thiazolidinediones ,Hemoglobin ,Drug Monitoring ,business ,Body mass index ,medicine.drug - Abstract
The peroxisome proliferator-activated receptor-gamma agonist pioglitazone is established as a drug to treat patients with type 2 diabetes mellitus. In addition to lowering blood glucose levels, one of the favorable effects of pioglitazone is improvement of systemic chronic inflammation particularly affecting vessel walls. The effect can be monitored by the measurement of the biomarker C-reactive protein in the range of 0-10 mg/L (high-sensitivity C-reactive protein [hsCRP]). This observational trial was performed to evaluate the effects of pioglitazone on hsCRP values in a large population under daily life conditions.A total of 1,170 subjects could be included into the final analysis (633 men, 537 women; age [mean +/- SD], 63.5 +/- 10.4 years, body mass index, 31.0 +/- 5.5 kg/m2; duration of diabetes, 6.9 +/- 8.1 years; glycosylated hemoglobin [HbA1c], 7.5 +/- 1.1%). All patients were glitazone-naive prior to study entry. The patients received pioglitazone alone or in combination with their previous treatment (acarbose, sulfonylurea drugs, and/or metformin). Patients were evaluated at baseline and after 10 +/- 2 weeks and 20 +/- 2 weeks of treatment. Observation parameters were fasting blood glucose, lipids, and blood pressure. The level of hsCRP was determined in a central laboratory at baseline and at end point.All markers showed a significant improvement at trial end point. A decrease of hsCRP (baseline 3.3 +/- 1.0 mg/L vs. end point 2.8 +/- 2.3 mg/L, P0.01), HbA1c (7.5 +/- 1.1% vs. 6.8 +/- 0.9%, P0.001), fasting blood glucose (8.7 +/- 2.6 mM vs. 7.2 +/- 2.1 mM, P0.001), low-density lipoproteins (3.3 +/- 1.0 mM vs. 3.2 +/- 0.9 mM, P0.001), and triglycerides (2.4 +/- 2.0 mM vs. 2.2 +/- 2.5 mM, P0.001) and an increase in high-density lipoproteins (1.3 +/- 0.4 mM vs. 1.4 +/- 0.4 mM, P0.001) was observed. Parallel to the metabolic improvement, both systolic and diastolic blood pressure values were reduced (141 +/- 17 mm Hg vs. 137 +/- 15 mm Hg and 83 +/- 9 mm Hg vs. 80 +/- 9 mm Hg, respectively; P0.001 in both cases).These observational results, obtained from a nonselected patient population under daily routine conditions, confirm the benefits of pioglitazone treatment on blood glucose, lipid metabolism, and blood pressure. The results show that pioglitazone treatment improves chronic vascular inflammation, which may be associated with reduced cardiovascular risk.
- Published
- 2008
19. Visfatin: a putative biomarker for metabolic syndrome is not influenced by pioglitazone or simvastatin treatment in nondiabetic patients at cardiovascular risk -- results from the PIOSTAT study
- Author
-
Andreas Pfützner, Georg Lübben, C Köhler, Matthias M. Weber, Markolf Hanefeld, E. Karagiannis, C. Hohberg, and Thomas Forst
- Subjects
Male ,medicine.medical_specialty ,Simvastatin ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Nicotinamide phosphoribosyltransferase ,Placebo ,Biochemistry ,Placebos ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Internal medicine ,Medicine ,Humans ,Nicotinamide Phosphoribosyltransferase ,Aged ,Hypolipidemic Agents ,Glycated Hemoglobin ,Metabolic Syndrome ,Adiponectin ,Pioglitazone ,business.industry ,Insulin ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,chemistry ,Cardiovascular Diseases ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,Metabolic syndrome ,business ,Biomarkers ,medicine.drug - Abstract
OBJECTIVE: The aim of the study was to analyze the effect of pioglitazone (PIO) and simvastatin (SIMVA) on adiponectin and visfatin concentrations in nondiabetic patients with metabolic syndrome and increased risk for cardiovascular complications in a prospective randomized clinical trial. RESEARCH DESIGN AND METHODS: One-hundred twenty-five nondiabetic patients with increased cardiovascular risk [78 females, 47 males, age (mean+/-STD:58.6+/-7.8years, BMI:30.8+/-4.2(kg/m2] were included after randomization to PIO+lacebo, SIMVA+placebo, or PIO+SIMVA treatment for 3 months. At baseline and endpoint, measurements of HbA1c, glucose, insulin, LDL cholesterol, adiponectin and visfatin were performed. Insulin resistance was assessed by means of the HOMAIR-score. RESULTS: Improvement in the HOMAIR-score was observed with PIO and the combination, but not with SIMVA alone, which was accompanied by an increase in adiponectin with PIO treatment groups, but a decrease with SIMVA alone (baseline/endpoint: PIO: 14.0+/-8.2 mg/l/ 27.6+/- 14.5 mg/l, p
- Published
- 2007
20. Review of the pleiotropic effects of peroxisome proliferator-activated receptor gamma agonists on platelet function
- Author
-
Marcus Borchert, Anke H. Pfützner, Georg Lübben, Thomas Forst, and Thomas Schöndorf
- Subjects
Blood Platelets ,medicine.medical_specialty ,Peroxisome proliferator-activated receptor gamma ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Peroxisome proliferator-activated receptor ,Endocrinology ,Internal medicine ,medicine ,Adipocytes ,Animals ,Humans ,Platelet ,Receptor ,Transcription factor ,chemistry.chemical_classification ,Cell Nucleus ,business.industry ,Thrombosis ,Peroxisome ,Platelet Activation ,PPAR gamma ,Medical Laboratory Technology ,medicine.anatomical_structure ,chemistry ,Diabetes Mellitus, Type 2 ,Models, Animal ,Thiazolidinediones ,Peroxisome proliferator-activated receptor alpha ,business ,Nucleus - Abstract
The primary target receptor for thiazolidinediones (TZDs) or peroxisome proliferator-activated receptor gamma (PPARgamma) agonists is a transcription factor in the nucleus of adipocytes and other metabolically active cells, where they improve insulin sensitivity and glucose utilization. TZDs are also able to modify gene expression in macrophages, smooth muscle cells, and endothelial cells. Although PPARgamma is considered to be a nuclear receptor, enucleate platelets also highly express this receptor. The aim of this review is to present the current understanding of a direct or indirect effect of TZDs on platelet function. By means of a comprehensive literature search (January 1990-June 2006), publications were obtained that contained specific information about in vitro and in vivo effects of TZDs on platelet function. The effects were studied for different risk biochemical markers, i.e., proteins found to be elevated in the state of procoagulant inflammation and endothelial dysfunction. Improvement of platelet function was reported for all TZDs-troglitazone, pioglitazone, and rosiglitazone. The described effects included reduction of platelet aggregation, suppression of thrombin-induced protein kinase C-alpha and -beta activation, decrease in plasma P-selectin and platelet P-selectin expression, increase in nitric oxide production, inhibition of the Rho/Rho kinase pathway, and inhibition of tissue factor- and platelet-activating factor-induced morphological changes in macrophages. These findings appeared in parallel with reduction of the plasma concentrations of pro-inflammatory risk markers. TZDs seem to have a direct pleiotropic positive influence on platelet function and coagulation and may be helpful in treating the prothrombotic state observed in patients with type 2 diabetes and metabolic syndrome.
- Published
- 2007
21. Postmarketing surveillance study of the efficacy and tolerability of pioglitazone in insulin-resistant patients with type 2 diabetes mellitus in general practice
- Author
-
Christof Schöfl and Georg Lübben
- Subjects
medicine.medical_specialty ,business.industry ,Postmarketing surveillance ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,Pharmacology ,medicine.disease ,Pharmacotherapy ,Tolerability ,Diabetes mellitus ,Internal medicine ,medicine ,Pharmacology (medical) ,business ,Pioglitazone ,medicine.drug ,Lipoprotein - Abstract
Objective: To evaluate the efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus treated in general practice settings. Design and setting: This was a postmarketing surveillance study involving 2537 primary-care physicians throughout Germany. Patients and interventions: A total of 8760 patients with type 2 diabetes were treated with pioglitazone 15 or 30mg once daily and followed for 16 weeks. Results: Treatment with pioglitazone 15 or 30mg once daily was associated with a reduction in both fasting plasma glucose (mean 50.1 mg/dL) and glycosylated haemoglobin (HbA1c) [mean 1.4%] compared with baseline. The proportion of patients with ‘normal’ fasting glucose levels (70–110 mg/dL) increased from 2.3% at baseline to 24.2% at the final evaluation. Pioglitazone therapy was associated with a reduction in levels of triglycerides, total cholesterol and low-density lipoprotein (LDL)-cholesterol, and an increase in levels of high-density lipoprotein (HDL)-cholesterol. The proportion of patients at high risk of developing vascular complications decreased progressively during pioglitazone therapy according to a number of parameters. Conclusions: Pioglitazone was well tolerated and effective in improving glycaemic control and lipid profiles in patients with type 2 diabetes. Pioglitazone may be effective in reducing the risk of vascular complications of diabetes.
- Published
- 2007
22. Pioglitazone lowers blood pressure in hypertensive patients with type 2 diabetes mellitus : an open, multicentre, observational study
- Author
-
Christine Franzen, Georg Lübben, and Thomas Konrad
- Subjects
medicine.medical_specialty ,business.industry ,medicine.drug_class ,Insulin ,medicine.medical_treatment ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,medicine.disease ,Metformin ,Insulin resistance ,Blood pressure ,Endocrinology ,Internal medicine ,Cardiology ,Medicine ,Pharmacology (medical) ,Thiazolidinedione ,business ,Pioglitazone ,medicine.drug - Abstract
Hypertension is frequently diagnosed in patients tance. [12] The thiazolidinedione pioglitazone targets with type 2 diabetes mellitus. Both conditions carry vascular insulin resistance in particular by improvan increased risk for cardiovascular and renal dis- ing endothelial dysfunction and inflammatory ease. [1-3] Hypertension accelerates the development processes in the arterial wall. [13,14] Clinical data of microalbuminuria and retinopathy in type 2 dia- clearly demonstrate that thiazolidinediones have betes, thus enhancing risks for vascular and renal blood pressure-lowering effects in hypertensive diacomplications. [1,3-7] Tight control of blood pressure betic and non-diabetic patients. [13,15-17] and glucose reduces progression of diabetic retino- There are numerous trials revealing a blood prespathy and deterioration in visual acuity in these sure-lowering effect of thiazolidinediones in diabetpatients. [8] Given the possibility of significant ic patients as well as in non-diabetic patients. Most co-morbidities, physicians prescribing treatments of these studies are well designed but have small that affect any of these aspects should also consider sample sizes. It is therefore important to study the their impact on other aspects. [9] effects of thiazolidinediones in larger and unThe most common approach to treating hyperten- selected populations of patients with type 2 diabetes. sion is through the use of antihypertensive drugs. The aim of this study was to investigate whether While it is recognised that certain co-morbidities treatment with pioglitazone in an unselected popularequire special attention and must be addressed (e.g. tion of patients with type 2 diabetes results in comhyperlipidaemia requires therapy with lipid-lower- parable blood pressure benefits to those reported in ing agents), the fundamental problem of insulin previous studies. resistance in hypertensive patients is rarely addressed. [10] Hyperglycaemia, central (visceral) obes- 1. Patients and Methods ity, hypertension, dyslipidaemia, hyperinsulinaemia, endothelial dysfunction and impaired fibrinolysis are found in both type 2 diabetes and hyper- This was an open, multicentre, observational tension, [9] as well as in the prediabetic state, [11] but study aimed at evaluating the effects of pioglitazone insulin resistance is the common metabolic disorder on blood pressure in a randomly selected population in patients with these two conditions. [10] of diabetic patients with arterial hypertension. The primary endpoint was change in blood pressure valThiazolidinediones (also known as glitazones)
- Published
- 2007
23. Relaxin expression correlates significantly with serum changes in VEGF in response to antidiabetic treatment in male patients with type 2 diabetes mellitus
- Author
-
Thomas, Schöndorf, Thomas, Forst, Cloth, Hohberg, Georg, Lübben, Franz Paul, Armbruster, Werner, Roth, Marcus, Borchert, Christiane, Köder, Mirjam, Löbig, Martin, Grabellus, and Andreas, Pfützner
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Time Factors ,Pioglitazone ,Relaxin ,Vascular Cell Adhesion Molecule-1 ,Middle Aged ,Intercellular Adhesion Molecule-1 ,Cohort Studies ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Humans ,Hypoglycemic Agents ,Thiazolidinediones ,Endothelium, Vascular ,Biomarkers ,Aged - Abstract
Recent studies indicate that relaxin as well as VEGF possess cardioprotective properties. This study aimed to determine the association of relaxin with VEGF in patients with type 2 diabetes. We therefore analyzed samples from a recent study showing the benefits of anti-diabetic treatment on cardiovascular risk markers independently from glycemic control. VEGF, relaxin and markers of endothelial dysfunction, s-ICAM-1 and s-VCAM-1, were compared after 26 +/- 2 weeks of antidiabetic treatment with pioglitazone or glimepiride with their base line values. A total of 151 data sets (patients age, 62.7 +/- 8.1 years, diabetes duration, 6.8 +/- 6.6 years, 57 women, 94 men) were available for the analysis. Baseline values were in median, relaxin: 27.4 pg/mL 125% quartile 15.8; 75% quartile: 45.21, s-ICAM-1: 294 ng/mL [25% quartile: 260; 75% quartile: 331], s-VCAM-1: 677 ng/mL [25% quartile: 589; 75% quartile 871], VEGF: 350 pg/mL [25% quartile: 251; 75% quartile: 514]. Parameter variation after therapy showed a significant correlation of relaxin expression with VEGF expression (p = 0.02) in the entire study group. The correlation was seen in the subgroup of male patients (p0.01) but did not reach significance in the female patients (p = 0.71). No further correlation was observed analyzing the other investigated parameters. Our data suggest that relaxin may exert its cardioprotective action possibly via VEGF increase, particularly in men. In women, other pathways may superimpose this effect. In conclusion, our study supports the hypothesis of different regulating pathways and effects of relaxin in men and women also in patients with type 2 diabetes.
- Published
- 2007
24. Evaluation der Wertigkeit von RBP4 als Marker des metabolischen Syndroms in einer prospektiven Interventionsstudie mit Pioglitazon
- Author
-
Georg Lübben, Thomas Forst, M. Löbig, Markolf Hanefeld, E. Karagiannis, C. Hohberg, Anke H. Pfützner, and C Köhler
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
25. Pioglitazon verbessert das kardiovaskuläre Risikoprofil bei nicht-diabetischen Patienten
- Author
-
M. Abdollahnia, E. Karagiannis, C. Hohberg, Anke H. Pfützner, Georg Lübben, and Thomas Forst
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
26. Pioglitazon reduziert die Intima-Media-Dicke (IMT) der Arteria carotis bei Patienten mit Typ-2-Diabetes Mellitus
- Author
-
M. Dietlein, J. Merke, E. Karagiannis, A. Grünerbel, C. Hofmann, Georg Lübben, C. Franzen, and R. A. Bierwirth
- Subjects
Endocrinology, Diabetes and Metabolism - Abstract
Einleitung: Der Typ-2-Diabetes (T2D) ist charakterisiert durch eine verminderte Insulinsensitivitat sowie eine pathologische Insulinsekretion. Das Vorliegen einer Insulinresistenz ist assoziiert mit kardiovaskularen Risikofaktoren wie der endothelialen Dysfunktion, einem erhohten Blutdruck sowie einer Veranderung des Lipidmetabolismus. Patienten mit Typ-2-Diabetes weisen ein erhohtes Risiko fur die Entwicklung von atherosklerotischen Lasionen auf, welche zu einer erhohten kardiovaskularen Morbiditat und Mortalitat fuhren. Die Intima-Media-Dicke (IMT) der Arteria carotis ist ein etablierter Surrogatparameter fur das kardiovaskulare Risiko, eine verdickte IMT korreliert mit kardiovaskularen Risikofaktoren und makrovaskularen Ereignissen. Fur Pioglitazon (PIO), einem PPARγ -Agonisten wurde eine Verlangsamung der Progression der IMT bei Patienten mit T2D gezeigt. Wir untersuchten die Wirkung einer PIO Monotherapie oder Kombinationstherapie zusatzlich zur bereits existierenden oralen antidiabetischen Therapie mit Metformin oder Sulfonylharnstoffen auf die IMT in einer Kohorte von T2D Patienten. Methoden: 1426 Patienten mit T2D wurden in hausarztlichen Praxen in Deutschland rekrutiert und mit PIO 30mg oder 45mg in einer multizentrischen Anwendungsbeobachtung behandelt. Zur Eingangsuntersuchung und nach 26±6 Wochen wurde die mittlere IMT der linken und rechten A. carotis gemessen (0,5–1cm proximal des Karotisbulbus). Der primare Endpunkt war die Veranderung der durchschnittlichen und maximalen IMT. Mittels Wilcoxon-Test wurden die Veranderungen im Vergleich zum Ausgangswert sowie zwischen den Gruppen berechnet. Mittels Mann-Whithney-test wurden die Unterschiede zwischen den Gruppen in Bezug auf die eingesetzte Dosierung von PIO berechnet. Ergebnisse: 725 Patienten wurden kontinuierlich mit PIO 30mg und 306 Patienten mit PIO 45mg therapiert. Unter PIO 30mg ging die mittlere IMT um 0,07±0,18mm (rechts) bzw. 0,07±0,16mm (links) zuruck, die maximale IMT reduzierte sich um 0,08±0,24 (rechts) bzw. 0,09±0,20mm (links). Unter PIO 45mg reduzierte sich die mittlere IMT um 0,11±0,22mm (rechts) bzw. 0,11±0,21mm (links) zuruck, die maximale IMT ging um 0,12±0,23 (rechts) bzw. 0,13±0,23mm (links) zuruck. Diese Veranderungen der mittleren und maximalen IMT nach Behandlung zeigten in allen Gruppen statistische Signifikanz (p
- Published
- 2007
27. Ödementwicklung unter Pioglitazontherapie: BNP ist ein möglicher Indikator für das Risiko zur Entwicklung einer Herzinsuffizienz bei Patienten mit Typ 2 Diabetes mit Glitazontherapie
- Author
-
B. Wilhelm, C. Hohberg, Anke H. Pfützner, Thomas Forst, Georg Lübben, and T. A. Mohr
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
28. Kardioprotektive und antinflammatorische Effekte einer Pioglitazontherapie gehen den metabolischen Effekten bei Typ 2 Diabetikern mit einer KHK voran
- Author
-
Thomas Forst, M. Morcos, E. Karagiannis, Thomas Schöndorf, Anke H. Pfützner, Georg Lübben, M. Borchert, M. Drexler, and PB Musholt
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
29. Einfluss von Pioglitazon auf die inflammatorische mRNA-Expression peripherer Monozyten bei Patienten mit Typ 2 Diabetes – Ergebnisse aus der PIOcard Studie
- Author
-
H. Hähnel, E. Tobiasch, Alexander Weise, Thomas Forst, N Thomé, E. Karagiannis, Anke H. Pfützner, and Georg Lübben
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
30. Prävalenz unentdeckter Diabeteserkrankungen bei Patienten von kardiologischen Schwerpunkteinrichtungen
- Author
-
E. Karagiannis, E. Erdmann, M. Grabellus, Georg Lübben, Thomas Forst, Anke H. Pfützner, and M. Löbig
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
31. Wirkung von Pioglitazon auf die Intima-Media-Dicke (IMT) der Arteria carotis und auf metabolische Parameter bei Patienten mit Typ-2-Diabetes Mellitus
- Author
-
C. Hofmann, A. Grünerbel, E. Karagiannis, Georg Lübben, J. Merke, M. Dietlein, C. Franzen, and R. A. Bierwirth
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2007
32. Während der erfolgreichen Umstellung von Insulin auf Pioglitazon verbessert sich das kardiovaskuläre Risikomarkerprofil bei Patienten mit Typ 2 Diabetes – Ergebnisse der PIOswitch-Studie
- Author
-
E. Karagiannis, C. Hohberg, Georg Lübben, Thomas Forst, W. Baurecht, and Anke H. Pfützner
- Subjects
business.industry ,Endocrinology, Diabetes and Metabolism ,Medicine ,business - Published
- 2007
33. Glycemic control and treatment failure with pioglitazone versus glibenclamide in type 2 diabetes mellitus: a 42-month, open-label, observational, primary care study
- Author
-
Thomas Forst, Andreas Pfützner, Georg Lübben, and Markolf Hanefeld
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Type 2 diabetes ,Glibenclamide ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Insulin-Secreting Cells ,Glyburide ,Insulin Secretion ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Prospective Studies ,Glycemic ,Aged ,Glycated Hemoglobin ,Pioglitazone ,Primary Health Care ,business.industry ,Type 2 Diabetes Mellitus ,General Medicine ,Middle Aged ,medicine.disease ,Metformin ,Surgery ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,Thiazolidinediones ,Insulin Resistance ,business ,medicine.drug - Abstract
Insulin resistance and declining beta-cell function are the core defects in type 2 diabetes mellitus. It has been suggested that deteriorating glycemic control is related to baseline hemoglobin A(1c) (HbA(1c)) values and remaining beta-cell function.We report glycemic data from a 3.5-year, open-label, observational, primary care study comparing 30 mg/day pioglitazone with 3.5 mg/day glibenclamide add-on to stable metformin monotherapy in 500 patients with type 2 diabetes. Insulin commencement was considered for patients with HbA(1c)or = 8.0% or when vascular complications occurred. The change in HbA(1c) compared with baseline and the difference in time to failure to maintain glycemic control were calculated.At endpoint, HbA(1c) had decreased by 1.0% in the pioglitazone group (p0.005) and by 0.6% in the glibenclamide group (p0.05). Annual progression rates to insulin treatment were 6.6% (pioglitazone) and 16.4% (glibenclamide; p0.001 between-group difference). Mean weight increases of 3.5 +/- 0.42 kg in the pioglitazone group and 3.3 +/- 0.38 kg in the glibenclamide group were noted. Overall, both treatments were well tolerated.Pioglitazone add-on to metformin revealed significant benefits in long-term glycemic control compared with glibenclamide. This difference may be explained by a large between-group difference in HOMA-S, which was shown to correlate significantly to the change in HbA(1c). This suggests that a strategy to reduce insulin resistance to lower the burden of the beta-cell is superior to treatment with glibenclamide.
- Published
- 2006
34. Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study
- Author
-
Markolf, Hanefeld, Nikolaus, Marx, Andreas, Pfützner, Werner, Baurecht, Georg, Lübben, Efstrathios, Karagiannis, Ulf, Stier, and Thomas, Forst
- Subjects
Adult ,Male ,Simvastatin ,Dose-Response Relationship, Drug ,Pioglitazone ,Middle Aged ,Risk Assessment ,Severity of Illness Index ,Drug Administration Schedule ,C-Reactive Protein ,Treatment Outcome ,Double-Blind Method ,Cardiovascular Diseases ,Confidence Intervals ,Humans ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,Prospective Studies ,Inflammation Mediators ,Aged ,Follow-Up Studies ,Probability - Abstract
The purpose of this study was to test the safety and efficacy of pioglitazone and simvastatin in combination versus each drug individually in non-diabetic subjects with cardiovascular disease (CVD) and elevated high-sensitivity C-reactive protein (hs-CRP) levels.Low-grade inflammation is a pathogenic factor for atherosclerosis. High-sensitivity CRP, matrix metalloproteinase (MMP)-9, and plasminogen activator inhibitor (PAI)-1 are markers of inflammation. Statins and peroxisome proliferator-activated receptor (PPAR)-gamma agonists lower inflammatory markers and reduce CVD in type 2 diabetes.In a 12-week, prospective, double-blind trial, 125 subjects were randomized to simvastatin or pioglitazone plus placebo or a simvastatin/pioglitazone combination. We tested changes in hs-CRP by analysis of covariance. A subgroup analysis was performed in patients with and without the metabolic syndrome (MetS). The correlation between changes in hs-CRP and homeostasis model assessment (HOMA; a measure of insulin resistance) was calculated with the Spearman's rank test.At baseline, there were no significant between-group differences. At 12 weeks, pioglitazone and simvastatin monotherapies significantly reduced hs-CRP (3.64 +/- 2.42 mg/l to 2.48 +/- 1.77 mg/l and 3.26 +/- 2.02 mg/l to 2.81 +/- 2.11 mg/l) and the combination regimen had an additive effect (from 3.49 +/- 1.97 mg/l to 2.06 +/- 1.42 mg/l, p0.001). For subgroups, the difference between monotherapy and combination therapy was only significant for simvastatin versus simvastatin plus pioglitazone in patients without MetS. Homeostasis model assessment decreased in those receiving pioglitazone, and the correlation between changes in HOMA and hs-CRP was significant (r = 0.43; p0.05). The PAI-1 decreased significantly in the pioglitazone groups only, and MMP-9 was also significantly lowered in the pioglitazone groups. No treatment-related serious adverse events occurred in any group.Pioglitazone, probably by reducing insulin resistance, has additive anti-inflammatory effects to simvastatin in non-diabetic subjects with CVD and high hs-CRP.
- Published
- 2006
35. Auswirkung von Pioglitazon und Simvastatin auf die Plasmaspiegel von Visfatin und Adiponektin bei Nichtdiabetikern
- Author
-
Anke H. Pfützner, E. Karagiannis, Georg Lübben, Markolf Hanefeld, Thomas Forst, and M. Löbig
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
36. Die Einschätzung des kardiovaskulären Risikos ist unterschiedlich zwischen Diabetes mellitus Typ 2– Patienten, den behandelnden Ärzten und unabhängigen Risiko-Scores
- Author
-
B. Jenke, Anke H. Pfützner, Georg Lübben, Thomas Forst, T. Reimer, C. Hohberg, Silvia Hehenwarter, and Thomas Schöndorf
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
37. Umstellung von Insulin auf Pioglitazon: Auswirkungen auf die Stoffwechselkontrolle bei Patienten mit Typ 2 Diabetes
- Author
-
Thomas Schöndorf, Georg Lübben, C. Hohberg, Thomas Forst, W. Roth, M. Borchert, and Anke H. Pfützner
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
38. Einfluss einer PPARγ Stimulation auf den postprandialen Glukosemetabolismus und die Proinsulinsekretion der Betazelle bei kardiovaskulären Risikopatienten ohne manifesten Diabetes mellitus
- Author
-
Thomas Forst, Anke H. Pfützner, B. Wilhelm, Georg Lübben, Matthias M. Weber, E. Karagiannis, and Markolf Hanefeld
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
39. Die Relaxin Expression korreliert mit Fibrinogen bei Frauen mit Typ 2 Diabetes unter oraler antidiabetischer Therapie
- Author
-
Thomas Schöndorf, Thomas Forst, Anke H. Pfützner, W. Roth, M. Borchert, C. Köder, and Georg Lübben
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
40. ß-Zellrestsekretion bei Patienten mit Typ 2 Diabetes nach 2 Jahren Insulintherapie
- Author
-
Thomas Forst, C. Köder, Georg Lübben, Anke H. Pfützner, C. Hohberg, and M. Borchert
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
41. IRIS IV-Studie: Zusatzbehandlung mit Pioglitazon führt zu einem dosisabhängigen Anstieg der Adiponektin-Werte bei Typ 2 Diabetes Patienten unter täglichen Routine-Bedingungen
- Author
-
Thomas Forst, B. Kerschgens, Thomas Schöndorf, E. Karagiannis, Anke H. Pfützner, Georg Lübben, and M. Grabellus
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
42. Effekte einer Therapie mit Pioglitazon und oder Simvastatin auf verschiedene Parameter des metabolischen Syndroms bei kardiovaskulären Risikopatienten ohne manifesten Diabetes mellitus
- Author
-
Georg Lübben, Markolf Hanefeld, Thomas Schöndorf, E. Karagiannis, Anke H. Pfützner, and Thomas Forst
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
43. Auswirkung einer Umstellung von Metformin-Monotherapie auf Pioglitazon-Monotherapie auf die Plasmaspiegel von Adiponektin, intaktem Proinsulin und hsCRP bei gut eingestellten Patienten mit Typ 2 Diabetes
- Author
-
G. Hanzl, H. J. Scholz, E. Rösler, F. Jürgensen, U. Schmidt, Georg Lübben, Thomas Forst, Anke H. Pfützner, J. M. Lindquist, and M Schneider
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
44. Abstract-Thema: Pioglitazone und Simvastatin haben komplementäre Effekte auf die subklinische Entzündung bei Patienten mit erhöhtem kardiovaskulären Risiko: Die Piostat-Studie
- Author
-
C. Koehler, Anke H. Pfützner, E. Karagiannis, Nikolaus Marx, Thomas Forst, U. Stier, J Müller, Georg Lübben, and Markolf Hanefeld
- Subjects
Endocrinology, Diabetes and Metabolism - Published
- 2006
45. Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2
- Author
-
Clothilde Hohberg, Thomas Forst, Andreas Pfützner, Christian Sachara, Peter H. Kann, Georg Lübben, Reiner Roßkopf, Christiane Friedrich, and Volker Gottschall
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endothelium ,Physiology ,Arbitrary unit ,Insulin resistance ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Molecular Biology ,Aged ,Pioglitazone ,business.industry ,Microcirculation ,Glucose clamp technique ,Middle Aged ,medicine.disease ,Glimepiride ,Endocrinology ,medicine.anatomical_structure ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Metabolic control analysis ,Glucose Clamp Technique ,Female ,Thiazolidinediones ,Endothelium, Vascular ,Insulin Resistance ,Cardiology and Cardiovascular Medicine ,business ,Blood Flow Velocity ,medicine.drug - Abstract
The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2.A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months.HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p.0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p.0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p.0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p.0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p.0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group.Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.
- Published
- 2005
46. Pioneer study: PPARgamma activation results in overall improvement of clinical and metabolic markers associated with insulin resistance independent of long-term glucose control
- Author
-
Peter H. Kann, Andreas Pfützner, C. Hohberg, Georg Lübben, Thomas Forst, S. Pahler, and A. Pfützner
- Subjects
Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Pilot Projects ,Biochemistry ,Endocrinology ,Insulin resistance ,Internal medicine ,Insulin-Secreting Cells ,medicine ,Humans ,Hypoglycemic Agents ,Prospective Studies ,Prospective cohort study ,Proinsulin ,Monitoring, Physiologic ,Adiponectin ,Pioglitazone ,business.industry ,Insulin ,Biochemistry (medical) ,Case-control study ,nutritional and metabolic diseases ,General Medicine ,medicine.disease ,PPAR gamma ,Glimepiride ,Sulfonylurea Compounds ,Case-Control Studies ,Thiazolidinediones ,Insulin Resistance ,business ,hormones, hormone substitutes, and hormone antagonists ,Biomarkers ,medicine.drug - Abstract
New scores and biochemical markers have recently been published for diagnosis of insulin resistance and beta-cell dysfunction (such as intact proinsulin, adiponectin, IRISII-score). One goal of this 6-month prospective controlled study was to evaluate the impact of pioglitazone (45 mg) vs. glimepiride (1-6 mg, in the intend to optimize therapy) on these markers. Observation parameters were: IRIS-II score, HOMA-score, ATP III score, HbA (1c), fasting glucose, lipids, intact proinsulin, adiponectin, and adverse events. The study was completed by 173 patients (66 female, 107 male, age +/- STD: 63 +/- 8 years, disease duration: 7.2 +/- 7.2 years, HbA (1c): 7.53 +/- 0.85 %, pioglitazone arm: 89 patients). The groups were not different for any of the observation parameters at baseline, and a similar reduction in HbA (1c) was seen in both groups (p < 0.001). In the pioglitazone group, reductions were observed for the IRIS-II and HOMA scores (p < 0.001 vs. glimepiride at endpoint) fasting glucose (p < 0.001), insulin (p < 0.001), LDL/HDL ratio (p < 0.001), hsCRP (p < 0.05), intact proinsulin (p < 0.001), and an increase was seen in HDL (p < 0.001), adiponectin (p < 0.001) and BMI (p < 0.001). In conclusion, treatment with pioglitazone resulted in an improvement of markers for insulin resistance and beta-cell dysfunction, independent from blood glucose control. Adiponectin, intact proinsulin, and the IRIS-II score may be suitable parameters for monitoring of these additional beneficial therapeutic effects.
- Published
- 2005
47. Pharmacological PPARgamma stimulation in contrast to beta cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with type 2 diabetes
- Author
-
Georg Lübben, Thomas Konrad, Thomas Forst, Matthias M. Weber, C. Sachara, S. D. Fuellert, C. Hohberg, V. Gottschall, M. Löbig, and A. Pfützner
- Subjects
Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Type 2 diabetes ,Biochemistry ,Endocrinology ,Insulin resistance ,Risk Factors ,Internal medicine ,Insulin-Secreting Cells ,medicine ,Humans ,Hypoglycemic Agents ,Proinsulin ,Aged ,Adiponectin ,Pioglitazone ,business.industry ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,Atherosclerosis ,PPAR gamma ,Glimepiride ,Carotid Arteries ,Sulfonylurea Compounds ,Intima-media thickness ,Diabetes Mellitus, Type 2 ,Metabolic control analysis ,Female ,Thiazolidinediones ,business ,Tunica Intima ,hormones, hormone substitutes, and hormone antagonists ,Biomarkers ,medicine.drug - Abstract
The role of intact proinsulin and adiponectin in endothelial dysfunction and insulin resistance has been receiving increasing attention. This study investigates the effect of PPARgamma stimulation or beta-cell stimulation on metabolic and vascular parameters in patients with type 2 diabetes. In our study, 173 type 2 diabetic patients were recruited and randomly assigned to pioglitazone 45 mg or glimepiride 1 - 6 mg treatment. Intima media thickness of the carotid artery, glycemic control, insulin resistance, adiponectin and intact proinsulin levels were assessed at baseline and after six months of treatment. Despite similar improvements in metabolic control (HbA (1c) after 24 weeks: - 0.8 +/- 0.9% [pioglitazone] vs. - 0.6 +/- 0.8% [glimepiride]; mean +/- SD; p < 0.0001, respectively), improvements in intima media thickness (- 0.033 +/- 0.052 mm; p < 0.0001), proinsulin intact (- 5.92 +/- 10.04 pmol/l; p < 0.0001), adiponectin (10.9 +/- 6.3 microg/ml; p < 0.0001) and HOMA score (- 2.21 +/- 3.40; p < 0.0001) were observed by pioglitazone but not glimepiride treatment. Reduction in intima media thickness was correlated with improved insulin sensitivity (r = 0.29; p = 0.0003), and proinsulin intact levels (r = 0.22; p = 0.006), while an inverse correlation was found with adiponectin levels (r = - 0.37; p < 0.0001). Measurement of adiponectin and intact proinsulin enables characterization of the metabolic situation and an estimation of atherosclerotic risk in patients with type 2 diabetes.
- Published
- 2005
48. IRIS II Study: Sensitivity and specificity of intact proinsulin, adiponectin, and the proinsulin/adiponectin ratio as markers for insulin resistance
- Author
-
Eberhard Standl, Hermann-Josef Strotmann, Sabine Pahler, Georg Lübben, Thomas Forst, Matthias R. Langenfeld, Peter H. Kann, and Andreas Pfützner
- Subjects
Adult ,Blood Glucose ,endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Disease duration ,Administration, Oral ,Type 2 diabetes ,Models, Biological ,Sensitivity and Specificity ,Endocrinology ,Insulin resistance ,Diabetes mellitus ,Internal medicine ,Odds Ratio ,Medicine ,Homeostasis ,Humans ,Hypoglycemic Agents ,Proinsulin ,Glycated Hemoglobin ,Adiponectin ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Medical Laboratory Technology ,Diabetes Mellitus, Type 2 ,Intercellular Signaling Peptides and Proteins ,Hemoglobin ,Insulin Resistance ,business ,hormones, hormone substitutes, and hormone antagonists ,Biomarkers ,Diabetic Angiopathies - Abstract
This study was performed to compare the specificity and sensitivity of intact proinsulin, adiponectin, and their ratio (proinsulin/adiponectin) in the prediction of insulin resistance as assessed by the homeostasis model assessment (HOMA) score (or =2 = resistant).Using a cross-sectional approach, 500 orally treated patients with type 2 diabetes (272 women, 238 men; mean +/- SD age, 64.8 +/- 11.6 years; hemoglobin A1c, 7.0 +/- 1.5%; disease duration, 5.8 +/- 6.1 years) were investigated. Various cutoffs for body mass index-adjusted adiponectin and proinsulin/adiponectin were compared with the established cutoff value of 10 pmol/L for fasting proinsulin.Fasting proinsulin correlated more closely with the HOMA score (r = 0.560, P0.001) than fasting adiponectin (r = -0.204, P0.001) or proinsulin/adiponectin (r = 0.355, P0.001). For proinsulin, specificity and sensitivity for insulin resistance in correlation to the HOMA score results were 96% and 70%, respectively. At a comparable specificity level to proinsulin, adiponectin did not reach a comparable sensitivity (14%), while the proinsulin/adiponectin ratio almost reached the same sensitivity (65%). Overall, patients with elevated proinsulin had a higher prevalence of micro- and macrovascular disease [odds ratio 1.47 (adiponectin, 1.08; proinsulin/ adiponectin, 1.48) and 1.34 (adiponectin, 1.32; proinsulin/adiponectin, 1.27), respectively].Elevation of fasting intact proinsulin seems to be the more specific marker for insulin resistance and increased cardiovascular risk than suppression of fasting adiponectin. Formation of the ratio does not lead to a further increase in the predictive value.
- Published
- 2005
49. Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus
- Author
-
Helmut Walter and Georg Lübben
- Subjects
medicine.medical_specialty ,business.industry ,medicine.drug_class ,Insulin ,medicine.medical_treatment ,Troglitazone ,Type 2 Diabetes Mellitus ,Administration, Oral ,Type 2 diabetes ,medicine.disease ,Islets of Langerhans ,Endocrinology ,Insulin resistance ,Diabetes Mellitus, Type 2 ,Internal medicine ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Thiazolidinediones ,Thiazolidinedione ,business ,Rosiglitazone ,Pioglitazone ,medicine.drug - Abstract
Worsening glycaemic control in type 2 diabetes mellitus relates to a decline in beta-cell function, associated with impaired negative feedback regulation of insulin release. Insulin resistance, the 'traditional' cornerstone defect of type 2 diabetes, leads to an array of adverse effects on beta cells, including hypertrophy, apoptosis and those caused by lipotoxicity and glucotoxicity. In particular, increased levels of free fatty acids and their metabolites are thought to diminish both insulin synthesis and glucose-stimulated insulin secretion. Thiazolidinediones are synthetic peroxisome proliferator-activated receptor-gamma agonists that decrease insulin resistance but, as in vitro and in vivo studies suggest, may have direct beneficial effects on pancreatic beta cells. Troglitazone, for example, demonstrated improvements in insulin secretory capacity in isolated pancreatic islets from Wistar rats and a hamster beta-cell line. In vivo studies reveal thiazolidinediones promote beta-cell survival and regranulation as well as maintenance of beta-cell mass and reduction in amyloid deposition. Clinical evidence for thiazolidinediones is largely derived from comparative trials, mainly against sulfonylureas and metformin. Data at 2 years from a number of trials are now available and establish the positive effects of thiazolidinediones on glycaemic control. Empirical evidence showing decreases in fasting plasma insulin levels with pioglitazone and rosiglitazone indicate thiazolidinediones also improve insulin sensitivity. A possible effect of thiazolidinediones on normalising asynchronous insulin secretion, as assessed in a short-term placebo-controlled study, is less established. However, recent and ongoing clinical studies are focusing attention on verifying animal and other data, which support the notion that thiazolidinediones have beneficial effects on beta-cell function. These clinical studies have shown thiazolidinediones capable of preventing or delaying the development of type 2 diabetes in a high-risk population; restoring the first-phase insulin response; and improving secretory responses to oscillations in plasma glucose levels. Many of these effects appear to be independent of improvements in insulin sensitivity. Other research efforts are examining the potential cardiovascular protective effects of thiazolidinediones. Available data imply thiazolidinediones are associated with cardiovascular risk reduction, although results from large, clinical outcome trials, currently in progress, are still needed. Improved understanding of the role that declining beta-cell function has in the development of type 2 diabetes has drawn attention to the need for hypoglycaemic agents that can address this process. Emerging evidence suggests thiazolidinediones offer specific benefits for preventing or delaying the decline in beta-cell function and, thereby, a substrate for early intervention efforts aimed at lowering the worldwide burden of type 2 diabetes.
- Published
- 2004
50. Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study
- Author
-
Andreas, Pfützner, Nikolaus, Marx, Georg, Lübben, Matthias, Langenfeld, Daniel, Walcher, Thomas, Konrad, and Thomas, Forst
- Subjects
Blood Glucose ,Male ,Pioglitazone ,Arteriosclerosis ,Middle Aged ,Blood Coagulation Factors ,Carotid Arteries ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Risk Factors ,Humans ,Hypoglycemic Agents ,Female ,Thiazolidinediones ,Prospective Studies ,Tunica Intima ,Tunica Media ,Biomarkers ,Acute-Phase Proteins ,Aged ,Ultrasonography - Abstract
This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control.Type 2 diabetes is associated with increased cardiovascular risk.A total of 192 patients were enrolled into a six-month, prospective, open-label, controlled clinical study. They were randomized to receive either pioglitazone (45 mg) or glimepiride (1 to 6 mg, with the intent to optimize therapy). Biochemical and clinical markers to assess therapeutic effects included HbA1c, fasting glucose, insulin, adiponectin, lipids, high-sensitivity C-reactive protein (hsCRP), intracellular adhesion molecule, vascular cell adhesion molecule, vascular endothelial growth factor, fibrinogen, von Willebrand factor, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, and carotid intima-media thickness (IMT).The study was completed by 173 patients (66 female, 107 male; age [+/- SD]: 63 +/- 8 years; disease duration: 7.2 +/- 7.2 years; HbA1c: 7.5 +/- 0.9%; pioglitazone arm: 89 patients). A comparable reduction in HbA1c was seen in both groups (p0.001). In the pioglitazone group, reductions were observed for glucose (p0.001 vs. glimepiride group at end point), insulin (p0.001), low-density lipoprotein/high-density lipoprotein ratio (p0.001), hsCRP (p0.05), MMP-9 (p0.05), MCP-1 (p0.05), and carotid IMT (p0.001), and an increase was seen in high-density lipoprotein (p0.001) and adiponectin (p0.001). Spearman ranks analysis revealed only one correlation between the reduction in cardiovascular risk parameters and the improvement in the metabolic parameters (MMP-9 and fasting blood glucose, p0.05)This prospective study gives evidence of an anti-inflammatory and antiatherogenic effect of pioglitazone versus glimepiride. This effect is independent from blood glucose control and may be attributed to peroxisome proliferator-activated receptor gamma activation.
- Published
- 2004
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.