The IRIS V Study: Pioglitazone Improves Systemic Chronic Inflammation in Patients with Type 2 Diabetes Under Daily Routine Conditions

Karagiannis, E.; Pfützner, Andreas; Forst, Thomas; Lübben, G.; Roth, W.; Grabellus, Martin; Flannery, Manja; Schöndorf, Thomas

doi:10.1089/dia.2008.0244

Cited by 26 publications

(20 citation statements)

References 40 publications

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“…Based on these observations, it can be speculated that the reduction in major cardiovascular events reported in the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study [30] and confirmed by meta-analyses, including all available pioglitazone trials [31][32], is partly due to some extraglycemic action of the drug. risk has been reported [33]. In the present study, the authors were able to show that in diabetic patients at low risk for cardiovascular disease, this beneficial (CRP-lowering) effect was superior to that achieved with metformin.…”

Section: Discussionsupporting

confidence: 55%

Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes

et al. 2013

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Section: Discussionsupporting

confidence: 55%

Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes

et al. 2013

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“…Indeed, studies have demonstrated that pioglitazone therapy benefits individuals with elevated hs-CRP values. [46][47][48][49][50][51][52][53] 54 published data of 136 Japanese type 2 diabetes patients showing that pioglitazone treatment (30 mg daily for 3 months) significantly reduced hyperglycemia and hs-CRP relative to an untreated control group. In fact, a stratification into glycemic control responders [>1% of reduction in hemoglobin A1c (HbA1c)] and nonresponders revealed that CRP reduction with pioglitazone occurred independently of changes in parameters related to glucose metabolism.…”

Section: Effects Of Pioglitazone Treatment On Hs-crp Reductionmentioning

confidence: 99%

“…After 20 weeks, hs-CRP levels had decreased significantly with pioglitazone therapy (baseline 3.3 ± 1.0 mg/liter vs end point 2.8 ± 2.3 mg/liter, p < 0.01). 50 The PIOglim study was a double-blind, parallel prospective study with 82 patients with type 2 diabetes mellitus treated previously with sulfonylurea monotherapy with insufficient glycemic control (HbA1c >7.0%). They were randomized either to uptitration of glimepiride (4 to 6 mg; n = 37; 22 males, 15 females, age: 60 ± 9 years, HbA1c: 7.5 ± 0.6%, BMI: 31.6 ± 5.7 kg/m²) or to receive a glimeperide + pioglitazone combination (uptitration possible with 2 mg + 30 mg, 4 mg + 30 mg, and 4 mg +45 mg; 30/45 mg, n = 45; 25 males, 20 females, age: 62 ± 8 years, HbA1c: 7.2 ± 0.6%, BMI: 33.5 ± 6.2 kg/m²) for the next 6 months.…”

Section: Effects Of Pioglitazone Treatment On Hs-crp Reductionmentioning

confidence: 99%

High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone

Pfützner

Schöndorf

Hanefeld

et al. 2010

J Diabetes Sci Technol

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Abbreviations: (BMI) body mass index, (CVD) cardiovascular disease, (HbA1c) hemoglobin A1c, (HOMA) homeostasis model assessment, (hs-CRP) high-sensitivity C-reactive protein, (LDL) low-density lipoprotein, (PPARγ) peroxisome proliferator-activated receptor-γ Keywords: atherosclerosis, diabetes, hs-CRP, inflammation, insulin resistance, pioglitazone AbstractSystemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals. Data suggest that hs-CRP may also participate directly in the process of atherogenesis. A growing number of clinical trials tested the hypothesis that antidiabetic drugs specifically targeting insulin resistance could benefit individuals by reducing inflammation, atherogenesis, and thus cardiovascular risk. One such class are the thiazolidinediones (pioglitazone and rosiglitazone). These agents act as selective ligands of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ). This article reviewed published data on hs-CRP changes with the thiazolidinedione agent pioglitazone. Here we found pronounced insulin-sensitizing and anti-inflammatory properties in different clinical settings, including diabetic and nondiabetic individuals. Coadministration of pioglitazone to antilipidemic statin therapy resulted in additional effects on low-grade inflammation, and hs-CRP reduction has been demonstrated to occur independently of glucose lowering. The anti-inflammatory effect appeared to be a rapid physiologic reaction on PPARγ activation and could be observed within a short-term interval after starting pioglitazone therapy. In summary, clinical study results underline the benefit of an early insulin resistance treatment to oppose systemic vascular inflammation and cardiometabolic syndrome in patients with elevated levels of high-sensitivity C-reactive protein.

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“…РАППγ угнетает продукцию жировой тканью и макрофагами провоспалительных цитокинов: ФНО-а, ИЛ-6, резистина и других провоспалительных цитокинов [13]. ТЗД, как и фибраты, обладают проти-вовоспалительной активностью как на системном, так и на локальном уровнях [14].…”

Section: раппγunclassified

PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR — PGC-1α — IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUM

Расін¹

2015

Ross. kardiol. ž.

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Рецепторы, активируемые пролифераторами пероксисом (PPAR) α и β/δ управ-ляют экспрессией генов окисления жирных кислот (ЖК), являющихся источником 70-90% АТФ в миокарде. PPARα контролирует окисление ЖК и влияет на энерге-тический гомеостаз миокарда, главным образом, через поставку циркулирующих ЖК из печени, а PPARγ предохраняет миокард от избытка ЖК и липотоксичности путем перераспределения потоков ЖК в адипоциты. PPARβ/δ является главным регулятором липидного обмена в мышцах, составляющих до 50% массы тела. Система PPAR/PGC-1α (главным образом, PPARα/PGC-1α) контролирует биоге-нез митохондрий и, таким образом, обеспечивает возможность приспособления миокарда к внезапно возникающей (стрессорной) нагрузке. Экспрессия PPARα/ PGC-1α увеличивается при физиологических формах гипертрофии миокарда: в постнатальном развитии и физической тренировке и уменьшается при патоло-гических формах гипертрофии миокарда и сердечной недостаточности. Дис-функция регуляторной системы -PPAR/ PGC-1α может быть одним из патогене-тических механизмов развития кардиомиопатий, а сигнальные пути этой сис-темы -объектом терапевтических воздействий. PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR -PGC-1α -IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUMRasin M. S. PPAR α controls FA oxydation and influences myocardial energy metabolism homeostasis, mostly through the supplement of circulating FA from the liver, and PPARγ prevent the excess of FA in myocardium with lipotoxicity prevented by switching the flow of FA to adipocytes. PPARβ/δ is the main regulator of lipid metabolism on muscles, that are 50% of body mass. The PPAR/PGC-1α system (mostly PPARα/PGC-1α) controls the biogenesis of mitochondria and hence makes available the possibility to adaptate myocardium for sudden (stress) exertion. Expression of PPARα/PGC-1α increases in physiologic forms of myocardial hypertrophy: in postnatal period and physical entraining, and decreases in pathological forms of myocardial hypertrophy and heart failure. Dysfunction of regulatory system PPAR/ PGC-1α might be one of the pathogenetic mechanisms of cardiomyopathy development, and signal pathways for the system -the object for therapeutic interventions.

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The IRIS V Study: Pioglitazone Improves Systemic Chronic Inflammation in Patients with Type 2 Diabetes Under Daily Routine Conditions

Cited by 26 publications

References 40 publications

Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes

Effect of Pioglitazone Versus Metformin on Cardiovascular Risk Markers in Type 2 Diabetes

High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone

PEROXYSOME PROLIFERATOR-ACTIVATED RECEPTORS AND THEIR COACTIVATOR — PGC-1α — IN PHYSIOLOGY AND PATHOLOGY OF MYOCARDIUM

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