Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X

Idzior−Waluś, Barbara; Sieradzki, Jacek; Rostworowski, W; Zdzienicka, Anna; Kawalec, Ewa; Wójcik, Jan; Zarnecki, A.; Blane, G. F.

doi:10.1046/j.1365-2362.2000.00734.x

Cited by 80 publications

(46 citation statements)

References 43 publications

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“…Despite the widespread use of PPAR-α agonists (i.e. FENO and gemfibrozil) for the treatment of hypertriacylglycerolaemia in type 2 diabetic patients, their effect on insulin sensitivity in humans has not been rigorously examined and conflicting results have been reported [9][10][11][12][13][14]. Studies in rodents conclusively demonstrate that PPAR-α activation with FENO and other more potent PPAR-α agents enhances peripheral (muscle) and hepatic insulin sensitivity [4][5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…Studies in rodents clearly demonstrate that PPAR-α agonists improve hepatic and muscle insulin resistance, decrease hepatic and intramuscular fat content, reduce plasma NEFA and enhance adiponectin (AD) expression [4][5][6][7][8]. Some [9][10][11], but not all [12][13][14], studies in humans with hypertriacylglycerolaemia and/or type 2 diabetes suggest that PPAR-α agonists, i.e. fibrates, enhance insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

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Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

et al. 2007

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Aims/hypothesis The aim of the study was to examine the effects of pioglitazone (PIO), a peroxisome proliferatoractivated receptor (PPAR)-γ agonist, and fenofibrate (FENO), a PPAR-α agonist, as monotherapy and in combination on glucose and lipid metabolism. Subjects and methods Fifteen type 2 diabetic patients received FENO (n=8) or PIO (n=7) for 3 months, followed by the addition of the other agent for 3 months in an openlabel study. Subjects received a 4 h hyperinsulinaemiceuglycaemic clamp and a hepatic fat content measurement at 0, 3 and 6 months. Results Following PIO, fasting plasma glucose (FPG) (p<0.05) and HbA 1c (p<0.01) decreased, while plasma adiponectin (AD) (5.5±0.9 to 13.8±3.5 μg/ml [SEM], p<0.03) and the rate of insulin-stimulated total-body glucose disposal (R d ) (23.8 ± 3.8 to 40.5 ± 4.4 μmol kg −1 min −1 , p < 0.005) increased. After FENO, FPG, HbA 1c , AD and R d did not change. PIO reduced fasting NEFA (784±53 to 546± 43 μmol/l, p<0.05), triacylglycerol (2.12±0.28 to 1.61± 0.22 mmol/l, p<0.05) and hepatic fat content (20.4±4.8 to 10.2±2.5%, p<0.02). Following FENO, fasting NEFA and hepatic fat content did not change, while triacylglycerol decreased (2.20± 0.14 to 1.59± 0.13 mmol/l, p<0.01).Addition of FENO to PIO had no effect on R d , FPG, HbA 1c , NEFA, hepatic fat content or AD, but triacylglycerol decreased (1.61±0.22 to 1.00±0.15 mmol/l, p<0.05). Addition of PIO to FENO increased R d (24.9±4.4 to 36.1± 2.2 μmol kg −1 min −1 , p<0.005) and AD (4.1±0.8 to 13.1± 2.5 μg/ml, p<0.005) and reduced FPG (p<0.05), HbA 1c (p<0.05), NEFA (p<0.01), hepatic fat content (18.3±3.1 to 13.5±2.1%, p<0.03) and triacylglycerol (1.59±0.13 to 0.96±0.9 mmol/l, p<0.01). Muscle adenosine 5′-monophosphate-activated protein kinase (AMPK) activity did not change following FENO; following the addition of PIO, muscle AMPK activity increased significantly (phosphorylated AMPK:total AMPK ratio 1.2±0.2 to 2.2±0.3, p<0.01). Conclusions/interpretation We conclude that PPAR-α therapy has no effect on NEFA or glucose metabolism and that addition of a PPAR-α agonist to a PPAR-γ agent causes a further decrease in plasma triacylglycerol, but has no effect on NEFA or glucose metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

et al. 2007

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“…23 In contrast to TZD, fibrates have been reported to induce no change in body weight or even to decrease it in some models of obesity in rodents 24,25 and in patients with metabolic X syndrome. 26 In the past few years, dual PPARa and PPARg agonists have been developed and their utility as antidiabetic drugs has been suggested. [27][28][29][30][31] Nevertheless, only few reports have explored the effects of cotreatment with PPARa and PPARg agonists, 7,30 particularly when focusing on body weight regulation.…”

Section: Introductionmentioning

confidence: 99%

Fenofibrate prevents Rosiglitazone-induced body weight gain in ob/ob mice

et al. 2005

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AIMS/HYPOTHESIS:Fibrates and thiazolidinediones are commonly used for the treatment of dyslipidemia and type 2 diabetes, respectively. The aim of this study was to investigate the effects on body weight as well as on glucose and lipid homeostasis of ligands for PPARa and PPARg, Fenofibrate and Rosiglitazone, alone or in association. METHODS: Ob/ob mice were divided into four groups: control, and mice daily injected (intraperitoneally), either with 10 mg/kg Rosiglitazone, 100 mg/kg Fenofibrate or both molecules. Body weight and food intake were monitored daily. After 13 days of treatment, mice were killed, and blood samples were collected for posterior metabolite quantification. The liver and adipose tissues were dissected and weighed. RESULTS: Body weight was significantly reduced or increased by Fenofibrate and Rosiglitazone, respectively. The effect of Rosiglitazone was prevented by coadministration of Fenofibrate. This was accompanied by a normalization of the daily food efficiency. Compared to those treated with Rosiglitazone, animals treated with Fenofibrate alone or in combination presented a decreased white adipose tissue mass. Fenofibrate or Rosiglitazone alone significantly reduced the levels of plasma lipid parameters. Surprisingly, Fenofibrate also decreased blood glucose levels in ob/ob mice, despite having no effect on insulin levels. By contrast, both glucose and insulin levels were decreased by Rosiglitazone treatment. Coadministration of both drugs improved all parameters as with Rosiglitazone. Fenofibrate restored almost normal hepatocyte morphology and significantly reduced the triglyceride content of the liver. This was accompanied by an increase in fatty acid oxidation in the liver in all groups receiving Fenofibrate. CONCLUSION/INTERPRETATION: These biological effects suggest that combined therapy with a PPARa and a PPARg ligand is more effective in ameliorating, specifically, lipid homeostasis than in activating any of this receptor separately. Furthermore, Fenofibrate prevents one of the most undesirable effects of Rosiglitazone, namely increased adiposity and body weight gain.

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“…The magnitude of the blood pressure effect matched that seen in a study of the effects of fibrate therapy on insulin resistance (14.7/9.8 mmHg). 56 Reductions in blood pressure through actions on insulin resistance and through lesser effects on hyperlipidaemia are seen with PPAR-gamma agonists (thiazolidinediones) or metformin; so an effect of fibrates on blood pressure might be predicted but there are no large-scale studies.…”

Section: Lipid-lowering Drugs and Blood Pressurementioning

confidence: 99%

“…Blood pressure data are not yet available from this study with regard to outcomes, but the predominant reductions in stroke are intriguing if fibrates have major antihypertensive effects. 56 Subgroup analyses of statin trials also indicate a 20-30% reduction in stroke in the secondary prevention trials. However, detailed data on the exact groups of antihypertensive drugs were not available, although a high usage of thiazide diuretics was likely.…”

Section: Trial Evidencementioning

confidence: 99%

Lipid lowering: another method of reducing blood pressure?

Wierzbicki

2002

J Hum Hypertens

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Modern management of cardiovascular risk depends on assessment of cardiovascular risk factors. Hypertension and hyperlipidaemia are synergistic risk factors for cardiovascular events. Both show a degree of crosscorrelation through sharing mechanisms of pathogenesis including insulin resistance and endothelial dysfunction. This article reviews the common pathways leading to dyslipidaemia and hypertension and the effects diet and lipid-lowering drug therapies have had on correcting blood pressure in patients with essential hypertension. Both statins and fibrates have shown a capability to lower blood pressure by up to 8/5 and 15/ 10 mmHg respectively, in some small-scale clinical trials and have effects on arterial wall structure and hence pulse wave velocity. This blood pressure action may account for some of the clinical effects of lipid-lowering drugs on cardiovascular risk. Thus, lipid lowering may provide an additional method of correcting hypertension in some high-risk patients. However, data from largescale intervention trials are either absent or ambiguous. Definitive large-scale trials to investigate the antihypertensive effects of lipid-lowering drugs are required, although end point studies examining the interaction of lipid-lowering and antihypertensive drugs to determine optimum combinations are already under way.

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Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X

Abstract: These favourable effects of comicronised fenofibrate both on lipid and non lipid parameters, including insulin sensitivity, may confer to this product a particular interest in the treatment of patients with polymetabolic syndrome X.

Cited by 80 publications

References 43 publications

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

Effects of peroxisome proliferator-activated receptor (PPAR)-α and PPAR-γ agonists on glucose and lipid metabolism in patients with type 2 diabetes mellitus

Fenofibrate prevents Rosiglitazone-induced body weight gain in ob/ob mice

Lipid lowering: another method of reducing blood pressure?

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