Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT)

Robins, Sander J.; Collins, Dorothea; McNamara, Judith; Bloomfield, Hanna E.

doi:10.1016/j.atherosclerosis.2007.01.029

Cited by 145 publications

(186 citation statements)

References 28 publications

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“…function and low-grade inflammation, and in line with this observation the impact of statins [8,9] and fibrates [10,11,13] on the investigated end-points in other large clinical trials did not differ between men and women.…”

Section: Prace Oryginalnesupporting

confidence: 63%

“…These agents were found to produce anti-inflammatory, antioxidant, and antithrombotic properties, to regulate the growth and migration of smooth muscle cells and to improve endothelial function [4][5][6][7]. These effects may explain why statins are effective in reducing cardiovascular events in high-risk subjects without elevated LDL-cholesterol, including type 2 diabetes patients [8] and apparently healthy persons with elevated Creactive protein (CRP) levels [9], whereas fibrates are effective in patients with low low-density lipoprotein (HDL) cholesterol and metabolic syndrome [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Porównanie wpływu leczenia hipolipemicznego na wydzielanie cytokin prozapalnych u kobiet i mężczyzn z cukrzycą typu 2 i dyslipidemią aterogenną

Krysiak

Gdula-Dymek

Marek

2015

Endokrynologia Polska

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Introduction: Statins and fibrates reduce monocyte release of proinflammatory cytokines, but it remains unknown whether this effect is sex dependent. Material and methods: We retrospectively analysed age-, weight-, and lipid-matched populations of type 2 diabetic patients of both sexes, who, because of atherogenic dyslipidaemia, were treated with simvastatin (40 mg daily), fenofibrate (200 mg daily), or simvastatin plus fenofibrate. Monocyte release of tumour necrosis factor a (TNF-a), inteleukin-1b, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1), as well as circulating levels of high-sensitivity C-reactive protein (hsCRP) and free fatty acids (FFA) were assessed separately for men and women before and after 12 weeks of treatment. Results: Baseline monocyte release of TNF-a, interleukin-1b, interleukin-6, and MCP-1, as well as plasma hsCRP and FFA levels were comparable in both sexes. Simvastatin, fenofibrate, and simvastatin/fenofibrate combination therapy reduced monocyte release of TNF-a, inteleukin-1b, interleukin-6, and MCP-1, with no difference between the treatment groups. The impact of simvastatin and fenofibrate administered alone on monocyte cytokine release and systemic inflammation did not differ between the men and women. The effect of simvastatin/fenofibrate combination therapy on monocyte release of interleukin-6 and MCP-1 was more pronounced in the male population. The impact of simvastatin administered together with fenofibrate on TNF-a, interleukin-1b, and hsCRP was also stronger in the men than in the women, but the difference did not reach the level of significance. Conclusions:The obtained results suggest that sex differences determine the strength of the monocyte-suppressing effect of simvastatin/ /fenofibrate combination therapy in type 2 diabetic patients with atherogenic dyslipidaemia. (Endokrynol Pol 2015; 66 (3): 224-230)

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Section: Prace Oryginalnesupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Porównanie wpływu leczenia hipolipemicznego na wydzielanie cytokin prozapalnych u kobiet i mężczyzn z cukrzycą typu 2 i dyslipidemią aterogenną

Krysiak

Gdula-Dymek

Marek

2015

Endokrynologia Polska

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“…These results may provide a potential explanation for the lack of an effect of FENO on the primary cardiovascular outcome in the recently published FIELD study [46]. However, it should be noted that gemfibrozil treatment in type 2 diabetic patients has previously been shown to reduce the risk of macrovascular complications in the VA-HIT study [47], suggesting that the two fibrates may have differing effects on macrovascular complications in type 2 diabetic patients.…”

Section: Discussionmentioning

confidence: 78%

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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“…Although all fibrates have been shown to increase HDL-C significantly, their beneficial effect on cardiovascular and all-cause mortality remains controversial (Saha et al 2007). The early VA-HIT and BIP secondary prevention trials have shown that treating CHD patients with low plasma HDL-C levels and especially In vitro data those with moderate triglyceride elevations and some degree of insulin resistance (Rubins et al 2002; The Bezafibrate Infarction Prevention (BIP) Study Group 2000) with a fibrate leads to significant reductions in the risk of a recurrent cardiovascular event, part of the effect being mediated by the fibrateinduced increase in HDL-C (Robins et al 2001). In the FIELD study in people with type 2 diabetes mellitus, fenofibrate induced a highly significant reduction of cardiovascular events in patients with low HDL-C levels, versus a minimal effectiveness of the drug in patients with higher HDL-C (The FIELD study investigators 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects of Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

Gomaraschi

Adorni

Banach

et al. 2014

Handbook of Experimental Pharmacology

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Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT)

Cited by 145 publications

References 28 publications

Porównanie wpływu leczenia hipolipemicznego na wydzielanie cytokin prozapalnych u kobiet i mężczyzn z cukrzycą typu 2 i dyslipidemią aterogenną

Porównanie wpływu leczenia hipolipemicznego na wydzielanie cytokin prozapalnych u kobiet i mężczyzn z cukrzycą typu 2 i dyslipidemią aterogenną

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 Established Hypolipidemic Drugs on HDL Concentration, Subclass Distribution, and Function

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