scholarly journals Type 2 Diabetes, Metabolic Syndrome, Lipid Metabolism

2008 ◽  
pp. 145-162
Author(s):  
Jacques Beltrand ◽  
Claire Levy-Marchal
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism

scholarly journals Preventing type 2 diabetes and cardiovascular disease in metabolic syndrome: the role of PPARα

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S12-S14 ◽  
Author(s):  
Jorge Plutzky
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Drug Target ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Central Target ◽  
The Metabolic Syndrome

The clustering of cardiovascular risk factors associated with the metabolic syndrome and type 2 diabetes suggests central mechanisms may exist that account for the presence of these abnormalities. Likewise, this clustering also suggests that key therapeutic targets may exist that could allow improvements in many of these parameters. Extensive data implicate peroxisome proliferator-activated receptor-alpha (PPARα) as an important transcriptional regulator of lipid metabolism, energy balance and inflammation. PPARα is also an established drug target. Experimental data show that activation of PPARα by agonists such as fenofibrate improves dyslipidaemia, increases cholesterol efflux and limits inflammation. All of these effects would also be predicted to decrease atherosclerotic risk. Evidence from surrogate markers in humans is also supportive of the concept that PPARα may act as a central target capable of influencing a variety of different pathways involved in lipid metabolism. Thus, fenofibrate offers the potential for inducing a co-ordinated PPARα response that may improve dyslipidaemia, repress inflammation and limit atherosclerosis in patients with the metabolic syndrome or type 2 diabetes.

scholarly journals An epigenome-wide association study of metabolic syndrome and its components

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marja-Liisa Nuotio ◽  
Natalia Pervjakova ◽  
Anni Joensuu ◽  
Ville Karhunen ◽  
Tero Hiekkalinna ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Waist Circumference ◽  
Association Study ◽  
Chromosome 21 ◽  
Chromosome 1 ◽  
European Ancestry ◽  
Serum Triglycerides

AbstractThe role of metabolic syndrome (MetS) as a preceding metabolic state for type 2 diabetes and cardiovascular disease is widely recognised. To accumulate knowledge of the pathological mechanisms behind the condition at the methylation level, we conducted an epigenome-wide association study (EWAS) of MetS and its components, testing 1187 individuals of European ancestry for approximately 470 000 methylation sites throughout the genome. Methylation site cg19693031 in gene TXNIP —previously associated with type 2 diabetes, glucose and lipid metabolism, associated with fasting glucose level (P = 1.80 × 10−8). Cg06500161 in gene ABCG1 associated both with serum triglycerides (P = 5.36 × 10−9) and waist circumference (P = 5.21 × 10−9). The previously identified type 2 diabetes–associated locus cg08309687 in chromosome 21 associated with waist circumference for the first time (P = 2.24 × 10−7). Furthermore, a novel HDL association with cg17901584 in chromosome 1 was identified (P = 7.81 × 10−8). Our study supports previous genetic studies of MetS, finding that lipid metabolism plays a key role in pathology of the syndrome. We provide evidence regarding a close interplay with glucose metabolism. Finally, we suggest that in attempts to identify methylation loci linking separate MetS components, cg19693031 appears to represent a strong candidate.

The role of fenofibrate in clinical practice

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S15-S20 ◽  
Author(s):  
Alberto Zambon ◽  
Kenneth Cusi
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Microvascular Complications ◽  
Alcoholic Fatty Liver

Clinical guidelines highlight the importance of dyslipidaemia management for reducing the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome. While statins represent the main focus of therapy, there is increasing evidence that the addition of a fibrate such as fenofibrate provides further reduction in risk. Fenofibrate also offers a number of benefits beyond lipid modification; these are mediated by peroxisome proliferator-activated receptor-alpha (PPARα) activation and appear to be independent of effects of glucose and lipid metabolism. Furthermore, as shown by the Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study, fenofibrate treatment has promising effects in preventing progression of diabetes-related microvascular complications. PPARα is critical to lipid metabolism in the liver. Recent findings which showed that pioglitazone, a PPARγ agonist with weak PPARα activity, improved fatty liver disease in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome or type 2 diabetes have prompted interest in whether more potent PPARα agonists, such as fenofibrate, may have a role in the management of non-alcoholic fatty liver disease (NAFLD). The combination of fenofibrate and a statin is well tolerated, with no apparent increase in the risk of myopathy, unlike gemfibrozil-statin combination therapy. In overview, the available evidence indicates that the combination of fenofibrate with a statin is a useful approach for optimising reduction in the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome, as well as delaying the progression of diabetes-related microvascular complications. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of this approach.

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