Metabolic syndromes

The wide range of inflammation-related factors that adipocytes secrete is linked to the inflammatory response that the tissue exhibits in obesity [1]. Obesity in general, like an increasing number of other diseases, is characterised by a state of mild chronic inflammation, and adipose tissue plays a central role in this. The production of most inflammation-related adipokines increases markedly in obesity and there is an elevated circulating level of a number of these factors as well as of other inflammatory markers such as C-reactive protein (CRP). The increased production of inflammatory adipokines (and decreased production of adiponectin with its anti-inflammatory action) in the obese is considered to play a critical role in the development of the obesity-associated pathologies, particularly type 2 diabetes and the metabolic syndrome [1]. 

Obese people are predisposed to diabetes and cardiovascular disease. The term diabesity (sometimes referred to as syndrome X or metabolic syndrome ) reflects the intricate association between these disorders. 

Metabolic Syndrome Insulin Receptor Glucose Transporters ATP-dependent K+ Channel Oral Antidiabetic Drugs... 

PPARy White adipose tissue, atherosclerotic lesions Insulin-sensitizing and glucoselowering re-directs TG from non-adipose tissues and visceral adipose depots for storage in subcutaneous adipose tissue slowed progression of atherosclerosis Fatty acids, eico-sanoids Th iazolid i ned iones pioglitazone (Actos ), rosiglita-zone (Avandia ) Type 2 diabetes, (insulin resistance, metabolic syndrome)... 

Shulman AI, Mangelsdorf DJ (2005) Retinoid X receptor heterodimers in the metabolic syndrome. N Engl J Med 353 604-615... 

Barish GD, Narkar VA, Evans RM (2006) PPARS a dagger in the heart of the metabolic syndrome. J Clin Invest 116 590-597... 

Mesolimbic System/Reward System Metabolic Syndrome Metabotropic Glutamate Receptors Metabotropic Receptor Metalloprote(in)ases Methicillin-resistant Staphylococci iV-Methyl D-aspartate Receptors Methylating Agents... 

In addition to the NOD mouse, Entelos has models for several human metabolic diseases (diabetes, obesity, and metabolic syndrome), inflammatory diseases (rheumatoid arthritis), and respiratory diseases (asthma and COPD). 

The editors have chosen topics from both important therapeutic areas and from work that advances the discipline of medicinal chemistry. For example, cancer, metabolic syndrome and Alzheimer s disease are fields in which academia and industry are heavily invested to discover new drugs because of their considerable unmet medical need. The editors have therefore prioritized covering new developments in medicinal chemistry in these fields. In addition, important advances in the discipline, such as fragment-based drug design and other aspects of new lead-seeking approaches, are also planned for early volumes in this series. Each volume thus offers a unique opportunity to capture the most up-to-date perspective in an area of medicinal chemistry. 

Patients with multiple risk factors, particularly those with diabetes, are at the greatest risk for IHD. Metabolic syndrome is a constellation of cardiovascular risk factors related to hypertension, abdominal obesity, dyslipidemia, and insulin... 

Control of existing risk factors and the presence of new risk factors for IHD should also be assessed regularly. Routine screening for the presence of metabolic syndrome will help in assessing the control of known major risk factors and identifying new risk factors. If new risk factors are identified and/or the presence of metabolic syndrome is detected, modify the pharmacotherapy regimen, as discussed previously, to control these risk factors and lower the risk of IHD and IHD-related adverse events. 

Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome an American Heart Association/ National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005 112( 17) 2735 2752. 

Patients with metabolic syndrome have an additional lipid parameter that needs to be assessed, namely non-high-density lipoprotein (non-HDL) cholesterol (total cholesterol minus HDL cholesterol). The target for non-HDL cholesterol is less than the patient s LDL cholesterol target plus 30 mg/dL (0.78 mmol/L). 

After assessment and control of LDL cholesterol, patients with serum triglycerides of 200 to 499 mg/dL (2.26 to 5.64 mmol/L) should be assessed for atherogenic dyslipidemia (low HDL cholesterol and increased small-dense LDL particles) and metabolic syndrome. 

Patients with serum triglycerides from 150-500 mg/dL (1.70-5.65 mmol/L) and serum HDL cholesterol less than 40 mg/dL (1.04 mmol/L) may have metabolic syndrome and need to be evaluated. 

Step 9 Identify Patients with the Metabolic Syndrome... 

The diagnosis of metabolic syndrome is made when three or more of the following risk factors are present 3,10... 

Patients with metabolic syndrome are twice as likely to develop type 2 diabetes and four times more likely to develop CHD.3,11 These individuals are usually insulin resistant, obese, have hypertension, are in a prothrombotic state, and have atherogenic dyslipidemia characterized by low HDL cholesterol and elevated triglycerides, and an increased proportion of their LDL particles are small and dense.3... 

NCEP ATP III identified metabolic syndrome as an important target for further reducing CHD risk. Treatment of metabolic syndrome starts with increased physical activity, weight reduction (which also enhances LDL cholesterol lowering and... 

What diagnostic parameters does MN have for the metabolic syndrome ... 

Determine the treatment goal for LDL cholesterol based on the patient s CHD risk and non-HDL cholesterol goal if patient meets criteria for metabolic syndrome. 

Once the LDL cholesterol goal is achieved, assess non-HDL cholesterol in those with metabolic syndrome and intensify LDL-lowering therapy further or consider adding niacin or fibrate. 

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