Metabolic syndrome and type 2 diabetes

Enzymes involved in TG synthesis continue to represent challenging and intriguing targets for small-molecule intervention against the worldwide epidemic of obesity, metabolic syndrome, and type 2 diabetes, as well as smaller market indications from rare familial diseases to veterinary use. There is also intriguing evidence that inhibition of these enzymes may be beneficial for diseases unrelated to the area of metabolic disorders, such... 

SIRTl as a Therapeutic Target in Metabolic Syndrome and Type 2 Diabetes 231... 

Potatoes have been valued around the world for centuries because they are an easily cultivated, easily prepared and readily assimilated source of carbohydrate energy. The ease with which potatoes are digested has, however, become a double-edged sword, as the interrelated epidemics of metabolic syndrome and type 2 diabetes become global crises linked to rising obesity. At the same time as carbohydrates have been blamed for obesity, glucose intolerance has become recognized as a core feature of the metabolic syndrome and type 2 diabetes (Seidell, 2000). 

B. Dairy food intake, metabolic syndrome, and type 2 diabetes... 

While the association between dairy food intake and obesity is less clear, observational studies have indicated that dairy food consumption may be protective against the development of metabolic syndrome and type 2 diabetes. Pereira et al. (2002) reported an inverse relationship between dairy product consumption and insulin resistance syndrome in a prospective study of 3157 young adults (18-30 years) with 10 years of follow-up. Further, Mennen et al. (2000) reported that more than four servings of dairy products per day was associated with a nonsignificant inverse association with the metabolic syndrome in women, while a significant association in men was found. 

Clinical Features of Obesity, Metabolic Syndrome, and Type 2 Diabetes.84... 

CLINICAL FEATURES OF OBESITY, METABOLIC SYNDROME, AND TYPE 2 DIABETES... 

The impact of niacin in insulin sensitivity is important as the majority of those who needs to be treated with niacin will have a degree of insulin resistance (individuals with metabolic syndrome and type 2 diabetes). Furthermore, recent meta-analyses suggest that statin administration is associated with the degree of insulin resistance. 

Tenenbaum A, Fisman EZ, Motto M (2003) Metabolic syndrome and type-2 diabetes mellitus focus on peroxisome prolifetatra- activated receptor (PPAR). Cardio Diahetol 2(4) l-7... 

Jay, M.A. and Ren, J. 2007. Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus. Current Diabetes Reviews, 3 33-39. 

Barre, D.E. The role of consumption of alpha-hnolenic, eicosapentaenoic and docosahexae-noic acids in human metabolic syndrome and type 2 diabetes A mini-review. J. Oleo Sci. 2007, 56, 319-325. 

The Endocrine System The metabolic syndromes, including Type 2 diabetes, obesity, and high blood pressure. 

The FABPs are a family of carrier proteins for fatty acids and other lipophilic substances, such as eicosanoids and retinoids. These proteins are thought to facilitate the transfer of fatty acids between extra- and intracellular membranes. Adipocyte fatty acid-binding protein (aP2 FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deflcient mice have shown that this lipid chaperone has a significant role in several aspects of the metabolic syndrome, including type 2 diabetes and atherosclerosis. FABP has also been introduced as a plasma marker of acute myocardial infarction. 

AA, EPA, DHA, GLA, DGLA, LXs and resolvins suppress lL-1, lL-2, lL-6, and TNF-a prodnction by T cells (110-112, 149, 176-180). This claim suggests that EFAs/PUFAs and their metabolites function as endogenous anti-inflammatory molecules and regulate immune response and thus are likely to be of benefit in obesity, insulin resistance, atherosclerosis, metabolic syndrome X, type 2 diabetes mellitus, CHD, depression, and Alzheimer s disease that are considered as diseases of low-grade systemic inflammation (1-8, 24, 120). Some beneficial actions of PUFAs in various inflammatory conditions are because of the formation of anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin Dl. 

Wannamethee SG, Shaper AG, Lennon L, Morris RW. Metabolic syndrome vs. Framingham risk score for prediction of coronary heart disease, stroke, and type 2 diabetes mellitus. Arch. Int. Med. 2005 165 2644-2650. 

Answer B. AIDS patients being treated with protease inhibitors (e.g., indinavir) have developed a syndrome involving derangement of lipid and CHO metabolism. Changes in lipid metabolism and distribution occur quite commonly, and type 2 diabetes has also been reported. Indinavir is also notable for its tendency to precipitate in the urinary tract, causing nephrolithiasis unless the patient is maintained in a high state of hydration. 

AGIs have beneficial pleiotropic effects on major components of the metabolic syndrome, which should add to their therapeutic benefit in the treatment of IGT and type 2 diabetes. 

As shown in a Swedish cohort of healthy 50-year-old men with 20 years follow-up, proportion of 14 0 and 16 0 in serum cholesterol esters predicted the development of metabolic syndrome, independently of other metabolic and lifestyle factors [105]. Besides serum lipids, proportion of PA in adipose tissue is also related to insulin sensitivity. Unlikely 14 0 and 18 0, which were positively associated with insulin sensitivity, PA inversely correlated with insulin sensitivity in 59 healthy British men and women [134]. Since the authors excluded the effect of dietary intake for any of these SFA, they concluded that the reason is de novo lipogenesis in adipose tissue. In human skeletal muscle phospholipids, SFA [135,135] and especially PA [137] have been negatively associated with insulin sensitivity and Type 2 diabetes, [138] which could partly reflect dietary intake [139], In a Finnish cohort study of 4 years follow-up, impaired fasting glucose and Type 2 diabetes incidence were associated with serum nonesterified 16 0 levels, but were not associated with baseline dietary 16 0 intakes assessed from dietary records [140], Recently published prospective follow-up study showed that erythrocyte membrane fatty acids nominaly predict incident type 2 diabetes [141], In the American Atherosclerosis Risk in Commimities (ARIC) study, 2909 middle-aged men and women were followed for 9 years. The incidence of Type 2 diabetes was associated with total SFA levels of plasma cholesterol esters (also observed for 16 0 independently) and phospolipids (also for 16 0 and 18 0) [101]. In a more recent 4-year case-... 

Obesity, often resulting from chronic excess of dietary energy, is strongly linked to both increased inflammatory status and type 2 diabetes." Visceral obesity, dysUpi-demia, and insuhn resistance are all conditions that, when they occur simultaneously, comprise what is termed the metabolic syndrome, increasing the risk for both diabetes and cardiovascular disease. Weight loss has been shown to decrease insulin concentration and increase insulin sensitivity." ... 

Glucose-6-phosphate Dehydrogenase Over Activation. The role of G6PDH over activation has recently been implicated in the development of S)mdrome X , also known as metabolic syndrome . Metabolic syndrome is a cluster of conditions that greatly increases the risk of cardiovascular disease (CVD) and type 2 diabetes (T2D). Currently, millions of individuals around the world are affected by this disease. Patients with this disease concurrently show insulin resistance, visceral obesity or belly fat, atherogenic dyslipidemia (comprises a triad of increased blood concentrations of small, dense low-density lipoprotein-LDL, decreased high-density lipoprotein-HDL and increased triglycerides) and hypertension. 

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]. 

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)... 

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