Insulin resistance syndromic associations

Benzothiophenes, (in), prepared by Yamasaki (2) and thiazole-benzoisothiazole dioxide derivatives, (IV), prepared by Petry (3) were effective as cGMP-PDE inhibitors and used as blood sugar level-depressing agents in the treatment of insulin resistance syndrome associated with Type II diabetes. 

Abdominal obesity is associated with a threatening combination of metabolic abnormalities that includes glucose intolerance, insulin resistance, hyperinsulinemia, dyslipidemia (low HDL and elevated VLDL), and hypertension. This clustering of metabolic abnormalities has been referred to as syndrome X, the insulin resistance syndrome, or the metabolic syndrome. Individuals with this syndrome liave a significantly increased risk for developing diabetes mellitus and cardiovascular disorders. For example, men with the syndrome are three to four times more likely to die of cardiovascular disease. 

Disorders associated with syndrome X (insulin resistance syndrome, metabolic syndrome)... 

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. 

Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, et al. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vase. Biol. 2003 23 1042-1047. 

Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC. Association of a polymorphism in the p3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995 333 348-351. 

Abdominal obesity is associated with the metabolic syndrome, which is a precursor to hypertension and insulin-resistance syndrome that may progress to type 2 diabetes, dyslipidemia, and ultimately, cardiovascular disease. ... 

The association of insulin resistance with a clustering of cardiovascular risk factors including hyperinsuhnemia, hypertension, abdominal obesity, dyslipidemia, and coagulation abnormahties has been referred to by a variety of names including the insuhn resistance syndrome, the metabolic syndrome, the dysmetabolic syndrome, and the deadly quartet, to name a few. Since the description of the insulin resistance syndrome by Reaven in 1988, the number of associated factors has continued to grow. 

The insulin resistance syndrome, also known as the metabolic syndrome, is a common pathophysiological condition which is implicated in the development of type 2 diabetes, atherosclerosis, dyslipidemia, and hypertension [31-34]. The leading cause of mortality in people with the metabolic syndrome is cardiovascular disease (CVD). The close association between the metabolic syndrome and CVD may be due to the dyslipidemia [35-38]. The dyslipidemia observed in the metabolic syndrome is characterized in part by high plasma triglycerides and low high-density lipoprotein—cholesterol concentrations [39 1]. 

Insulin resistance has been associated with a number of other cardiovascular risks, including abdominal obesity, hypertension, dyslipidemia, hypercoagulation, and hyperinsulinemia. The clustering of these risk factors has been termed metabolic syndrome. It is estimated that 50% of the United States population older than 60 years of age have metabolic syndrome. The most widely used criteria to define metabolic syndrome were established by the National Cholesterol Education Program Adult Treatment Panel III Guidelines (summarized in Table 40-2). 

Because of the polyfactorial nature of disease states, such as obesity, type 2 diabetes, and Metabolic Syndrome, it is expected that drugs targeting the lipid synthesis and metabolism pathways will be used in the context of combination therapy [7]. Pre-clinical and clinical results to date indicate that pronounced efficacy could be achieved toward the management of associated lipid levels and insulin resistance, and thus, investigation in these areas provides significant promise. 

Some patients receiving indinavir exhibit nephrolithiasis/urolithiasis including flank pain that may be accompanied by hematuria. The frequency of nephrolithiasis is dependent on the period of treatment with indinavir. Other side effects associated with indinavir include insulin resistance, hyperglycemia, asymptomatic hyperbilirubinemia, HIV lipodystrophy syndrome and skin abnormalities. Indinavir should not be coadministered with drugs that affect the cytochrome P-450 system (CYP3A4). Antacids are not recommended within 2 h of its administration, specifically didano-sine containing an antacid buffer. 

Soon after the introduction of highly active antiretroviral combination treatments (HAART), lipodystrophy was associated with the use of protease inhibitors, and several reports have confirmed that a syndrome of peripheral lipodystrophy, central adiposity, breast hypertrophy in women, hyperlipidemia, and insulin resistance with hyperglycemia is an adverse event associated with the use of potent combination antiretroviral therapy, particularly including HIV-1 protease inhibitors (982-987). 

Lipodystrophy, a syndrome characterized by fat redistribution, hyperglycemia/insulin resistance, and dyslipidemia, can be associated with long-term HIV infection or with highly active antiretroviral therapy (HAART). In 1035 patients, those who took stavudine were 1.35 times more likely to report lipodystrophy (1076). However, the study was retrospective, and other factors unrelated to specific drug therapy may have had a greater effect on the adjusted odds ratio. 

Lifestyle factors have been associated with ED in both cross-sectional and longitudinal studies. In particular, obesity and sedentary lifestyle are clear-cut risk factors for ED, both in men with comorbid illnesses such as hypertension and diabetes, and especially in men without overt cardiovascular disease (50). Other lifestyle factors, such as smoking and alcohol consumption, have been implicated in some, but not all, studies to date. Intervening on cardiovascular and lifestyle factors may have broader benefits beyond restoration of erectile function. This important concept needs careful consideration, as recent studies have implicated the role of the metabolic syndrome, obesity, insulin resistance, and lack of exercise as independent risk factors for both ED and cardiovascular disease (51,52). 

Excess adiposity, particularly the abdominal obesity associated with increased waist circumference, is associated with insulin resistance, hypertension, and proinflammatory states. The prevalence of this complex of comorbidities associated with obesity, now referred to as the metabolic syndrome, is reaching epidemic proportions in the United States (Grundy et al., 2004 Roth et al., 2002). Indeed, increased abdominal adiposity is one of a cluster of factors that are used in the diagnosis of metabolic syndrome. Abdominal tissue in the trunk occurs in several compartments, including subcutaneous and intraperitoneal or visceral fat. Visceral fat in particular appears to contribute to perturbed fuel metabolism by at least two mechanisms. First, hormones and free fatty acids released from visceral fat are released into the portal circulation and impact directly on metabolism of the liver. Second, the visceral adipose depot produces a different spectrum of adipocytokines than that produced by subcutaneous fat (Kershaw and Flier, 2004). 

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