Insulin resistance hypertension and

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). 

Al-Awwadi, N. A., Araiz, C., Bomet, A., Delbosc, S., Ciistol, J. R, Linck, N., Azay, J., Teisse-dre, P. L., Cros, G. (2005). Extracts enriched in different polyphenoUc families normalize increased cardiac NADPH oxidase expression while having differential effects on insulin resistance, hypertension, and cardiac hypertrophy in high-fructose-fed rats. J. Agric. Food Chem., 53, 151-157. 

NIDDM is more common in obese people, and especially those with abdominal rather than subcutaneous obesity (section 6.2.3). Significant weight loss can often restore normal glycaemic control without the need for any other treatment. The so-called metabolic syndrome (also known as syndrome X) is the simultaneous development of insulin resistance, hypertension and hypertriglyceridaemia, all associated with (abdominal) obesity. 

Depression and Diabetes Mellitus. Patients with chronic medical illness have a high prevalence of major depressive disorder [59], Depression may be three times more prevalent in the diabetic population when compared with its occurrence in nondiabetic individuals [60], In addition, microalbuminuria, hypertension, and hyperinsulinemia are another three independent risk factors for cardiac disease in non-insulin-dependent diabetes mellitus (NIDDM) [61], Nosadini et al. showed that peripheral insulin resistance, hypertension, microalbuminuria, and lipid abnormalities are associated with NIDDM [61], Further, Helkala et al. determined that cognitive and memory dysfunction are associated with NIDDM and explored the disease s relationship with depression, metabolic control, and serum lipids. The results showed that the NIDDM patients had impaired control of their learning processes [62], Obviously, future research examining the causal relationship of depression to the onset on diabetes and the effect of depression on the natural course of diabetes is needed [60]. 

Rocchini, A.P. 1995. Insulin resistance, obesity and hypertension. J Nutr 125 1718S—1724S. 

Kasiske BL, O Donnell MP, Keane WE. The Zucker rat model of obesity, insulin resistance, hyperlipidemia, and renal injury. Hypertension 1992 19(1 suppl) 1110-5. 

H. Duplain, R. Burcelin, C. Sartori, S. Cook, M. Egli, M. Lepori, P. Vollenweider, T. Pedrazzini, P. Nicod, B. Thorens, U. Scherrer, Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 104, 342-5 (2001). 

There is an increased CHD risk associated with the insulin-resistant, prediabetic state described under the rubric of metabolic syndrome, a constellation of abdominal obesity, hypertension, insulin resistance, hypertriglyceridemia, and low HDL. Treatment should focus on weight loss and increased physical activity, since being overweight or obese usually precludes optimal risk factor reduction. Specific treatment of hpid abnormalities should also be undertaken. 

Interest in GA arose following findings that have implicated the role of increased activation of GC receptors in the development of MetS symptoms such as central obesity and hyperlipidemia. Overexpression of llp-HSD type 1 (llp-HSDl) in white adipose tissue of mice, for example, resulted in increased intracellular GC level, abdominal obesity, insulin resistance, hypertension, hyperglycemia, and dyslipidemia [47]. 

Insulin and Amylin. Insulin is a member of a family of related peptides, the insulin-like growth factors (IGFs), including IGF-I and IGF-II (60) and amylin (75), a 37-amino acid peptide that mimics the secretory pattern of insulin. Amylin is deficient ia type 1 diabetes meUitus but is elevated ia hyperinsulinemic states such as insulin resistance, mild glucose iatolerance, and hypertension (33). Insulin is synthesized ia pancreatic P cells from proinsulin, giving rise to the two peptide chains, 4. and B, of the insulin molecule. IGF-I and IGF-II have stmctures that are homologous to that of proinsulin (see INSULIN AND OTHER ANTIDIABETIC DRUGS). 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

Overactivation of the sympathetic nervous system (SNS) may also play a role in the development and maintenance of primary hypertension for some individuals. Among other effects, direct activation of the SNS may lead to enhanced sodium retention, insulin resistance, and baroreceptor dysfunction.9 Regardless of which mechanism(s) underlie the role the SNS may play in the development of primary hypertension, the SNS remains a target of many antihypertensive agents. 

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... 

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). 

Differential diagnoses include diabetes mellitus and metabolic syndrome because patients with these conditions share several similar characteristics with Cushing s syndrome patients (e.g., obesity, hypertension, hyperlipidemia, hyperglycemia, and insulin resistance). In women, the presentations of hirsutism, menstrual abnormalities, and insulin resistance are similar to those of polycystic ovary syndrome. Cushing s syndrome can be differentiated from these conditions by identifying the classic signs and symptoms of truncal obesity, "moon faces" with facial plethora, a "buffalo hump" and supraclavicular fat pads, red-purple skin striae, and proximal muscle weakness. 

Barroso I et al. Dominant negative mutations in human PPAR-y associated with severe insulin resistance, diabetes melli-tus and hypertension. Nature 1999 402 880-883. 

For cardiovascular risk detecting and correcting factors like hypertension, obesity, insulin resistance, and type 2 diabetes or abnormal lipid profile, according to preestablished guidelines, can dramatically diminish the number of events. 

In relatively recent years, it has become clear that under-nntrition of mother leads to low birth weight of the baby and this can increase the risk of development of degenerative disease in later life, e.g. hypertension, obesity, type 2 diabetes. One hypothesis is that the foetus adapts meta-bolically to deficiencies by increasing the number of cells in organs that perform specific functions that can overcome the deficiency, e.g. an increase in the number of liver cells that carry out gluconeogenesis, an increase in cells in the adrenal cortex to produce more of the chronic stress hormone, cortisol. These changes are carried over into adnlthood which can lead to an inadequate response of the liver to insulin so that insulin resistance develops. So far, however, it is unclear whether deficiencies in specific nntrients or undemutrition per se are responsible for snch changes (Chapter 15). 

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