Glucose metabolism

Abnormalities in glucose tolerance are commonly noted in individuals with central obesity. As outlined in Chapter 1, it is now well accepted that the presence of insulin resistance in an individual will need to be compensated for by hyperinsulinemia in order to maintain normal glucose tolerance. In those individuals who develop diabetes, a progressive loss of the insulin secretory capacity fails to compensate for the insulin resistance and results in a progressive hyper-glycemia (see Chapter...

Atherogenic Dyslipidemia

Insulin resistant states such as the metabolic syndrome are commonly associated with an atherogenic dyslipidemia that contributes to significantly higher risk of atherosclerosis and cardiovascular disease. Emerging evidence suggests that insulin resistance and its associated metabolic dyslipidemia result from perturbations in key molecules of the insulin signaling pathway, including overexpression of key phos-phatases, and downregulation and or activation of key protein kinase cascades, leading...

Inflammatory Markers

An improved understanding of the pathophysiology of atherosclerosis and atherothrombosis has given rise to an increasing interest in the role of inflammation in the pathogenesis of cardiovascular disease. Chronic inflammation, including a strong macrophage response triggered by vascular injury, oxidized LDL cholesterol, and possibly infection, drives the process of atherosclerosis leading to the development of vulnerable plaques88 (Figure 7.23). Rupture of these vulnerable atherosclerotic...

Adipocyte Dysfunction And Insulin Resistance

Adipose tissue plays a key role in directing whole-body glucose disposal, although it accounts for only about 10 of insulin-stimulated glucose disposal. There is now substantial evidence that factors that regulate adipocyte function can ultimately lead to insulin sensitization in muscle. Along these lines, the discovery of the peroxisome proliferator-activated receptors (PPARs) in the early 1990s has revolutionized Figure 4.6 CD68+ macrophages in human white adipose tissue. A hypertrophic...

Classification and evolution of increased cardiometabolic risk states

It has been accurately observed that certain risk factors in humans appear to 'cluster' with clinical states such as obesity and type 2 diabetes. Specifically, this risk factor clustering, and the association with insulin resistance, led investigators to propose the existence of a unique pathophysiological condition1. Many names have been provided to describe this clinical state including 'metabolic syndrome', 'syndrome X', and 'insulin resistance syndrome'1. The particular names that refer to...

Metabolism or storage

Glucose uptake, Glucose, lipid oxidation Glucose uptake, Glucose, lipid oxidation Figure 4.9 The EC system has effects that modulate whole-body energy metabolism. Specifically, the system acts as a major contributor to the energy balance by altering dietary intake. In addition, the system has effects on digestion, absorption, and metabolism of substrates. PYY, peptide YY GLP-1, glucagon-like protein-1 receptor (knockout mice) are lean and appear to be resistant to diet-induced obesity32....

Diabetes

Historically, strict blood glucose control in diabetics was only shown to reduce or delay the onset of microvascular disease such as retinopathy and neuropathy (Figures 8.21, 8.22 and 8.23)29. The UK Prospective Diabetes Study (UKPDS) compared conventional glucose control (fasting glucose < 15 mmol L) with an intensive strategy (< 6 mmol L) in over 4000 patients. Early data demonstrated the relationship between glycosylated hemoglobin (HbAlc) and microvascular events, and also hinted at a...

Impaired Glucose Tolerance Impaired Fasting Glucose Insulin Resistance And Diabetes

Impaired glucose tolerance, impaired fasting glucose, insulin resistance, and diabetes mellitus represent a spectrum of disorders that is associated with an elevated risk of cardiovascular complications. Impaired glucose tolerance, impaired fasting glucose, and insulin resistance are also risk factors for the development of overt diabetes. Importantly, the NCEP ATP III considers diabetes to be a coronary heart disease risk equivalent, conferring the same risk for coronary events as would be...

Liporegulation

Fat metabolism and carbohydrate metabolism are inherently related. Lipid abnormalities have been shown to have profound effects on carbohydrate metabolism as exemplified by the 'lipotoxicity' hypothesis. This hypothesis suggests that the abnormal accumulation of lipids, e.g. triglycerides and fatty acyl-CoA in muscle and liver, results in insulin resistance15,16. Several lines of evidence support this observation such Figure 4.2 Health care professionals typically assess metabolic measurements...

Increased

Reverse Cholesterol Transport

Figure 5.6 Schematic of the biological effects of advanced glycation end products (AGE) at the vessel wall. AGE are the short-and long-term modification products of glycation or glycoxidation of proteins and lipids and have been linked to premature atherosclerosis in diabetic patients as well as in non-diabetic subjects. AGE are a heterogeneous group of compounds that have multiple biological effects, some of which are mediated by interacting with receptors, including the receptor for AGE...

Hypertension

Elevated blood pressure has been recognized as a risk factor for cardiovascular disease for several decades and the definition of what constitutes hypertension 1.25 1.74 2.59 a 2.59 Triglycerides (mmol L) I Cholesterol < 5.0 mmol L Cholesterol < 5.7 mmol L Cholesterol < 6.4 mmol L Cholesterol > 6.5 mmol L I Cholesterol < 5.0 mmol L Cholesterol < 5.7 mmol L Cholesterol < 6.4 mmol L Cholesterol > 6.5 mmol L Figure 5.18 Data from the Whitehall II study showing the isolated and...

References

Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome time for a critical appraisal. Diabetes Care 2005 28 2289-304 2. DeFronzo RA. Insulin resistance, hyperinsulinemia, and coronary artery disease a complex metabolic web. J Cardiovasc Pharmacol 1992 20 Suppl 11 S1-16 3. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988 37 1595-607 4. Haffner SM. The insulin resistance syndrome revisited. Diabetes Care 1996 19 275-7 5. Liese AD, Mayer-Davis...

Smoking

Smoking remains one of the most potent modifiable risk factors for cardiovascular disease. Despite numerous studies documenting the cardiovascular sequelae of smoking and multiple public education campaigns, a significant subset of the US population continues to smoke. Smokers not only place themselves at risk for cardiovascular events, but also those around them as increasing data suggest that second-hand smoke is an underestimated and under-recognized risk factor. Smoking is a significant and...

Antiplatelet therapy

Antiplatelet therapies, the cornerstone of pharmacological cardiovascular prevention, play a vital role in minimizing events, although they do not actually modify an individual's cardiovascular risk factors. Aspirin has long been found significantly to reduce a host of events, with the expected effect magnification in more high-risk patients. This was quantified in a meta-analysis by Hayden et al., which identified a 28 reduction in non-fatal MI or coronary death, and statistically...

B

Figure 7.4 Impact of high-normal blood pressure on the cumulative incidence of cardiovascular disease among women a and men b . Optimal blood pressure is defined as a systolic blood pressure of lt 120mmHg and diastolic blood pressure of lt 80 mmHg. Normal blood pressure is defined as a systolic blood pressure of 120-129 mmHg or a diastolic blood pressure of 80-84 mmHg. High-normal blood pressure is defined as a systolic blood pressure of 130-139 mmHg and a diastolic blood pressure of 85-89...