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Metabolic Syndrome Diabetes Plus

Metabolic syndrome is a constellation of problems that often includes diabetes or prediabetes. What are the other conditions Being overweight, especially when extra pounds accumulate around the midsection having high or borderline-high blood pressure having high triglyceride levels and having low HDL (good) cholesterol. Specifically, you have metabolic syndrome if you have diabetes or prediabetes and two or more of the following researchers think that the impact of the metabolic syndrome on health is more than the sum of its parts. Over the years, this collection of health risks has gone by many names. Besides the deadly quartet, it has also been called syndrome X, insulinresistance syndrome, diabesity, and the dysmetabolic syndrome. Metabolic syndrome, although not as flashy or memorable as some of the other names, is the term used by most clinicians and researchers today.

Why Diabetes and Metabolic Syndrome Matter

The ultimate impact on health of type 2 diabetes and metabolic syndrome is through cardiovascular disease. The cluster of features associated with type 2 diabetes or the metabolic syndrome is a highly potent recipe for heart disease and stroke. People with type 2 diabetes or the metabolic syndrome have at least a two-to fivefold increased risk of cardiovascular disease. The relative risks are even higher in women with diabetes compared with their counterparts who are nondiabetic. In addition, in the United States, type 2 diabetes is the major cause of blindness, kidney failure, amputations, and neurological complications, such as impotence. Type 2 diabetes decreases life span by an average of seven to twelve years.

How The Definition Of The Metabolic Syndrome Oyerlaps That Of Insulin Resistance

As reported above, the NCEP ATP III report designated a cluster of related CvD risk factors as a definition of the metabolic syndrome, and stated that this syndrome is closely linked to insulin resistance (25). Insulin resistance and or compensatory hyperinsulinemia are undoubtedly CVD risk factors (10). On the other hand, although insulin resistance is believed to be the basic pathophysiological alteration leading to the metabolic syndrome, neither assessment of insulin resistance nor hyperin-sulinemia were among the criteria proposed by the NCEP ATP III report. This omission was justified by the lack of adequate sensitivity and specificity of the different insulin assays used in clinical practice and other potential limitations. This is of importance, because there are patients with the metabolic syndrome who are unlikely to have insulin resistance and vice versa (35). There are several other considerations emphasizing why different definitions of the metabolic syndrome and of the...

Metabolic syndrome definitions

In 1998, the WHO proposed a set of criteria11 to define metabolic syndrome. Its definition required the presence of insulin resistance as a component of the diagnosis. Insulin resistance was defined as the diagnosis of type 2 diabetes mellitus, impaired fasting glucose, impaired glucose tolerance or, for those with normal fasting glucose levels (< 100 mg dL), glucose uptake below the lowest quartile for the background population under investigation under hyperinsuline-mic, euglycemic conditions. In addition to the presence of insulin resistance, the WHO criteria require the presence of two additional risk factors that may include hypertension or treatment with antihypertensive medications, hypertriglyceri-demia, low HDL cholesterol, BMI > 30 kg m2, and urinary albumin excretion rate > 20 ag min (Table 1.1). In 2001, the National Cholesterol Education Program (NCEP) introduced definitions of metabolic syndrome, a constellation of major risk factors, life-habit risk factors, and...

Conclusion inflammation hypothesis of metabolic syndrome

In conclusion, the pro-inflammatory state of obesity and metabolic syndrome originates with excessive caloric intake and is probably due to over-nutrition in a majority of patients in the U.S. The pro-inflammatory state induces insulin resistance leading to clinical and biochemical manifestations of the metabolic syndrome. This resistance to insulin action further promotes inflammation through increases in lipolysis and plasma FFA concentrations on one hand and interference with the anti-inflammatory effect of insulin on the other. While these factors may be the most important ones in a majority of patients with metabolic syndrome, it is possible that genetic factors may also contribute to the inflammatory stress in metabolic syndrome. These factors may be important in ethnic groups such as Asian Indians who may have increased amounts of upper abdominal fat in spite of normal BMI values.82 Since excessive nutritional intake probably accounts for the inflammation at least in...

Metabolic Syndrome as a Link between Insulin Resistance and CVD

Metabolic syndrome refers to a constellation of risk factors that is apparently associated with risk for both CVD and type 2 diabetes (Figure 2.7). Although a clustering of risk factors had been recognized as early as the 1920s, Gerald Reaven's Banting lecture in 1988 (Reaven, 1988) disseminated the concept to a wider audience and stimulated considerable further research. Reaven linked 'upstream' insulin resistance to a 'downstream' clustering of risk factors potentially responsible for the excess vascular risk in diabetes. He included glucose intolerance, hypertriglyceridaemia, low HDL-cholesterol and hypertension in his clustering, which he termed 'syndrome X', but interestingly obesity was not included (Reaven, 1988). The syndrome has since been variably termed the insulin resistance syndrome, Reaven's syndrome and the dysmetabolic syndrome. However, as it is not a discrete entity caused by a single Figure 2.7 Scheme displaying the concept of metabolic syndrome as a link between...

Rationale for defining metabolic syndrome

In the past decade, sedentary lifestyles, atherogenic high calorie diets, and weight gains have characterized adolescents and adults in the United States and in many countries across the globe.1,2 Indeed, a recent report2 estimated the prevalences of overweight and obese people in the U.S. above 60 and 30 , respectively. This is not a unique burden for the U.S., but reflects a worldwide trend demonstrating an increased prevalence in metabolic risk factors3,4 including visceral obesity, insulin resistance, dyslipidemia with abnormal values for triglycerides and high density lipoprotein cholesterol (HDL-c), hypertension, and (if measured) pro-thrombotic and inflammatory markers. In addition to the appreciation that weight gain and obesity are increasing global problems and that the location of body fat has both prognostic and therapeutic importance is the recognition of atherogenic risk factor clustering. This concept was noted by Framingham investigators who found it was common in both...

The Metabolic Syndrome An Overview

A WHO expert committee in 1998 proposed that the metabolic syndrome should be diagnosed in patients who show evidence of glucose intolerance and or insulin resistance together with two other components of the syndrome (Table 14.1). The expert committee decided to define insulin resistance as insulin sensitivity under hyperinsulinemic euglycemia clamp conditions below the lowest quartile for the population under investigation. This definition of insulin resistance matches the degree of insulin sensitivity in patients with Type 2 diabetes mellitus (Beck-Nielsen et al 1999). Epidemiological studies indicate that the metabolic syndrome is prevalent in industrialized countries. When applying the WHO definition of the metabolic syndrome to the European Group for the study of Insulin Resistance (EGIR) database (Ferran-ninni et al 1996), the prevalence of the syndrome was estimated at 15.6 among healthy Caucasians in Europe (Beck-Nielson et al 1999). Data from the Danish Twin Register (Kyvik,...

Prevalence of the metabolic syndrome

As is the case for the diagnosis of diabetes, the application of different diagnostic criteria for the metabolic syndrome results in differing figures of prevalence and the identification of different individuals. It is still too early to see how the new IDF definition of the metabolic syndrome will fare, but application of the NCEP ATPIII and WHO diagnostic criteria to individuals aged > 20 years in the National Health and Nutritional Examination Survey (NHANES) cohort resulted in an age-adjusted prevalence of 23.9 and 25.1 , respectively. Particular differences were noted in the prevalence for certain subgroups, such as African-American males, in whom the WHO estimates were higher (Ford and Giles, 2003). An earlier study by the same authors, using the NCEP ATPIII criteria, had estimated similar overall prevalence figures (though as high as 43.5 in the 60-69-year age group), and suggested that this translated to 47 million US residents using the 2000 census data (Ford etal., 2002)....

The Metabolic Syndrome CardiovASCuLar Risk Factors And Cardiovascular Events In Women

In 1988, Reaven proposed that individuals who displayed the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia were at significant risk for CvDs (10). Over the last 15 years, the concept underlying the common aggregation of major abnormalities associated with an insulin-resistant state has emerged as a unique entity, the so-called metabolic syndrome. Although there is a concept that insulin resistance is ontologically different from the metabolic syndrome, for many years these two expressions have nonetheless often been used more or less synonymously. This issue is, however, a matter of great controversy at the present time. One of the reasons is certainly represented by the difficulty of measuring the insulin resistance state and the need for more reliable parameters defining the risk for CVD. The need to simplify the definition of the metabolic syndrome for epidemiological studies contrasts with the complexity of the geographical and...

The metabolic syndrome and cardiovascular risk

The DECODE study group have undertaken similar studies in the metabolic syndrome in an attempt to clarify its prevalence and also to define its relationship with cardiovascular mortality. Using a modification of the WHO definition of the metabolic syndrome and excluding patients with diabetes, the non-diabetic adult prevalence of metabolic syndrome in Europeans was found to be 15.7 in males and 14.2 in females. Over a median follow-up of 8.8 years the hazard ratio for all-cause and cardiovascular mortality was 1.44 and 2.26 in men and 1.38 and 2.78 in women, respectively, after adjustment for age, cholesterol and smoking status (Hu etal.,2004). Interesting comparisons between the cardiovascular risk associated with the diagnosis of the metabolic syndrome have been made. While there is no doubt that the application of both sets of criteria identifies at-risk individuals, there remains debate about the best method of factoring insulin resistance as a discrete variable. Insulin...

Metabolic Syndrome Definition and classification

The association of insulin resistance, dysglycaemia, hypertension, obesity and dyslipidaemia was first described formally by Reaven in 1988 in his Banting lecture (Reaven, 1988). Since then this syndrome has been referred to as the 'insulin resistance syndrome' and the 'metabolic syndrome' as well as 'syndrome X'. More recently there have been attempts to assemble diagnostic criteria for what has become known as the 'metabolic syndrome' and apply these criteria to populations so that prevalence figures may be obtained. The World Health Organization (WHO) (World Health Organization, 1999), the National Cholesterol Education Programme (NCEP) Adult Treatment Panel (ATP) III (NCEP ATPIII, 2001) and the International Diabetes Federation (IDF) (Alberti etal., 2006) have disseminated similar although not identical criteria that are based on the presence of several core metabolic and cardiovascular criteria such as hypertension, dyslipidaemia, obesity and elevation of either fasting insulin...

Endothelial Dysfunction Insulin Resistance And The Metabolic Syndrome

Dyslipidaemia, and that endothelial dysfunction merely represents the impact of hyperglycaemia and other features of the metabolic syndrome. An alternative concept is that endothelial dysfunction is at the heart of the metabolic syndrome. According to this concept, the endothelial dysfunction in large arteries that is an early and prominent event in atherothrombotic disease is parallelled by endothelial dysfunction in resistance vessels and metabolically important capillary beds that contributes to the development of the metabolic syndrome 50 .

Metabolic Syndrome and Risk of Colorectal Adenoma Development

Two Asian-Pacific Epidemiologic Studies showed an increased risk of colorectal adenoma development associated with MeS (1) the Self-Defense Forces Health Study, carried out between 1995 and 2002 at two Self Defense Forces hospitals in Japan 44 and (2) one study carried out at the Center for Health Promotion, Samsung Medical Center, Seoul, Korea, between March 2004 and December 2005 45 . Both studies included subjects who underwent colonoscopy as a screening examination for polyps. Apart from the association of MeS with colorectal adenoma, an increased risk for MeS was more evident for proximal than distal colon, for multiple ( 3), and for advanced adenoma. Abdominal obesity of the individual components of MeS was an important risk factor for colorectal adenoma. Thus, the MeS appears to be a crucial entity with regard to the prevention of colorectal adenoma and consequently colorectal cancer.

Central Visceral Obesity

Central obesity (obesity localized to central visceral fat depots) is the most prevalent precursor of Type 2 diabetes mellitus (Ohlsson et al 1985). Insulin resistance, which is more prominent in visceral obesity than generalized obesity or that localized to peripheral gluteofemoral depots, is considered to be related to this pattern of obesity (Peiris et al 1986). Free fatty acids have been implicated in the pathogenesis of insulin resistance in muscle through their interface with critical steps in glycolysis. Muscle tissue is the main regulator of systemic insulin sensitivity (Bjorntrop and Rosmond 1999). Compared with subcutaneous fat, visceral fat has increased sensitivity to lipolytic stimuli and has decreased antilipolytic effects to insulin. This means that the potential per unit mass of visceral adipose tissue to mobilize free fatty acid is much larger than that of subcutaneous fat (Bjorntrop 1994). Acute reductions in caloric intake has been shown to improve insulin...

Whole body fat distribution subcutaneous and visceral fat

Even though the total fat mass determines the plasma pool of FFA and thereby the FFA flux from adipose to non-adipose tissue (Lewis et al. 2002), there are differences in the relationship of subcutaneous and visceral fat depots to features of peripheral and hepatic insulin sensitivity (Misra et al. 1997). Visceral fat cells are more sensitive than subcutaneous fat cells to the lipolytic effect of catecholemines and less sensitive to the antilipolytic and fatty acid re-esterification effects of insulin (Kahn & Flier 2000). Furthermore, the venous effluent of visceral fat depots leads directly into the portal vein, resulting in greater FFA flux to the liver. This makes the visceral fat depots more efficient than subcutaneous fat in influencing the carbohydrate metabolism in the human body (Kissebah 1996). Whole-body MRI and CT are the methods of choice for the quantitation of visceral fat accumulation and whole-body fat distribution. Their noninvasive nature and easy-to-follow...

Metabolic Syndrome see also Chapter

Hypertension is frequently associated with insulin resistance (and concomitant hyperinsulinaemia), central obesity and a characteristic pattern of dislipidaemia (high triglycerides and low HDL-cholesterol) (Reaven etal., 1996 Reaven, 2002). The relation between insulin resistance and hypertension is well established (Modan etal., 1985 Ferrannini etal., 1987 Swislocki etal., 1989 B hler etal., 1990 Ferrari and Weidmann, 1990) but, despite this association, insulin resistance contributes only modestly to the prevalence of hypertension (Hanley etal., 2002). This constellation of risk factors is known as the (cardiovascular) metabolic syndrome. There are various definitions but all agree on the essential components - glucose intolerance, obesity, hypertension and dyslipidaemia. Almost one-quarter of adults in the USA has the metabolic syndrome (Ford etal., 2002). This is likely to rise in the next several years primarily because of the rapid increase in obesity. People with the metabolic...

Section I Oxidative Stress Metabolic Syndrome Obesity Diabetes and Uncoupling Proteins

The Metabolic Syndrome The Metabolic Syndrome The Question of Balance between the Pro-Inflammatory Effect of Macronutrients and the Anti-Inflammatory Effect of Metabolic Syndrome Due to Early Life Nutritional Modifications 47 Obesity, Nutrigenomics, Metabolic Syndrome, and Type 2 Diabetes 107

The Metabolic Syndrome in PCOS

Due to the high prevalence of insulin resistance in PCOS, some recent studies used the NCEP ATP III criteria to assess the prevalence of the metabolic syndrome in PCOS women. Glueck et al. (95) studied 138 PCOS patients and found a prevalence rate of 46 , whereas, more recently, Apridonidze et al. (82) found a prevalence of 43 by retrospectively reviewing the medical charts of 106 PCOS women attending the Endocrine Clinic of Richmond, Virginia. Both these studies, therefore, described a prevalence of the metabolic syndrome in PCOS women nearly twofold higher than that reported in the general population investigated in the cited NHANES III report (96), matched for age and body weight. Apridonidze et al. (82) also described higher free testosterone and lower SHBG levels in those women with the metabolic syndrome compared with those without it, as well as a higher prevalence of acanthosis nigricans and a tendency toward a greater family history for PCOS. These results were in accordance...

Metabolic Syndrome and Risk of Prostate Cancer

MeS was found to predict prostate cancer during 27 years of follow-up, indicating an association between insulin resistance and the incidence of prostate cancer 33 . Features of the MeS, specifically abdominal obesity and hypertension, are also associated with prostate cancer in African-American men 34 , a population which is more prone to developing MeS symptoms.

Metabolic Syndrome

About 47 million adults in the United States have a group of risk factors, called metabolic syndrome, that can increase the chances of developing diabetes as well as heart disease and stroke. The five conditions, which must occur together to be considered metabolic syndrome, are

Insulin resistance syndrome metabolic perspective

Reaven's original description of the metabolic syndrome consisted of obesity, insulin resistance, hypertension, impaired glucose tolerance or diabetes, hyper-insulinemia, and dyslipidemia characterized by elevated triglyceride and low HDL concentrations.1 All these features serve as risk factors for atherosclerosis and thus metabolic syndrome constitutes a significant risk for coronary heart disease2-5 (Table 2.1). The features of obesity or overweight and insulin resistance also provide significant risks for developing type 2 diabetes.5,6 The risks for CHD and diabetes with metabolic syndrome are greater than those for simple obesity alone without insulin resistance and therefore the understanding of the pathogen-esis and, through it, a rational approach to its therapy are of prime importance.

Series Editors Introduction

Type 2 Diabetes, Pre-Diabetes, and the Metabolic Syndrome The Primary Care Guide to Diagnosis and Management is an important addition to the literature for primary care physicians. It covers concisely and with attention to clinical relevance the full spectrum of insulin resistance and diabetes. This book gives a practical, no-nonsense approach to understanding the basic pathophysiology of diabetes and the metabolic syndrome, an approach to treatment with oral agents and insulin, and an approach to risk factor management. By putting all this information in one readable text, Dr. Codario provides a service to us all, facilitating the understanding of a body of knowledge that cannot be obtained through any attempt to read portions of much larger textbooks in the field. This textbook will serve as a resource for medical students, residents in family medicine and internal medicine, and attending physicians who wish to update and improve their knowledge in the field of diabetes and the...

Risk factors for diabetes

The increase in prevalence of type 2 diabetes is paralleled by the rising rate of obesity and metabolic syndrome. As body mass index (BMI) increases, the risk of developing type 2 diabetes increases correspondingly. The prevalence of type 2 diabetes is three to seven times higher in obese patients and is 20 times higher in those with a BMI greater 35 kg m2 than in those with a BMI between 18.5 and 24.9 kg m2 7-8 . This increased prevalence, however, may vary among ethnic groups. Obesity is a component of metabolic syndrome. The National Cholesterol Education Program Adult Treatment Panel (NECP-ATP III) defines metabolic syndrome using the objective clinical criteria given in Table 1 9 . Metabolic syndrome is defined as the presence of any three of the risk factors. The clustering of risk factors associated with this syndrome predicts development of manifest diabetes and cardiovascular disease. Hence, prevention of type 2 diabetes should aim to treat and prevent components of Clinical...

WHO World Health Organization

Definition of the metabolic syndrome includes diabetes mellitus or impaired glucose tolerance or impaired fasting glucose and or insulin resistance. It should be noted that it is extremely difficult to determine the presence of insulin resistance at an individual level if the corresponding values of the reference population are not known. Usually we consider that insulin resistance is present when a person has values higher than the upper quintile for the method used (method of choice is the hyperinsulinaemic euglycaemic clamp). The definition of the metabolic syndrome also includes two of the following

What is the proper treatment of dyslipidaemia in DM

In Type 2 DM - where obesity and insulin resistance usually coexist -weight loss with diet and physical activity constitute the cornerstone of treatment. It is remarkable, however, that although weight loss and better metabolic control of DM with antidiabetic pills or insulin usually improve the dyslipidaemia, they do not completely restore it to normal levels. The reduction of the particularly elevated cardiovascular risk of these diabetic individuals requires the multifactorial and simultaneous confrontation of all risk factors that are related to the metabolic syndrome (glycaemia, hypertension, obesity and dyslipidaemia) and also the cessation of smoking. Although blood sugar control per se, when the other elements of the metabolic syndrome coexist, does not appear to decrease - at least to the expected degree - the risk for cardiovascular complications, reduction of the levels of the individual components of this syndrome (including dyslipidaemia) has been proven to decrease

T Bobbert and Joachim Spranger contents

Obesity is among the most frequently encountered metabolic diseases worldwide. Moreover, its incidence and prevalence are rising rapidly.1,2 More than half the world population is considered overweight.3 Being overweight constitutes a health risk because it is associated with several co-morbidities including dyslipidemia, hypertension, type 2 diabetes, and atherosclerotic cardiovascular disease.45 Adipose tissue was initially believed to be only a fat storage organ, but it is now acknowledged to be an active participant in energy homeostasis and other physiological functions. Adipose tissue is known to express and secrete a variety of novel adipocytokines that have been implicated in the development of insulin resistance and atherosclerosis.6,7 Dysregulation of adipocytokine production is directly involved in the pathophysiology of metabolic syndrome, and normalization of plasma concentrations of adipocytokines reverses the phenotype of metabolic syndrome.8,9

Hyperglycaemia as a risk for CVD in diabetes

However, questions have been raised about the relative importance of hyperglycaemia as a CVD risk factor in T2D. In the United Kingdom Prospective Diabetes Study (UKPDS), more intensive glycaemic control did not result in significantly fewer CVD events, despite a significant linear association between HbA1c and CVD events on cross-sectional analysis (Stratton etal., 2000). One reason for this anomaly may be related to the difficulty in lowering glucose levels in T2D, and the difference in HbA1c between the two groups was simply insufficient to show significant outcome differences. An alternative explanation is that glycaemia, in the context of T2D, is predominantly a surrogate marker for other more potent CVD risk factors. The most obvious of these is insulin resistance, which is thought to be the main feature underpinning the metabolic syndrome (Figure 10.2). While glucose dysregulation is an integral feature of this syndrome, the cumulative effect of other factors, including...

Female Sexual Dysfunction

Female sexual dysfunctions (FSD) include persistent or recurrent disorders of sexual interest desire, disorders of subjective and genital arousal, orgasm disorder, pain and difficulty with attempted or completed intercourse. The scientific knowledge on sexual dysfunction in women with diabetes is rudimentary. Sexual dysfunction was observed in 27 of type 1 diabetic women. FSD was not related to age, BMI, HbA1c, duration of diabetes, and diabetic complications. However, FSD was related to depression and the quality of the partner relationship (153). Recently, the prevalence of FSD in premenopausal women with the metabolic syndrome was compared to the general female population. Women with the metabolic syndrome had reduced mean full Female Sexual Function Index (FSFI) score, There is evidence to suggest that in men with diabetes, sexual dysfunction is related to somatic and psychological factors, whereas in women with diabetes, psychological factors are more predominant (153). The...

How Our Lifestyle Has Made Us Vulnerable to Diabetes

In 1985, an estimated 30 million cases of diabetes existed worldwide. This number increased to 177 million in 2000 and is estimated to rise to at least 370 million by 2030, almost all from type 2 diabetes associated with aging, obesity, and inactivity. In the United States, the numbers of cases of diabetes and obesity have risen in parallel. Diabetes and prediabetes affect 18 million and almost 40 million persons, respectively, and the metabolic syndrome affects almost 25 percent of the U.S. population.

Insulin resistance and hyperglycaemia

Insulin resistance (hyperinsulinaemia) is a characteristic finding in patients with type 2 diabetes. It often clusters with obesity, central obesity, elevated blood pressure, elevated levels of total triglycerides, haemostatic abnormalities and low-grade inflammation (Laakso, 1996). This clustering of cardiovascular risk factors (the metabolic syndrome) predicts CAD events in non-diabetic subjects (Lempiainen etal., 1999) and in patients with type 2 diabetes (Lehto etal., 2000). Prospective studies are still missing to show that insulin resistance is an independent risk factor for CAD in patients with type 2 diabetes. Several population-based prospective studies have shown a positive association between hyperglycaemia and cardiovascular disease in type 2 diabetic patients (Laakso, 1999). However, this risk is not particularly strong for CAD.

Recent Developments

Increased tissue levels of triglyceride are associated with insulin resistance and other features of metabolic syndrome. Magnetic resonance spectroscopy studies demonstrate hepatic lipid accumulation in vivo in obese patients with type 2 diabetes,3 and the presence of elevated serum hepatic transaminase levels in the West of Scotland Coronary Prevention Study (WOSCOPS) predicted development of type 2 diabetes.4 Also, triglyceride accumulation in skeletal muscle impairs the efficiency of substrate utilization and contributes to peripheral insulin resistance. Interaction between components of the diet and genes involved in the pathogenesis of metabolic syndrome is an area of research interest. For example, polyunsaturated fatty acids and a common polymorphism of the PPAR-7 gene interact to regulate peripheral levels of triglyceride. Further study in this area may identify more effective dietary manipulations and therapies tailored to individual genotype.5

EGIR European Group for Insulin Resistance

According to this group, the metabolic syndrome is defined by the presence of hyperinsulinaemia (insulin level higher than the upper quartile of the reference population), together with two of the following 3. waist circumference > 80 cm (31 in) for women, > 94 cm (37 in) for men According to these criteria, which were very recently (April 2005) reported, the metabolic syndrome definition includes the presence of central obesity (waist circumference more than 80 cm 31 in for women and more than 94 cm 37 in for men), as well as at least two of the following According to this new definition, central obesity (as defined by high waist circumference values with upper limits lower than those set by NCEP ATP-III) is - as mentioned already - mandatory, and regarding the other coexistent metabolic disturbances, the lower upper limit for fasting plasma glucose at 100 mg dl (5.6 mmol L) is noteworthy. The recognition of a difference between various ethnic groups as regards anthropometric...

Identifying Polycystic Ovarian Syndrome

Another feature that women with PCOS have in common with metabolic syndrome is obstructive sleep apnea. This sleep apnea results in daytime sleepiness and high blood pressure. The major health risks for someone with PCOS, besides infertility, are the occurrence of impaired glucose tolerance and type 2 diabetes, as well as ges-tational diabetes. In addition, just like patients with the metabolic syndrome (see Chapter 5), these women are at greater risk for high blood pressure, abnormal blood fats, and cardiovascular disease.

Eating Well for Type Diabetes

The person with type 2 diabetes has to be very aware of the fats in his or her diet. The metabolic syndrome (see Chapter 5) is commonly found in this type of diabetes. You must pay attention to foods that increase triglycerides, which lead to the production of small, dense LDL particles that are connected to coronary artery disease.

Implications of obesityassociated diabetes

The consequences of obesity are serious. Obese individuals are predisposed to a cluster of metabolic disturbances known as 'syndrome X' or the metabolic syndrome, which comprises glucose intolerance (the inability to metabolize glucose adequately), type 2 diabetes mellitus, hypertension, dyslipidaemia (high triglyceride levels accompanied by a raised concentration of low-density lipopro-teins and diminished high-density lipoproteins), leading to an increased risk of stroke and cardiovascular disease (Ramirez, 1997 Reaven 1988, 1995 Walker 2001). In addition, obesity is also a risk factor for some malignancies such as endometrial cancer (Iemura et al., 2000). The more life-threatening, chronic health problems have been categorized into four main areas by WHO. These include cardiovascular problems including hypertension, stroke and coronary heart disease conditions associated with insulin resistance, namely type 2 diabetes certain types of cancer as well as gall bladder disease.

When Does Endothelial Dysfunction Occur In Diabetes

In type 1 diabetes, ED precedes and may cause diabetic microangiopathy, but it is not clear whether hyperglycemia is a sufficient cause of ED (30-36). In our view, it is more likely that hyperglycemia predisposes to the development of ED and that other factors, genetic or environmental, play a role in determining who among type 1 diabetic patients goes on to develop ED, nephropathy and aggressive angiopathy, and who does not. In type 2 diabetes, ED is present from the onset of the disease and is strongly related to adverse outcomes (4,16). Type 2 diabetes mostly occurs in the setting of the metabolic syndrome, but ED in type 2 diabetes is not explained by hypertension, obesity, or dyslip-idemia (37). It is not clear whether this diabetes-specific ED is caused by hyperglycemia or other factors. An important potential determinant is increased inflammatory activity (Fig. 1). In addition, part of the ED in type 2 diabetes may be primary, i.e., cause of diabetes rather than caused by...

Key Issues in the Treatment Strategy

The novel classes of antidiabetic agents, incretin mimetics and DPP-4 inhibitors, may hold two additional promises A reduction in cardiovascular complications typically associated with type 2 diabetes 188 and the metabolic syndrome, and a positive influence on the natural history of type 2 diabetes, which with current treatment options is characterized by a steady loss of P-cell function 189,190 , which in turn determines a rather short durability of successful glycemic control with any choice of antidiabetic agents 191,192 .

Maternal Diabetes and Cardiovascular Disease Risk

GDM confers a sixfold risk for future maternal diabetes, independent of other significant risk factors such as weight, visceral adiposity and physical activity (58, 59). Up to a third of women with diabetes may have been affected by prior GDM (60). Additionally, GDM is associated with vascular dysfunction and future cardiovascular disease. Heitritter et al. found that women with a GDM history had greater vascular resistance, lower stroke volume and lower cardiac output than women without a GDM history (61). In a cross-sectional study, Carr et al. found that women with a GDM history were more likely to have metabolic syndrome and to experience cardiovascular events than women without a GDM history and, moreover, that these cardiovascular events occurred at a younger age (8). Shah et al. found that this increased risk of cardiovascular events, although

Nafld As A Cardiovascular Risk Factor

Data is emerging that NAFLD is an independent risk factor for vascular disease, which is the most common cause of death among patients with diabetes (1). Patients with NAFLD have a greater carotid intima-media thickness as well as a higher prevalence of carotid atheromatous plaques (51). The presence of NAFLD among patients with type 2 diabetes is associated with an increased risk of developing vascular disease, which is only partly associated with the presence of the metabolic syndrome (52,53). Similarly, ALT is independently predictive of the development of coronary heart disease (54). The mechanisms through which NAFLD may result in increased vascular disease are unclear and it is difficult to distinguish whether this is an association with the abnormal metabolic milieu that occurs in association with NAFLD or whether it is related to the increased lipid oxidation, inflammation and abnormal hepatic lipid metabolism that occurs with NAFLD. Certainly, lipid profiles among diabetics...

Comprehensive Risk Reduction of Cardiovascular Risk Factors in the Diabetic Patient An Integrated Approach

The excess CV mortality and morbidity in the diabetic population seems to reflect the strong association of diabetes with insulin resistance and with well-established coronary risk factors. During the past 2 decades, significant advances have been made in elucidating the pathophysiologic determinants and consequences of the metabolic perturbations in the diabetic state. The disease is characterized by insulin resistance and is commonly associated with the metabolic syndrome. Sensitivity to insulin is variable in the population at large. Cellular insulin resistance develops as the result of a complex interplay of genetic and environmental factors. Hyperinsulinemia occurs as an adaptive response to the increasing insulin resistance. Type 2 diabetes develops when insulin-resistant individuals cannot maintain the degree of excess insulin secretion needed to overcome insulin resistance. There are two aspects to the type 2 diabetic state hyperglycemia and hyper-insulinemia. Insulin...

Risk Factors For Dementia And Their Relation To Adiposity Hyperinsulinemia And Type Diabetes

In terms of vascular risk factors, hypertension, dyslipidemia, diabetes, hyperinsulinemia, the metabolic syndrome, homocysteine, smoking, and heart disease are potential risk factors for Alzheimer's disease and vascular dementia (22). High adiposity, hyperinsulinemia, and diabetes are clearly related to the metabolic syndrome (29), dyslipidemia (40), and hypertension (41), and these can be reversed or prevented by weight loss, by the reduction of insulin resistance, and by the prevention of T2D (3, 42, 43). Smoking, another potential risk factor for AD (22), is related to weight loss and low weight and thus may produce the appearance of a relation between low BMI and AD through confounding. This type of confounding may partially explain the U-shaped associations found between BMI and other outcomes such as mortality (44).

Population lessons from the pcos paradigm

The androgen balance is profoundly affected in the presence of metabolic disorders, particularly obesity and the metabolic syndrome (2). Androgens have an important impact on both glucose and lipid metabolism, and on fat homeostasis, therefore it is not unlikely that androgen imbalance may play a role in the pathophysiology of the metabolic syndrome. Although the few large prospective studies have not confirmed a significant association, cross-sectional studies have nonetheless provided some evidence for a linkage between low testosterone levels and CHD events, particularly in men (2). One reason for the failure to obtain conclusive information from clinical and epidemiological studies may be partly dependent on the sex-related different behavior of sex hormones in the presence of obesity. On the other hand, this hypothesis has attracted scientific concern since low testosterone in men and a condition of relative hyperandrogenism in women are associated with abdominal obesity,...

Obesity type diabetes and insulin resistance

Insulin resistance is a common feature of obesity and its incidence rises with increasing BMI. Visceral obesity is an even better predictor than BMI of hyperin-sulinaemia, insulin resistance and type 2 diabetes (Despres, 1998 Ferrannini and Camastra, 1998). The clustering of cardiovascular risk factors with insulin resistance was first described as syndrome X by Reaven in 1988 and included central obesity, hypertension, glucose intolerance and dyslipidaemia (the 'deadly quartet') (De Fronzo and Ferrannini, 1991 Reaven, 1993 Williams, 1994). Other features of the syndrome have since been added to include a pro-coagulant state and accelerated atherosclerosis, appropriately called the 'cardiometabolic syndrome'. Recent guidelines from the National Cholesterol Education Programme (Adult Treatment Panel III, ATP III) suggests that clinical criteria for definition of insulin resistance or metabolic syndrome should be based upon any three of the following (Executive Summary, 2002 Figure...

Guidelines For Exercise

Improved insulin sensitivity correlates with lowered cardiovascular risk. Weight loss combined with exercise and diet therapy significantly decreases intra-abdominal fat and is associated with a better sense of well-being, better mood, and higher self-esteem. The matter in which exercise is attempted is strictly the patient's preference. The participants in this study were young white and black men and women (ages 1830) who completed treadmill testing and then were followed from 1985 to 2001. Glucose, lipids, and blood pressures were measured and physical activity was assessed by interview and self-reporting. Outcome measurements included hypercholesterolemia, metabolic syndrome, hypertension, and type-2 diabetes. 2. Metabolic syndrome 10.2. Patients with low fitness (< 20th percentile) were three to six times more likely to develop diabetes, hypertension, and metabolic syndrome than patients with higher fitness (> 60th percentile). Adjustment for BMI lowered the strength of the...

Effect of glycemic control on cardiovascular disease

Role in a variety of other metabolic abnormalities, including high levels of plasma triglycerides, low levels of high-density lipoprotein (HDL) cholesterol, hypertension, abnormal fibrinolysis, and coronary heart disease 15,16 . This cluster of abnormalities has been called the insulin resistance syndrome or the metabolic syndrome 17 . The National Cholesterol Education Program Adult Treatment Panel III recently recognized the metabolic syndrome as a secondary therapeutic target for the prevention of cardiovascular diseases 15 . Patients who have the metabolic syndrome meet at least three of the following criteria triglycerides that are greater than 150 mg dL, HDL that is less than 40 mg dL, blood pressure that is greater than 130 85 mm Hg, fasting blood glucose that is greater than 110 mg dL, and waist circumference that is greater than 40 cm in men or 50 cm in women (Table 1) 15 .

Lifestyle and Type Diabetes

In addition to advancing age, being overweight or obese, and inactivity, inheritance plays a large role in diabetes. Although all of the specific genes that underlie obesity, the metabolic syndrome, and diabetes have not been identified, it is clear that the risk of developing these conditions and diseases is inherited. But how can we explain the widespread inheritance of diseases, the effects of which are so devastating How would Darwin explain the natural selection process that leads to diabetes The widespread inheritance of risk for obesity, diabetes, and the insulin resistance that underlies much of type 2 diabetes does make sense according to a theory called the thrifty gene hypothesis. Until just a few centuries ago, human beings lived in peril of famine. During times of famine, thrifty genes that decreased energy expenditure were highly advantageous to human survival because the energy people took in was small, and because of difficulty in finding food, burning less energy...

Cardiovascular Disease In Type Diabetes

Type 2 diabetes is very different from type 1 diabetes in its underlying etiology and its natural history. Insulin resistance, which is defined as a less than normal effect of insulin on in vivo glucose uptake and metabolism, occurs in a high proportion of the population of societies embracing western culture (10,26). Factors responsible for the development of insulin resistance are only partially understood. Fetal malnutrition predisposes to insulin resistance in postnatal life (27). Excess calorie intake and reduced physical activity lead to exaggerated lipid deposits and obesity. The proportion of excess calories deposited as lipids in subcutaneous adipose tissue relative to visceral adipose tissue is both genetically and hormonally determined (28). An increase in visceral adiposity but not subcutaneous adiposity is highly correlated with insulin resistance and the components of the metabolic syndrome (29,30). There is a significant correlation between visceral adiposity and both...

Dietary nutrient composition in type diabetes

LDL, low-density lipoprotein VLDL, very low density lipoprotein HDL, high-density lipoprotein SNS, sympathetic nervous system IGT, impaired glucose tolerance CVS, cardiovascular system. Figure 6.3 Metabolic syndrome. LDL, low-density lipoprotein VLDL, very low density lipoprotein HDL, high-density lipoprotein SNS, sympathetic nervous system IGT, impaired glucose tolerance CVS, cardiovascular system.

Continuing Medical Education

The overall goal of this activity is to update the knowledge of clinicians on strategies and techniques needed to comprehensively manage patients with type 2 diabetes, pre-diabetes, and or the metabolic syndrome. After completing this CME activity, participants should have improved their overall knowledge and attitudes in regard to treating type 2 diabetes, pre-diabetes, and or the metabolic syndrome. Specifically, participants should be able to Understand the pathophysiology of type 2 diabetes and metabolic syndrome Appreciate, understand and apply a comprehensive strategy for risk reduction in diabetes and metabolic syndrome

Other Metabolic Risk Factors

Since the introduction of the concept of the metabolic syndrome, several other metabolic abnormalities have been defined to be related to insulin resistance and increased risk of CVD. The plasminogen activator in-hibitor-1 (PAI-1) levels have been shown to be elevated in subjects with insulin resistance (Bastard and Pieroni 1999). In one study, PAI-1 levels were directly associated with the amount of visceral fat in obese men but not women. These levels decreased substantially when subjects lost weight (Kocks et al 1999). High PAI-1 levels may cause reduced endogenous fibrinolytic activity and have been linked to increased risk of CVD (Nordt et al 1999). Data from the Framingham offspring study (Meigs et al 2000) demonstrated an association between insulin resistance and abnormalities in several other hemostatic factors. In this study, elevated fasting insulin levels were associated with increased serum concentration of tissue-type plasminogen activator (tPA) antigen, and von...

Summary And Caveats Of The Evidence

Measures of adiposity and risk factors that are part of the metabolic syndrome change with age in ways that may underestimate the effects of high adiposity, dyslipidemia, and blood pressure. In fact, high adiposity in the oldest old may be a marker of health and is related to decreased mortality (71). Lastly, we attempt a reductionist approach to separate the effects of glucose, insulin, components of the metabolic syndrome (hypertension, dyslipi-demia), and possibly products of adipose tissue (adipokines, cytokines) on the risk of cognitive impairment. We also try to separate the associations of these conditions with AD and vascular cognitive impairment. There is such overlap in these conditions that this reductionist approach is a very difficult if not an impossible task. However, we should not be discouraged in isolating the mechanisms relating these conditions to AD and VD, in particular because of the potential for interventions including specific drugs, but should always take...

What is the frequency of hypertension in DM

For Type 2 DM, however, the relationship of hypertension and DM is more complex. Hypertension often coexists from the beginning of DM diagnosis, together with the other parameters of the metabolic syndrome (obesity, dyslipidaemia, insulin resistance, increased thrombogenesis, endothelial dysfunction). Thus, roughly 40 percent of Type 2 diabetics have hypertension at the time of DM diagnosis. As a whole, roughly up to 75 percent of patients with Type 2 DM develop hypertension during their lifetime.

And Insulin Sensitivity

In experimental rodent models, ACE inhibition has been shown to enhance glucose transport skeletal muscle and adipose tissue in insulin-resistant obese Zucker rats and spontaneously hypertensive rats (147-150). Angiotensin AT1 receptor antagonism has been shown to improve insulin sensitivity and glucose uptake in skeletal muscle of normotensive diabetic KK-Ay mice (151), partially reduce insulin resistance in Wistar fatty rats (114), and increase 2DG uptake and GLUT-4 expression in skeletal muscle in obese Zucker rats (152). Because insulin resistance and the metabolic syndrome accelerate CVD (153) inhibition of the RAS may improve cardiovascular outcomes, in part, by increasing insulin sensitivity and improving metabolic control.

Dyslipidaemia And Other Cardiovascular Risk Factors

The dyslipidaemia of ESRF is characterised by raised plasma triglycerides with a normal cholesterol level. This form of dyslipidaemia becomes worse after starting CAPD. The lipid profile on CAPD is generally more atherogenic than with other dialysis modalities. A possible contributory factor for this atherogenic lipid profile is the glucose absorption from the dialysates giving rise to enhanced triglyceride synthesis. Chronic hyperinsulinaemia is a major component of the metabolic syndrome and a recognised risk factor for atherosclerosis (36). There is a preferential sieving of the smaller cardioprotective lipoprotein HDL-cholesterol among the proteins lost into the dialysate rather than that of other lipoproteins (37).

The role of antiobesity drugs in diabetic management

Given the overwhelming evidence that obesity is of fundamental importance in the aetiology of type 2 diabetes, as well as many of its co-morbid conditions such as hypertension, dyslipidaemia and other aspects of the metabolic syndrome, it is surprising how little attention has been given to weight management, compared to the extensive studies that have been conducted with drugs to control hyperglycaemia, hypertension and dyslipidaemia. There is little doubt that reduction of excess body weight can be very effective treatment. Dietary intervention studies suggest that a weight loss of approximately 10 per cent is required to significantly improve HbA1c in subjects with established type 2 diabetes, although some subjects may respond dramatically to lesser degrees of weight loss (Wing et al., 1987). Modest weight loss early in the course of the disease, combined with other changes to diet and lifestyle can also be extremely effective, as was shown during the first 3 months of dietary...

Calcium Channel Blockers

Clinical studies have shown that at least 65 of hypertensive patients require two or more drugs to achieve the target BP of less than 130 80 (86). Calcium channel blockers (CCBs) have been proven effective as second-line therapy as adjuncts to the above mentioned agents. CCBs are not only effective antihypertensive agents, they have also been shown to reduce insulin resistance or new-onset DM among people with cardio-metabolic syndrome (85,87-90). Both the ALLHAT and the RENAAL trials showed that the dihydropyridine calcium antagonists are reno-protective when used in combination with the agents that block the RAS (85,91). Nondihydropyridine calcium antagonists, such as verapamil and diltiazem, have also been shown to have additional benefits of reducing proteinuria when used in combination with RAAS blockers (92,93).

Therapeutic Strategies in Diabetes and Cardiovascular Disease

With management strategies for preventing and treating the cardiovascular complications of diabetes. I am indebted to Dr. Deedwania and the group of experts he has assembled for these two important issues. Editing one issue is a big job, let alone two. However, Dr. Deedwania has had a long-standing academic and clinical interest in diabetes and metabolic syndrome in cardiovascular disease. His dedication to improving care for these individuals is evident in these two issues of the Cardiology Clinics.

Does Exercise Correct Overweight Obesity

In the metabolic syndrome diabetes type 2 overweight and physical inactivity are the most conspicuous problems (Fig. 4). Theoretically, overweight could be corrected by an increase of physical activity in order to burn 0.1 kg of fat 700kcal need to be expended, i.e., 90min of bicycle exercise at an intensity of 100 Watts. Requirements to loose significant amounts of weight (> 10 kg) and maintain it by exercise only are impressive 2500 to 2800 kcal need to be expended per week requiring a minimum of 5 to 6 h of exercise at moderate levels (500 kcal h) (30-35). It is quite obvious that only exceptionally motivated patients are willing to invest the time and the effort to achieve this goal. Moreover, as a result of excessive overweight many patients have lost the capability to undergo such demanding exercise programs. After having been inactive for the better part of their life it would be quite unrealistic to expect radical changes from patients after the age of 50. Thus, most studies...

Epidemiologic Evidence Of The Relation Between Type Diabetes And Related Conditions To Mild Cognitive Impairment And

Adiposity parameters in relation to dementia onset (68) is critical for interpretation of study findings. Third, anthropometric characteristics of populations vary around the world. If baseline BMI, whether measured at mid-life or late-life, is within a healthy range (e.g., < 25 kg m2), with low prevalence of overweight and obesity, the risky effects of high adiposity may be less likely observed. Finally, another potential explanation is ethnicity. One study in Japanese Americans showed no association of high adiposity with AD (63). A study in Northern New York City (69) found that in younger elderly (65-76 years of age), the association between BMI quartiles and AD resembles a U-shaped curve, while in the oldest old (> 76 years) higher BMI is related to a lower AD risk. This U-shaped association has been reported for the relation between adiposity and cardiovascular mortality (70) and underscores the difficulty in studying the effects of adiposity in older age (71). This study...

Risk of Cardiovascular Disease in Prediabetes

Both IGT and IFG also predict CVD incidence. In parallel with the meta-regression analysis described above, analyses from the DECODE study (combining data from 13 prospective European studies) have demonstrated all-cause mortality hazard ratios of 1.20 (95 CI 1.04-1.38) for IFG and 1.50 (95 CI 1.33-1.69) for IGT when compared with normoglycaemia. However, when the analyses were confined to CVD events and adjusted for body mass index (BMI), systolic blood pressure (SBP), cholesterol and smoking, IGT remained a significant predictor (hazard ratio 1.34 95 CI 1.14-1.57) whereas the effect of IFG was lost (hazard ratio 1.09 95 CI 0.90-1.30), implying that a 2-h oral glucose tolerance test (OGTT) level may be the optimal glucose parameter for cardiovascular event prediction. The question remains whether there are mechanistic explanations for these observations - for example, could exaggerated postprandial glucose excursions play a key role in accelerating atheromatous lesions Or could...

Thi azoli di nedi ones

In a recent review (Diamant and Heine, 2003) - suggesting that thiazolidinediones have pleiotropic effects that may reduce CVD risk in addition to improving glucose regulation. As well as increasing insulin sensitivity and improving pancreatic beta-cell function, peroxisome proliferator activator receptor-gamma (PPAR-7) agonists also exert anti-inflammatory effects, lower blood pressure, reduce the atherogenic lipid profile characteristic of the metabolic syndrome, alter body fat distribution and improve vascular endothelial function (Diamant and Heine, 2003). In the PROactive study in patients with T2D and established vascular disease, pioglitazone significantly reduced the main secondary endpoint, which was a composite of cardiovascular death, myocardial infarction and stroke. As expected, glycosylated haemoglobin (HbA1c) was reduced, and there were reductions in blood pressure, triglycerides and LDL-cholesterol and improvements in HDL-cholesterol (Dormandy etal., 2005), but markers...

Macronutrients and origin of inflammation

In addition to obesity and increased macronutrient intake, genetic and other environmental factors may induce the activation of inflammatory mechanisms and the induction of oxidative stress. These factors may be relevant in those ethnic groups in whom metabolic syndrome has been shown to occur in the absence of obesity. in these groups, migration to western countries like the U.S. and U.K. results in increased adiposity with a sedentary lifestyle that results in a phenotype of the metabolic syndrome against an appropriate genetic background (Figure 2.3).

The Effect of PPARy Ligands on the Enhancement of Insulin Sensitizing Action Via Improving Hyperglycemia

Blood pressure control is important in the treatment of chronic kidney diseases including DN (66). Hypertension is commonly linked to obesity and insulin resistance (67). This syndrome, in which insulin resistance, hypertension, obesity, dyslipidemia, and microalbuminuria are associated has been termed the metabolic syndrome (68,69). TZDs have the ability to lower blood pressure as well as to enhance of insulin sensitivity both in type 2 diabetic patients and animal models (70-74). Therefore, TZDs could also be effective agents in the treatment of the metabolic syndrome (75). It has been suggested that the antihypertensive effect of TZDs is a result of improved insulin resistance because insulin sensitivity has been found to be related to blood pressure

Current state of affairs and future directions

The best approach for the problem of diabetes mellitus and associated CV disease is to prevent or delay the onset of diabetes mellitus. A truly comprehensive approach to reducing the risks posed by diabetes should explore the possibility of preventing or delaying the onset of diabetes. From a public health perspective, this approach, with the potential of wide application, might be the most cost effective strategy. Of course, the assumption is that prevention of diabetes will also lead to prevention of atherosclerosis, and this assumption is yet to be substantiated by prospective trials. To demonstrate this association, individuals at risk must be identified early in the course of development of the disease. For this reason the Western Working Group, NCEP, ADA, and other major groups have emphasized the importance of the metabolic syndrome as a potential prediabetic state 9,22,47 . Although data are lacking regarding the benefit of intervention in patients with the metabolic syndrome,...

Risk factors for PAD in patients with diabetes Table

The high PAD risk in patients with diabetes is due to the complex interplay between the various haemodynamic and metabolic components of the metabolic syndrome. Diabetes is no longer considered to be a disease confined to hyperglycaemia but rather part of a syndrome comprising various risk factors, all of which confer an increased risk of atherosclerosis and cardiovascular events (see also Chapter 2). Hence, although the diagnosis and symptoms of diabetes are still defined by hyperglycaemia, other features of the syndrome, especially hypertension and dyslipidaemia, are equally if not more important in the pathogenesis of diabetes-related macrovascular complications such as PAD. Thus, the development of atherothrombotic complications in larger lower limb arteries is multifactorial, reflecting interactions between high glucose, lipids and blood pressure. For example, hypercholesterolemia and hypertriglyceridaemia have been associated with the increased risk of intermittent claudication...

The Nature Of Complications

The discovery that metabolic consequences of type 1 diabetes (insulin deficiency attributable to failure of pancreatic beta cells, generally induced by autoimmune phenomena) could be corrected by administration of pancreatic extracts and ultimately purified insulin gave rise to a powerful belief system in which insulin deficiency is embraced as the cause of diabetes under all circumstances. We now know that more than 90 of individuals with diabetes have type 2 diabetes, a condition in which insulin resistance is among the primary defects. However, the evolution of diabetes is such that at any given level of insulin resistance the pancreatic compensatory mechanism is inadequate to meet demands and insulin deficiency is a relatively late manifestation of the disorder. Surprisingly, this dichotomy was anticipated in the 1930s. Himsworth was interested in the causes of hyperglycemia in patients with diabetes and performed what Gerald Reaven described as ''a series of simple, but elegant...

Role of metabolic programming in etiology of obesity epidemic

Population-based evidence and studies of early nutritional experiences in animals suggest that different nutritional insults during fetal or neonatal life may result in increased risks of developing metabolic diseases such as obesity and metabolic syndrome later in life.10 Metabolic programming is a phenomenon in which a stimulus or insult that occurs during a critical period of organogenesis in early life results in permanent alterations in the structures and functions of affected organs and increased susceptibility to adult disease (Figure 4.1).17,18

Benefits of weight loss

New therapeutic lifestyle change (TLC) treatment programmes involve prescription diet and exercise based on an individual patient's eating habits and activity profile, combined with behavioural care provided through telephone, mail or attending a clinic (Perri et al. 1988 Perri, 1992). TLCs have been shown to improve the risks factors involved in the metabolic syndrome and to treat associated co-morbidities. Behavioural therapy was found to be an important part of the programme. The longer the duration of the behavioural therapy, the better the long-term weight loss outcome compared with standard treatment (Wadden et al., 1994, 1997). The basic dietary therapy in TLC is reduction in saturated fat with an increase in the polyunsaturated and monounsaturated fats. The total percentage of fat is less than 30 per cent of total calories.

Cardiovascular disease risk factors

A number of cohort studies have examined cardiovascular disease (CVD) risk profiles in children (Daniels et al., 1999 Freedman et al., 1999b Morrison et al., 1999a, b Sinaiko et al., 1999). One impressive study is the Bogalusa Heart Study which began in 1973 and is a cross-sectional and longitudinal study of the early natural history of atherosclerosis (Berenson et al., 1980). The survey has included school age children and young adults in a biracial (one-third African-American) cohort. This study has published a number of papers that have highlighted the link between overweight and obesity and an abnormal CVD risk profile even in young children. This includes changes in lipid, blood pressure and insulin profiles (Bao et al., 1996 Freedman et al., 1999b). The Bogalusa Heart Study demonstrated that insulin resistance tracked strongly from childhood to adulthood and resulted in a 36-fold increase in the prevalence of obesity, a 2.5-fold increase in hypertension and a 3-fold increase in...

Pharmacological Treatment

The Hypertension Optimal Treatment (HOT) trial demonstrated that diabetic patients had a 51 reduction of risk in cardiovascular events when their diastolic BP was treated to less than 80 mmHg, in comparison with those whose target was less than 90 mmHg (57). Epidemiological analysis of the data from the UKPDS cohort has also shown a linear relationship between CVD risk and increasing systolic BP starting at 120 mmHg and above (58). In addition, results from the Systolic Hypertension in the Elderly Program and Systolic Hypertension in Europe trials strongly support the aggressive antihypertensive treatment of diabetic patients with isolated systolic HTN (59,60). A recent survey, utilizing the Framingham algorithm to evaluate coronary risk in National Health and Nutrition Examination Survey (NHANES) III individuals with the metabolic syndrome, estimated that controlling BP to normal levels (120-129 80-84 mmHg) would prevent 28.1 of coronary events in men and 12.5 of events in women...

Establishing a Third Category IFG Why and What is IFG

As already discussed, the DECODE-study showed that while IGT is associated with an increased risk of developing CVD this is only the case in IFG-individuals if they also have abnormal 2-h glucose values 11,13 . In other words, isolated IFG is not associated with increased risk of CVD or increased all cause mortality. It has also been shown that while IGT is often associated with other abnormalities associated with the metabolic syndrome as dyslipidemia and hypertension, this is not the case for isolated IFG (at least not to the same extent) 18 .

Diabetes And CardiovASCuLar Risk Factors In Women

In general, estimates of CHD incidence in patients with diabetes vary across studies and countries, mainly because of differences in selection criteria and risk assessment. In a recent study performed in a large cohort of 6,032 women and 5,612 men, sampled from a nationwide network of hospital-based diabetes clinics in Italy and followed up for 4 years, it was reported that the age-standardized rate (per 1,000 person-year) of the first CHD event was 28.0 (95 CL 5-4-32.2) in men and 23.3 (20.2-26.4) in women (48). Major CHDs were less frequent in women than in men, with a sex ratio of 0.5. However, by multivariate Cox analysis, age and diabetes duration were risk factors for both sexes, whereas glycemic control and treated hypertension were additional risk factors for men, and higher triglyceride low HDL-cholesterol and microvascular complications were independent risk factors for women. These data further indicate that specific risk factors may be different between the sexes,...

The Irs As Risk Factor For

Prospective studies, now a decade old first suggested that hyperinsulinemia may be an important risk factor for ischemic heart disease. The Quebec Heart Study studied men who were 45 to 76 years of age and who did not have ischemia heart disease (13). A first ischemic event occurred in 114 men who were then matched for age, body mass index (BMI), smoking habits, and alcohol consumption with a control selected from among the 1989 men who remained free of ischemic heart disease during follow-up. Fasting insulin concentrations at base line were 18 higher in the case patients than in the controls. High fasting insulin concentrations were an independent predictor of ischemic heart disease in these men after adjustment for systolic blood pressure, family history of ischemic heart disease, plasma triglyceride, apolipoprotein B, low-density lipoprotein cholesterol, and high-density lipopro-tein cholesterol concentrations. Similarly, hyperinsulinemia was associated with increased all-cause and...

Diabetes And Neuropsychiatry Disorders

There is an emerging body of evidence that diabetes may accelerate age-related cognitive decline and leads to an almost twofold increase in the risk of both vascular and Alzheimer's dementia (21,22). An association with cognitive impairment has also been observed in pre-diabetic states of IFG (23), the metabolic syndrome (24) and insulin resistance (25). Diabetes may accelerate global cognitive decline, but psychomotor slowing has been reported as a characteristic finding in patients with diabetes (26). Although the increased prevalence of CVD may be a contributing factor, diabetes-associated dementia may occur independently of clinically significant micro or macrovascular disease (22,27). Proposed biological mechanisms for diabetes-associated central nervous system dysfunction include free radical-mediated oxidative stress, formation of advanced glycation end-products and alterations in neuronal insulin signaling pathways. In addition, a direct relationship between insulin metabolism

Protease Inhibitors PI

The introduction of highly active antiretroviral therapy (HAART) has significantly improved the survival and quality of life of HIV-infected individuals. However, HARRT-regimen, especially those including PIs have also resulted in increased incidence of metabolic syndrome and diabetes. Eleven PIs are now available in US and at least eight of them are clearly

Arterial hypertension

In Type 1 DM, hypertension is usually a result of diabetic nephropathy and manifests at the stage of microalbuminuria. In Type 2 DM, hypertension is present at the time of diagnosis of diabetes in a third of the patients and may coexist with other parameters of the metabolic syndrome X, a common pathogenetic mechanism which is insulin resistant. It may also be due to diabetic nephropathy, coexistent idiopathic arterial hypertension, renal vascular disease or other causes.

Summary and Conclusions

We are currently in the midst of a global epidemic of type 2 diabetes, which may well reverse the downward trend in CVD mortality seen in recent decades. The epidemic is being driven by the increasing prevalence of 'unhealthy lifestyle' involving a combination of obesity, physical inactivity and a diet high in saturated fat and refined carbohydrate. While established diabetes has long been regarded as an important cardiovascular risk factor, and hyperglycaemia has been shown to promote vascular dysfunction by a variety of mechanisms, there is increasing awareness that by the time a typical obese middle-aged subject is diagnosed with type 2 diabetes, he has already accrued significant cardiovascular risk in terms of hypertension, endothelial dysfunction, coagulopathy, atherogenic lipid profile and circulating pro-inflammatory adipocytokines. Indeed, there is now evidence that the overlapping conditions of pre-diabetes (encompassing both IFG and IGT) and the metabolic syndrome confer...

New Diagnostic Criteria for Diabetes Mellitus

The reason for changing these criteria was based largely on observations of the significance of a fasting plasma glucose level of > 7.8 mmol l versus a postprandial glucose level of > 11.1 mmol l (the previous diagnostic thresholds). Furthermore, data from the Framingham offspring study have shown that there is a continuous relationship between fasting glucose and risk of subsequent development of cardiovascular disease, even at plasma glucose concentrations below the diagnostic range for diabetes. As such these new criteria were an attempt to better identify those at risk of developing micro- and macrovascular complications. This change in the criteria appears to have identified more young and obese patients as having diabetes. The additional category of impaired fasting glucose highlights those who are at risk of developing diabetes in the longer term and also those who have an elevated macrovascular risk. This diagnostic category has also been proposed as one of the criteria in...

Introduction classifying diabetes

Diabetes mellitus is a heterogeneous metabolic syndrome with several different causes characterized by chronic hyperglycaemia with partial or total lack of insulin secretion and a reduced sensitivity to the hormone in peripheral tissues. If monitored inadequately and associated with other lipid and protein disorders, long-term complications may develop in several organs and systems, resulting in both high morbidity and mortality rates. Many of the long-term complications can be attributed to microangiopathy such as retinopathy, in the worst case leading to reduced sight or blindness to nephropathy leading to insufficient kidney function and to neuropathy, leading to motor-sensitivity deficit, a predisposing factor to the formation of ulcers and articular deformations of the feet. However, the most important epidemiological and clinical complications are those derived from macroangiopathy, primarily responsible for causing cardiovascular pathologies (chronic ischaemic cardiopathy,...

Dietary and lifestyle alterations

Currently Diabetes UK recommends energy intake prescriptions for diabetes patients to be that required to maintain a BMI of 25 kg m2 (Diabetes UK, 2003). In the obese diabetes patient this may be too strict an energy deficit to allow longer-term adherence with consequent patient and treatment failure. It is more appropriate to induce small changes in energy intake to allow an approximate deficit of 500-600 kcal per day (Lean and James, 1986). This standard approach to BMI of 25 kg m2 is reasonable for Caucasian populations, although rarely attainable in practice. In Asian populations the susceptibility to type 2 diabetes and metabolic syndrome increases dramatically at a lower BMI (23 kg m2). Certainly in disease prevention such targets should be considered as maximal desirable within the relevant populations.

The Difference between Type and Type Diabetes

Risk factors for type-2 diabetes include aging, exposure to toxins such as dioxin, obesity, family history, physical inactivity, ethnicity, and impaired glucose metabolism. Type-2 diabetes is also a prominent risk of metabolic syndrome, a constellation of conditions that includes insulin resistance along with hypertension, lipid disorders, and overweight. Type 2 diabetes is the type of diabetes that is growing in epidemic proportions. There is now a new type called type 1 1. It combines elements of both type 1 and type 2

Role of Adipocyte Products and Inflammation

While circulating NEFA and several adipokines are increased in visceral obesity, the levels of the adipose-specific protein adiponectin are decreased, reducing its insulin-sensitizing effects in liver and muscle (19,30). Adiponectin signals via AMP kinase, a stress-activated signaling enzyme implicated in a variety of metabolic responses, including suppression of hepatic gluconeogenesis, glucose uptake in exercising skeletal muscle, fatty acid oxidation, and inhibition of lipolysis, which may explain its beneficial metabolic effects (30-34). In addition to their effects on insulin signaling, the circulating adipose tissue factors strongly influence vascular endothelial function, linking the increased vascular risk in the metabolic syndrome with mechanisms of cellular insulin resistance (30,40). Adipose secretory factors also recruit and activate inflammatory cells, which can further perpetuate a systemic inflammatory milieu that can strongly influence vascular function and...

Tracking Cholesterol and Other Fats

Diabetes adds its own complication because of the metabolic syndrome (see Chapter 5). In the metabolic syndrome, the total cholesterol may not be very high, but the HDL cholesterol is low and the triglycerides are elevated. These patients also have a lot of a dangerous form of LDL cholesterol, so they are at higher risk for coronary artery disease. This increased risk must be taken into account in considering treatment for the fats.

Evaluation Of Diabetic Renal Disease And Classification

In contrast to type 1 diabetes, patients with type 2 diabetes quite often have hypertension related to abnormalities of obesity and the metabolic syndrome (17). They may also exhibit signs of loss of renal autoregulation meaning that a high blood pressure is inflicted on the glomeruli (18). However, over the years, there is an increasing thickening of the basement membrane and expansion of the mesangium. GFR may even be high because of glycemic dysregulation (19). Normal serum creatinine and somewhat elevated GFR (but not to the same extent as in type 1 diabetes). Some patients may have microalbuminuria at clinical diagnosis due to undiagnosed diabetes. Blood pressure may be elevated since essential hypertension may be related to the metabolic syndrome and type 2 diabetes.

Management Of The

Since many individuals with the metabolic syndrome are overweight, dietary treatment should be primarily focused on weight reduction. While the effect of weight reduction on the components of the IRS are widely accepted, there remains some controversy about specific diets to achieve weight loss. Insulin sensitivity can also be influenced by diet composition (101,102). There is evidence that a higher saturated fat intake is associated with impaired insulin action, some of which may be mediated by changes in body weight. In contrast, a high-monounsaturated-fat diet significantly improves insulin sensitivity compared to a high-saturated-fat diet. Independent of its effects on insulin sensitivity, diet composition can influence the factors clustering in the metabolic syndrome. Dietary carbohydrate increases blood glucose levels, particularly in the post-prandial period, and consequently also insulin levels and plasma triglycerides. The detrimental effects of a high-carbohydrate diet on...

Effects of Estrogen on Risk Factors for Diabetes

The changes in lipid metabolism that occur with the menopause, including increased total and LDLC, triglycerides and Lp(a), and decreased HDL-C, resemble those of type 2 diabetes and the metabolic syndrome (12). Adverse changes in carbohydrate metabolism also emerge with the menopause including decreased insulin sensitivity and insulin secretion (128). These together with increased central adiposity contribute to the increased risk of CVD in postmenopausal women. The effects of estrogen on lipid parameters are discussed in detail in the first part of this chapter. A number of observational studies have also reported that estrogen improves insulin resistance in postmenopausal women, a factor that is predictive for the development of type 2 diabetes (125,129). Estrogen therapy also appears to prevent central fat distribution, a factor that is strongly associated with insulin resistance (126). Thus, estrogen can potentially prevent the insulin resistance associated with central obesity...

Dietary strategies for preventing the onset of diabetes

The association between abdominal obesity (waist circumference > 102 cm in men, > 88 cm in women10), high low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol, hypertriglyceridaemia, high blood pressure, high fasting glucose (impaired glucose tolerance IGT > 110mg dL and < 126mg dL), and insulin resistance (known as metabolic syndrome) is highly predictive of type 2 diabetes and potential coronary disease. Recently, a large clinical trial, the 'Diabetes Prevention Program' (DPP),11 investigated whether diet and physical activity were more effective than metformin in preventing or delaying the onset of type 2 diabetes in subjects with impaired glucose tolerance and a family history of type 2 diabetes. The results of this study showed that the group that underwent lifestyle changes, intensive nutrition and exercise counselling (150 minutes a week) and behaviour modification lost 7 per cent of their body weight, with a 58 per cent reduction in...

Use of Lipid Altering Therapy

More recently, a once-daily, extended-release formulation of niacin (Nias-pan) has been approved by the U.S. Food and Drug Administration. This agent has been tested extensively in unselected patients with dyslipidemia as well as in diabetic patients with dyslipidemia and or features of the metabolic syndrome. Niaspan was shown to be efficacious in lowering elevated triglycerides and raising HDL cholesterol levels. Further, Niaspan was safe in diabetics and did not worsen glycemic control. Statin monotherapy is frequently suboptimal in diabetic < j

Therapeutic targets for reducing oxidant stress in overweight and obese patients

Emerging evidence has implicated increased dietary intake of fish oil containing large amounts of polyunsaturated fatty eicosapentaenoic acid (20 5, o> -3, EPA) and docosahexaenoic acid (22 6, ra-3, DHA), as beneficial in the prevention and treatment of a number of diseases in which environmental and lifestyle factors play roles. These include atherosclerotic cardiovascular disease and sudden death, metabolic syndrome, neurodegeneration, and various inflammatory disorders among others, but the mechanisms by which fish oil is protective are unknown.54-57 Recent data, however, suggest that the anti-inflammatory effects and other biologically relevant properties of ra-3 fatty acids are due, in part, to the generation of various bioactive oxidation products.58-63

Physical activity and type diabetes

The specific benefits of physical activity to improved glucose tolerance and control are associated with regular bouts of exercise that repeatedly provoke the acute effects of a single bout. These and other improvements in metabolic control associated with physical activity are not only important to those with type 2 diabetes but also to the sedentary and overweight, and those who have the metabolic syndrome. Significant improvements in metabolic fitness have been associated with increased physical activity that may not be sufficient in intensity to increase the more traditional measures of fitness such as maximal oxygen uptake (Vo2 max, the maximum rate at which an individual can take up and utilize oxygen while breathing air at sea level (Astrand and Rodahl, 1986)). However, sustained changes in activity levels are required for the benefits of exercise or physical activity to positively affect insulin action (Ivy et al., 1999 Albright et al., 2000 ADA, 2002). According to the ACSM...

Triglyceride and highdensity lipoprotein intervention

Unlike the plethora of trial evidence of CHD risk reduction with statins, the evidence from drugs to decrease triglycerides or increase HDL cholesterol is sparse. A meta-analysis of 17 observational studies suggested a significant relationship of triglycerides with CHD, even after adjustment for HDL cholesterol, especially in women 33 . In the 4S trial, in post hoc analyses, patients who had the lipid triad (elevated LDL, elevated triglyceride, decreased HDL cholesterol) had the highest event rates in the placebo arm and the greatest risk reduction with simvastatin 34 . Despite a mechanistic plausibility of increased risk with these lipid abnormalities in patients who had metabolic syndrome and diabetes, few long-term randomized trials have been completed (Table 2).

Role of renin angiotensin aldosterone system activation

Less well studied but seems to mediate beneficial effects that include vasodilation, inhibition of cell growth, and proliferation as well as cell differentiation 48,49 . The differential effects are shown in Fig. 1. The sequential progression of cardiovascular disease begins with the risk factors of hypertension, diabetes, smoking, metabolic syndrome, and dyslipidemia. These risk factors are independently associated with levels of angioten-sin II that in turn trigger the cascade of events. Progression to atherosclerotic disease and left ventricular hypertrophy leads to plaque destabili-zation in the face of uncontrolled risk factors, with acute coronary syndrome and myocardial infarction as the sequelae 50 . Loss of cardiac muscle eventually leads to remodeling of the left ventricle progressing relentlessly to heart failure and end-stage cardiomyopathy (Fig. 2).

Ramachandiran Cooppan

Diabetes mellitus is a chronic disease that results in major morbidity and mortality. As with any chronic illness the goals of therapy are to alleviate the acute symptoms and complications and then focus on preventing the long-term consequences. While the initial goals can be reasonably achieved in most instances, the long-term complications can prove to be more of a challenge. This is in part due to the fact that the disease is not a single entity but a complex metabolic syndrome that results in hyperglycemia. This can be due to an absolute deficiency of insulin or either defects in insulin secretion and insulin action or a combination of both. Clinically, it is convenient to classify the patient as having either type 1 or type 2 diabetes mellitus. This approach is based more on the underlying pathophysiology than on treatment, since many patients with type 2 diabetes will eventually require insulin for treatment.

Management of dyslipidaemia

Sedentary lifestyle is a major risk factor for CHD which increases lipid and non-lipid risk factors seen in obesity, metabolic syndrome and type 2 diabetes. Weight loss and exercise can reduce TG, increase HDLc and, in some persons, lower LDLc levels (Wood et al., 1988 Goldstein, 1992). Regular physical activity should be a standard part on any lipid management programme. The American Diabetes Association (ADA) suggests a reduction in the proportion of dietary saturated fats with increase in carbohydrate or monounsaturated fat or both. The ATP III recommends therapeutic lifestyle changes including dietary changes combined with regular exercise and weight management as the first line treatment for all risk factors associated with metabolic syndrome (National Cholesterol Education Program, 2002). Diets high in trans fatty acids, like margarine, biscuits and white bread, that can raise LDLc as well as lower HDLc should be avoided. National Cholesterol Education Program and ADA recommend...

Risk Factors For Stroke In Diabetic Subjects

Metabolic Syndrome (MS) as Stroke Risk Factor The term metabolic syndrome (MS) refers to a cluster of risk factors, including hypertension, dyslipidemia, obesity, and abnormalities in glucose metabolism that are closely associated with DM (in particular type 2 DM) and with cardiovascular disease, including stroke. Although the fact that these risk factors often co-occur is not debated, it is yet uncertain if the whole concept of the MS entails more than its individual components. The clustering of risk factors complicates the assessment of the contribution of individual components to the risk of vascular events, as well as assessment of synergistic or interacting effects. In addition, there is no general agreement on the actual definition of the syndrome (NCEP, 2001, 2005 WHO, 1999 IDF, 2005), and it is yet unclear if the presence of the MS has a higher predictive value for cardiovascular disease than widely used prediction scores such as Framingham, PROCAM, and SCORE (73-75). In the...

Eating Disorders And Depression Screening And Treatment

Antipsychotic agents are occasionally used in individuals with depression, either to augment a primary antidepressant's effectiveness or in the treatment of depression with psychotic features. Atypical antipsychotics (i.e., risperidone, olanzapine, clozapine, quetiapine, aripiprazole and ziprasidone) are now used more frequently than older antipsychotic medication. It has become clear that these medications can have significant negative effects on weight, lipid metabolism, and glucose homeo-stasis, contributing to the constellation of cardiac risk factors that constitutes metabolic syndrome (147). Of these medications, aripiprazole and ziprasidone appear to be least likely to promote weight gain, and, to date, have not been found to be associated with an increased risk of worsening glucose homeostasis, although there have been occasional case reports of sudden onset diabetic ketoacidosis or worsening of the lipid profile (147). Both risperidone and quetiapine have an intermediate...

Modified LDL Antibodies and LDLContaining Immunocomplexes

As suggested by recent reports showing that common carotid and femoral IMT are directly related to the levels of IgG oxLDL antibodies and inversely related to the levels of IgM oxLDL antibodies (196). Also of interest is the fact that the levels of IgG oxLDL and MDA-LDL antibodies are associated with the metabolic syndrome and smoking (197).

The Insulin Resistance Syndrome

Insulin resistance and hyperinsulinemia are frequently associated with a cluster of clinical and biochemical abnormalities that have been described with increasing detail and given a variety of names including deadly quartet, syndrome X, insulin resistance syndrome, metabolic syndrome, and cardiovascular dysmeta-bolic syndrome (9-13). Many prefer to call it insulin resistance syndrome because insulin resistance and the resulting hyperinsulinemia appear to be the underlying abnormalities from which the other features of the syndrome are derived (see Chap. 7). The hallmarks of insulin resistance syndrome are obesity, particularly central or intra-abdominal obesity, glucose intolerance, or type 2 diabetes mellitus, hypertension, a dyslipidemia characterized by elevated triglycerides, low HDL cholesterol and small dense LDL cholesterol, a hypercoagulable state characterized by alterations in both thrombosis and fibrinolysis and increased

Insulin resistance in the general female population

A great deal of research has been carried out in the last two decades, focusing on the impact of insulin resistance on chronic metabolic disorders. In most cases, particularly in epidemiological studies, simple tests have been used, although in large clinical single-center studies complex tests have been used. Insulin resistance and compensatory hyperinsulinemia precede the development of DM2 in most women, particularly when obesity is present. Moreover, there is worldwide agreement that excess insulin concentration and reduced insulin sensitivity are associated with a greater risk of developing CvDs. Data supporting the concept that there is a substantial difference and heterogeneity between the sexes in the prevalence of the insulin resistance state are, however, very sparse and still inconsistent, at least from the epidemiological point of view (9, 10). This is partly due to the fact that the majority of the studies did not segregate for sex in their analysis, but sex differences...

Fire Up Your Core

Fire Up Your Core

If you weaken the center of any freestanding structure it becomes unstable. Eventually, everyday wear-and-tear takes its toll, causing the structure to buckle under pressure. This is exactly what happens when the core muscles are weak – it compromises your body’s ability to support the frame properly. In recent years, there has been a lot of buzz about the importance of a strong core – and there is a valid reason for this. The core is where all of the powerful movements in the body originate – so it can essentially be thought of as your “center of power.”

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