Week 4 - Metabolic Syndrome.pdf

WEEK 4: METABOLIC SYNDROME EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 Clinical Exercise Physiology, 5th Edition - Chapter 12 METABOLIC SYNDROME  Th...

WEEK 4: METABOLIC SYNDROME EHR522: EXERCISE FOR METABOLIC AND MENTAL HEALTH CONDITIONS Subject Coordinator: Tim Miller [email protected] 02 6338 4442 Clinical Exercise Physiology, 5th Edition - Chapter 12 METABOLIC SYNDROME  The metabolic syndrome is a collection of inter- related cardiometabolic risk factors that are present in a given individual more frequently than may be expected by a chance combination  Patients with the metabolic syndrome are usually categorised as overweight or obese and have significantly greater prospective risk for developing atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes METABOLIC SYNDROME  The metabolic syndrome has also been referred to as  Syndrome x  Dyslipidaemic hypertension  The deadly quartet  Insulin resistance syndrome  Dysmetabolic syndrome  Plurimetabolic syndrome  Metabolic syndrome is a widely recognised public health term, but the clinical diagnosis and classification of the condition have been debated METABOLIC SYNDROME METABOLIC SYNDROME  Whereas several previous definitions incorporated compulsory factors (eg. insulin resistance and abdominal obesity), the newest definition recommends that a diagnosis of metabolic syndrome reflect the presence of any three or more abnormal findings  Although this diagnostic scheme is superior to previous recommendations, there is still some disagreement pertaining to the definition and cut points for elevated waist circumference. This is due to the significant variability in abdominal obesity phenotypes between sexes and among races and ethnic groups, as well as the subsequent association with other metabolic risk factors and predictive values for ASCVD and diabetes METABOLIC SYNDROME - SCOPE  Before the harmonised definition was proposed, the reported prevalence of metabolic syndrome varied widely depending on the criteria used for diagnosing the condition  According to a recent study, nearly 35% of adults and 50% of older adults (> 60 years) satisfied the criteria for metabolic syndrome METABOLIC SYNDROME - SCOPE NORMAL-WEIGHT OBESITY  Abdominal obesity (defined as ≥ 88cm for women and ≥ 102cm for men) increases with age even more so than BMI-assessed obesity  There is a well-documented and robust association between obesity and the metabolic syndrome; however, there are exceptions in which these do not overlap  Accordingly, overweight and obesity has been identified as the major driver of metabolic syndrome  One exception, the metabolically healthy obese phenotype, is characterised by high body mass index (BMI) yet subclinical (ie. normal) cardiometabolic health. A primary example is athletes with greater muscle mass proportional to adipose tissue  Conversely, there are also cases of normal-weight obesity, in which an individual is classified in the normal range for body mass or BMI but has elevated adiposity or risk factors (or both) for metabolic syndrome, ASCVD or diabetes NORMAL-WEIGHT OBESITY  Normal-weight obesity is strongly associated with cardiometabolic dysregulation, high prevalence of metabolic syndrome and increased risk of cardiovascular disease  BMI and waist circumference can be somewhat problematic since such metrics do not discriminate between adipose tissue and muscle and lack sensitivity to identify non-obese individuals with excessive body fat  Prevalence of metabolic syndrome increases with age and peaks among individuals around age 60 PAEDIATRIC METABOLIC SYNDROME  Previous studies of paediatric populations have classified metabolic syndrome as presenting three of the following factors  A waist circumference in the 90th percentile for age and sex  Either systolic or diastolic blood pressure in the 90th percentile for height, age and sex  Triglyceride concentration ≥ 1.25 mmol/L  HDLc concentration ≤ 1.0 mmol/L  Glucose concentration ≥ 5.5 mmol/L  The utility of identifying and diagnosing metabolic syndrome in paediatrics has been heavily debated PAEDIATRIC METABOLIC SYNDROME  Since the risk for cardiometabolic diseases can originate during childhood, screening children to identify emergent risk is crucial for early intervention and public health preventative efforts  A recent expert committee has recommended that children and adolescents aged 2 through 19 years at or above the 95th percentile of BMI for age be labelled obese and that children between the 85th and 95th percentiles be labelled overweight  The use of current adult criteria to stratify children and adolescent patients with metabolic abnormalities could significantly underestimate cardiometabolic risk ECONOMIC BURDEN  Although much debate currently surrounds the definition, criteria and diagnostic utility for the metabolic syndrome, high prevalence rates combined with the morbidity and mortality associated with this condition imply significant economic consequences  Recent analysed data from three healthcare delivery systems in the US indicate 60% greater healthcare costs in adults with metabolic syndrome compared against those without metabolic syndrome PATHOPHYSIOLOGY  Metabolic syndrome is characterised by a co- occurrence of atherogenic dyslipidaemia, hypertension, elevated glucose, chronic low-grade inflammation and prothrombosis  In conjunction with several behavioural factors (ie. sedentary behaviour and atherogenic diet), genetic predisposition, and advancing age, the clustering of multiple risk components within the metabolic syndrome is widely thought to occur as a result of obesity (more specifically, abdominal obesity) and insulin resistance  However, although obesity and insulin resistance are considered two hallmarks of chronic health risk, not all obese or insulin-resistant individuals develop the metabolic syndrome INSULIN RESISTANCE AND THE METABOLIC SYNDROME  Gradual decreases in cardiometabolic health start to occur long before an individual reaches obesity or is diagnosed as insulin resistant  In a healthy, insulin-sensitive person, glucose stimulates the release of insulin from pancreatic beta cells, which in turn reduces plasma glucose concentration through suppression of hepatic glycogenolysis and gluconeogenesis and simultaneous glucose uptake, utilisation and storage by the liver, muscle and adipose tissue  Conversely, under conditions of insulin resistance, there is a chronic failure of insulin to maintain glucose homeostasis INSULIN RESISTANCE AND THE METABOLIC SYNDROME  The role of insulin resistance in the development of the metabolic syndrome has been controversial, as a direct causal link has not yet been identified  Research continues to emerge that confirms a pathophysiologic link not only between insulin resistance, the metabolic syndrome and glucose intolerance, but also with ASCVD  Evidence also links systemic inflammation, oxidative stress and endothelial dysfunction in both animal and human models to metabolic syndrome METABOLIC SYNDROME OBESITY AND ADIPOSITY DISTRIBUTION ABNORMALITIES  Obesity is an independent risk factor for insulin resistance, hyperglycaemia, hypercholesterolaemia and hypertension. Left untreated, this combination of pathophysiologic factors precipitates increased risk for chronic disease and early all-cause mortality  In conjunction with several abnormalities in adipose tissue metabolism, abnormal fat distribution and partitioning may actually be the pathophysiologic link between obesity and the numerous hormonal and metabolic derangements that compose the metabolic syndrome  Accumulation of fatty acids in non-adipose tissue depots is robustly associated with skeletal muscle insulin resistance MITOCHONDRIAL DYSFUNCTION  Concurrent with an increased storage of ectopic adiposity, reductions in mitochondrial size, density and function have been implicated in the aetiology of insulin resistance, metabolic syndrome and diabetes  More specifically, obese, sedentary and insulin- resistant individuals have smaller and fewer mitochondria, with impaired function  Diminished mitochondrial density and function may lead to or coincide with decreased or incomplete lipid oxidation and subsequent accumulation of lipid metabolites, impaired insulin signalling, metabolic inflexibility and oxidative stress MITOCHONDRIAL DYSFUNCTION  Moreover, each of these outcomes is also thought to cause further impairment of mitochondrial function, and thus provokes a chronic circular cause and consequence of cardiometabolic events  Impaired mitochondrial function may also lead to diminished adenosine triphosphate (ATP) production, energy deficit and decreased functional capacity  Sedentary behaviour is a robust predictor of mitochondrial dysfunction; and more importantly, evidence suggests improvements in ATP synthesis and fatty acid oxidation after exercise interventions, independent of weight loss PROINFLAMMATORY AND PROTHROMBOTIC CHARACTERISTICS  Adipose tissue is considered a dynamic organ  Previous research among obese adults with diabetes has revealed significantly elevated levels of adipocyte-derived hormones and cytokines, which are significant contributors to insulin resistance  Specifically, ectopic adiposity is known to play a role in secreting proinflammatory cytokines (eg. tumour necrosis factor alpha (TNF-a) and interleukin-6 (IL-6)), adipocytokines (eg. leptin, resistin and adiponectin) and chemokines (eg. monocyte chemoattractant protein (MCP-1)) PROINFLAMMATORY AND PROTHROMBOTIC CHARACTERISTICS  Produced by adipose tissue macrophages, the inflammatory cytokines IL-6 and TNF-a are positively associated with triglycerides and total cholesterol, are inversely associated with HDLc, are capable of interfering with insulin signalling and can result in cellular oxidative stress  Moreover, IL-6 stimulates hepatic production of C- reactive protein (CRP), an acute-phase protein and robust predictor of various features in the metabolic syndrome  Clinically, high sensitivity C-reactive protein (hs-CRP) has become accepted as a useful biomarker for chronic, low-grade inflammation, and elevated hs- CRP is known to be robustly associated with ASCVD PROINFLAMMATORY AND PROTHROMBOTIC CHARACTERISTICS  Augmented levels of hs-CRP have been shown to be robustly associated with ASCVD and inversely associated with vigorous physical activity  Markers of thrombosis (ie. clotting factors) are also known to be increased in the metabolic syndrome, thus representing an additional link with ASCVD  Specifically, elevated levels of plasma plasminogen activator inhibitor-1 (PAI-1) and fibrinogen are linked to thrombosis and fibrosis, insulin resistance and abdominal obesity CLINICAL CONSIDERATIONS  According to the most recent WHO Expert Consultation Group, the diagnostic criteria for metabolic syndrome do not add predictive value beyond the sum of the individual risk factors in forecasting future CVD, diabetes or disease progression  In conjunction with the elevated risk for cardiometabolic disease and mortality, secondary clinical outcomes that are associated with the metabolic syndrome include non-alcoholic fatty liver (NAFLD), cholesterol gallstones, polycystic ovarian syndrome and sleep apnoea  Moreover, among older adults, studies suggest that metabolic syndrome is associated with an increased risk of age-related dementia and overall cognitive decline  Healthy lifestyle interventions can reverse most of the metabolic risk factors; however, drug therapies or bariatric surgery may become necessary in some individuals SIGNS AND SYMPTOMS  In addition to the actual diagnostic risk components of the metabolic syndrome (ie. elevated glucose, hypertension, elevated triglyceride levels, low HDLc levels and abdominal obesity), many patients also present with  Microalbuminuria  Hyperuricaemia  Fatty liver disease (NAFLD)  High levels of PAI-1 and fibrinogen (ie. prothrombotic state)  Elevated hs-CRP (chronic proinflammatory state)  Cholesterol gallstones  Polycystic ovarian syndrome (PCOS)  Disordered sleeping (eg. sleep apnoea) SIGNS AND SYMPTOMS  Many patients diagnosed with metabolic syndrome also have hyperglycaemia (ie. type 2 diabetes). Thus, it is extremely important to take into consideration specific precautions related to the screening, diagnosis and physical exam for patients with diabetes  Since many GPs do not specifically monitor abdominal obesity (ie. height, weight and BMI calculations are more common), an assessment for this should be a fundamental aspect of your patient history and physical examination. A simple clinical measure of waist circumference is highly predictive of this risk factor SIGNS AND SYMPTOMS  Regarding individual parameters, estimates of relative risk for ASCVD incrementally and significantly increase as the number of syndrome components increase  Thus, individuals who present with one or two of the components are at significantly lower risk for cardiac events, as well as for mortality from coronary heart disease and CVD, than individuals with three or more risk components DIAGNOSTIC TESTING  In addition to the five risk components of the metabolic syndrome, and especially in the case of a positive diagnosis, laboratory screening for diabetes should also take place  Additional testing may be warranted to screen for  Clinical inflammation and thrombosis  Hyperandrogenaemia (to exclude PCOS)  Microalbuminuria  Hyperuricaemia  Cholesterol gallstones  Sleep apnoea EXERCISE TESTING  In accordance with the ACSM, patients with metabolic syndrome do not require an exercise test prior to beginning a low- to moderate- intensity exercise program  Because patients with metabolic syndrome are typically overweight or obese, exercise testing recommendations specific for those individuals should be followed.  Standardised treadmill protocols starting with a low initial workload (2 – 3 METs) with small increments (0.5 – 1.0 METs) are recommended and are often well tolerated by those with obesity and metabolic syndrome EXERCISE TESTING  For individuals with morbid obesity, walking may not be practical because of gait abnormalities. In such instances, testing for aerobic fitness may be performed using a seated recumbent cycle ergometer or upper body ergometer  Patients diagnosed with the metabolic syndrome should be assessed for muscular fitness (ie. muscle strength and local muscular endurance), as well as for flexibility and ROM  Because of the risk for hypertension in this population, it is important for you to carefully follow the blood pressure protocols during and after the exercise testing TREATMENT  The primary goals in the management of metabolic syndrome are to reduce the risk for clinical ASCVD and to prevent type 2 diabetes  All five risk components of the metabolic syndrome are modifiable, but abdominal obesity is often considered the primary driver of the other risk components. Thus, treatment strategies should address the contributing risk factors for abdominal obesity, which in turn should positively influence all other components  In addition to managing abdominal obesity through improvements in diet quality and participation in physical activity, patients should quit smoking, where applicable. Smoking is a lifestyle risk factor for ASCVD that should continue to be directly targeted EXERCISE TESTING SUMMARY EXERCISE PRESCRIPTION  The exercise prescription review for metabolic syndrome is representative of the collective recommendations by the ACSM  Since a subset of the metabolic syndrome population also has diabetes, specific constraints related to exercise prescription may be relevant (next two weeks of lectures) CARDIORESPIRATORY EXERCISE  The ACSM recommendation for metabolic syndrome is that cardiorespiratory exercise training should be performed at a moderate intensity (40 – 59% VO2R or HRR), increasing intensity when appropriate (≥ 60% VO2R of HRR)  For optimal health and fitness improvements, a minimum of 150 minutes/week or 30 minutes/day on most days of the week is recommended  However, to reduce body weight, a gradual increment to 250 to 300 minutes/week or 50 – 60 minutes/day on at least 5 days/week is necessary. This daily physical activity can be subdivided into multiple daily bouts of at least 10 minutes in duration CARDIORESPIRATORY EXERCISE  Gradual progression in duration and intensity may be effective for chronic weight maintenance, additional weight loss, or further improvement in aerobic fitness capacity beyond the baseline requirements for health  Activities such as brisk walking, swimming and cycling are usually well tolerated by those with the metabolic syndrome  Unless specified by a GP or Cardiologist, individuals may also progress to other modalities such as jogging, running, hiking, rowing and stair climbing RESISTANCE EXERCISE  Recent research has begun to shed light on the utility of resistance exercise in stimulating positive cardiorespiratory, endocrine, metabolic, neuromuscular and morphological adaptations, independent of weight loss  Current minimum recommendations call for resistance exercise training to supplement cardiorespiratory exercise and to be performed on 2 (preferably 3) non-consecutive days per week, using a single set of 5 – 10 exercises for the whole body, and at a moderate level of intensity that allows 10 – 15 repetitions RESISTANCE EXERCISE  Suggestions on progression in resistance exercise include  Gradual increases in intensity from very light (40% of 1RM) to light (50% of 1RM), moderate (60% of 1RM) and vigorous intensity (70% of 1RM)  Gradual increases in the number of sets from two sets to as many as four sets per muscle group  Gradual decreases in the number of repetitions performed to coincide with progressively heavier loading, going from 10 – 15 repetitions per set to approximately 8 – 12 repetitions per set  Progression in mode from primarily machine-based resistance exercise to machine plus free-weight resistance exercise RANGE OF MOTION EXERCISE  ROM and flexibility training may be included as an adjunct modality to supplement cardiorespiratory and resistance exercise for individuals with metabolic syndrome EXERCISE PRESCRIPTION SUMMARY EXERCISE TRAINING  When compared with physical activity interventions, data suggest that purely diet-induced weight loss may have limited utility for establishing a sustainable, insulin-sensitive phenotype  Emerging evidence suggests improved cardiometabolic profile and improved insulin sensitivity after cardiorespiratory exercise and resistance exercise, independent of weight loss. These changes may in part be attributable to enhanced muscle function and cardiorespiratory fitness, insulin-stimulated glucose disposal and fatty acid oxidation  There is an inverse association between adiposity and muscle function even among non-obese individuals CARDIORESPIRATORY EXERCISE  The utility of cardiorespiratory exercise is suggested to be dose dependent, such that greater volumes of physical activity are associated with greater cardiometabolic health risk reduction  It is commonly thought that the health benefits of physical activity for individuals with metabolic syndrome are directly related to mobilisation of free fatty acids and gross decreases in adiposity  Since extended-duration cardiorespiratory exercise is effective for absolute energy expenditure, recommendations to prioritise this type of exercise are intuitive for the promotion of weight loss  Recent research suggests that improvements in metabolic disturbances are possible with exercise interventions independent of overall weight loss or changes in body composition CARDIORESPIRATORY EXERCISE  During the acute phase, a single bout of exercise can significantly increase whole-body glucose disposal and thus temporarily attenuate hyperglycaemia  Moreover, for several hours after a given bout of exercise, insulin sensitivity is increased  Lastly, repeated bouts of exercise lead to a chronic adaptive response, characterised by enhanced cardiorespiratory function and global improvements in insulin action CARDIORESPIRATORY EXERCISE  Cardiorespiratory exercise is also effective for  Improving blood pressure and lipid profiles  Decreasing visceral adiposity even in the absence of weight loss  Enhancing fatty acid oxidation  Increasing mitochondrial function and content  Attenuating the proinflammatory state RESISTANCE EXERCISE  According to the ACSM position stand, resistance exercise does not promote clinically significant weight loss  However, regarding the restoration of cardiometabolic health among at-risk, obese individuals, mounting evidence indicates that resistance training may be a viable treatment option, comparable to aerobic exercise  Several longitudinal studies examining the role of exercise in metabolic disturbance have reported significantly improved insulin sensitivity and glucose tolerance with structured, progressive resistance exercise interventions  Moreover, several studies have documented the superiority of resistance exercise over traditional aerobic exercise for glycaemic control and insulin sensitivity among type 2 diabetic adults RESISTANCE EXERCISE  Chronic resistance training has been traditionally regarded as an appropriate means to augment or preserve skeletal muscle tissue and thus improve 24-hour energy expenditure and decrease body fat in the long-term  Combining diet-induced energy restriction and resistance training has shown to prevent loss in muscle tissue – an effect that seems to be augmented when sufficient protein is consumed in the diet  Despite the well-known independent value of resistance exercise for cardiometabolic health, strong evidence exists to confirm the superiority of combined aerobic and resistance exercise over either individual modality RESISTANCE EXERCISE RANGE OF MOTION EXERCISE  Although stretching is commonly recommended to improve joint range of motion, very little if any research supports the utility of this modality in the treatment or prevention of cardiometabolic disease RESISTANCE EXERCISE CONCLUSION  Diagnosis of the metabolic syndrome requires the presence of three or more of the following risk factors 1) Elevated waist circumference 2) Elevated triglycerides 3) Reduced HDL cholesterol 4) Elevated blood pressure 5) Elevated fasting glucose