Obesity and Metabolic Syndrome A Reversible Life-Threatening Condition Yi-Jen Hung, MD Tri-Service General Hospital Mar, 19, 2014

淺談代謝症候群 1: 由於社會結構快速轉型，我國產業層面，從農業為主的發展中國家，轉型成以工商業為主的先進社會。當國人生活型態呈現明顯的轉型，與富裕生活相關之慢性疾病盛行率則不斷日趨增加。 2: 在我國十大死因中，與心臟血管有關的疾病包括了腦血管疾病、心臟病、糖尿病及高血壓等，佔了國人死因百分之三十以上。在勞工十大死因部分，則約佔了勞工死因百分之二十左右。 3: 造成心臟血管相關疾病的最大禍首便是高血壓、高血脂及高血糖等「三高」。當血壓、血糖或血脂等各項危險因子接近異常範圍進而演變成心血管疾病和糖尿病後，個案只能以藥物控制卻無法痊癒，因此面對這些慢性疾病最好的防治方法是要能早期發現及早預防。

台灣地區98 & 99年十大死因

台灣代謝症候群及組成因子盛行率 86年國民營養健康調查 91年三高盛行率調查 男 女 合計 代謝症候群* 16.9% 13.8% 14.99% 組成因子 高血壓(15歲) 24.9% 18.2% 21.38% 高三酸甘油酯 20.3% 11.3% 15.6% 高低密度膽固醇 6.5% 6.3% 6.4% 高血糖(19歲↑) 3.7% 5% 8.8% 7.2% 8.0% 高血糖(45歲↑) 7.9% 17.3% 15.5% 14.0% 高血糖(65歲↑) 7.8% 19.6% 18.8 % 22.8% 糖尿病前期 3.2% 高膽固醇 10.8% 10.9% *91年代謝症候群：（定義：以5個危險因子，大於等於3個計之。五個危險因子：1.腹部肥胖：男腰圍≧90公分、女腰圍≧80公分；2.三酸甘油脂：≧150mg/dL；3.HDL-C：男≦40 mg/dl、女≦50 mg/dl；4.SBP≧130/DBP≧85mmHg或服用降血壓藥；5.空腹血糖≧110 mg/dl或服用OHA）

2005-2008 國人代謝症候群（Metabolic Syndrome）之狀況

Metabolic Syndrome: Prevalence Increases with Age 47 million or 23% of US adults have the metabolic syndrome Metabolic Syndrome—Prevalent and Problematic in the US Currently, approximately 1 in 4 adults in the United States, or 23%, have metabolic syndrome. The incidence of metabolic syndrome is comparable to that of hypertension, which is 24%. These statistics may reflect what physicians see in their own clinical practices. The similarity between metabolic syndrome and hypertension in terms of prevalence should lead one to consider an association between the 2 conditions. As the US population ages, the rate of metabolic syndrome steadily increases among men and women in almost all categories of age. The prevalence of metabolic syndrome among older segments of the population may approach 50%. At 70 years of age and thereafter, the syndrome plateaus in women and declines in men. In terms of race and ethnicity, Mexican Americans have the highest age-adjusted prevalence of the metabolic syndrome—nearly 32%. Significantly lower rates are seen among whites (24%), African Americans (22%), and people reporting an “other” race or ethnicity (20%). Given the prevalence of metabolic syndrome and its strong association with emerging cardiovascular disease and type 2 diabetes, the burden imposed by this syndrome on the US healthcare system is enormous and may seriously strain resources for delivering care as well as escalate cost. Ford ES, Giles WH, Dieta WH. Prevalence of the metabolic syndrome among US adults. Findings From the Third National Health and Nutrition Examination Survey. JAMA. 2002;287:356-359. Adapted from: Ford ES, et al. JAMA 2002;287:356-359.

台灣地區肥胖盛行率

2005-2008 國人血漿血糖異常之狀況

98年度單方藥品健保申報排行 1 2 3 4 5 6 7 8 9 10 排行 成分名稱 藥理分類 98年申報金額 （單位：億元） 降血壓藥 AMLODIPINE 降血壓藥 45 2 ATORVASTATIN 降血脂藥 17 3 VALSARTAN 16 4 FACTOR VIII 血友病用藥 5 CLOPIDOGREL 血栓溶解劑 15 6 GLIMEPIRIDE 降血糖藥 14 7 IMATINIB 抗癌藥 12 8 ROSUVASTATIN 9 PIOGLITAZONE 11 10 LOSARTAN 小計 169

2009國民健康局正規劃將代謝症候群 納入成人預防保健服務 2009國民健康局正規劃將代謝症候群 納入成人預防保健服務  上稿時間：2009/12/10 16:46:43  更新日期：2009/12/10 16:46:48 依據國民健康局2007年三高（高血壓、高血糖、高血脂）追蹤調查研究顯示，我國20歲以上民眾每5人就有1人罹患代謝症候群，且隨年齡上升而有增加的趨勢。而代謝症候群的核心異常除胰島素阻抗之外，還有一個很重要之因素是腹部肥胖。而依據研究亦發現體態「中廣」的民眾，其未來罹患代謝症候群風險，將是一般人的4至6倍。另腹部肥胖者中，亦有50％機率會罹患代謝症候群，而代謝症候群的民眾未來罹患「糖尿病」、「高血壓」、「高血脂症」、「心臟病及腦中風」的機率，分別為一般人的6倍、4倍、3倍、2倍，其衍生醫療費用支出及家庭、社會的負擔與日俱增，儼已成為我國及全世界已開發國家重要的健康議題。鑑於上述等原因，國民健康局除已建議勞委會將量腰圍列為之勞工健康檢查項目中，另國民健康局業已經研議於明（99）年7月將代謝症候群（含腰圍測量）納入成人預防保健服務，以早期發現代謝症候群高危險群，早期執行飲食、運動等健康行為。 民眾如果您對代謝症候群有任何問題，都歡迎上國民健康局網站查詢(網址http://www.bhp.doh.gov.tw)。

Metabolic Syndrome 1920s: first noted that certain symptoms associated with diabetes 1970s & 1980s: cluster of symptoms with increased heath risks for CVD & diabetes 1988: Gerald Reaven labeled the cluster “Syndrome X” (史丹佛大學GM Reaven教授 將自八零年代後臨床觀察到的現象加以歸納，提出“胰島素阻抗性症候群”的概念)。 emphasizing the role of insulin resistance 1990s: Health agencies around the world began writing their own definitions 直到1999年左右，醫界為了方便醫師對病人解釋，才以較通俗的新陳代謝症候群定名。

The Emerging Threat of Cardiovascular Disease Cardiovascular disease will be the number one killer in the world in the 21st century Increase due to rising prevalence of risk factors Cigarette smoking Obesity Metabolic syndrome Type 2 diabetes

Cardiovascular Risk Factors: An Evolving Landscape Adapted from J.P. Després Québec Heart Institute, Laval Hospital Research Center, Québec, Canada The metabolic syndrome is largely caused by our sedentary affluent environment where our population is exposed to a diet dense in calories (fat and/or refined sugar). This “toxic” environment produces a positive energy balance and weight gain, which explains the epidemic proportions reached by type 2 diabetes and obesity worldwide. In this context, the metabolic syndrome has become a major issue because of its impact on cardiovascular disease risk. Hyperglycaemia does not appear to be the main culprit responsible for the increased cardiovascular disease risk in this population. Rather, a cluster of metabolic abnormalities which includes an atherogenic dyslipidaemic state, an impaired glucose/insulin homeostasis, a prothrombotic/inflammatory profile as well as an endothelial dysfunction substantially increases the risk of coronary heart disease in type 2 diabetic patients independently from the level of glycaemic control. Furthermore, even non-diabetic patients with the features of the metabolic syndrome are at increased risk of coronary heart disease. The epidemic proportions reached by the metabolic syndrome will require integration of medical specialties for the proper evaluation and management of this condition.

The Metabolic Syndrome: An Evolving Concept Scott M. Grundy MD, PhD. University of Texas Southwestern Medical Center, Dallas, Texas The metabolic syndrome represents a constellation of metabolic risk factors for atherosclerotic cardiovascular disease (ASCVD) occurring in a single individual. There are five metabolic risk factors that accompany the metabolic syndrome: atherogenic dyslipidaemia (elevated apolipoprotein B, elevated triglyceride, small LDL particles, and low HDL-cholesterol), elevated blood pressure, elevated glucose, a prothrombotic state, and a proinflammatory state. The major underlying risk factors for the metabolic syndrome are obesity and insulin resistance. Other factors that can worsen the syndrome are lack of physical activity, advancing age, and hormonal factors (e.g. androgens and corticosteroids). Several different criteria have been proposed for clinical diagnosis of the metabolic syndrome. There is a large amount of overlap among these different criteria, but emphasis is different. For example, the World Health Organization criteria emphasis insulin resistance as the major underlying risk factor, whereas the USA National Cholesterol Education Program places more emphasis on obesity. Most organisations however are in agreement that ASCVD is the major clinical outcome of metabolic syndrome. There is further agreement that metabolic syndrome is a major risk factor for type 2 diabetes. In fact, a significant portion of the ASCVD that develops in patients with the metabolic syndrome occurs in persons after they have developed type 2 diabetes. The underlying risk factors, prevalence and clinical manifestations of the metabolic syndrome vary among different populations. These differences likely represent variations in genetic susceptibilities of the different populations. Regardless, the rising prevalence of obesity in the world heralds a marked increase in the prevalence of metabolic syndrome along with its major outcomes ASCVD and type 2 diabetes. More recently, the IDF has proposed a new definition of the syndrome (derived from the ATP III) with a lower threshold for impaired fasting glucose and ethnic specific cut-points for waist circumference.

1998年WHO代謝性症候群的定義 Insulin resistance (必要條件) type 2 diabetes, IFG>110, IGT* Plus any 2 of the following Elevated BP BP >140/90 or drug Rx Plasma TG TG > 150 mg/dl HDL-C HDL <35 mg/dl (men); <39mg/dl (women) Obesity BMI >30 and/or W/H >0.9 (men), >0.85 (women) Microproteinuira Urinary albumin >20 mg/min; Alb/Cr >30 mg/g (*Note that 1999 WHO uses hyperinsulinemic euglycemic clamp whereas 1998 WHO and EGIR use HOMA-IR. )

2005 Revised ATP III Clinical Screening Criteria to Identify Metabolic Syndrome (AHA and NHLBI) Measure (any 3 of 5 constitute diagnosis of metabolic syndrome) Categorical cutpoints Elevated waist circumference ≥102 cm in men ≥88 cm in women Elevated triglycerides ≥150 mg/dl (1.7 mmol/l) or on drug treatment for elevated triglycerides Reduced HDL-cholesterol <40 mg/dl (0.9 mmol/l) in men <50 mg/dl (1.1 mmol/l) in women Or on drug treatment for reduced HDL-C Elevated blood pressure ≥130 mmHg systolic blood pressure or ≥85 mmHg diastolic blood pressure or on antihypertensive drug treatment in a patient with a history of hypertension Elevated fasting glucose ≥100 mg/dl or on drug treatment for elevated glucose

Diagnosis of The Metabolic Syndrome IDF CRITERIA (2005) Central obesity waist circumference 94 cm for Europid men 80 cm for Europid women ethnicity specific values for other groups Plus any two of the following four factors TG 150 mg/dl HDL <40 mg/l in males and <50 mg/l in females Systolic BP 130 or diastolic BP 85 mmHg Fasting plasma glucose 100 mg/dl If above 100 mg/dl, OGTT is strongly recommended but is not necessary to define presence of the syndrome

Diagnosis of The Metabolic Syndrome IDF CRITERIA (2005) Ethnic-specific cut-points for waist circumference Country/Ethnic group Waist circumference (as measure of central obesity) Europids Male Female 94 cm 80 cm South Asians 90 cm Chinese Japanese 85 cm

Definitions of metabolic syndrome

以下五項危險因子中，若包含三項或以上者，即可診斷為代謝症候群 界定代謝症候群之臨床診斷準則(93年台灣) 以下五項危險因子中，若包含三項或以上者，即可診斷為代謝症候群 危　險　因　子 異　常　值 腹部肥胖(central obesity)或 身體質量指數（BMI） 腰圍（waist）: 男性 ≧90 cm 女性 ≧80 cm ；或BMI ≧27 血壓(BP)上升 SBP ≧130 mmHg / DBP ≧85 mmHg 高密度酯蛋白膽固醇(HDL-C)過低 男性 <40 mg/dl 女性 <50 mg/dl 空腹血糖值(Fasting glucose)上升 FG ≧110 mg/dl 三酸甘油酯(Triglyceride)上升 TG ≧150 mg/dl 備註：上項危險因子中「血壓上升」、「空腹血糖值上升」之判定，包括依醫師處方使用降血壓或降血糖 等藥品(中、草藥除外)，血壓或血糖之檢驗值正常者。

Prevalence of overweight and obesity in 10-year old girls and boys in selected countries.

臺灣歷次全國營養調查兒童肥胖盛行率 9.0~11.3 5.6~15.7 5.4~12.6 6.9~15.4 9.1~16.4 性別 調查別、對象及指標 男 生 女 生 體重過重% 肥胖% 第一次(1980~1982) 8~12歲 體重過重：110%<BW<120%ABW 肥胖：BW>120%ABW 9.0~11.3 5.6~15.7 5.4~12.6 6.9~15.4 第二次(1986~1988) 6~12歲 9.1~16.4 8.8~15.5 第三次(1993~1996) 2~18歲 BMI=BW(kg)/BH(M)2 11 9 第四次(2001~2002) 15.5 14.7 14.4 9.1 備註：１．第一、二次全國營養調查對「肥胖」定義並無共識。 　　　２．衛生署於2002年08月訂定「臺灣兒童與青少年的肥胖定義」， 全國均以 BMI 做為指標，第三、四次之數據係以BMI計算出。

肥胖標準的界定 (BMI)

Obesity and Type 2 Diabetes are Interrelated Epidemics Global epidemic of overweight, obesity and diabetes The generalisation of modern urban lifestyle has resulted in inadequate changes in diet and physical activity: Overconsumption of energy-dense foods: increased calorie intake Sedentary habits: reduced energy expenditure The combination of the two is the recipe for generating more and more obese individuals Mokdad, et al. Diabetes Care. 2000;23(9):1278-1283. Mokdad, et al. JAMA. 2000;286(10):1195-1200.

The Global Menace of The Metabolic Syndrome The metabolic syndrome is a predictor of type 2 diabetes The metabolic syndrome is a risk factor for cardiovascular disease (CVD)

Consequences of metabolic syndrome Non-diabetic subjects 4-fold increased risk for type 2 diabetes 30% increased risk for CVD Diabetic patients 40-70% increased risk for CVD Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA 2001;285:2486-2497.

Metabolic Syndrome And Risk of Type 2 Diabetes Incident diabetes after stratification by age or BMI, IGT, and the metabolic syndrome (San Antonio Heart Study) This slide examines the risk of the NCEP metabolic syndrome for the development of type 2 diabetes in the San Antonio Heart Study over a 7 year period of follow up. Overall, the metabolic syndrome is associated with a 3.5 fold increased risk of type 2 diabetes. Among subjects with normal glucose tolerance (NGT) subjects with the metabolic syndrome have a 4 fold increased risk of type 2 diabetes. Among subjects with impaired glucose tolerance, subjects with the NCEP metabolic syndrome have about a 2.5 fold risk of diabetes. Note that subjects who have both impaired glucose tolerance and the NCEP metabolic syndrome have almost a 60% chance of developing type 2 diabetes. In such a high-risk group for type 2 diabetes, the clinician may consider pharmacological interventions as well as behavioral interventions to delay/prevent the onset of type 2 diabetes (Steven M. Haffner). Lorenzo, et al. Diabetes Care. 2003;26:3153-3159.

Metabolic Syndrome And Risk of Type 2 Diabetes Risk of type 2 diabetes per unit change in risk trait levels San Antonio Heart Study In the San Antonio Heart Study, obesity and fasting glucose were the strongest predictors of the development of type 2 diabetes, in contrast to a previous slide showing predictors of CHD. Thus, it is difficult to answer the question "which components of the metabolic syndrome are most important?" without specifying the particular endpoints being studied (Steven M. Haffner). Stern MP, et al. Ann Intern Med 2002;136:575-581.

Metabolic Syndrome and Cardiovascular Risk Individuals without diabetes or CVD, but with the metabolic syndrome are at increased risk for long-term CV outcomes In the Atherosis Risk In Communities (ARIC) study, 12 089 individuals (mean age 54  5.7 years) had an average of 11 years of follow-up. 31.4% of men and 32.0% of women had the metabolic syndrome at baseline as defined with revised NCEP/ATP III criteria (inferior limit for impaired fasting glucose 100 mg/dL). Among the male participants without diabetes or CVD at baseline, the crude incidence rate of Coronary Heart Disease (CHD) during follow-up was 138.4/10 000/year for those with metabolic syndrome and 92.3/10 000/year for those without metabolic syndrome. The equivalent crude incidence for women was 57.5 versus 22.7. Among the male participants without diabetes or CVD at baseline, the crude incidence rate of stroke during follow-up was 24.6 /10 000/year for those with metabolic syndrome and 18.1/10 000/year for those without metabolic syndrome. The equivalent crude incidence for women was 19.0 versus 8.5. As shown on this slide, the relative risk of CHD or stroke in the participants was 50% more in men and twice in women. In both sexes, the risk increases with the increase of the number from 1 to 4 of the components of the metabolic syndrome (figure not shown). Among the component of the metabolic syndrome, high blood pressure and low HDL-cholesterol exhibited the strongest association with the risk of CHD. Schmidt MI, et al. (ARIC study) Diabetes Care 2005;28:385-390.

Metabolic Syndrome and CHD Risk Prevalence of CHD in patients with the metabolic syndrome (Botnia Study) This study shows data on the prevalence of coronary heart disease in subjects in the Botnia Study which was done in Western Finland. The prevalence of the metabolic syndrome is higher in subjects with the metabolic syndrome, and increases as glucose tolerance worsens from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to diabetes (DM). (Steven M. Haffner, MD) Adapted from Isomaa B, et al. Diabetes Care. 2001;24:683-689.

Increased CVD and All-cause Mortality 1209 Finnish men (See previous info.) Lakka H, et al. JAMA 2002;288;2709-2716.

Association Between The Number of Metabolic Syndrome Components and Incident CVD In this population-based study, 4 423 subjects without diabetes were evaluated first in 1988-90 and again 5 years later. The WHO definition was used to identify subjects with metabolic syndrome. On this slide, the risk of incident cardiovascular disease (angina, heart attack or stroke) is presented as a function of the number of components of the metabolic syndrome. It clearly shows that the risk of subsequent cardiovascular disease progressively increases with the number of components at baseline. Klein BEK, et al. (Beaver Dam Study). Diabetes Care 2002;25:1790-1794.

The Association of Microalbuminuria/CKD and Metabolic Syndrome Cardiorenal syndrome The Association of Microalbuminuria/CKD and Metabolic Syndrome Is Metabolic Syndrome a Risk Factor for CKD ?

Odds Ratios (95% CI) of MA Associated with Individual and Several Components of the MetS Ann Intern Med. 2004 Feb 3;140(3):167-74

Odds Ratios of CKD Associated with Individual or Several Components of the MetS Ann Intern Med. 2004 Feb 3;140(3):167-74

CKD, Microalbuminuria and Metabolic Syndrome Background: The MetS is a common risk factor for CVD. Objective: To examine the association between the MetS and risk for CKD and microalbuminuria (MA). Design: Cross-sectional study. Setting: The Third NHANES. Patients: 20 years of age or older were studied in the CKD (n 6217) and MA (n 6125) analyses. Measurements: The MetS was defined by NCEP. CKD was defined as a GFR less than 60 mL/min per 1.73 m2, and MA was defined as a urinary albumin–creatinine ratio of 30 to 300 mg/g. Ann Intern Med. 2004 Feb 3;140(3):167-74

Metabolic Syndrome and the Risk for CKD among Nondiabetic Adults The metabolic syndrome is independently associated with an increased risk for incident CKD in nondiabetic adults. J Am Soc Nephrol 2005

Metabolic Syndrome Dual Pathways: Dual Outcomes

How Does Abdominal Obesity Cause Insulin Resistance Reduced Physical Activity Excessive food intake Inflammation insulin receptor Substrate (IRS-1 & IRS-2)  IL-6 Genetic factors  TNF-  various cytokines adiponectin  As a consequence of the modern and urban way of life, there is an increasing imbalance between excessive food intake, especially with high glycaemic index food, and decreased level of physical activity leading to accumulation of fat in adipocytes, the number and size of which increase in various degrees according to genetic factors. Adipocyte accumulation is located at various sites among which abdominal location (visceral fat) has been demonstrated to have important metabolic consequences. One of these consequences is the release of free fatty acids in the blood stream, which is directly responsible for insulin resistance. In addition, overloaded adipocytes also produce various cytokines involved in subclinical inflammatory process and oxidative stress. An important effect of these adipocytokines is the alteration of insuline receptor sbustrate which is also involved in the insulin resistance process. ABDOMINAL OBESITY Insulin resistance  leptin Hormones  blood FFA

MS/Insulin Resistance The Insulin Signaling Pathway MS/Insulin Resistance J. Clin. Invest. 114:1187-1195 (2004).

Common insulin resistance (IR) underlies most cases of T2DM, central obesity and metabolic syndrome driven by overweight/obesity, as a result of adipokines/FFA imbalance and lipotoxicity represents a  in insulin-mediated glucose uptake (IMGU) and glycogen synthesis, mostly in skeletal muscle, liver and adipocyte Beck-Nielsen et al. in Insulin Resistance, Kumar & O’Rahilly eds. 2005 John Wiley & Sons, Ltd

Insulin Resistance: Multisystem Disorder Adipose tissue Increased NEFA and adipokine release Muscle Decreased glucose disposal Liver Increased gluconeogenesis and hepatic glucose output Endothelium Endothelial dysfunction

Pathophysiology of the metabolic syndrome leading to atherosclerotic CV disease Genetic variation Environmental factors Abdominal obesity Adipokines Cytokines Adipocyte Inflammatory markers Monocyte/ macrophage Insulin resistance  Tg Metabolic syndrome  HDL  BP Pathophysiology of the metabolic syndrome leading to atherosclerotic CV disease A complex series of interactions of metabolic risk factors with genetic and environmental influences underlies the adverse influence of the metabolic syndrome on cardiovascular prognosis. Abdominal obesity is an important cause of multiple sources of cardiovascular risk within this system. Bioactive substances (adipokines, inflammatory cytokines and other agents) derived from intra-abdominal adipocytes, the liver and/or inflammatory cells help to drive the progression of the cluster of risk factors characteristic of the metabolic syndrome. In turn, exacerbation of these risk factors, in addition to the direct pro-atherogenic effects of adipokines, accelerates the atherosclerotic changes that increased the risk of an occlusive thromboembolic coronary event. It is difficult to intervene successfully once the vicious cycle of promotion of cardiovascular risk factors and atherogenesis is established. Intervening at an earlier stage, for example to combat directly the development of intra-abdominal adiposity, may provide a more successful prospect for intervention to reduce the risk of a cardiovascular event. Reilly MP, Rader DJ. The metabolic syndrome: more than the sum of its parts? Circulation 2003;108:1546-51. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415-28. Atherosclerosis Plaque rupture/thrombosis Reilly & Rader 2003; Eckel et al 2005 Cardiovascular events

Acanthosis Nigrican

Insulin Resistance (IR) Insulin resistance (IR) and the Metabolic Syndrome (MetS) are the most frequent metabolic conditions affecting adult subjects in Westernized countries. They are strongly associated with sedentarity and increased abdominal fat in predisposed subjects. IR and MetS are major players in the development of cardiovascular disease (CVD), in both subjects with normal glucose tolerance (NGT) and subjects with T2DM. Thus, about one-fifth of subjects with IR are unable to compensate this state of IR with increased insulin secretion in the long-term; these are prone to develop both type 2 diabetes and CVD as a result of the presence of IR and MetS. A minority of subjects with T2DM however do not show the features associated with IR and MetS, and their state of hyperglycaemia is not particularly associated with CVD. IS: Insulin Sensitive Haffner SM et al. Diabetes Care, 1999; 22: 562-568.

Who has insulin resistance? % Patients Who has insulin resistance? Insulin resistance is relatively common in clinical practice, as indicated by results from seven studies show on the slide. As expected, the vast majority of patients with diabetes are also insulin resistant. Insulin resistance is highly prevalent among patients with low levels of high-density lipoprotein cholesterol (HDL-C) and high triglyceride levels. Approximately half of all patients referred to a cardiologist are also insulin resistant, as are many patients with stroke and CHD. 40% of patients aged 40 to 74 years, as well as at least half of patients with hypertension, are also insulin resistant. DM21 ↓HDL + ↑TG2 HTN3 Stroke4 CHD5 Refer to cardiol.6 Age 40 to 747 1Haffner et al. Diabetes. 1997. 2McLaughlin et al. Am J Cardiol. 2005. 3Reaven et al. N Engl J Med. 1996. 4NIH. www.clinicaltrials.gov. 5Lankisch et al. Clin Res Cardiol. 2006. 6Savage et al. Am Heart J. 2005. 7www.diabetes.niddk.nih.gov/.

Risk of CVD rises as IR increases Quintile of HOMA-IR adjusted for age, sex, ethnicity, LDL-Cholesterol, triglycerides, HDL-Cholesterol, systolic blood pressure, smoking, alcohol consumption, leisure time exercise and waist circumference (median split). Patients without diabetes and CVD at baseline. HOMA uses a mathematical model that enables the degree of insulin resistance and ß-cell function to be estimated from FPG + FPI readings.2 The HOMA technique has a level of accuracy comparable to that of the glucose clamp technique3 or other reference methods.4,5 FPG = Fasting Plasma Glucose FPI = Fasting Plasma Insulin 2. Matthews DR, et al. Diabetologia 1985; 28:412–419. 3. Bonora E, et al. Diabetes Care 2000; 23:57–63. 4. Hermans MP et al., Diabetelogia 1999; 42: 678-687. 5. Hermans MP et al., Diabetes 1999; 48: 1779-1786. Hanley A.J. et al. Diabetes Care 2002; 25: 1177-1184. (San Antonio Heart Study)

Current approaches for assessing insulin sensitivity and resistance in vivo AJP-Endocrinol Metab • 294 • JAN 2008

The Metabolic Syndrome Is A Metabolic Time Bomb With the elevated risk of diabetes and cardiovascular disease from the metabolic syndrome, there is an urgent need for strategies to defuse this metabolic time bomb

What Can We Do For Patients With the Metabolic Syndrome? 1. Ensure appropriate lifestyle changes - Primary treatment of the metabolic syndrome 2. Implement better use of current therapies Improve compliance Better use of combination treatments 3. Use new agents to target underlying defects Obesity Hyperglycaemia Dyslipidaemia Hypertension Other “vascular risk factors”

導致糖尿病、腦血管疾病、心臟病等盛行率、死亡率不斷攀升 代謝症候群防治工作重要性 導致糖尿病、腦血管疾病、心臟病等盛行率、死亡率不斷攀升 醫療資源花費上漲 相關疾病併發症影響生活品質 健康照護系統負荷增加

代謝症候群之防制策略 減重 健康飲食 增加體力活動 戒菸 藥物治療 高血糖 高血壓 高血脂 ASA Etiology of Obesity: Numerous Complex, Interrelated Factors 1,2 Obesity is a complex, multifactorial disease involving the disciplines of genetics, neuroscience, physiology, and biochemistry, as well as environmental, cultural, and psychosocial factors To be effective, strategies to manage obesity should address as many components as possible 戒菸

代謝症候群防治策略 初段預防 次段預防 一般大眾 高危險群 1.早期發現個案，與目前篩檢策略合併，如： (1)成人健檢(健保局) (2)三高到點篩檢 (3)複合式篩檢 2.俟該疾病列入國際疾病分類(ICD-9)代碼後，再參考目前糖尿病、高血脂及高血壓，訂定醫療照護指引 3.提供有效照護 (1)研發個案管理模式 (2)建立品管監測制度 1.多元化大眾傳播促進認知 (1)教材及工具(如腰尺等)之研發 (2)訂定衛教指引 2.導引國人建立健康生活型態 1.界定群體 (1)糖尿病、高血脂及高血壓家族史 (2)曾罹患妊娠糖尿病(GDM) (3)肥胖 2.早期健康促進 (1)重點 a.體重控制、b.均衡營養 c.體適能促進 (2)對象 a.村里社區、b.學校、 c.職場、d.軍中、e.社區健康中心 1.衛生局及醫事人員共識之建立及照護能力之提升、2.進行相關流行病學調查及科技研究 3.增強支持系統(包括病友團體等)、4.成本效益分析 1.均衡營養、體重控制(食品處)、 2.拒菸戒菸(衛教中心) 3.壓力調適(醫事處)、4.體適能促進（本局社區健康組） 5.社區、學校、職場等健康營造（本局社區健康組） 疾病照護之健保給付(健保局ICD9之分類)

~10% Weight loss = ~30% Visceral adipose tissue loss Figure 33 A modest loss of body weight in patients with truncal/visceral obesity is associated with substantial reductions in major atherogenic risk factors. A 10% loss of body weight roughly corresponds to a 30% loss of adipose tissue. KW: risk factor, obesity

Weight Reduction Moderate weight loss with a very low calories diet in obese patients with the metabolic syndrome markedly improves all aspects of the metabolic syndrome Among 185 consecutive obese patients enrolled in a structured weight loss programme during one year, 125 (68%) had a metabolic syndrome according to the NCEP definition : BMI 40.7 ± 9,7 and weight 261,2 ± 72,4 lbs with metabolic syndrome versus BMI 35.7 ± 5,8 and weight 219,8 ± 41,7 lbs without metabolic syndrome. The rapid weight loss programme has well established nutritional and behavioural components. Weight loss is induced by a protein-sparing, very low calorie diet with a total intake of 600-800 kcal per day. After 4 weeks of very low calorie died, a significant decrease was observed on the risk factors especially on those associated with the metabolic syndrome (BMI, high blood pressure, blood glucose, triglycerides). As shown on this slide, these improvements were sustained at the end of active weight loss (average 16,7 weeks, total weight loss 15.1%). Esposito K, et al. JAMA 2004;292:1440-1446.

Effect of Weight Loss on Insulin Sensitivity -17.2 % - (-8.0 %) -7.9 % - (-1.5 %) -1.4 % - 10.0 % Tertiles of weight change (DPS) Changes in insulin sensitivity index (SI) by tertiles of 4-year weight change, both groups combined. The p value for the difference among the tertiles after adjustment for age, gender and study group.

( DPP )

Optimal management of the metabolic syndrome includes: Conclusion Optimal management of the metabolic syndrome includes: Identification of patients with the metabolic syndrome Appropriate lifestyle changes Improved understanding of therapeutic targets: combination therapy often needed Use of pharmacotherapy to target underlying defects Prevention of DM & CHD                      

Thank you for your attention Metabolic Syndrome – For preventive purposes Thank you for your attention