Cardiovascular Disease and the Patient with Diabetes and ...


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  • Patients with type 2 diabetes are at high risk for atherosclerosis and other cardiovascular disease (CVD). Insulin resistance is related to the elevated risk of CVD. Evidence suggests that hyperglycemia may contribute to endothelial dysfunction and ultimately lead to accelerated atherogenesis. Many individuals with type 2 diabetes are not diagnosed until they have experienced a cardiovascular event. People with impaired glucose tolerance or IGT (considered “prediabetes”) who do not have chronic hyperglycemia have a twofold increase in the risk of coronary artery disease (CAD) compared with normal subjects. Patients with type 2 diabetes have a threefold increased risk of CAD. In an effort to decrease the high level of morbidity and mortality associated with type 2 diabetes and to facilitate early diagnosis, the American Diabetes Association (ADA) guidelines now include a lower fasting plasma glucose (FPG) level for diagnosis of diabetes: >=126 mg/dL, reduced from the previous level of 140 mg/dL. The ADA also recently reduced the cutpoint for impaired fasting glucose (IFG) to 100 mg/dL, and redefined IFG as an FPG of 100 to 125 mg/dL. American Diabetes Association. Diabetes Care. 2003;26:3160-3167. Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953. Hsueh WA, et al. Am J Med. 1998;105(1A):4S-14S. American Diabetes Association. Diabetes Care. 1998;21:310-314.
  • ATP III identifies 5 components of the metabolic syndrome: abdominal obesity, elevated triglycerides (TG), decreased HDL-C, hypertension, and hyperglycemia.[ATP III] At least 3 of these components—all of which have been shown to be highly predictive of cardiovascular risk[Isomaa et al]—are required for the diagnosis of metabolic syndrome. Although metabolic syndrome is often thought of as a precursor to the development of type 2 diabetes mellitus, impaired fasting glucose may or may not be present. Diabetes is NOT a criterion: in fact, hypertension, obesity and impaired lipids more commonly make the diagnosis. Also, there is an inverse relationship between triglycerides and HDL-C, where high triglycerides are usually associated with low HDL-C levels. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA . 2001;285:2486-2497. Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care . 2001;24:683-689.
  • IDF criteria: abdominal obesity and waist circumference thresholds This slide shows the diagnostic criteria for abdominal obesity, based on the measurement of waist circumference, from the metabolic syndrome as defined by the IDF and NCEP ATP III criteria. Anthropometric variables differ greatly between different ethnic groups. For example, certain South Asian populations are at increased risk for cardiovascular events at lower values of body mass index (BMI) compared with Europid populations, so that waist circumference measurements may need modification for use in other populations. The new IDF criteria for the metabolic syndrome have addressed this issue. However, the choice of the cutpoint may be questioned. It is clear that South Asians are at an increased risk for metabolic disease at the same waist circumference as Caucasians. Therefore, the lower cutpoints in South Asians is clearly desirable. However, the lower cutpoints in Europids than in Caucasians in North America is problematic because there is not evidence that Europids are more susceptible to metabolic abnormalities than are Caucasians in North America. With the old definitions, Europeans had lower levels of obesity and a lower prevalence of the metabolic syndrome, suggesting that obesity is an important environmental cause of the metabolic syndrome. With the new definition of the metabolic syndrome by the IDF, levels of obesity and the metabolic syndrome are similar in both regions, therefore suggesting that obesity is not important. The lower cutpoints for waist circumference in Chinese subjects might suggest that they were uniquely sensitive to upper body obesity as were the South Asians. However, data from Tan et al. do not suggest this is true, at least in Singapore. Lastly, the cutpoint for waist circumference in Japan is actually higher in women than in men, which is counterintuitive. This probably occurred because the assessment of which cutpoint to use for waist circumference came from visceral fat studies rather than prospective studies of waist circumference and cardiovascular disease. A recent study from Japan by Sone et al. does not suggest that the IDF criteria are superior to the NCEP. References: Alberti KG, Zimmet P, Shaw J, for the IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet 2005;366:1059-1062. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497. Tan CE, Ma S, Wai D, Chew SK, Tai ES. Can we apply the National Cholesterol Education Program Adult Treatment Panel definition of the metabolic syndrome to Asians? Diabetes Care 2004;27:1182-1186. Sone H, Tanaka S, Ishibashi S, Yamasaki Y, Oikawa S, Ito H, Saito Y, Ohashi Y, Akanuma Y, Yamada N, for the Japan Diabetes Complications Study (JDCS) Group. The new worldwide definition of metabolic syndrome is not a better diagnostic predictor of cardiovascular disease in Japanese diabetic patients than the existing definitions: additional analysis from the Japan Diabetes Complications Study. Diabetes Care 2006;29:145-147.
  • Age-Specific Prevalence of the Metabolic Syndrome Among 8814 US Adults aged at least 20 years, by Sex, National Health and Nutrition Examination Survey III, 1988-1994
  • Diabetes: Atherosclerotic Complications Atherosclerotic cardiovascular disease is the primary cause of death in people with diabetes. In addition, most hospitalizations resulting from diabetes-associated complications are a consequence of atherosclerotic cardiovascular disease. Incidence of atherosclerotic cardiovascular disease is 2- to 4-fold higher in individuals with diabetes than without the disease. A likely explanation for the elevated post-infarction mortality rate among individuals with diabetes is the diffuse pattern of atherosclerosis generally observed in this patient population. . Dyslipidemia correlates with elevated risk for coronary artery disease (CAD) in patients with and without diabetes. It is therefore suggested that aggressive management of lipid level abnormalities may dramatically decrease the incidence of CAD in the diabetic patient population. The “50% with CAD” is likely an overestimate, given the prevalence of T2DM now in children and young adults Reference Lewis GF. Diabetic dyslipidemia: a case for aggressive intervention in the absence of clinical trial and cost effective data. Can J Cardiol . 1995;11(suppl C):24C-28C.
  • Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study) Prior to completion of this study, little data existed to compare mortality rates from coronary heart disease (CHD) in patients with diabetes, but without prior myocardial infarction (MI), and patients without diabetes, but with a history of MI. To sort out the risks among the groups and determine whether patients with diabetes and no MI history should be treated as aggressively for cardiovascular (CV) risk factors as patients who have had an MI, the 7-year incidence MI in 2432 patients (1059 with diabetes, 1373 without diabetes) was quantified. Results indicate, the 7-year incidence of MI in patients with diabetes was 45.0% for those with a previous MI, and 20.2% for patients without an MI at baseline ( P <0.001). Among patients without diabetes, but with a positive history for prior MI, 7-year incidence of MI was 18.8%. Kaplan-Meier estimates that the probability of death from CHD reveals similar outcomes for patients with diabetes/no history of MI and no diabetes/history of MI. The hazard ratio for death from CHD for the 2 groups was not significantly different from 1.0 (hazard ratio, 1.4; 95% confidence interval [CI]) of 0.7 to 2.6). This hazard ratio remained close to 1.0 even after adjustment for total cholesterol, hypertension, and smoking. These data support that treatment of CV risk factors in patients with diabetes and no history of MI should be as aggressively treated as with patients without diabetes, but with a history of previous MI. Reference Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med . 1998;339:229-234.
  • Type 2 Diabetes: A1C Predicts CHD The relationship between metabolic control of diabetes and CHD events was evaluated in a 3.5-year follow-up study of 1298 Finnish subjects, aged 65 to 74 years. At baseline, 1069 subjects did not carry a diagnosis of diabetes. Mortality rates during the follow-up period were 3.4% and 14.8% for subjects without and with diabetes, respectively. CV risk factors evaluated in the study were: sex, previous MI, current smoking, waist-to-hip ratio, BP, HDL cholesterol, glycated hemoglobin A1C levels, and duration of diabetes. Results indicated that only baseline glycated hemoglobin A1C and duration of diabetes were significant to predict CHD death and all CHD events. The significant dose-response relationship between glycated hemoglobin A1C and CHD events or mortality incidence are presented on the slide. The importance of consistent metabolic control in patients with diabetes in order to reduce risk of CHD events is evident from these findings. Reference Kuusisto J, Mykkanen L, Pyorala K, Laakso M. NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes . 1994;43:960-967.
  • UKPDS Relative Risk Reduction for Intensive vs Less Intensive Glucose Control In the UK Prospective Diabetes Study (UKPDS), a total of 3,867 patients, median age 54 years, with newly diagnosed diabetes and who had a mean of two fasting plasma glucose (FPG) concentrations of 6.1-15.0 mmol/L were randomized to intensive glucose control with sulphonylurea (chlorpropamide or glibenclamide) or insulin (n=2,729), or conventional control with diet (n=1,138). The primary aggregate endpoints were diabetes-related endpoints, death-related to diabetes, and death from all causes. To assess the differences between chlorpropamide, glibenclamide, and insulin, the additional endpoint aggregates of myocardial infarction (fatal and non-fatal) and sudden death; stroke (fatal and non-fatal); amputation or death due to peripheral vascular disease; and microvascular complications (retinopathy requiring photocoagulation, vitreous hemorrhage, and or fatal or non-fatal renal failure) were used. Median follow-up for endpoint analysis was 10 years, and 11.1 years for the comparison of agents. The most significant impact of intensive control was seen in the risk reduction of microvascular complications. In the intensive glucose control group there was a 12% reduction in risk for any diabetes-related endpoint (P=0.03), which was mostly due to a reduction in microvascular endpoints of 25% (P<0.01). In the surrogate endpoints, there was a significant reduction in risk for retinopathy (P=0.02), and for microalbuminuria at 12 years (P<0.01). Reference: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837-853.
  • Metformin markedly and significantly reduced the incidence of myocardial infarction, by 39% compared with diet alone (p = 0.01). No significant changes were observed with the intensive regimen based on sulphonylureas or insulin. Consistent with the effects on myocardial infarction, metformin also significantly reduced the incidence of coronary deaths, by 50% compared with diet (p = 0.02). No published data on fatal heart attacks have been given for overweight patients assigned to sulphonylureas or insulin. Slide 29. UKPDS: Myocardial Infarction in Metformin Study. Improving the Prognosis of Patients with Type 2 Diabetes
  • The UKPDS also investigated the effects of blood pressure control on the prevention of complications of diabetes. One thousand one hundred forty-eight (1,148) of the randomized (4,297) patients had hypertension (mean BP160/94 mm Hg). Patients were randomized to either an ACE inhibitor or a beta-blocker to achieve either tight BP control (<150/85 mm Hg) or less tight control (180/105 mm Hg), with avoidance of treatment with ACE inhibitors or beta-blockers. However, medications were permitted in each group if required to achieve or maintain goals. Mean BP was reduced significantly during the follow-up period (median 8.4 years) in the tight control group compared with the less tight control group, with mean BP of 144/82 mm Hg and 154/87 mm Hg, respectively. However, after 9 years of follow-up, three or more medications were required in the tight control group to sustain goal BP. Statistically significant reductions in both microvascular and macrovascular complications were observed in the tight control group vs the less tight control group. These reductions are illustrated on this slide. It should be noted that a reduction (not shown here) in all-cause mortality did not reach statistical significance. The investigators also found that the studied ACE inhibitor and beta-blocker were equally safe and effective. UK Prospective Diabetes Study Group. BMJ . 1998;317:703-713. UK Prospective Diabetes Study Group. BMJ . 1998;317:713-720.
  • Diabetic Patients CV Event Rate: Effect of BP Control The importance of reducing diastolic BP in patients with diabetes was demonstrated in the Hypertension Optimal Treatment (HOT) trial. In the HOT trial, 18,790 patients with hypertension and diastolic BP between 100 and 115 mm Hg were randomized to 1 of 3 target diastolic BP groups:  90 mm Hg,  85 mm Hg, or  80 mm Hg. A subgroup of 1501 patients had DM at baseline. A 5-step treatment regimen that started with initial felodipine therapy was used to lower BP. At the study end, 78% of patients were still taking felodipine, usually with an angiotensin converting enzyme inhibitor (41%), or a  -blocker (28%). The incidence of major CV events (MI, stroke, CV mortality) did not differ significantly among the 3 target BP groups in patients who did not have diabetes. Events per 1000 patient-years were 9.9, 10.0, and 9.3 for the  90 mm Hg,  85 mm Hg, or  80 mm Hg, respectively. In patients with diabetes mellitus, there was a 51% reduction in major CV events in the target group  80 mm compared with target group  90 mm ( P for trend = .005). Events per 1000 patient-years were 24.4, 18.6, and 11.9 ( P =0.005 for trend) for those with diabetes in the  90 mm Hg,  85 mm Hg, or  80 mm Hg, respectively. Reference Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. HOT Study Group. Lancet . 1998;351:1755-1762.
  • Scientific Statements: Diabetes, CV Disease, and Hypertension In 1999, the American Heart Association published a scientific statement for health care professionals that examined both the cardiovascular complications of diabetes and potential approaches for preventing the complications. Diabetes is associated with specific cardiovascular diseases, including atherosclerotic coronary heart disease, diabetic cardiomyopathy, and stroke. In addition, a severe and common complication of diabetes is renal disease. Management of diabetic nephropathy involves the following: controlling hyperglycemia, treating hypertension, preferably with ACE inhibitors, because they are likely to slow progression of nephropathy, restricting sodium, and restricting dietary protein. Of note, patients with type 4 renal tubular acidosis or hyporenin/hypoaldosteronism are at risk of hyperkalemia when ACE inhibitors are administered. 1 More recently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of Blood Pressure developed new guidelines for prevention and management of hypertension. Special considerations and treatment recommendations suggested by the panel are listed on the slide. 2 References 1. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation. 1999;100:1134-1146. 2. Chobanian AV, Bakris GL, Black HR, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572.
  • LDL as a Predictor of CAD in Diabetic Patients The contribution of low-density lipoprotein (LDL) cholesterol levels to CV risk in individuals with impaired glucose tolerance is not obvious because LDL cholesterol levels frequently are normal or near normal in these patients. Instead, diabetic dyslipidemia is characterized by elevated triglyceride levels, reduced high-density lipoprotein (HDL) cholesterol levels, and small LDL particles. Howard, et al analyzed data from 2034 individuals with diabetes to assess the importance of LDL-cholesterol levels in determining CV risk in this population. Patients with diabetes exhibited the expected dyslipidemia. Compared with 1634 nondiabetic controls, individuals with diabetes had significantly lower levels of HDL-cholesterol, higher triglycerides levels, and smaller LDL particle size. However, mean LDL-cholesterol levels were lower among those with diabetes (109 ± 33 mg/dL vs 118 ± 32 mg/dL). Nonetheless, the incidence of fatal and nonfatal CV events increased with increasing quartiles of LDL cholesterol levels in these individuals. For each 10-mg/dL increase in LDL-cholesterol levels, the risk of CVD increased by 12%. Even at levels below the 2000 National Cholesterol Education Program target of 130 mg/dL, LDL-cholesterol is a strong independent predictor of CVD in the diabetic population. Reference Howard BV, Robbins DC, Sievers ML, et al. LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: The Strong Heart Study. Arterioscler Thromb Vasc Biol . 2000;20:830-835.
  • The Collaborative Atorvastatin Diabetes Study (CARDS) was designed to evaluate the efficacy and safety of atorvastatin, 10 mg/day, in the primary prevention of cardiovascular disease in patients with type 2 diabetes with unremarkable cholesterol levels. CARDS included 2,838 patients with type 2 diabetes and an LDL cholesterol of 160 mg/dL or less who were randomized to 10 mg/day of artorvastatin or placebo. At baseline, the mean LDL cholesterol level was 118 mg/dL in the placebo recipients and 119 mg/dL in those assigned to atorvastatin. After a median follow-up of approximately 4 years, atorvastatin was associated with a 37% relative reduction (p =0.001) in the risk of major coronary events. References Thomason MJ, et al. Diabet Med. 2004 Aug;21(8):901-5. Colhoun HM, et al. Diabetic Medicine 2002;19(3):201.
  • In the HPS, the proportional reductions in the risk of first major vascular events were similar irrespective of baseline LDL cholesterol levels in individuals both with and without diabetes. The reduction in risk among the participants with diabetes whose pretreatment LDL cholesterol values were <116 mg/dL was 27% ( P =0.0007), which was similar to the 20% ( P =0.0009) reduction observed in the non-diabetics with LDL cholesterol levels <16 mg/dL.   A substudy of the HPS, lowering LDL cholesterol from <116 mg/dL to <77 mg/dL in patients with diabetes reduced the risk of macrovascular disease risk by about one fourth.   Reference HPS Collaborative Group. Lancet. 2003;361:2005-2016.
  • Statin Therapy – Number Needed to Treat Absolute risk reduction is the difference between the event rate or risk of outcome in the experimental group and the control group. The number-needed-to-treat (NNT) is the reciprocal of the absolute risk reduction, and indicates the number of patients in the population described that a clinician would need to treat with a particular therapy in order to avoid one event. As seen in the Heart Protection Study, statin therapy in diabetic patients has a pronounced effect on absolute risk; therefore, the NNT is low (14). 1 As observed in the 4S study, in higher-risk diabetic patients (eg, those with CAD), a comparable reduction in relative risk results in an even larger reduction in absolute risk. 2 Consequently, the NNT in diabetic patients with CAD is lower than in those without CAD. References 1. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet . 2002;360:7-22 2. Pyorala K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care . 1997;20:614-620.
  • Non-HDL cholesterol has been identified by ATP III as a secondary target of therapy in patients with elevated levels of triglycerides (200 mg/dL or greater). Non-HDL cholesterol is calculated by subtracting the HDL cholesterol level from the total cholesterol level. The non-HDL cholesterol goal is 30 mg/dL greater than the LDL cholesterol goal in these patients.
  • In patients with a low level of HDL cholesterol, the primary target of therapy is reduction of LDL cholesterol. If metabolic syndrome is present, management of its underlying causes is a first-line therapy. If triglycerides are 200 mg/dL or greater in the patient with low HDL cholesterol, non-HDL cholesterol is a secondary target of therapy. For patients with low HDL cholesterol who have CHD or CHD risk equivalents, nicotinic acid or fibric acid derivatives should be considered. LACK OF DATA FOR treating the HDL as a target to reduce risk.
  • Ask at every visit Advise as to benefits of cessation Assess patient’s willingness to make a quit attempt Set quit date Spend time before quit date planning for alternative behaviors for anticipated triggers Reduce ETOH Support group/family Ask about previous quit attempts Provide info regarding withdrawal symptoms, relapse More likely to need pharmacologic assistance if Smoke more that 20 cig/d Smoke within 30 minutes of awakening in am Significant withdrawal symptoms and early relapse (w/in 1 week of cessation) Current or past history of psychiatric disorder When patients commit to a quit date arrange for follow up visit to reinforce and support quit attempt
  • Coronary Heart Disease (CHD) Mortality Rates (by Degree of Glucose Tolerance) Subsequent to an 11-year follow-up, CHD mortality data from the Paris Prospective Study, an investigation of cardiovascular (CV) diseases in a population of 7164 men, aged 43 to 54 years, were assessed. Initial work suggested a threshold for blood sugar concentration measured 2 hours post-oral glucose load, above which CHD mortality rates double. Using the World Health Organization (WHO) Expert Committee on Diabetes Mellitus 1980 definition of impaired glucose tolerance, the annual CHD mortality rates per 1000 were computed. Results in the graph demonstrate the marked difference in CHD mortality rates between subjects with normal glucose tolerance, those with impaired glucose tolerance, and those that were known to have diabetes at the start of the study. Reference Eschwege E, Richard JL, Thibult HN, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. Horm Metab Res Suppl . 1985;15:41-46.
  • Study participants were randomized to one of three groups: treatment with metformin, intensive lifestyle intervention, or placebo. Randomization to placebo and metformin was double-blinded. Subjects assigned to the metformin arm received 850 mg a day for 1 month, which was titrated to 850 mg bid thereafter. Those assigned to lifestyle intervention were expected to engage in moderate exercise (eg, brisk walking) for at least 150 minutes a week and to achieve and maintain a weight loss of at least 7%. A 16-lesson curriculum that covered diet, exercise, and behavior modification was taught by case managers on a 1-to-1 basis during the first 24 weeks after study enrollment. The average follow-up was 2.8 years with a range of 1.8 to 4.6 years. Diabetes Prevention Program Research Group. N Engl J Med . 2002;346:393-403.
  • Lifestyle reduced the incidence of diabetes by 58% (95% CI, 48%-66%) and metformin reduced the incidence by 31% (95% CI, 17%-43%). The incidence of diabetes was 39% lower (95% CI, 24%-51%) in the lifestyle group than in the metformin group. Treatment effects did not differ significantly according to sex or to race or ethnic group. The lifestyle intervention was highly effective in all subgroups. Its effect was significantly greater among persons with lower base-line glucose concentrations two hours after a glucose load than among those with higher base-line glucose values. The advantage of lifestyle intervention over metformin was greater in older persons and those with a lower body-mass-index than in younger persons and those with a higher body-mass-index. The effect of metformin was less with a lower body-mass-index or a lower fasting glucose concentration than with higher values for those variables. The investigators concluded that, compared with placebo, 1 case of diabetes can be prevented for every 7 persons treated with lifestyle changes for 3 years and for every 14 persons treated with metformin for 3 years. Diabetes Prevention Program Research Group. N Engl J Med . 2002;346:393-403.
  • It has become well accepted that moderate weight loss improves cardiovascular and metabolic risk factors. In a study by Case and colleagues of obese individuals enrolled in a medically supervised rapid weight loss program study, 1 year of consecutive patients’ charts was reviewed to determine the response to diet-induced weight loss. Out of 185 individuals, 125 (68%) met the NCEP definition of the metabolic syndrome. At 4 weeks, a moderate decrease in weight (6.5%) induced by a very low calorie diet resulted in substantial reductions of systolic (11.1 mm Hg) and diastolic (5.8 mm Hg) blood pressure, glucose (17 mg/dL), triglycerides (94 mg/dL) and total cholesterol (37 mg/dL) (all P <0.001). These improvements were sustained at the end of active weight loss (average 16.7 weeks; total weight loss 15.1%), with further significant reductions in blood pressure and triglycerides. Weight loss was related to the changes in each criterion of the metabolic syndrome. The authors concluded that moderate weight loss markedly improved all aspects of the metabolic syndrome. Case CC, Jones PH, Nelson K, O’Brian Smith E, Ballantyne CM. Impact of weight loss on the metabolic syndrome. Diabetes Obes Metab . 2002;4:407-414.
  • Cardiovascular Disease and the Patient with Diabetes and ...

    1. 1. Cardiovascular Disease and the Patient with Diabetes and Metabolic Syndrome Nathan D. Wong, PhD, FACC, FAHA Professor and Director Heart Disease Prevention Program Division of Cardiology University of California, Irvine President, American Society for Preventive Cardiology
    2. 2. Presenter Disclosure <ul><li>Dr. Wong has received research support through Bristol-Myers Squibb, Novartis, and Forest Laboratories through the University of California, Irvine </li></ul>
    3. 3. Presentation Objectives <ul><li>Review the epidemiology implicating metabolic syndrome and diabetes in cardiovascular risk </li></ul><ul><li>Discuss the clinical trial evidence for the role of lifestyle management, glycemic, lipid, and blood pressure control. </li></ul><ul><li>Address the ABCs of lifestyle and clinical management of metabolic syndrome and diabetes aimed to reduce cardiovascular disease risk. </li></ul>
    4. 4. Diagnosed Diabetes in the US: 2008 CDC BRFSS: Self-Reported Diabetes: 8.2% Nationwide 4 – 6% 6 – 8% 8 – 10% 10 – 12%
    5. 5. Prevalence of physician-diagnosed diabetes in Adults age 20 and older by race/ethnicity and sex (NHANES: 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.
    6. 6. The Continuum of CV Risk in Type 2 Diabetes Adapted from American Diabetes Association. Diabetes Care . 2003;26:3160-3167. Tsao PS, et al. Arterioscler Thromb Vasc Biol. 1998;18:947-953. Hsueh WA, et al. Am J Med . 1998;105(1A):4S-14S. American Diabetes Association. Diabetes Care . 1998;21:310-314.
    7. 7. Diagnostic Criteria for Metabolic Syndrome: Modified NCEP ATP III AHA/NHLBI Scientific Statement; Circulation 2005; 112:e285-e290. ≥ 3 Components Required for Diagnosis Components Defining Level Increased waist circumference Men Women ≥ 40 in ≥ 35 in Elevated triglycerides ≥ 150 mg/dL (or Medical Rx) Reduced HDL-C Men Women <40 mg/dL <50 mg/dL (or Medical Rx) Elevated blood pressure ≥ 130 / ≥ 85 mm Hg (or Medical Rx) Elevated fasting glucose ≥ 100 mg/dL (or Medical Rx)
    8. 8. IDF Criteria: Abdominal Obesity and Waist Circumference Thresholds <ul><li>AHA/NHLBI criteria: ≥ 102 cm (40 in) in men, ≥ 88 cm (35 in) in women </li></ul><ul><li>Some US adults of non-Asian origin with marginal increases should benefit from lifestyle changes. Lower cutpoints (≥ 90 cm in men and ≥ 80 cm in women) for Asian Americans </li></ul>Alberti KGMM et al. Lancet 2005;366:1059-1062. | Grundy SM et al. Circulation 2005;112:2735-2752. Men Women Europid ≥ 94 cm (37.0 in) ≥ 80 cm (31.5 in) South Asian ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in) Chinese ≥ 90 cm (35.4 in) ≥ 80 cm (31.5 in) Japanese ≥ 85 cm (33.5 in) ≥ 90 cm (35.4 in)
    9. 9. Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994 Age (years) Ford E et al. JAMA . 2002(287):356. 1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+) NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women Prevalence (%) 0 5 10 15 20 25 30 35 40 45 20-29 30-39 40-49 50-59 60-69 > 70 Men Women
    10. 10. Diabetes and CVD <ul><li>Atherosclerotic complications responsible for </li></ul><ul><ul><li>80% of mortality among patients with diabetes </li></ul></ul><ul><ul><li>75% of cases due to coronary artery disease (CAD) </li></ul></ul><ul><ul><li>Results in >75% of all hospitalizations for diabetic complications </li></ul></ul><ul><li>50% of patients with type 2 diabetes have preexisting CAD. (This number may be less now that more younger people are diagnosed with diabetes.)  </li></ul><ul><li>1/3 of patients presenting with myocardial infarction have undiagnosed diabetes mellitus </li></ul>Lewis GF. Can J Cardiol . 1995;11(suppl C):24C-28C Norhammar A, Lancet 2002;359;2140-2144
    11. 11. Risk of Cardiovascular Events in Patients with Diabetes: Framingham Study <ul><li> Age-adjusted </li></ul><ul><li> Biennial Rate Age-adjusted </li></ul><ul><li> Per 1000 Risk Ratio </li></ul><ul><li>Cardiovascular Event Men Women Men Women </li></ul><ul><li>Coronary Disease 39 21 1.5** 2.2*** </li></ul><ul><li>Stroke 15 6 2.9*** 2.6*** </li></ul><ul><li>Peripheral Artery Dis. 18 18 3.4*** 6.4*** </li></ul><ul><li>Cardiac Failure 23 21 4.4*** 7.8*** </li></ul><ul><li>All CVD Events 76 65 2.2*** 3.7*** </li></ul><ul><li>Subjects 35-64 36-year Follow-up **P<.001,***P<.0001 </li></ul>_________________________________________________________________ _________________________________________________________________
    12. 12. Diabetes as a CHD Risk Equivalent: Type 2 DM and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study) No Diabetes Diabetes 3.5% 18.8% 20.2% 45.0% P <0.001 P <0.001 7-year incidence rate of MI CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus Haffner SM et al. N Engl J Med . 1998;339:229-234.
    13. 13. Cardiovascular Disease (CVD) and Total Mortality: U.S. Men and Women Ages 30-74 * p<.05, ** p<.01, **** p<.0001 compared to none * *** *** *** ** *** *** *** *** *** *** Malik and Wong, et al., Circulation 2004; 110: 1245-1250. (Risk-factor adjusted Cox regression) NHANES II Follow-Up (n=6255) ***
    14. 14. Odds of CVD Stratified by CRP Levels in U.S. Persons (Malik and Wong et al., Diabetes Care 2005; 28: 690-3) <ul><li>* p<.05, **p<.01, **** p<.0001 compared to no disease, low CRP </li></ul><ul><li>CRP categories: >3 mg/l (High) and < 3 mg/L (Low) </li></ul><ul><li>age, gender, and risk-factor adjusted logistic regression (n=6497) </li></ul>* * *** ** *** Odds Rat io
    15. 15. Example of Significant Coronary Calcification from Multidetector CT (Siemens Sensation 64) scanner
    16. 16. 10-Year CHD Event Rates (per 1000 person years) by Calcium Score by CAC Categories in Subjects with Neither MetS nor DM, MetS only, or DM Coronary Heart Disease Coronary Artery Calcium Score 0 1-99 100-399 400+ CHD events per 1000 person years Diabetes MetS Neither MetS/DM Malik and Wong et al. (AHA 2009)
    17. 17. Under-Treatment of Cardiovascular Risk Factors Among U.S. Adults with Diabetes <ul><ul><li>NHANES Survey 2001-2002, 532 (projected to 15.2 million) or 7.3% of adults aged >/=18 years had diabetes </li></ul></ul><ul><ul><li>50.2% not at HbA1c goal <7% </li></ul></ul><ul><ul><li>64.6% not at LDL-C goal <100 mg/dl </li></ul></ul><ul><ul><li>52.3% not at recommended HDL-C >/=40 (M), >/=50 (F) </li></ul></ul><ul><ul><li>48.6% not at recommended triglycerides <150 mg/dl </li></ul></ul><ul><ul><li>53% not at BP goal of <130/80 mg/dl </li></ul></ul><ul><ul><li>Overall, only 5% of men and 12% of women at goal for HbA1c, BP, and LDL-C simultaneously </li></ul></ul>Malik S, Wong ND et al. Diab Res Clin Pract 2007;77:126-33.
    18. 18. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    19. 19. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    20. 20. A1c Target Aspirin Therapy <ul><li>A1c Target : In persons with diabetes, glucose lowering to achieve normal to near normal plasma glucose, as defined by the HbA1c<7% </li></ul><ul><li>Aspirin Daily : Patients with type 2 DM >40 years of age or with prevalent CVD, OR those with metabolic syndrome without DM who are at intermediate or higher risk (e.g., >=10% 10-year risk of CHD) </li></ul>
    21. 21. Type 2 Diabetes: A1C Predicts CHD CHD Mortality Incidence (%) in 3.5 Years All CHD Events Incidence (%) in 3.5 Years A1C=hemoglobin A1C * P <0.01 vs lowest tertile ** P <0.05 vs lowest tertile 0 2 4 6 8 10 12 Low <6% High >7.9% * Middle 6-7.9% 0 5 10 15 20 25 Middle 6-7.9% High >7.9% ** Low <6% Adapted with permission from Kuusisto J et al. Diabetes . 1994;43:960-967.
    22. 22. UKPDS Relative Risk Reduction for Intensive vs. Less Intensive Glucose Control % relative risk reduction P=0.03 P<0.01 P<0.01 P=0.05 P=0.02 UKPDS Group. Lancet. 1998;352:837-853. Over 10 years, HbA 1c was 7.0% (6.2-8.2) in the intensive group (n=2,729) compared with 7.9% (6.9-8.8) in the conventional group (n=1,138).
    23. 23. UKPDS Metformin Sub-Study: CHD Events UKPDS 34, Lancet 352: 854, 1998 n= 411 951 342 411 342 #Events 73 139 39 36 16 Myocardial Infarction 0 5 10 15 20 Incidence per 1000 patient years Conventional Diet Insulin SU’s Metformin p=0.01 NS 39% Reduction Coronary Deaths 0 2 4 6 8 10 p=0.02 50% Reduction Metformin Incidence per 1000 patient years Conventional Diet
    24. 24. Recent Trials Show No Reduction in CV Events with More Intensive Glycemic Control 1 ACCORD Study Group. N Engl J Med. 2008;358:2545-2559. 2 ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572. Number at Risk Intensive 5570 5369 5100 4867 4599 1883 Standard 5569 5342 5065 4808 4545 1921 0 12 24 36 48 60 Cumulative incidence (%) Months of follow-up ADVANCE: Primary Outcome Number at Risk Intensive 5128 4843 4390 2839 1337 475 448 Standard 5123 4827 4262 2702 1186 440 395 Patients with events (%) ACCORD: Primary Outcome 25 20 15 10 5 0 Standard therapy Intensive therapy 0 1 2 3 4 5 6 25 20 15 10 5 0 Years Standard therapy Intensive therapy
    25. 25. Was Intensive Glycemic Control Harmful? A closer look at ACCORD AND ADVANCE <ul><li>ACCORD was discontinued early due to increased total and CVD mortality in the intensive arm. Major hypoglycemia 3-fold higher too. </li></ul><ul><li>And the VA Diabetes Trial did show severe hypoglycemia to be a powerful predictor of CVD events. </li></ul><ul><li>But a more recent analysis of ACCORD just published (Diabetes Care, May 2010) showed deaths to be associated with unsuccessful intensive therapy where A1c remained high . </li></ul><ul><li>However, in both ACCORD AND ADVANCE, the subgroups without macrovascular disease at baseline had an actual benefit in the primary endpoint. </li></ul>
    26. 26. 2009 ADA/AHA/ACC Statement Recommendations <ul><li>Goal of A1c<7% remains reasonable </li></ul><ul><ul><li>for uncomplicated patients </li></ul></ul><ul><ul><ul><li>ACC/AHA Class I (A) </li></ul></ul></ul><ul><ul><li>and for those with macrovascular disease </li></ul></ul><ul><ul><ul><li>ADA Level B; ACC/AHA Class IIb (A) </li></ul></ul></ul><ul><li>Incremental microvascular benefit may be obtained from even lower goals </li></ul><ul><ul><ul><li>ADA Level B; ACC/AHA Class IIa (C) </li></ul></ul></ul><ul><li>Less stringent goals may be appropriate for those with labile glucose control or with advanced micro- or macrovascular disease </li></ul><ul><ul><ul><li>ADA Level C; ACC/AHA Class IIa (C) </li></ul></ul></ul>Circulation 2009; 119: 351-357
    27. 27. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    28. 28. Prevalence of Hypertension* in Adults with Diabetes: NHANES III 1988-1994 % with Hypertension Geiss LS, et al. Am J Prev Med. 2002;22:42-48. *BP ≥130/85 or therapy for hypertension
    29. 29. HTN Control Rate Remains Poor in US Adults with MetS and DM from NHANES 2003-2004 (Wong ND et al., Arch Intern Med 2007) <ul><li>Only 35% of those with DM on treatment for HTN are controlled to a goal of <130/80 mmHg </li></ul><ul><li>Only 47% of those with MetS on treatment for HTN have a blood pressure of <130/85 mmHg </li></ul><ul><li>Thus, JNC-7 recommendations to begin with combination therapy to improve goal attainment should be adhered to, esp. if SBP/DBP exceeds 20/10 mmHg from goal. </li></ul>
    30. 30. UKPDS: Effects of Tight vs. Less-Tight Blood Pressure Control UK Prospective Diabetes Study Group. BMJ. 1998; 317:703-713.
    31. 31. HOT Trial: Effect of BP Control on CV Event Rate Hansson L et al. Lancet . 1998;351:1755-1762. Diastolic Blood Pressure goal Patients without Diabetes Patients with Diabetes Major CV events per 1000 patient-years
    32. 32. ACCORD: Effects of Intensive BP Control (NEJM 2010: 362: 1575-85) <ul><li>4733 participants with type 2 DM randomly assigned to intensive therapy targeting a SBP <120 mmHg vs. standard therapy targeting a SBP<140 mmHg. </li></ul><ul><li>Mean follow-up 4.7 years. </li></ul><ul><li>SBP after 1 year was 119 vs. 133 mmHg. </li></ul><ul><li>No difference in the primary endpoint of nonfatal MI, stroke, or CVD death (annual rate): 1.9% vs. 2.1% (HR=0.88), p=0.20. </li></ul><ul><li>Stroke annual rates significantly lower 0.32% vs. 0.53%, HR=0.59, p=0.01. Thus, overall benefit may be greater in populations with higher stroke risk. </li></ul>
    33. 33. Scientific Statements: Diabetes, CV Disease and Hypertension <ul><li>JNC VII Report on Diabetic Hypertension </li></ul><ul><ul><li>BP goal (<130/80 mm Hg) </li></ul></ul><ul><ul><ul><li>Commonly requiring combinations of ≥2 drugs </li></ul></ul></ul><ul><ul><li>ACEIs, CCBs, Thiazide-diuretics,  -blockers, and ARBs shown to reduce CVD/CVA risk </li></ul></ul><ul><ul><li>ACEIs/ARBs reduce progression of diabetic nephropathy and reduce albuminuria </li></ul></ul><ul><ul><li>ARBS reduce progression of macroalbuminuria </li></ul></ul>Grundy SM, et al. Circulation . 1999;100:1134-1146. Chobanian AV, et al. JAMA . 2003;289:2560-2572.
    34. 34. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    35. 35. LDL-C as a Predictor of CAD in Patients with Diabetes Hazard ratio LDL-C quartile mean Adapted with permission from Howard BV et al. Arterioscler Thromb Vasc Biol . 2000;20:830-835. LDL=low-density lipoprotein cholesterol; CAD=coronary artery disease.
    36. 36. CARDS: Primary Endpoint Relative Risk Reduction 37% (95% CI: 17-52) Years 328 305 694 651 1074 1022 1361 1306 1392 1351 Atorva Placebo 1428 1410 Placebo 127 events Atorvastatin 83 events Cumulative Hazard (%) 0 5 10 15 0 1 2 3 4 4.75 P = 0.001 Colhoun HM et al. Lancet 2004;364:685-96.
    37. 37. HPS Substudy: First Major Vascular Event by LDL-C and Prior Diabetes Status Simvastatin (10,269) Placebo (10,267) Rate ratio (95% CI) Statin better Placebo better LDL-C and diabetes status <116 mg/dL With diabetes 191 (15.7%) 252 (20.9%) No diabetes 407 (18.8%) 504 (22.9%)  116 mg/dL With diabetes 410 (23.3%) 496 (27.9%) No diabetes 1,025 (20.0%) 1,333 (26.2%) All patients 2,033 (19.8%) 2,585 (25.2%) 24% reduction ( P <0.0001) 0.4 0.6 0.8 1.0 1.2 1.4 HPS Collaborative Group. Lancet . 2003;361:2005-2016.
    38. 38. Reducing CVD Risk with Statin Therapy in Patients with Diabetes <ul><li>Number needed to treat to prevent 1 major CVD event </li></ul><ul><ul><li>From HPS and 4S </li></ul></ul><ul><ul><ul><li>Without coronary disease 14 </li></ul></ul></ul><ul><ul><ul><li>With coronary disease 4 </li></ul></ul></ul><ul><ul><li>From meta-analysis </li></ul></ul><ul><ul><ul><li>Without vascular disease 39 </li></ul></ul></ul><ul><ul><ul><li>With vascular disease 19 </li></ul></ul></ul>HPS Collaborative Group. Lancet . 2003;361:2005-2016. Pyorala K, et al. Diabetes Care . 1997;20:614-620 Kearney PM Lancet;2008:371:227-239
    39. 39. Lipid Goals for Persons with Metabolic Syndrome and DM (Grundy et al., 2005) <ul><li>LDL-C targets, ATP III guidelines </li></ul><ul><ul><li>– High Risk: CHD, CHD risk equivalents ( incl. DM or >20% 10-year risk ): <100 mg/dL (option <70 mg/dl if CVD present) </li></ul></ul><ul><ul><li>– Moderately High Risk (10-20%) 2 RF: <130 mg/dL, option <100 mg/dL </li></ul></ul><ul><ul><li>– Moderate Risk (2+ RF, <10%) <130 mg/dL </li></ul></ul><ul><ul><li>-- Low Risk: 0-1 RF: <160 mg/dL </li></ul></ul><ul><li>HDL-C : >40 mg/dL (men) </li></ul><ul><ul><ul><li>>50 mg/dL (women) </li></ul></ul></ul><ul><li>TG : <150 mg/dL </li></ul>
    40. 40. <ul><li>Non-HDL: Secondary Target </li></ul><ul><li>Non-HDL = TC – HDL </li></ul><ul><li>Non-HDL: secondary target of therapy when serum triglycerides are  200 mg/dL (esp. 200-499 mg/dl) </li></ul><ul><li>Non-HDL goal: LDL goal + 30 mg/dL </li></ul>Specific Dyslipidemias: Elevated Triglycerides
    41. 41. <ul><li>Management of Low HDL </li></ul><ul><li>LDL is primary target of therapy </li></ul><ul><li>Weight reduction and increased physical activity (if the metabolic syndrome is present) </li></ul><ul><li>Non-HDL is secondary target of therapy (if triglycerides  200 mg/dL) </li></ul><ul><li>Consider nicotinic acid or fibrates (for patients with CHD or CHD risk equivalents) </li></ul>Specific Dyslipidemias: Low HDL Cholesterol
    42. 42. ACCORD Lipid Study Results (NEJM 2010; 362: 1563-74) <ul><li>5518 patients with type 2 DM treated with open label simvastatin randomly assigned to fenofibrate or placebo and followed for 4.7 years. </li></ul><ul><li>Annual rate of primary outcome of nonfatal MI, stroke or CVD death 2.2% in fenofibrate group vs. 1.6% in placebo group (HR=0.91, p=0.33). </li></ul><ul><li>Pre-specified subgroup analyses showed possible benefit in men vs. women and those with high triglycerides and low HDL-C. </li></ul><ul><li>Results support statin therapy alone to reduce CVD risk in high risk type 2 DM patients. </li></ul>
    43. 43. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    44. 44. Smoking Cessation <ul><li>What you do does matter. Physicians who intervene influence cigarette smoking behavior. </li></ul><ul><li>How do you get your patients to quit smoking? </li></ul><ul><ul><li>Identify i.e.: in vitals signs </li></ul></ul><ul><ul><li>Interventions as brief as 3 minutes can significantly increase quit rates </li></ul></ul><ul><ul><li>Dose dependent changes in behavior </li></ul></ul><ul><ul><li>5-10% may quit within 1 year with MD advice alone </li></ul></ul><ul><li>Smoking cessation aids </li></ul>
    46. 46. The 5 “A’s” for Effective Smoking Intervention <ul><li>ASK about smoking </li></ul><ul><li>ADVISE to quit </li></ul><ul><li>ASSESS willingness to make a quit attempt </li></ul><ul><li>ASSIST if ready - offer therapy and consultation for quit plan and if not, then offer help when ready </li></ul><ul><li>ARRANGE follow up visits </li></ul>
    47. 47. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    48. 48. CHD Mortality Rates (by Degree of Glucose Tolerance) Incidence rate/1000 *Indicates patients known to have diabetes prior to the study. CHD=coronary heart disease; NGT=normal glucose tolerance; IGT=impaired glucose tolerance Adapted with permission from Eschwege E et al. Horm Metab Res Suppl . 1985;15:41-46.
    49. 49. Most Cardiovascular Patients Have Abnormal Glucose Metabolism 35% 31% 34% 37% 18% 45% 37% 27% 36% GAMI n = 164 EHS n = 1920 CHS n = 2263 GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey Prediabetes Normoglycemia Type 2 Diabetes Anselmino M, et al. Rev Cardiovasc Med . 2008;9:29-38.
    50. 50. D iabetes P revention P rogram: Protocol Design
    51. 51. D iabetes P revention P rogram: Reduction in Diabetes Incidence
    52. 52. Benefit of Comprehensive, Intensive Management: STENO 2 Study <ul><li>Treatment Goals: </li></ul><ul><ul><li>Intensive TLC </li></ul></ul><ul><ul><li>HgbA1c <6.5% </li></ul></ul><ul><ul><li>Cholesterol <175 </li></ul></ul><ul><ul><li>Triglycerides <150 </li></ul></ul><ul><ul><li>BP <130/80 </li></ul></ul>0 0 10 20 40 50 60 Conventional Therapy Intensive Therapy 30 Months of Follow Up Primary End Point=CV events (%) 12 24 36 48 60 72 84 96 n =80 n =80 Gaede, P. et al, NEJM 2003;348:390-393
    53. 53. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    54. 54. Metabolic Syndrome: Lifestyle Management: Obesity / Physical Activity <ul><li>Obesity / weight management : low fat – high fiber diet resulting in 500-1000 calorie reduction per day to provide a 7-10% reduction on body weight over 6-12 mos, ideal goal BMI <25 </li></ul><ul><li>Physical activity : at least 30, pref. 60 min moderate intensity on most or all days of the week as appropriate to individual </li></ul>Grundy SM, Hansen B, Smith SC, et al. Clinical management of metabolic syndrome. Report of the American Heart Association / National Heart, Lung, and Blood Institute / American Diabetes Association Conference on Scientific Issues Related to Management. Circulation 2004; 109: 551-556
    55. 56. Physical Inactivity: A Call to Arms 10,000 Steps Daily 30 minutes most days
    56. 57. Physical Activity Recommendations <ul><li>Aerobic exercise a minimum of 30 minutes, 5 times weekly </li></ul><ul><li>Optimal physical activity is at least 30 minutes daily </li></ul><ul><li>Resistance exercise training using free weights or machines 2 days a week in the absence of contraindications </li></ul>
    57. 58. Summary of Care: ABC's for Providers A A1c Target Aspirin Daily B Blood Pressure Control C Cholesterol Management Cigarette Smoking Cessation D Diabetes and Pre-Diabetes Management E Exercise F Food Choices
    58. 59. ADA Nutritional Guidelines <ul><li>Patients with pre-diabetes should receive individualized Medical Nutrition Therapy (MNT) </li></ul><ul><li>Weight loss recommended for all overweight or obese individuals who have or are at risk for diabetes </li></ul><ul><li>Physical activity and behavior modification effective for weight loss and maintenance </li></ul><ul><li>Fiber 14 g/1000 kcal intake </li></ul><ul><li>Saturated fat 7% with minimal trans fat </li></ul>
    59. 60. Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet <ul><li>Nutrient Recommended Intake </li></ul><ul><li>Saturated fat Less than 7% of total calories </li></ul><ul><li>Polyunsaturated fat Up to 10% of total calories </li></ul><ul><li>Monounsaturated fat Up to 20% of total calories </li></ul><ul><li>Total fat 25–35% of total calories </li></ul><ul><li>Carbohydrate 50–60% of total calories </li></ul><ul><li>Fiber 20–30 grams per day </li></ul><ul><li>Protein Approximately 15% of total calories </li></ul><ul><li>Cholesterol Less than 200 mg/day </li></ul><ul><li>Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight/ prevent weight gain </li></ul>
    60. 61. Effect of Mediterranean-Style Diet in the Metabolic Syndrome <ul><li>180 pts with metabolic syndrome randomized to Mediterranean-style vs. prudent diet for 2 years </li></ul><ul><li>Those in intervention group lost more weight (-4kg) than those in the control group (+0.6kg) (p<0.01), and significant reductions in CRP and Il-6 </li></ul>Esposito K et al. JAMA 2004; 292(12): 1440-6.
    61. 62. Conclusions <ul><li>Metabolic syndrome and diabetes are associated with increased levels of atherosclerosis and cardiovascular disease event risk </li></ul><ul><li>Lifestyle measures focusing on weight reduction, dietary, and physical activity guidance are crucial in initial management. </li></ul>
    62. 63. Conclusions (cont.) <ul><li>Clinical management emphasizes achievement of BP and lipid goals, glycemic control, and antiplatelet therapy. </li></ul><ul><li>Multidisciplinary programs including primary care physicians, specialists (endocrinologists and cardiologists), dietitians, and exercise specialists are key for the successful management of these conditions. </li></ul>
    63. 64. Thank you for your attention! Now Published from Informa Healthcare … For more information visit our website at
    64. 65. Question #1 <ul><li>Which of the following statements is true? </li></ul><ul><ul><li>Diabetes prevalence is higher in African Americans and Hispanics compared to Caucasians </li></ul></ul><ul><ul><li>The prevalence of diabetes is approaching the prevalence of obesity </li></ul></ul><ul><ul><li>The impact of diabetes on CVD is similar in men and women </li></ul></ul><ul><ul><li>All of the above </li></ul></ul>
    65. 66. Question #2 <ul><li>What are the recommended target levels for LDL-C and BP for most uncomplicated patients with DM? </li></ul><ul><ul><li>LDL-C <100 mg/dl and 120/80 mmHg </li></ul></ul><ul><ul><li>LDL-C <100 mg/dl and 130/80 mmHg </li></ul></ul><ul><ul><li>LDL-C <70 mg/dl and 140/90 mmHg </li></ul></ul><ul><ul><li>None of the above </li></ul></ul>
    66. 67. Question #3 <ul><li>Diabetes has been considered a CHD risk equivalent because: </li></ul><ul><ul><li>Nearly all persons with CHD also have diabetes </li></ul></ul><ul><ul><li>Persons with diabetes have a similar risk of developing CHD than those who already have CHD (e.g., myocardial infarction) </li></ul></ul><ul><ul><li>Both a and b </li></ul></ul>
    67. 68. Question #4 <ul><li>Recent large clinical trials such as ACCORD and ADVANCE suggest: </li></ul><ul><ul><li>Aggressive glycemic control significantly reduces the risk of future CVD events in high risk persons with diabetes </li></ul></ul><ul><ul><li>The HbA1c target should be set closer to 6% than the conventional target of <7% </li></ul></ul><ul><ul><li>A less stringent goal than <7% for HbA1c might be considered in more complicated patients with diabetes (e.g., those difficult to control, with known macrovascular disease, or with long-standing diabetes) </li></ul></ul>
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