1. Cardiometabolic Risk : Evaluation & Treatment in Your Patient Population Cardiometabolic Risk Mohammad Saifur Rohman, MD. PhD Interventional Cardioloy Consultant Lab. Cardiology and Vascular Medicine Faculty of Medicine University of Brawijaya

2. Why Focus on Cardiometabolic Risk?  A comprehensive approach to patient care; Multiple disease pathways and risk factors are considered to facilitate earlier intervention  Early assessment and targeted intervention are needed to treat and prevent all risk factors associated with CVD and diabetes  A comprehensive approach to patient care; Multiple disease pathways and risk factors are considered to facilitate earlier intervention  Early assessment and targeted intervention are needed to treat and prevent all risk factors associated with CVD and diabetes

3. Cardiometabolic Risk  Gives a comprehensive picture of a patient’s health and potential risk for future disease and complications  Is inclusive of all risks related to metabolic changes associated with CVD  Accommodates emerging risk factors as useful predictive tools  Focuses clinical attention to the value of systematic evaluation, education, disease prevention and treatment  Supports an integrated approach to care  Gives a comprehensive picture of a patient’s health and potential risk for future disease and complications  Is inclusive of all risks related to metabolic changes associated with CVD  Accommodates emerging risk factors as useful predictive tools  Focuses clinical attention to the value of systematic evaluation, education, disease prevention and treatment  Supports an integrated approach to care Kahn, et al. The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care. 2005;28 (9)2289-2304. Kahn, et al. The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care. 2005;28 (9)2289-2304.

4. Definition of Metabolic Syndrome A cluster of cardiovascular risk includes Insulin resistance, obesity, hypertension and atherogenic dyslipidemia Definition of Metabolic Syndrome has been proposed by: WHO, 1998 Europian Group for the study of Insulin Resistance (EGIR), 1999 The National Cholesterol Education Program (NCETP) Adult Treatment Panel III (ATP-III), 2001 American Association of Clinical Endocrinologists (AACE), 2003 The third report of the national cholesterol education program (NCEP), JAMA 2001; 285: 2486-2497. Alberti KG, et al. Report of a WHO consultation. Diabet Med 1998; 15: 539-553.

5. Criteria of Metabolic Syndrome

6. Prevalence : 24 % of US men and women 44% of over 50 population Estimated at 47 million Americans JAMA 2002; 288: 2709-2716 Arch Intern Med 2003; 163:274-436

7. The State of Risk  2 out of 3 Americans are overweight or obese  More than 70 million (nearly 1 in 4) Americans have varying degrees of insulin resistance  There are an estimated 54 million (more than 1 in 6) Americans with prediabetes  Nearly 1 in 4 U.S. adults has high cholesterol  1 in 3 American adults has high blood pressure  2 out of 3 Americans are overweight or obese  More than 70 million (nearly 1 in 4) Americans have varying degrees of insulin resistance  There are an estimated 54 million (more than 1 in 6) Americans with prediabetes  Nearly 1 in 4 U.S. adults has high cholesterol  1 in 3 American adults has high blood pressure

8. Increasing of the trends in US

10. Metabolic syndrome in other countries In Europe : 15.7% (man) and 14.2 % (women) from non diabetic population. In Australia : 20% In korea 13% Hu G, et al. Arch Intern Med 2004: 164; 1066-1076. Dunstan DW, et al.Diabetes Care 2002: 25; 829-834. Oh JY, et al. Diabetes Care 2004: 27: 2027-2032.

11. Current WHO weight status recommendations for Asia and the USA Asia USA Underweight < 18.5 Healthy weight 18.5- 22.9 18.5– 24.9 Overweight 23.0- 24.9 25.0– 29.9 Obese  25  30 Waist Circ for ASIA: >90 cm (men), > 80 cm (women) The Nutrition Transition Program The University of North Carolina at Chapel Hill

12. Metabolic Syndrome in Indonesia In Bali : 20.3%, Urban > rural, Increased by 60 yo. In depok : 26%. In Jakarta (aged 55-85 yo) : 36%. Budhiarta AAG, et al. Naskah lengkap Surabaya Metabolic Syndrome Update-1. 2005; 139-147. Suyono S, et al. Naskah lengkap Surabaya Metabolic Syndrome Update-1. 2005; 9-20.

13. Abnormal Lipid Metabolism LDL  ApoB  HDL  Trigly.  Abnormal Lipid Metabolism LDL  ApoB  HDL  Trigly.  Cardiometabolic Risk Global Diabetes / CVD Risk Overweight / Obesity Inflammation Hypercoagulation Hypertension Smoking Physical Inactivity Unhealthy Eating Smoking Physical Inactivity Unhealthy Eating Age, Race, Gender, Family History  Glucose  BP  Lipids Age Genetics Insulin Resistance ? ? Insulin Resistance Syndrome Insulin Resistance Syndrome Cardiometabolic Risk - Graphic

14. Non-modifiable  Age  Race/ethnicity  Gender  Family history  Age  Race/ethnicity  Gender  Family history  Overweight  Abnormal lipid metabolism  Inflammation, hypercoagulation  Hypertension  Smoking  Physical inactivity  Unhealthy diet  Insulin resistance  Overweight  Abnormal lipid metabolism  Inflammation, hypercoagulation  Hypertension  Smoking  Physical inactivity  Unhealthy diet  Insulin resistance Cardiometabolic Risk Factors Modifiable

15. Case - Mr. Martin  47-year-old African American man, hasn’t seen doctor in years  Works as a truck driver, eats mostly fast food  Smokes 1 pack per day  At health fair found to have BP = 146/86, total cholesterol = 210  Weight = 230 lbs; BMI = 29 kg/m²  Family history of HTN and diabetes  47-year-old African American man, hasn’t seen doctor in years  Works as a truck driver, eats mostly fast food  Smokes 1 pack per day  At health fair found to have BP = 146/86, total cholesterol = 210  Weight = 230 lbs; BMI = 29 kg/m²  Family history of HTN and diabetes

16. What’s Mr. Martin’s Cardiometabolic Risk?  Age47  Race/ethnicityAfrican American  GenderMale  Family historyHTN and diabetes  Overweight/obesityBMI = 29  Abnormal lipid metab TC = 210  HypertensionBP = 146/86  Smoking1 pack per day  Physical InactivityYes  Unhealthy dietFast food diet  Age47  Race/ethnicityAfrican American  GenderMale  Family historyHTN and diabetes  Overweight/obesityBMI = 29  Abnormal lipid metab TC = 210  HypertensionBP = 146/86  Smoking1 pack per day  Physical InactivityYes  Unhealthy dietFast food diet

17. Overweight/Obesity

18. Understanding Cardiometabolic Risk: Broadening Risk Assessment and Management Cardiometabolic Risk Factors Desired Goals for Healthy Patients Overweight/obesity Source: CDC, ADA Prevention of overweight/obesity as measured by BMI (normal = 18.5–24.9). In those who are overweight/obese, the goal is to lose 5–7% of body weight. Abnormal lipid metabolism High LDL cholesterol Low HDL cholesterol High triglycerides Source: NHLBI, ATP III Guidelines, ADA Desirable levels are less than 100 mg/dL. Desirable levels are greater than 40 mg/dL in men and greater than 50 mg/dL in women. Desirable levels are less than 150 mg/dL Hypertension Source: NHLBI, JNC7 <140/90 mm/Hg or 130/80 mm/Hg for people with diabetes (Ideal is less than 120/80 mm/Hg) Fasting blood glucose Source: ADA Below 100 mg/dL Physical inactivity Source: CDC At least 30 minutes of moderate activity most days Smoking Source: ADA Quit or never start Children Source: ADA Maintain healthy weight for age, sex, and height.

19. Screening: Overweight  Measure BMI routinely at each regular check-up.  Classifications: BMI 18.5-24.9 = normal BMI 25-29.9 = overweight BMI 30-39.9 = obesity BMI ≥40 = extreme obesity  Measure BMI routinely at each regular check-up.  Classifications: BMI 18.5-24.9 = normal BMI 25-29.9 = overweight BMI 30-39.9 = obesity BMI ≥40 = extreme obesity Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health.

20. Measuring Waist Circumference  Large waist circumference (WC) can identify some at increased risk over BMI alone  If BMI and other cardiometabolic risk factors are assessed, currently there is insufficient evidence to: –Substitute WC for BMI –Measure WC in addition to BMI  Large waist circumference (WC) can identify some at increased risk over BMI alone  If BMI and other cardiometabolic risk factors are assessed, currently there is insufficient evidence to: –Substitute WC for BMI –Measure WC in addition to BMI Klein, et al. Waist Circumference and Cardiometabolic Risk. Diabetes Care. 2007 0: dc07-9921v1-0.

21. Primary Metabolic Disturbance Primary Metabolic Disturbance Intermediate Vascular Disease Risk Factor Intravascular Pathology Intravascular Pathology Clinical Event Clinical Event Atherosclerosis Hypercoagulability Coronary arteries Carotid arteries Cerebral arteries Aorta Peripheral arteries Hypertension Dyslipidemia Hyperinsulinemia Hyperglycemia Inflammation Impaired Fibrinolysis Endothelial Dysfunction Insulin Resistance CVD Despres JP, et al. Abdominal obesity and metabolic syndrome. Nature. 2006;444:881-887. Multiple Factors Associated With Obesity Give Rise to Increased Risk of CVD Overnutrition CVD: Cardiovascular disease

22. Body Weight and CVD <100 110-129 130+ <110 110-129 130+ 0 0 100 150 200 250 300 50 125 200 267 105 121 128 *Metropolitan Relative Weight percent (percentage of desirable weight) *Metropolitan Relative Weight percent (percentage of desirable weight) Hubert HB et al. Circulation. 1983;67:968-977 Men Women Incidence of CVD per 1,000 Incidence of CVD per 1,000 n=56 n=75 n=30 n=191 n=199 n=78

23. Risk Management Overweight  Lifestyle modification Reduce caloric intake by 500-1000 kcal/day (depending on starting weight) Target 1-2 pound/week weight loss Increase physical activity Healthy diet Diabetes Prevention Program DASH diet  Lifestyle modification Reduce caloric intake by 500-1000 kcal/day (depending on starting weight) Target 1-2 pound/week weight loss Increase physical activity Healthy diet Diabetes Prevention Program DASH diet Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health. Diabetes Prevention Program (DPP) Diabetes Care 25:2165–2171, 2002. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, NIH Publication No. 04-5230, August 2004

24. Risk Management, cont. Overweight  Consider pharmacologic treatment BMI  30 with no related risk factors or diseases, or BMI  27 with related risk factors or diseases As part of a comprehensive weight loss program incl. diet & physical activity  Consider surgery BMI  40 or BMI  35 with comorbid conditions  Consider pharmacologic treatment BMI  30 with no related risk factors or diseases, or BMI  27 with related risk factors or diseases As part of a comprehensive weight loss program incl. diet & physical activity  Consider surgery BMI  40 or BMI  35 with comorbid conditions Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health. Diabetes Prevention Program (DPP) Diabetes Care 25:2165–2171, 2002

25. Abnormal Lipid Metabolism

26. Total Cholesterol Goals34 Desirable — Less than 200 mg/dL Borderline high risk — 200–239 mg/dL High risk — 240 mg/dL and over Desirable — Less than 200 mg/dL Borderline high risk — 200–239 mg/dL High risk — 240 mg/dL and over American Diabetes Association. Understanding Cardiometabolic Risk: Broadening Risk Assessment and Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center

27. Abnormal Lipid Metabolism Increased:  Triglycerides  VLDL  LDL and small dense LDL  ApoB Increased:  Triglycerides  VLDL  LDL and small dense LDL  ApoB Decreased:  HDL  Apo A-I Decreased:  HDL  Apo A-I American Diabetes Association. Diabetes Care. 2007;30:S4-41.

28. Major Risk Factors Affecting Lipid Goals36 Cigarette smoking Hypertension (≥140/90 mm Hg or on antihypertensive medication) Low HDL-C (<40 mg/dL) Family history of early heart disease Age (men ≥45 years; women ≥55 years) Cigarette smoking Hypertension (≥140/90 mm Hg or on antihypertensive medication) Low HDL-C (<40 mg/dL) Family history of early heart disease Age (men ≥45 years; women ≥55 years)

29.  Statins (also called HMG-CoA reductase inhibitors) work by increasing hepatic LDL-C removal from the blood.  Resins (also called bile acid sequestrants) bind to bile acids in the intestines and prevent their reabsorption, leading to increased hepatic LDL-C removal from the blood.  Cholesterol absorption inhibitors help lower LDL-C by reducing the amount of cholesterol absorbed in the intestines; increases LDL receptor activity.  Statins (also called HMG-CoA reductase inhibitors) work by increasing hepatic LDL-C removal from the blood.  Resins (also called bile acid sequestrants) bind to bile acids in the intestines and prevent their reabsorption, leading to increased hepatic LDL-C removal from the blood.  Cholesterol absorption inhibitors help lower LDL-C by reducing the amount of cholesterol absorbed in the intestines; increases LDL receptor activity.

30.  Fibrates (also called fibric acid derivatives) activate an enzyme that speeds the breakdown of triglyceriderich lipoproteins while also increasing HDL-C.  Niacin (also called nicotinic acid) reduces the liver’s ability to produce VLDL. When given at high doses, it can also increase HDL-C.  Fibrates (also called fibric acid derivatives) activate an enzyme that speeds the breakdown of triglyceriderich lipoproteins while also increasing HDL-C.  Niacin (also called nicotinic acid) reduces the liver’s ability to produce VLDL. When given at high doses, it can also increase HDL-C. American Diabetes Association. Understanding Cardiometabolic risk: Broadening risk Assessment and Management, Dyslipidemia Richard M Bergenstal, MD International Diabetes Center

31. Cholesterol Management  For patients >20 years of age, cholesterol should be checked every 5 years  Ordering a fasting lipid panel is preferred to gauge the patient’s total cholesterol, LDL-C, HDL-C and triglycerides  Treatment priorities  For patients >20 years of age, cholesterol should be checked every 5 years  Ordering a fasting lipid panel is preferred to gauge the patient’s total cholesterol, LDL-C, HDL-C and triglycerides  Treatment priorities

32. Cholesterol Management Category of riskLDL-C Goal 0-1 risk factor*< 160 mg/dL or lower Multiple (2+) risk factors*< 130 mg/dL or lower People with coronary heart disease or risk equivalent (e.g., diabetes) < 100 mg/dL or lower Known CAD and DM < 70 mg/dL or lower may be ideal LDL-C-lowering

33. Cholesterol Management  Improve glucose control if diabetes is present  Weight loss if overweight  Daily exercise  Smoking cessation  Dietary modifications including low saturated fat (fat intake less than 30% of total calories and saturated fat less than 7% of total calories), low cholesterol (no more than 200 mg daily) diet  Pharmacologic treatment frequently necessary  Risk factors include hypertension; HDL 45 years old; female > 55 years old; smoking.  Improve glucose control if diabetes is present  Weight loss if overweight  Daily exercise  Smoking cessation  Dietary modifications including low saturated fat (fat intake less than 30% of total calories and saturated fat less than 7% of total calories), low cholesterol (no more than 200 mg daily) diet  Pharmacologic treatment frequently necessary  Risk factors include hypertension; HDL 45 years old; female > 55 years old; smoking.

34. Screening for Dyslipidemia Persons without Diabetes  Test at least every 5 years, starting at age 20, including adults with low-risk values Persons with Diabetes  In adults, test at least annually  Lipoproteins: measure at after initial blood glucose control is achieved as hyperglycemia may alter results Preventing Cancer, Cardiovascular Disease, and Diabetes: A Common Agenda for The American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation. 2004;109:3244-3255. American Diabetes Association. Standards of Medical Care in Diabetes 2007. Available at: http://care.diabetesjournals.org/cgi/reprint/30/suppl_1/S4

35. Healthy Lipid Goals Targets for Patients Without DM or CVD 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); National Cholesterol Education Program, National Heart, Lung, and Blood Institute, National Institutes of Health. NIH Publication No. 01-3670, May 2001 Total<200 mg/dL LDL<70 mg/dL HDL>40 men mg/dL >50 women mg/dL Triglycerides< 150 mg/dL

36. Risk Management Abnormal Lipids  Lifestyle modification Increased physical activity Diet: reduced saturated fat, trans fat, and cholesterol Weight loss, if indicated  Lifestyle modification Increased physical activity Diet: reduced saturated fat, trans fat, and cholesterol Weight loss, if indicated American Diabetes Association. Diabetes Care. 2007;30:S4-41.

37.  Pharmacologic treatment: primary goal is LDL lowering Without overt CVD: If over 40, statin therapy recommended to achieve 30-40% LDL reduction With overt CVD: All patients should receive statin therapy to achieve 30-40% LDL reduction Lowering triglycerides and raising HDL with a fibrate is associated with fewer cardiovascular events in patients with clinical CVD, low HDL, and near-normal LDL  Pharmacologic treatment: primary goal is LDL lowering Without overt CVD: If over 40, statin therapy recommended to achieve 30-40% LDL reduction With overt CVD: All patients should receive statin therapy to achieve 30-40% LDL reduction Lowering triglycerides and raising HDL with a fibrate is associated with fewer cardiovascular events in patients with clinical CVD, low HDL, and near-normal LDL American Diabetes Association. Diabetes Care. 2007;30:S4-41. Risk Management Abnormal Lipids

38. Hypertension

39. Hypertension: Evaluation and Screening Persons without Diabetes  BP should be measured at each regular visit or at least once every 2 years if BP <120/80 mmHg  BP measured seated after 5 min rest in office Persons without Diabetes  BP should be measured at each regular visit or at least once every 2 years if BP <120/80 mmHg  BP measured seated after 5 min rest in office Persons with Diabetes  BP should be measured at each regular visit  BP measured seated after 5 min rest in office  Patients with ≥130 or ≥80 mmHg should have BP confirmed on a separate day Persons with Diabetes  BP should be measured at each regular visit  BP measured seated after 5 min rest in office  Patients with ≥130 or ≥80 mmHg should have BP confirmed on a separate day Preventing Cancer, Cardiovascular Disease, and Diabetes A Common Agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation. 2004;109:3244-3255. American Diabetes Association. Diabetes Care. 2007;30:S4-41.

40. Management of Hypertension Non-pharmacologic  DASH diet Dietary Approaches to Stop Hypertension High in whole grains, fruits, vegetables, and low-fat dairy Low in saturated and trans fat, cholesterol  Physical Activity  Weight loss, if applicable Non-pharmacologic  DASH diet Dietary Approaches to Stop Hypertension High in whole grains, fruits, vegetables, and low-fat dairy Low in saturated and trans fat, cholesterol  Physical Activity  Weight loss, if applicable The Dash Diet. http://dashdiet.org. American Diabetes Association. Diabetes Care. 2007;30:S4-41.

41. Management of Hypertension Pharmacologic  Drug therapy indicated if BP ≥140/ ≥90 mm Hg  Combination therapy often necessary  Treatment should include ACE or ARB  Thiazide diuretic may be added to reach goals  Monitor renal function and serum potassium Pharmacologic  Drug therapy indicated if BP ≥140/ ≥90 mm Hg  Combination therapy often necessary  Treatment should include ACE or ARB  Thiazide diuretic may be added to reach goals  Monitor renal function and serum potassium The Dash Diet. http://dashdiet.org. American Diabetes Association. Diabetes Care. 2007;30:S4-41.

42. Complications of Hypertension in Patients with Diabetes Microvascular  Renal disease  Autonomic neuropathy  Eye disease (glaucoma, retinopathy with potential blindness) Microvascular  Renal disease  Autonomic neuropathy  Eye disease (glaucoma, retinopathy with potential blindness) Macrovascular  Cardiac disease  Cerebrovascular disease  Reduced survival and recovery rates from stroke  Peripheral vascular disease Macrovascular  Cardiac disease  Cerebrovascular disease  Reduced survival and recovery rates from stroke  Peripheral vascular disease American Diabetes Association. Diabetes Care. 2007;30:S4-41..

43. Physical Inactivity

44.  35% of coronary heart disease deaths in the US can be attributed to an inactive lifestyle*  Consistent exercise can reduce CVD risk*  Exercise, combined with healthy diet and weight loss, is proven to prevent/delay onset of type 2 diabetes   35% of coronary heart disease deaths in the US can be attributed to an inactive lifestyle*  Consistent exercise can reduce CVD risk*  Exercise, combined with healthy diet and weight loss, is proven to prevent/delay onset of type 2 diabetes  * American Diabetes Association. Diabetes Care. 2007;30:S4-41.  Diabetes Prevention Program Diabetes Care 25:2165–2171, 2002. Physical Activity

45. Guidelines  Fit into daily routine  Aim for at least 150 minutes/week of moderate aerobic exercise  Start slowly and gradually build intensity  Wear a pedometer (10,000 steps)  Encourage patients to take stairs, park further away or walk to another bus stop, etc. Guidelines  Fit into daily routine  Aim for at least 150 minutes/week of moderate aerobic exercise  Start slowly and gradually build intensity  Wear a pedometer (10,000 steps)  Encourage patients to take stairs, park further away or walk to another bus stop, etc. American Diabetes Association. Diabetes Care. 2007;30:S4-41. Physical Activity

46. Benefits of Exercise  Increased insulin sensitivity  Improved lipid levels  Lower blood pressure  Weight control  Improved blood glucose control  Reduced risk of CVD  Prevent/delay onset of type 2 diabetes Benefits of Exercise  Increased insulin sensitivity  Improved lipid levels  Lower blood pressure  Weight control  Improved blood glucose control  Reduced risk of CVD  Prevent/delay onset of type 2 diabetes American Diabetes Association. Diabetes Care. 2007;30:S4-41. Physical Activity

47. Exercise Precautions Related to Complications of Diabetes  Peripheral neuropathy can cause loss of sensation in feet; educate about preventive care measures for foot protection  Pre-existing CVD can cause arrhythmias, myocardial ischemia, or infarction during exercise  In presence of PDR or severe NPDR, vigorous exercise or resistance training may be contraindicated because of risk of vitreous hemorrhage or retinal detachment  Peripheral neuropathy can cause loss of sensation in feet; educate about preventive care measures for foot protection  Pre-existing CVD can cause arrhythmias, myocardial ischemia, or infarction during exercise  In presence of PDR or severe NPDR, vigorous exercise or resistance training may be contraindicated because of risk of vitreous hemorrhage or retinal detachment American Diabetes Association. Diabetes Care. 2007;30:S4-41.

48. Smoking

49. Impact of Baseline Smoking on MI in Type 2 Diabetes: UKPDS R C Turner, H Millns, H A W Neil, I M Stratton, S E Manley, D R Matthews, and R R Holman. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom prospective diabetes study (UKPDS: 23) BMJ. 1998;316:823-828. Hazards Ratio (95% CI) Never Smoked1 Ex-Smoker1.08 (0.75 - 1.54) Current Smoker1.58 (1.11 - 2.25) Hazards Ratio (95% CI) Never Smoked1 Ex-Smoker1.08 (0.75 - 1.54) Current Smoker1.58 (1.11 - 2.25)

50. Smoking – Screening and Intervention  Obtain documentation of history of tobacco use  Ask whether smoker is willing to quit –If no, initiate brief, motivational discussion regarding: the need to stop using tobacco risks of continued use encouragement to quit, as well as support when ready –If yes, assess preference for and initiate either minimal, brief, or intensive cessation counseling.  Obtain documentation of history of tobacco use  Ask whether smoker is willing to quit –If no, initiate brief, motivational discussion regarding: the need to stop using tobacco risks of continued use encouragement to quit, as well as support when ready –If yes, assess preference for and initiate either minimal, brief, or intensive cessation counseling. American Diabetes Association. Diabetes Care. 2004;27:S27:S74-S75.

51. Provide Smoking Cessation Resources  Set a Plan  Offer counseling and referrals  Offer medication assistance  Offer combined pharmacologic and behavioral intervention  Set a Plan  Offer counseling and referrals  Offer medication assistance  Offer combined pharmacologic and behavioral intervention American Diabetes Association. Diabetes Care. 2004;27:S27:S74-S75.

52. Inflammation

53. Inflammation / Hypercoagulation  Proinflammatory/prothrombotic factors underlie cardiometabolic risk  Inflammation is a major component of atherogenesis and other cardiometabolic problems  Obesity is associated with inflammation  Proinflammatory/prothrombotic factors underlie cardiometabolic risk  Inflammation is a major component of atherogenesis and other cardiometabolic problems  Obesity is associated with inflammation Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340:115-126. Ballantyne CH, Nambi V. Markers of inflammation and their clinical significance. Atherosclerosis suppl 2005; 6: 21-9. McLaughlin T et al. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation. 2002;106:2908-2912.

54. Risk Management: Inflammation  High-sensitivity CRP tests may be used to further evaluate underlying risk Relative risk categories Low risk<1 mg/L Average risk1-3 mg/L High risk>3 mg/L  Aspirin and statins reduce CRP levels  Unclear whether CRP should be a treatment target  Reduce weight  High-sensitivity CRP tests may be used to further evaluate underlying risk Relative risk categories Low risk<1 mg/L Average risk1-3 mg/L High risk>3 mg/L  Aspirin and statins reduce CRP levels  Unclear whether CRP should be a treatment target  Reduce weight Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med.1999;340:115- 126. Ballantyne CH.

55. Insulin Resistance Insulin Resistance

56. Factors affecting insulin resistance Overweight/ fat distribution Age Genetic predisposition Activity level Medications Puberty Pregnancy Overweight/ fat distribution Age Genetic predisposition Activity level Medications Puberty Pregnancy

57. IFG and IGT Impaired Fasting Glucose (IFG): a condition in which the blood glucose level is between 100 mg/dL to 125mg/dL after an 8- to 12-hour fast. Impaired Glucose Tolerance (IGT): a condition in which the blood glucose level is between 140 and 199 mg/dL at 2 hours during an oral glucose tolerance test (OGTT). Impaired Fasting Glucose (IFG): a condition in which the blood glucose level is between 100 mg/dL to 125mg/dL after an 8- to 12-hour fast. Impaired Glucose Tolerance (IGT): a condition in which the blood glucose level is between 140 and 199 mg/dL at 2 hours during an oral glucose tolerance test (OGTT).

58. Interpreting Blood Glucose Levels Healthy BG FPG < 100 mg/dL Pre-diabetes FPG 100–125 mg/dL Diabetes FPG ≥126 mg/dL Healthy BG FPG < 100 mg/dL Pre-diabetes FPG 100–125 mg/dL Diabetes FPG ≥126 mg/dL

59. Criteria for testing for type 2 diabetes in asymptomatic children50  Overweight (BMI > 85th percentile for age and sex, weight for height > 85th percentile, or weight  >120 percent of ideal for height) Plus any two of the following: Family history Race/ethnicity Signs of insulin resistance or conditions associated with insulin resistance Maternal history of diabetes or GDM  Overweight (BMI > 85th percentile for age and sex, weight for height > 85th percentile, or weight  >120 percent of ideal for height) Plus any two of the following: Family history Race/ethnicity Signs of insulin resistance or conditions associated with insulin resistance Maternal history of diabetes or GDM

60. Criteria for testing for diabetes in asymptomatic adult individuals50 1.Testing should be considered in all overweight adults (BMI ≥25 kg/m2*) and have additional risk factors:  Physical inactivity  First-degree relative with diabetes  Members of a high-risk ethnic population  Women delivering baby weighing >9 lb or were diagnosed with GDM  Hypertension (≥140/90 mmHg) 1.Testing should be considered in all overweight adults (BMI ≥25 kg/m2*) and have additional risk factors:  Physical inactivity  First-degree relative with diabetes  Members of a high-risk ethnic population  Women delivering baby weighing >9 lb or were diagnosed with GDM  Hypertension (≥140/90 mmHg) Continued

61. Criteria for testing for diabetes in asymptomatic adult individuals50  HDL cholesterol level 250 mg/dl (2.82 mmol/l)  Women with polycystic ovarian syndrome (PCOS)  IGT or IFG on previous testing  Other clinical conditions associated with insulin resistance (e.g., severe obesity and acanthosis nigricans)  History of CVD  HDL cholesterol level 250 mg/dl (2.82 mmol/l)  Women with polycystic ovarian syndrome (PCOS)  IGT or IFG on previous testing  Other clinical conditions associated with insulin resistance (e.g., severe obesity and acanthosis nigricans)  History of CVD

62. Criteria for testing for diabetes in asymptomatic adult individuals50 2. In the absence of the above criteria, testing for pre- diabetes and diabetes should begin at age 45 years 3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status. *At-risk BMI may be lower in some ethnic groups. 2. In the absence of the above criteria, testing for pre- diabetes and diabetes should begin at age 45 years 3. If results are normal, testing should be repeated at least at 3-year intervals, with consideration of more frequent testing depending on initial results and risk status. *At-risk BMI may be lower in some ethnic groups.

63. Pre-Diabetes and Diabetes Prevention

64. Pre-Diabetes  Pre-diabetes is an important risk factor for future diabetes and cardiovascular disease  Recent studies have shown that lifestyle modification can reduce the rate of progression from pre-diabetes to diabetes  Pre-diabetes is an important risk factor for future diabetes and cardiovascular disease  Recent studies have shown that lifestyle modification can reduce the rate of progression from pre-diabetes to diabetes American Diabetes Association, Diabetes Care. 2007:30:S4-41..

65. Glucose Tolerance Categories Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2004; Supplement 1 Fasting Plasma Glucose Fasting Plasma Glucose 126 mg/dL Normal 2-hour Plasma Glucose On OGTT 200 mg/dL 140 mg/dL Diabetes Mellitus Impaired Glucose Tolerance Normal Diabetes Mellitus Any abnormality must be repeated and confirmed on a separate day* * One can also make the diagnosis of diabetes based on unequivocal symptoms and a random glucose >200 mg/dL “Pre-Diabetes” 100 mg/dL Impaired Fasting Glucose

66. ADA Consensus Conference on IFG and IGT: Implications for Diabetes Care October 16-18, 2006 Results:  Treat IFG and IGT with aggressive lifestyle modification  For certain patients with both IFG and IGT consider metformin Results:  Treat IFG and IGT with aggressive lifestyle modification  For certain patients with both IFG and IGT consider metformin Nathan D, et al. Impaired Fasting Glucose and Impaired Glucose Tolerance: Implications for Care. Diabetes Care. 2007 30: 753-759.

67. Cumulative Incidence of Diabetes (%) Years 40 30 20 10 0 0 0 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Placebo Metformin Lifestyle Knowler WC, et al. NEJM. 2002;346:393-403.

68. Behavior Medication Results of Recent Randomized Trials 58% 31% 25% 55% 45% 61%/NS 31% 25% 55% 45% 61%/NS Metformin Acarbose Troglitazone Orlistat Rosiglitazone/Ramipril Metformin Acarbose Troglitazone Orlistat Rosiglitazone/Ramipril IGT Prior GDM IGT Prior GDM IGT US DPP STOP- NIDDM TRIPOD XENDOS DREAM US DPP STOP- NIDDM TRIPOD XENDOS DREAM Lifestyle IGT Finnish DPS US DPP Finnish DPS US DPP Relative Risk Reduction Intervention Subjects Study

69. <180 mg/dL Postprandial plasma glucose 90-130 mg/dL Preprandial glucose <7.0% A1C* † * For non-pregnant individuals † As close to normal (<6%) as possible without significant hypoglycemia American Diabetes Association. Diabetes Care. 2007:30:S4-41.. Goals for Glycemic Control

70.  Fasting plasma glucose at least every 3 yrs starting at age 45  Consider at younger age, or more frequently, if patient is overweight and has one or more of the following risk factors (or two if not overweight): Family history of diabetes Overweight (BMI 25 kg/m 2 ) Habitual physical inactivity (continued)  Fasting plasma glucose at least every 3 yrs starting at age 45  Consider at younger age, or more frequently, if patient is overweight and has one or more of the following risk factors (or two if not overweight): Family history of diabetes Overweight (BMI 25 kg/m 2 ) Habitual physical inactivity (continued) American Diabetes Association. Diabetes Care. 2007:30:S4-41.. Screening For Diabetes

71. Additional risk factors: Race/ethnicity (e.g., African-Americans, Hispanic- Americans, Native Americans, Asian-Americans, and Pacific Islanders) Previously identified IFG or IGT Hypertension (140/90 mmHg in adults) HDL cholesterol (35 mg/dl [0.90 mmol/l] and/or a triglyceride level 250 mg/dl [2.82 mmol/l]) History of GDM or delivering baby weighing >9 lbs Polycystic ovary syndrome (PCOS) Additional risk factors: Race/ethnicity (e.g., African-Americans, Hispanic- Americans, Native Americans, Asian-Americans, and Pacific Islanders) Previously identified IFG or IGT Hypertension (140/90 mmHg in adults) HDL cholesterol (35 mg/dl [0.90 mmol/l] and/or a triglyceride level 250 mg/dl [2.82 mmol/l]) History of GDM or delivering baby weighing >9 lbs Polycystic ovary syndrome (PCOS) American Diabetes Association. Diabetes Care. 2007:30:S4-41.. Screening For Diabetes

72.  Age47  Race/ethnicityAfrican American  GenderMale  Family historyHTN and diabetes  Overweight/obesityBMI = 29  Abnormal lipid metab TC = 210  HypertensionBP = 146/86  Smoking1 pack per day  Physical InactivitySedentary  Unhealthy dietFast food diet  Age47  Race/ethnicityAfrican American  GenderMale  Family historyHTN and diabetes  Overweight/obesityBMI = 29  Abnormal lipid metab TC = 210  HypertensionBP = 146/86  Smoking1 pack per day  Physical InactivitySedentary  Unhealthy dietFast food diet

73.  Identify at-risk patients by evaluating a spectrum of predisposing risk factors  The existence of any one risk factor is an alert to evaluate patient for others  Integrate evidence-based risk management strategies to target modifiable risk factors  Identify at-risk patients by evaluating a spectrum of predisposing risk factors  The existence of any one risk factor is an alert to evaluate patient for others  Integrate evidence-based risk management strategies to target modifiable risk factors Kahn, et al. The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28 (9)2289-2304.

74. What Should We Do?