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1 The Epidemic of Obesity, Diabetes, and the Metabolic Syndrome Holly Novak, MD, FACC Obesity Trends* Among US Adults BRFSS, 1985 BRFSS=Behavioral Risk Factor Surveillance System. *Body Mass Index (BMI) 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1986 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25.
2 Obesity Trends* Among US Adults BRFSS, 1987 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1988 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1989 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25.
3 Obesity Trends* Among US Adults BRFSS, 199 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1991 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Adapted with permission from Mokdad AH et al. JAMA. 21;286: Obesity Trends* Among US Adults BRFSS, 1992 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25..
4 Obesity Trends* Among US Adults BRFSS, 1993 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1994 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1995 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25.
5 Obesity Trends* Among US Adults BRFSS, 1996 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1997 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 1998 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25.
6 Obesity Trends* Among US Adults BRFSS, 1999 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Obesity Trends* Among US Adults BRFSS, 2 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Adapted with permission from Mokdad AH et al. JAMA. 21;286: Obesity Trends* Among US Adults BRFSS, 21 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25.
7 Obesity Trends* Among US Adults BRFSS, 22 *BMI 3, or 3 lbs overweight for 5 4 woman. Accessed August 9, 25. Diabetes Can Appear Right Under Your Nose Midwest Heart Foundation.
8 Diabetes Mellitus: Prevalence in the US Diagnosed diabetes (in millions) x increase Year Adapted with permission from Diabetes Overview. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; NIDDK publication NIH Kenny SJ et al. In: Diabetes in America. 2nd ed. Bethesda, Md: National Diabetes Data Group, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; 1995: NIH publication No Midwest Heart Foundation. Diabetes: Atherosclerotic Complications Responsible for 8% of diabetic mortality 75% cases due to coronary artery disease (CAD) Results in >75% of all hospitalizations for diabetic complications 5% of type 2 diabetes patients have preexisting CAD 1/3 of patients presenting with myocardial infarction have undiagnosed diabetes mellitus Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28C. Midwest Heart Foundation. Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study) 7-year incidence rate of MI P<.1 P<.1 45.% 18.8% 2.2% 3.5% No DM, No MI No DM, MI DM, No MI DM, MI Nondiabetic Diabetic CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus. Haffner SM et al. N Engl J Med. 1998;339:
9 Post-MI Survival (5 Year): Diabetic Patients vs Nondiabetic Patients Survival (%) Men Women No DM DM Time from MI (months) Adapted with permission from Sprafka JM et al. Diabetes Care. 1991;14: Year Mortality in Diabetic and Nondiabetic Subjects After a First MI Days 1 year Hospitalization 28 days Out of hospital Mortality (%) DSW1 Diabetes No diabetes Diabetes No diabetes Men Women Miettinen H, et al. Diabetes Care. 1998;21: Midwest Heart Foundation. Age-Adjusted CVD Death Rates (MRFIT) Age-adjusted CVD death rate per 1, person years Nondiabetic Diabetic None Only 1 Only 2 All 3 No. of risk factors (total cholesterol, HTN, smoking) CVD=cardiovascular disease; MRFIT=Multiple Risk Factor Intervention Trial. Adapted with permission from Stamler J et al. Diabetes Care. 1993;16:
10 Slide 26 DSW1 What is Midwest Heart Foundation. If it's a reference, it seems incomplete. wordsetc@chesco.com, 8/11/25
11 Proteinuria Predicts Stroke and CHD Events in Type 2 Diabetes A: U-Prot <15 mg/l B: U-Prot 15 3 mg/l C: U-Prot >3 mg/l Survival curves for CV mortality Overall: P<.1 A B C Incidence (%) P< Months Stroke CHD Events U-Prot=Urinary protein concentration. Adapted with permission from Miettinen H et al. Stroke. 1996;27: LDL-C as a Predictor of CAD in Diabetic Patients 2 Hazard ratio LDL-C quartile mean LDL=low-density lipoprotein cholesterol; CAD=coronary artery disease. Adapted with permission from Howard BV et al. Arterioscler Thromb Vasc Biol. 2;2: HOT Trial: Effect of BP Control on CV Event Rate 3 Diabetic patients 25 Nondiabetic patients Major CV events per 1 patient-years <9 <85 <8 <9 <85 <8 Diastolic BP goal BP=blood pressure. Hansson L et al. Lancet. 1998;351:
12 The Effect of ASA on CV Risk in Patients With Diabetes Events per 1 patient-yrs % Reduction P<.2 Placebo ASA ASA=aspirin. N=452. BMJ. 1994;38: Ticking Clock Hypothesis Macrovascular Disease Microvascular Disease NGT IGT Hyperglycemia Haffner SM et al. JAMA. 199;263: Nurses Health Study: Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetes Relative risk Nondiabetic throughout the study Prior to diagnosis of diabetes After diagnosis of diabetes Diabetic at baseline Adapted with permission from Hu FB et al. Diabetes Care. 22;25:
13 Clinical Identification of the Metabolic Syndrome (NCEP)* 1 Abdominal obesity (waist circumference) Men >4 in (>12 cm) Women >35 in (>88 cm) Triglycerides 15 mg/dl High-density lipoprotein (HDL) Men <4 mg/dl Women <5 mg/dl Blood pressure 13/ 85 mm Hg Fasting glucose 1 mg/dl 2 *Diagnosis is established when 3 of these risk factors are present. 1. National Institutes of Health. Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive Summary. May 21. NIH Publication No Grundy SM et al. Circulation. 24;19: Metabolic Syndrome and Mortality All-Cause Mortality Cumulative hazard (%) Metabolic Syndrome Yes No RR % vs 92% Follow-up (y) Kuopio Ischaemic Heart Disease Risk Factor Study. Adapted with permission from Lakka H-M et al. JAMA. 22;288:279. Hazard Ratio* for CVD Mortality with the Metabolic Syndrome (Orange=Women; Blue=Men) No MetSyn MetSyn No Diabetes (.72, 6.) 1.96 (.99, 3.88) Diabetes 3.53 (.75, 16.7) 2.34 (.7, 7.82) 8.19 (3.51, 19.1) 3.9 (1.49, 6.43) San Antonio Heart Study. *Adjusted for age and ethnicity. 1.=no cardiovascular disease at baseline; MetSyn=metabolic syndrome (as defined by NCEP). Hunt KJ, et al. Circulation. 24;11:
14 Incident Diabetes After Stratification by IGT and the Metabolic Syndrome* P< P=.18 P<.1 IGT IGT NGT No Yes MetS *As defined by NCEP criteria. Adapted with permission from Lorenzo C et al. Diabetes Care. 23;26: Approaches to Therapy: Metabolic Syndrome/Diabetes The Basis for the Project Behavioral therapy Weight loss and increased physical activity Treat existing risk factors For nondiabetic patients with MetS, management should be intensified over and above global risk, but not to the level of a CHD risk equivalent Use of insulin-sensitizing therapies in nondiabetic patients with MetS No clinical trials support use in patients with MetS alone Some clinical trial support use for MetS patients with IGT DPP, STOP-NIDDM, TRIPOD OGTT=oral glucose tolerance test. Chiasson JL, et al, for the STOP-NIDDM Trial Research Group. Diabetologia. 24;47: Orchard TJ, et al, for the Diabetes Prevention Program Research Group. Ann Intern Med. 25;142: The Epidemic Key Takeaway Points The prevalence of obesity, metabolic syndrome, and diabetes continues to increase Diabetes is a major US health problem associated with atherosclerotic disease Renal function, LDL-C levels, and blood pressure are all predictive of CV risk in diabetic patients An increased risk of macrovascular complications precedes the development of hyperglycemia The metabolic syndrome increases risk for CVD mortality and is an independent predictor of diabetes LDL-C=low-density lipoprotein cholesterol.
15 Diabetes Education Initiative: A Collaboration for Intervention The American College of Cardiology Foundation in Collaboration With the Midwest Heart Foundation Diabetes and Cardiovascular Health: Reducing the Risk Holly Novak, MD, FACC Statins Should every patient get one?
16 4S Study Lowering Total Cholesterol Reduces Mortality in Patients With and Without Diabetes % risk reduction 24.7% Simvastatin Placebo Mortality (%) % 29 % risk reduction 7.9% 1.9% 5 With diabetes Without diabetes Pyorala K et al. Diabetes Care. 1997;2: Midwest Heart Foundation. Heart Protection Study Primary Prevention of CV Events in Patients With Diabetes and Without High LDL-C Diabetic patients in the Heart Protection Study 5963 High-risk patients >4 years Mean baseline LDL-C = 124 mg/dl Simvastatin 4 mg vs placebo 5-Year follow-up 22% Reduction in major CV events (P<.1) 27% reduction in 2462 patients with LDL-C <116 mg/dl 33% reduction in 2912 patients without CVD DSW3 HPS Collaborative Group. Lancet. 23;361:
17 Slide 44 DSW3 Is red font deliberate? 8/11/25
18 Statin Therapy Number Needed to Treat* Diabetic patients NNT Without CAD 14 With CAD 4 CAD=coronary artery disease. *Based on the HPS and 4S studies. HPS Collaborative Group. Lancet. 23;361: Pyorala K, et al. Diabetes Care. 1997;2: Primary Prevention of CV Events in Patients With Diabetes and Without High LDL-C Diabetic patients in CARDS Diabetic patients without CVD Mean baseline LDL-C = 116 mg/dl At least 1 additional CV risk factor Atorvastatin 1 mg vs placebo, 3.9-year follow-up 37% Decrease in major CV events (P=.1) ASCOT LLA Diabetic patients with no CHD Mean baseline LDL-C = 128 mg/dl At least 2 additional CV risk factors Atorvastatin 1 mg vs placebo, 3.3-year follow-up 23% Decrease in major CV events or procedures (P=.36) In diabetics without CAD, data support statin therapy regardless of LDL-C level CARDS=Collaborative Atorvastatin Diabetes Study. ASCOT-LLA=Anglo-Scandinavian Cardiac Outcomes Trial Lipid-Lowering Arm. 1. Colhoun HM et al. Lancet. 24;364: Sever PS et al. Diabetes Care. 25;28: TNT: Low LDL-C Benefits Patients With Diabetes and CHD Post hoc analysis: 151 subjects with CHD Mean baseline LDL-C <1 mg/dl Atorvastatin 8 mg vs atorvastatin 1 mg, 4.9 year follow-up Atorvastatin 8 mg: LDL=77 mg/dl Atorvastatin 1 mg: LDL=99 mg/dl 25% reduction in risk of major CV events with atorvastatin 8 mg, compared to the 1-mg group (P=.26) Lowering LDL levels below suggested guidelines continues to benefit high-risk patients Shepherd J on behalf of the TNT Diabetes Subcommittee and the TNT Steering Committee. Presented at the Annual Meeting of the American Diabetes Association; June 13, 25; San Diego, California. Webcast available at Accessed August 1, 25.
19 ACEIs/ARBs Should every patient get one? ACE Inhibitors Reduce CV and Renal Risk in Patients With Diabetes UKPDS Tight blood pressure control reduced micro- and macrovascular risk UKPDS, FACET, CAPPP, ABCD meta-analysis ACEIs reduce risk of CV and renal disease more effectively than other antihypertensive agents MICRO-HOPE ACEIs reduce CV risk in patients who are normotensive at baseline ACEI=angiotensin converting enzyme inhibitors UKPDS=UK Prospective Diabetes Study; FACET=Fosinopril vs Amlodipine Cardiovascular Events CAPPP=Captopril Prevention Project;ABCD=Appropriate BP Control in Diabetes. MICROHOPE = Microalbuminuria, Cardiovascular Renal Outcomes: Heart Outcomes Prevention Evaluation. UK Prospective Diabetes Study Group. BMJ. 1998;317:73-713; UK Prospective Diabetes Study Group. BMJ. 1998;317:713-72;Pahor M, et al. Diabetes Care. 2;23: ; HOPE Study Investigators. Lancet. 2;355:
20 Effect of Intensive Multiple Risk Factor Management on CV Endpoints in Patients with Type 2 Diabetes and Microalbuminuria 6 N=16; follow-up=7.8 years Primary composite end point* (%) 4 2 Conventional therapy 2% Absolute Risk Reduction Aggressive treatment of : Intensive therapy Microalbuminuria with ACEIs, ARBs, or combination Hypertension Hyperglycemia Dyslipidemia Secondary prevention of CVD Months of follow-up Primary composite end point: conventional therapy (44%) and intensive therapy (24%). * Death from CV causes, nonfatal MI, CABG, PCI, nonfatal stroke, amputation, or surgery for peripheral atherosclerotic artery disease. Behavior modification and pharmacologic therapy. Adapted with permission from Gaede P et al. N Engl J Med. 23;348: Steno 2: Key Takeaway Compared to conventional treatment, aggressive management of risk factors results in significant decreases in CV risk Treat to Goal!
21 Scientific Statements: Diabetes, CV Disease, and Hypertension AHA Scientific Statement on Diabetes and CVD BP goal in hypertension: <13/85 mm Hg ACE inhibitors favored as antihypertensive agents ACE inhibitors probably slow progression of nephropathy, even in normotensive patients JNC VII Report on Diabetic Hypertension Combinations of 2 or more drugs to achieve BP goal (13/8 mm Hg) Thiazide-diuretics, β-blockers, ACEIs, ARBs, CCBs reduce CVD and stroke incidence ACEIs/ARBs reduce progression of diabetic nephropathy and reduce albuminuria ARBS reduce progression of macroalbuminuria Grundy SM, et al. Circulation. 1999;1: Chobanian AV, et al. JAMA. 23;289: ADA 22 Clinical Practice Guidelines Treatment of hypertension in patients with diabetes Initial drug therapy: ACEI, ARBs, β-blockers, diuretics If >55 yrs, without hypertension but with another CV risk factor, consider an ACE inhibitor Treat to target of <13 mm Hg systolic With diabetic nephropathy Hypertensive type 2 diabetic patients ARBs are the drugs of choice Type 1 diabetic patients ACE inhibitors are preferred Combination of ACEI and ARBs will decrease albuminuria more than either agent alone If ACEI or ARBs are used, monitor serum potassium for development of hyperkalemia American Diabetes Association. Diabetes Care. 22;25(suppl 1):S71-S73, S85-S89 Recommendation ACEIs and ARBs in DM Recommend the use of an ACEI and/or ARB in all type 2 DM patients with at least 1 additional CV risk factor, and/or microalbuminuria Consider the use of ACEI and/or ARB in all other patients with type 2 DM
22 β-blockers Should every patient get one? Does it matter which one you use? β-blockers in Diabetes: UKPDS UKPDS (1998) Captopril vs atenolol 9-year follow-up Similar decreases in BP Similar decreases in diabetic complications UKPDS=UK Prospective Diabetes Study. UK Prospective Diabetes Study Group. BMJ. 1998;317: β-blockers in Diabetes: Gemini Study Design Carvedilol vs metoprolol 1235 diabetic patients with hypertension and receiving RAS blockers 35 week follow up Results* Similar decreases in BP Carvedilol had no effect on A1C; metoprolol A1C Carvedilol albumin/creatinine ratio, compared to metoprolol (16%, P=.3) * At 5 months.gemini=glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives. Bakris GL, et al. JAMA. 24;292:
23 Effect of Antihypertensive Medication on Renal Function in Hypertensive Patients With Type 2 Diabetes 52 Patients with NIDDM, nephropathy, and hypertension Annual decline in creatinine clearance (ml/min/1.73m 2 ) with each medication ACE inhibitor 1. Non-DCCP 1.4 β-blocker 3.5* *P=.1 vs ACE I; P=.4 vs Non-DCCP. Bakris GL, et al. Kidney Int. 1996;5: Recommendation β-blockers in DM Recommend the use of β-blocker in all type 2 DM patients with heart failure, CAD and/or history of MI Consider the use of β-blocker in all other patients with type 2 DM Remember the ABCs for Diabetes Care A aspirin/a1c (goal 6.5%) B blood pressure control (goal <13/8 ) C cholesterol (LDL <1, non-hdl <13) D diet E exercise Treat to Goal! LDL=low density lipoprotein; HDL=high density lipoprotein.
24 Diabetes and Heart Failure Epidemiology of Diabetic Heart Failure Framingham Study (risk of HF in diabetic patients) 2x diabetic males 5x diabetic females 4x young diabetic males 8x young diabetic females US HMO prevalence study With diabetes, HF developed at a rate of 3.3% per year Each 1% elevation in hemoglobin A1C leads to a 15% increase in frequency of HF HF=heart failure. Kannel WB et al. JAMA. 1979;241: Nichols GA. Diabetologia. 2;43(suppl A2):7. Chue CU et al. Circulation. 1998;98(suppl 1):721. Framingham Heart Study 3-Year Follow-up of CVD Events in Patients With Diabetes (Ages 35 64) 1 8 Men Women Risk ratio Total CVD CHD Cardiac Intermittent Stroke failure claudication P<.1 for all values, except stroke (P<.5). Wilson PWF, Kannel WB. In: Ruderman N et al, eds. Hyperglycemia, Diabetes and Vascular Disease. New York, NY: Oxford University Press; ( Figure 2.5 from HYPERGLYCEMIA, DIABETES AND VASCULAR DISEASE, edited by Neil Ruderman et al, copyright 1992 by American Physiological Society. Used by permission of Oxford University Press, Inc.)
25 Insulin Resistance in CHF Fasting insulin (pmol/l) % * Insulin sensitivity (1-5 min/pmol/l) 6 3 7% Normal HF *P=.1; P=.7. Swan JW et al. Eur Heart J. 1994;15: Therapies Demonstrated to Reduce Mortality in HF ACEI (ARB) β-blockers Aldosterone antagonists Hydralazine-isosorbide dinitrate ICD LVEF 35, Class I, II, or III Cardiac resynchronization LVEF 35%, QRS 13 ms, Class III or IV* *By NY Heart Association criteria. ACEI=angiotensin converting enzyme inhibitor; ARB=angiotensin receptor blocker; ICD=implantable cardioverter defibrillator; LVEF=left ventricular ejection fraction. 1. The CONSENSUS Trial Study Group. N Engl J Med. 1987;316: Packer M et al. N Engl J Med. 1996;334: Pitt B et al. N Engl J Med. 1999;341: Moss A et al. N Engl J Med. 1996;335: Abraham WT et al. N Engl J Med. 22;346: Aldosterone Blockade in HF Probability of survival (%) RALES: Randomized Aldactone Evaluation Study Follow-up (months) Spironolactone Placebo RR.7 (.6.82) P<.1 NYHA=New York Heart Association patients NYHA II, III, and IV, average age 65 and LVEF.35, on ACEI, loop diuretic, ± digoxin randomized to spironolactone 25 mg PO qd vs placebo. Adapted with permission from Pitt B et al. N Engl J Med. 1999;341:
26 Aldosterone Blockade With Eplerenone Reduces Mortality Post-MI in Diabetes and Nondiabetic Patients CV mortality or CV hospitalization No DM Diabetes Heterogeneity P= Eplerenone better Placebo better MI=myocardial infarction; CV=cardiovascular; DM=diabetes mellitus. N=6632, 32% diabetic patients. Pitt B et al. N Engl J Med. 23;348: Reprinted with permission. 23 Massachusetts Medical Society. Conclusions Diabetic patients are at elevated risk for HF Combined neurohormonal blockade with the use of ACEI, aldosterone antagonists, and β-blockers is essential in the treatment of the type 2 diabetic patient with HF β-blockers and ACEI are useful in type 2 diabetic patients across the CVD continuum: before a CV event, for secondary prevention, and as soon as possible in HF Simple Steps to Reduce CV Events in Patients With Type 2 Diabetes ASA in all patients Statin in all patients ACE/ARB in all patients with additional risk factor; consider in all patients β-blocker in all patients with CAD/CHF or history of MI; consider in all patients Diet and exercise therapy Encourage smoking cessation Glucose management for small-vessel disease
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