Presentation on theme: "Reducing Cardiovascular Risk in Patients With Diabetes"— Presentation transcript:
1Reducing Cardiovascular Risk in Patients With Diabetes Robert J Bulgarelli DO FACC CMADirector Integrative Cardiology - MLHSCMO – the Habit Change CompanyWe would like to thank GlaxoSmithKline for sponsoring this. In regards to the CME credit that is being offered, I do need to let you know that the faculty have been asked to disclose any conflicts, use generic names whenever possible, and disclose if they’ll be talking about a product outside its labeling. So, let’s begin.
3CVD Deaths: 1979–1998 520 500 480 460 440 420 NCEP I NCEP II NCEP III Deaths (in thousands)440420NCEP INCEP IINCEP III400And one thing I think we should keep in mind as we’re thinking about approaching this. Despite our war on cholesterol, despite the national guidelines calling for aggressive detection and treatment of hyperlipidemia; if we look at the impact we’ve actually had on cardiovascular morbidity and mortality in this country age adjusted, since the release and application of these national guidelines, we see here in men no fall in cardiac mortality and actually a rise in women. And certainly when we look at what is behind this, we see the growing incidence of metabolic syndrome, diabetes accounting for much of this increased or failure to see a reduction in cardiovascular morbidity and mortality despite our guidelines calling for the application of pharmacologic approaches to control risk factors. It’s very important to keep that in mind as we go forward.7981838587899193959798YearsMenWomenUnited States: 1979–1998 mortality. American Heart Association Heart and Stroke Statistical Update
5Diagnosis Metabolic Syndrome 34% of U.S. adults 3 or more of the followingHypertension > 130/85Waist > 40” men, >35” womenHDL < 40 for men, < 50 in womenTriglycerides > 150Fasting glucose > 110So you might think that this is the boring part, but in fact, I think this is the interesting part of the metabolic syndrome. And it is my opinion that the metabolic syndrome is the most important medical problem facing our society today for two reasons. Number one, it’s so prevalent, as we’ll talk about, and number two, the pathophysiologic manifestations of it are so broad and they really impact upon most of the diseases that kill us.Like I tell my patients that, you know, these days everybody reads the paper and they get paranoid about, you know, E.coli or dying in a plane crash or any number of bizarre and, you know, dramatic deaths. But, you know, the chances of those kinds of things happening are less than 1%, even car crashes are low.On the other hand, cardiovascular disease kills half of us, half of us in this room. Even, as Greg just pointed out, even with all we know about heart disease and how to prevent it and LDL cholesterol, you’d think that we have the answer to it. We don’t. Half of us still die from this disease. It’s endemic in our society, atherosclerosis. So clearly, it’s a major problem, yet clearly, we’re not addressing the underlying problem and the underlying problem is, for most people, for most of our society is the metabolic syndrome.There’s been a breakthrough in the metabolic syndrome, recently, and that is we’ve finally figured out what to call it. There have been, you know, a bunch of names for it for a lot of years and it’s fun to now have a name that we can all settle on, that’s the metabolic syndrome as described by the National Cholesterol Education Program about a year ago and you should memorize this. It’s three or more of the following, hypertension, that is blood pressures above 130 over 85. That’s a pretty low bar for the diagnosis of hypertension. Waist size, 40 inches in men and 35 in women and we might say that’s actually a pretty liberal criteria because in South Asians, people from India, for example, or a lot of other people, males in particular, can have the metabolic syndrome with excess abdominal obesity with a waist size a lot less than 40 inches. HDL of less than 40 for men and less than 50 for women, triglycerides over 150 and fasting glucose above 110, three or more of those.
6Cardiovascular Mortality p < 0.001Diabetes Carelarge population with / without the metabolic syndromesix-fold higher CV mortality in the people that had the metabolic syndrome.Diabetes Care 2001;24:683
7Obesity Metabolic Syndrome (Met S) Insulin resistance / Obesity / HTN / DyslipidemiaHigh association with development of DM Type II and CAD11 year prospective study of Finnish men without CAD or DM but who met NCEP and or WHO criteria for Metabolic Syndrome3.6X CHD Mortality3.2X CVD Mortality2.3X All Cause MortalityJAMA Dec 4, 2002 Vol. 288 No. 21
8Patterns of Body Fat Distribution AbdominalLower body(android)(gynoid)female pattern - gynecoid obesity male pattern - android obesity.dramatically different effects on the metabolic syndrome
9(*BMI 30, or about 30 lbs. overweight for 5’4” person) Obesity TrendsAmong U.S. Adults(*BMI 30, or about 30 lbs. overweight for 5’4” person)199019982007No Data <10% %–14% %–19% %–24% %–29% ≥30%
10(*BMI 30, or about 30 lbs. overweight for 5’4” person) Obesity TrendsAmong U.S. Adults(*BMI 30, or about 30 lbs. overweight for 5’4” person)199010 States had a prevalence of obesity less than 10%0 States had prevalence equal to or greater than 15%.19980 States had prevalence less than 10%7 States had a prevalence of obesity between 20-24%0 States had prevalence equal to or greater than 25%.20071 State (Colorado) had a prevalence less than 20%30 States had a prevalence equal to or greater than 25%3 States (Alabama, Mississippi and Tennessee) had a prevalence of obesity equal to or greater than 30%.
11Type 2 DM in Children and Adolescents Recent TrendsType 2 DM in Children and AdolescentsObesity, low level of physical activity, as well as exposure to diabetes in utero, may be major contributorsGenerally between 10 and 19 years old, obese, have a strong family history for type 2 diabetes, and have insulin resistance and have poor glycemic control (A1C = 10% - 12%).CDC estimates that among new cases of childhood diabetes, the proportion of those with type 2 diabetes ranges between 8 percent and 43 percent.
12Diet, Lifestyle, and Risk of Type 2 Diabetes Mellitus in Women Nurses’ Health Study (84,941) female nurses followed for 18 years3300 new cases of type 2 diabetes mellitusLack of exercise, poor diet also major risk factorsBMI most important risk factorBMI > 35 RRBMI RRU.S Nurses’ Health Study that showed the power of obesity.39-fold increased risk of Type 2 diabetes in people who had a BMI above 35 and a relative risk of 39, huge.20 million Type 2 diabetes in American today, 19 million are obeseHu et al. NEJM 2001;345:790
13Prevalence CAD Risk Factors in Type 1 vs. Type Dyslipidemia Hypertriglyceridemia Low HDL Small, dense LDL Increased apo BHypertensionHyperinsulinemia/insulin resistanceCentral obesityFamily history of atherosclerosisCigarette smoking+–+++–Prevalence of Cardiovascular Risk Factors in Diabetic Subjects Relative to NondiabeticsCompared with nondiabetics, patients with type I diabetes tend to have more hypertension and more hypertriglyceridemia but they do not have many of the disorders that are characteristic of patients with type 2 diabetes, such as low HDL cholesterol concentration, small dense LDL particles, increased apolipoprotein (apo) B concentration, and central obesity. Type 2 diabetics have more multiple metabolic abnormalities. While CHD rate is increased in both types of diabetes, the reason for the increase with type 1 diabetes is not clear.Reference:Chait A, Bierman EL. Pathogenesis of macrovascular disease in diabetes. In: Kahn CR, Weir GC, eds. Joslin's Diabetes Mellitus. 13th ed. Philadelphia: Lea & Febiger, 1994:+ = moderately increased compared with nondiabetic population++ = markedly increased compared with nondiabetic population– = not different compared with nondiabetic populationAdapted from Chait A, Bierman EL. In: Joslin’s Diabetes Mellitus. Philadelphia: Lea & Febiger, 1994:
14Risk Factors for IHD* Odds Ratio P Elevated fasting insulin 5.5 .001 Elevated triglyceridesElevated ApoBSmall dense LDLElevated LDL-CReduced HDL-CAnd, in fact, in a later paper from that study, this group said, let's get beyond LDL; because, if your LDL is elevated, you have a 2.5-fold increase in cardiac events, but if you're insulin resistant, you've a 5.5-fold increase. The reason for the independent risk factor, of course, is the effect on the endothelium. And endothelial function can be improved by lowering insulin resistance.*Data from the Quebec Heart Study.Adapted from Lamarche B et al. JAMA. 1998;279:1955–1961.
16The Importance of Targeting Insulin Resistance Over 90% of Type 2’s are Insulin ResistantComplexDyslipidemia TG, sdLDL HDLEndothelialDysfunctionSystemicInflammationInsulinResistanceDisorderedFibrinolysisAtherosclerosisVisceralObesityHypertensionType 2 DiabetesAdapted from the Consensus Development Conference of the American Diabetes Association.Diabetes Care ;21(2):Haffner SM, et al. Diabetes Care ;22(4):Pradhan AD, et al. JAMA ;286(3):
17Mortality in Patients With Diabetes Causes of Death Deaths (%)We need to be very aggressive in these patients in lowering the risk.CHF/CADDiabetesCancerStrokeInfectionOtherGeiss LS et al. In: Diabetes in America. 2nd ed. 1995; ch 11.
18Incidence of CHD* Events in Patients With and Without Diabetes 7-Year Follow-up (%)Incidence Duringn=130418.8Non diabetics with no prior MINon diabetics with prior MIDiabetics with no prior MIDiabetics with prior MIn=69n=890n=1690.53.03.27.83.545.020.2P<.001Incidence of Fatal or Nonfatal MI During a 7-Year Follow-up in Relation to History of MI in Nondiabetic vs Diabetic Subjects: East-West StudyIn the East-West Study, diabetics with prior myocardial infarction had a higher incidence of myocardial infarction than diabetics without prior myocardial infarction, but more importantly, diabetics without prior myocardial infarction had a 20.2% incidence of myocardial infarction at 7-year follow-up, compared with an 18.8% incidence in nondiabetics with prior myocardial infarction. These results were important in establishing diabetes as a CHD risk equivalent. Although this study was criticized because it was conducted in a relatively high-risk population for CHD, namely Finland in the early 1980s, a subsequently published analysis of the Organization to Assess Strategies for Ischemic Syndromes (OASIS) Registry, which included prospective data from 6 countries (Australia, Brazil, Canada, Hungary, Poland, and the United States), also found that diabetic patients without prior cardiovascular disease had the same event rates as nondiabetic patients with prior cardiovascular disease.References: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:Malmberg K, Yusuf S, Gerstein HC, Brown J, Zhao F, Hunt D, Piegas L, Calvin J, Keltai M, Budaj A. Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry. Circulation 2000;102:Keywords: coronary heart disease, diabetes, myocardial infarction, secondary preventionSlide type: graphEvents per Person-yr*Coronary heart diseaseHaffner SM et al. N Engl J Med. 1998;339:229–234.
19The Need for Tight BG Control According to the United Kingdom Prospective Diabetes Study (UKPDS) 35, every 1% increase in A1c resulted in:Increasein risk of microvascularcomplicationsIncrease in any diabetes- related endpointIncrease in risk of MIIncrease in risk of stroke21%14%12%37%Adapted from the United Kingdom Prospective Diabetes Study. Stratton IM, et al. BMJ. 2000;321(7258):
20Diabetes Control and Complications Trial (DCCT) 1983 – 199311,441 pts. / 29 centers in US and CanadaDM > 1yr and < 15yr ; no eye diseaseStandard care vs intensive managementIntensive insulin therapyDiet and exerciseBehavioral therapyCarotid intima-media thickness
21Diabetes Control and Complications Trial (DCCT) Results76% reduction in eye disease6% reduction in neuropathy54% reductions in urine albumin secretion50% reduction in nephropathyOverall improvements in BP, Hgb A1c, HDL and LDL
22Treatment of CAD Risk in DM: Are We Doing a Good Job? Do We Reach Treatment Goals?SuboptimalOptimalHbA1c <7.0HDL >45 (men)HDL >55 (women)LDL <100Triglycerides <200BP <130/85BMI <25100%80%60%40%20%0%10%40%60%80%100%George PB et al. Am Heart J. 2001;142:857–863.Prospective observational study of 235 treated (oral or insulin) CAD patients with Diabetes
23Treatment of CAD Risk in DM: Are We Doing a Good Job? Do We Prescribe Optimal Cardiovascular Drug Therapy?% Patients Treated by MedicationLipid-loweringdrugs-BlockersACE inhibitorsAspirinGeorge PB et al. Am Heart J. 2001;142:857–863.Prospective observational study of 235 treated (oral or insulin) CAD patients with Diabetes
2460% Type 2’s Not At ADA HgbA1c Goal <6% GOAL SurveyHgbA1c26.5%40.3%>8%59.4%>7%13.8%% Of SubjectsN = 37119.1%Abstract TitleControl of Risk Factors for Vascular Disease in US Adults with DiabetesAbstract InformationAbstract Number: 979-PAuthors: SHARON H. SAYDAH, JUDITH FRADKIN, CATHERINE C. COWIEInstitution: Silver Spring, MD; Bethesda, MDResults: Individuals with diabetes are at increased risk of vascular diseases. Control of blood glucose, blood pressure and cholesterol levels can help reduce this risk. We examined national data on treatment and control of these risk factors in adults age years with previously diagnosed diabetes who participated in the interview and examination components of the Third National Health Examination Survey (NHANES III, , n=999) and the NHANES (n=371).Participants with diabetes were similar by age and sex in the two surveys, however the percent who were nonHispanic white decreased significantly from 72.5% to 59.6%, p<.05. Age at diagnosis of diabetes decreased during the decade (from mean 47.8 to 44.3 yrs, p<.05) and duration of diabetes increased (from mean 8.7 to 11.3 yrs, p<.05). Only 40.6% of adults with diabetes in the NHANES have HbA1c levels <7.0%, the goal recommended by the American Diabetes Association, with 40.3% having levels >8.0% and 26.5% having levels >9.0%. These percentages did not change significantly over the past decade. Diabetes treatment shifted to greater use of oral medications either alone (from 43.9% to 51.0%) or in combination with insulin (from 4.1% to 11.1%, p<.05). The percent with systolic blood pressure [ge]140 mmHg and/or diastolic blood pressure [ge]90 mmHg increased from 22.1% in the NHANES III to 36.3% in the NHANES , p<.05. Treatment for blood pressure (e.g., use of antihypertensive medication, weight or exercise control) did not change significantly during this period. No change occurred in total cholesterol levels during the decade (mean mg/dl, 54.6% with levels [ge]200 mg/dl in NHANES ), despite an increase in the report of total cholesterol being checked and use of medication to reduce cholesterol (from 26.0% to 55.4%, p<.001). The percent who smoke significantly decreased from 23.1% to 16.2%, p<.05. Mean body mass index significantly increased from 30.9 to 33.1, p<.05.Expanded efforts are needed to improve control of blood glucose, blood pressure, lipids and other risk factors for vascular disease in US adults with diabetes.Category: Epidemiology40.6%Adults aged y with previously diagnosed diabetes who participated in the interview and examination components of the National Health Examination Survey (NHANES),Saydah et al. Diabetes. 2003;52(suppl 1):A228 (Abstract 979-P).
25Traditional Therapies Do Not Maintain A1c Control Over Time United Kingdom Prospective Diabetes Study (UKPDS)98Conventional*InsulinMedian A1c (%)Glibenclamide (glyburide)7ADA goalMetformin636910Time from Randomization (Years)*Conventional=diet therapy.UK Prospective Diabetes Study (UKPDS 34) Group. Lancet. 1998;352:
27Primary Prevention: Status and 2010 Goals Now2010Moderate physical activityVegetable intake of >3 servingsPrimary prevention: status and goals in 2010This slide compares current findings for several lifestyle variables with the goals for 2010 set forth in Healthy People To reach the goal for healthy weight, more Americans will need to increase their physical activity and eat better.Reference:National Cholesterol Education Program. Adult Treatment Panel III ReportSaturated fat <10% of caloriesNCEP. Adult Treatment Panel III Report
28Primary Prevention: Status and 2010 Goals NowFruit >2 servings/dSmoking cessationPrimary prevention: status and goals in 2010 (continued)This slide continues the comparison of current findings for several lifestyle variables with the goals for 2010 set forth in Healthy People 2010.Reference:National Cholesterol Education Program. Adult Treatment Panel III ReportHealthy weightNCEP. Adult Treatment Panel III Report
40Healthy Eating and Heart Disease Good Fats / MediterraneanLyon Diet Study2nd prevention trialMediterranean vs. SAD70% reduction in recurrent coronary events / cardiac death post MI!Maintained out to 4 years!Lorgeril etal Lancet 1994 ;343:
49Physical Fitness and Heart Disease Exercise-based rehabilitation for patients with coronary heart disease: meta-analysisAmerican Journal of Medicine Volume 116, Issue 10, Pages (15 May 2004) Rod S Taylor, MSc; etal48 trials with a total of 8940 patientsReduced All-Cause mortality (odds ratio [OR] = 0.80; 95% confidence interval [CI]: 0.68 to 0.93)Reduced Cardiac mortality (OR = 0.74; 95% CI: 0.61 to 0.96)Reduced Total cholesterol (weighted mean difference, –0.37 mmol/L [–14.3 mg/dL]; 95% CI: –0.63 to –0.11 mmol/L [–24.3 to –4.2 mg/dLReduced Triglycerides (weighted mean difference, –0.23 mmol/L [–20.4 mg/dL]; 95% CI: –0.39 to –0.07 mmol/L [–34.5 to –6.2 mg/dL]Reduced Systolic blood pressure (weighted mean difference, –3.2 mm Hg; 95% CI: –5.4 to –0.9 mm Hg)Reduced rates of self-reported smoking (OR = 0.64; 95% CI: 0.50 to 0.83)
50Physical Fitness and Diabetes Resistance Training in the Treatment of the Metabolic Syndrome: A Meta-AnalysisSports Medicine, Volume 40, Number 5, 1 May 2010 , pp (19) Strasser, Barbara1; Siebert, Uwe; Schobersberger, Wolfgang1 University for Health Sciences, Medical Informatics and Technology, Institute for Sport Medicine, Alpine Medicine and Health Tourism, Hall i. T., AustriaMetabolic consequences of reduced muscle mass, as a result of normal aging or decreased physical activity, lead to a high prevalence of metabolic disordersMeta-Analysis – 13 RCT’s – Effect of Resistance TrainingHbA1c by 0.48% (95% CI −0.76, −0.21; p = 0.0005)Fat mass by 2.33 kg (95% CI −4.71, 0.04; p = 0.05)Systolic blood pressure by 6.19 mmHg (95% CI 1.00, 11.38; p = 0.02)No statistically significant effect of RT on:total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride and diastolic blood pressure
52Exercise Weight and Heart Health 22,000 Men / 8 years% body fat and exercise treadmill testingThin / Fit = 1/3 cardiac related death c/w Thin / Un-FitFit / Obese men had lower death rates than Unfit / Thin men!Lee et al, Am J of Clin Nutrition 1999; 69: 373
53Fitness / Fatness and Heart Health Aerobically fitUnfitRelative Risk of CVD MortalityFatness, fitness and cardiovascular disease mortalityIn addition to the beneficial effects of physical activity on body weight, aerobic fitness can independently modify the risk of developing cardiovascular disease. This figure illustrates the data obtained from a large observational cohort study involving more than 20,000 men, aged 30 to 83 years, who were followed for an average of 8 years . The results show that increasing adiposity is associated with an increased risk of cardiovascular mortality. However, among each category of body fatness, those who were fit, defined by their maximal ability to consume oxygen during exercise, had a lower incidence of cardiovascular mortality than those who were unfit. Moreover, participants who were obese and fit had a lower risk of cardiovascular death than participants who were lean but unfit. Aerobic fitness, independent of body fatness, also is associated with a decreased risk of developing diabetes .Lee CD, Blair SN, Jackson AS. Cardiorespiratory fitness, body composition, and all-cause and cardiovascular disease mortality in men. Am J Clin Nutr 1999;69:Wei M, Gibbons L, Mitchell T, et al. The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men. Ann Intern Med 1999;130:89-96.Keywords: fitness, cardiovascular disease mortality, CVD, relative risk, body fatLean <16.7%Normal 16.7%-24.9%Obese >25%Body Fat Category (% Weight as Fat)Lee et al. Am J Clin Nutr 1999;69:373.
54Pedometers: Taking the first steps! Great motivational toolLow upfront costHealthcare cost savingsPreliminary outcome data particularly in diabeticsProblems:No standards yet (10,000 steps/day)First Step Program – US and CanadaTudor-Locke Dept. Exercise and Wellness ASUPresident’s Council on Physical Fitness and Sports 2001
55“As a man thinketh in his heart, so shall his life be made” Osler
63Stress and Heart Disease Psycho-social factors, particularly depression, negatively predict:Adherence and outcomes of Cardiac RehabAdherence to Smoking cessation programsAdherence to weight management programsGlazer et al, J of CardioPulm Rehab 2002; 22: Psychological predictors of adherence and outcomes among patients in cardiac rehab
64Stress Management and Heart Disease Psycho-social interventions designed to modify these factors have been shown in large meta-analyses to reduce fatal and non fatal events by 30 – 50%Dusseldorp et al, Health Psych 1999; 18:Sustained effectivenessCompared to diet / exercise (temporary)Luskin et al. Alternative Therapies May 1998 A review of mind body approaches to CHD
65Dis-stress and Diabetes In people with diabetes, dis-stress alters blood glucose levels Direct:Stress-mediated production of:Cortisol, Norepinephrine, Beta endorphin, Glucagon, and Growth hormoneIndirect:People when under stress often make poor health choicesLess physical activityPoor meal choicesCheck BG less frequently
66Stress Management and Diabetes Stress management improves long-term glycemic control in type 2 diabetesSurwit RS, Diabetes Care Jan;25(1):30-4108 patients with type 2 diabetesFive-session group diabetes education program with or without stress management training.HbA(1c) tests, questionnaires assessing perceived stress, anxiety, and psychological health were administered at regular intervals to evaluate treatment effectsStress management training was associated with a small (0.5%) but significant reduction in HbA(1c)CONCLUSIONS: The current results indicate that a cost-effective, group stress management program in a "real-world" setting can result in clinically significant benefits for patients with type 2 diabetes
67Stress Management and DM Diabetes Care 25:30-34, 2002Stress Management Improves Long-Term Glycemic Control in Type 2 DiabetesRichard S. Surwit, PHD etal., Duke University Medical Center, Durham, North Carolina
68Stress Management and Children with Diabetes Stress Management Training for Adolescents with DiabetesJournal of Pediatric Psychology 18(1) pp , 1993Ronald H. Boardway Wayne State University School of MedicineEffects of stress management training (SMT) for adolescents with diabetes9-month controlled treatment-outcome studyDiabetes-specific stress decreased significantly for patients in the SMT group
69Social connection decreases stress and depression Group SupportSocial connection decreases stress and depressionEmotional quality > Structural qualityPerceived low social support strongly associated with:angerdepression
70149 men and women with angina Group Support and CAD149 men and women with anginaQuestioned pre-catheterization regarding feeling loved and supportedThose with the greatest perception of love and support had the least amount of CADSeeman, TE and SL Syme, Psychosomatic Medicine, 1987;49(4):341-54
71Medicine and Faith in 1910: Immeasurable? “Nothing in life is more wonderful than faith -- the one great moving force which we can neither weigh in the balance nor test in the crucible…mysterious, indefinable, known only by its effects, faith pours out an unfailing stream of energy while abating neither jot nor tittle of its potency.”Sir William Osler (1910). “The faith that heals,” British Medical Journal, 1:
72Ornish Pilot Project 10 patients with severe CAD 30 day residential study62% increase in time on treadmill90% reduction in anginal frequencyimprovements in myocardial perfusion as measured by exercise thallium scintigraphyOrnish, Gotto, Miller et al. Clin. Res.1979, 27:720A
73The Lifestyle Heart Trial One-Year Data 48 patients with severe coronary artery diseaseOutpatient 1 year intervention extended to 4Percent diameter lesion stenosisimproved in the experimental group and worsened in the control group (p = 0.001).Ornish, Brown, Scherwitz et al, Lancet. 1990, 336:
74Ornish – 1 year Data Analysis TreatmentControl37% decrease – LDL91% decrease - Angina82% decrease - StenosisLDL – Increase or same165% - Increase Angina53% - Progression
75Ornish - Five-Year Data Continued angiographic improvement in the experimental group and continued progression in the control groupPET scans showed improvement in myocardial perfusion99% of patients stopped or reversed the progression of disease as measured by PET scanChanges in stenosis associated withadherence to the interventionImproved Lipid ProfileThe risk ratio for total cardiac events was 2.5 times greater in the control group than in the experimental groupOrnish D, Scherwitz L, Billings J, et al. JAMA ;280:Gould, Ornish, Scherwitz et al. JAMA. 1995, 274:
76Finnish Diabetes Prevention Study Design522 middle-aged overweight (BMI 31)172 men and 350 womenMean duration 3.2 yearsIntervention Group: Individualized counselingReducing weight, total intake of fat and saturated fatIncreasing uptake of fiber, physical activityDoes treating the metabolic syndrome make a difference? Finnish Diabetes Prevention StudyThis slide describes the Finnish Diabetes Prevention Study, which looked at 522 middle-aged overweight men and women with glucose intolerance. Subjects were randomized to two groups. The intervention group had individualized counseling.Reference:Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:Tuomilehto J et al. N Engl J Med 2001;344:
77Finnish Diabetes Prevention Study GoalsInterventionControlsP value% of subjectsWt reduction >5%43130.001Fat intake < 30% energy4726Sat fat <10% energy11Fiber >15 g/1000 kcal2512Exercise > 4 hr/wk8671Treating the metabolic syndromeThe results were striking. The intervention group achieved significant improvements in five lifestyle behavioral areas as contrasted with the control group.Reference:Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:Tuomilehto J et al. N Engl J Med 2001;344:
78Finnish Diabetes Prevention Study After 4 years — risk of diabetes reduced by58%23%11%Benefit of treating the metabolic syndromeThe benefits were highly signficant, as after 4 years the risk of diabetes mellitus was reduced by 58%. This suggests that lifestyle change can reduce risk for CHD, as diabetics are assumed to have as high a risk for coronary events as nondiabetics with CHD.Reference:Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:(6–15 CI)(17–29 CI)InterventionControl% with DiabetesTuomilehto J et al. N Engl J Med 2001;344:
79Diabetes Prevention Program 3,234 men and women with impaired glucose tolerance (fasting plasma glucose 95–125 mg/dL and 2-hr postload glucose 140–199 mg/dL) and BMI 2445% from minority groups with increased prevalence of type 2 diabetes: African Americans, Hispanic Americans, Asian Americans, and American Indians27 centers nationwideRandomization to lifestyle changes to include at least 7% weight loss and exercise 150 min/wk, metformin 850 mg b.i.d., or placeboPrimary endpoint: development of diabetesFollow-up: designed for 3.5–5 years, but discontinued 1 year early because of conclusive results (mean 2.8 years)The Diabetes Prevention Program (DPP) studied the onset of diabetes in 3,234 men and women with impaired glucose tolerance, defined as fasting plasma glucose 95–125 mg/dL (125 mg/dL or less in American Indian centers) and 2-hour postload glucose 140–199 mg/dL. Patients were 25 years of age or older and had body mass index (BMI) of 24 kg/m2 or higher (22 kg/m2 or higher in Asian Americans). Patients were randomized to intensive lifestyle intervention (reduction in body weight of at least 7% through diet and exercise, physical activity of moderate intensity for at least 150 min/week), metformin 850 mg twice daily plus standard lifestyle recommendations (diet, weight reduction, exercise), or placebo plus standard lifestyle recommendations. The primary endpoint was development of diabetes. The study was conducted in 27 centers nationwide and was designed to have a follow-up period of 3.5–5 years.More than 45% of patients were racial or ethnic minorities: 20% were African American, 16% Hispanic, 5% American Indian, and 4% Asian American. The patient population was 68% female, and 20% of patients were aged 60 years or older (overall mean age at baseline, 51±11 years). Mean baseline BMI was 34.0±6.7 kg/m2; BMI was 30 kg/m2 or greater in 68% of patients (57% of men and 73% of women). Mean fasting plasma glucose was 106.5±8.3 mg/dL, and mean postload glucose was 164.6±17.0 mg/dL.Diabetes Prevention Program. Diabetes Care 1999;22:Diabetes Prevention Program. Diabetes Care 2000;23:
80Diabetes Prevention Program Trial was discontinued 1 year early because of clear results31% reduction58% reductionPatients Developing Diabetesin Mean 3-Year Follow-up (%)The study was stopped 1 year early (mean follow-up 2.8 years) because the data were already conclusive. Compared with placebo, patients randomized to intensive lifestyle intervention had a 58% reduction in onset of type 2 diabetes (by 1997 American Diabetes Association criteria), which was significantly greater than the 31% reduction in the metformin group. Mean weight loss with intensive lifestyle intervention was 12 lb; 50% achieved the weight loss goal of 7% by the end of the 24-week instruction period, and 74% met the physical activity goal at that time. Daily calorie intake in this group was reduced by 450 kcal (vs. 296 kcal in the metformin group and 249 kcal in the placebo group), and total fat intake was reduced by 6.6% (vs. 0.8% in both the metformin and placebo groups).142229LifestyleMetforminPlacebo5-7% reduction in body weight; exercise 30 min/dKnowler WC, et al. N Engl J Med 2002;346: