Metabolic Syndrome, Diabetes Metabolic Syndrome, Diabetes and Cardiovascular Disease: and Cardiovascular Disease: Strategies for ManagementStrategies for Management

Nathan D. Wong, PhD, FACC, FAHANathan D. Wong, PhD, FACC, FAHAProfessor and Director, Heart Disease Professor and Director, Heart Disease Prevention Program, Division of Prevention Program, Division of Cardiology, University of California, IrvineCardiology, University of California, IrvinePast President, American Society of Past President, American Society of Preventive CardiologyPreventive Cardiology

Global Global Distribution Distribution of Diabetes, of Diabetes, WHO 2011WHO 2011

Diabetes: A Growing ChallengeDiabetes: A Growing ChallengePrevalence in the United StatesPrevalence in the United States

0

1

2

3

4

5

6

7

19

58

19

61

19

64

19

67

19

70

19

73

19

76

19

79

19

82

19

85

19

88

19

91

19

94

19

97

20

00

20

03

20

06

0

2

4

6

8

10

12

14

16

18

20

Percentage of Population

Number (Millions)

Centers for Disease Control and Prevention, Division of Diabetes Translation. National Diabetes Surveillance System. Available at http://www.cdc.gov/diabetes/statistics.

Diagnosed Diabetes

% o

f P

op

ula

tio

n

# o

f P

atie

nts

in M

illio

ns

Age-Adjusted Prevalence of Type 2 DM: California Adults Aged Age-Adjusted Prevalence of Type 2 DM: California Adults Aged >>18 18 Including Hispanic and Asian Subgroups 2009Including Hispanic and Asian Subgroups 2009

N.D. Wong, California Health Interview Survey (unpublished)

Narayan et al. JAMA 2003;290:1884-1890.

Diabetes Mellitus:Diabetes Mellitus:Lifetime RiskLifetime Risk

Years from diagnosis

0 5-10 -5 10 15Onse

tDiagnosis

Insulin secretion

Postprandial glucose

Ramlo-Halsted BA et al. Prim Care. 1999;26:771-789Nathan DM et al. NEJM 2002;347:1342-1349

Fasting glucose

Natural History of Type II Diabetes Natural History of Type II Diabetes MellitusMellitus

Insulin resistance

Microvascular complications

Macrovascular complications

Type II diabetesPre-diabetes

Diagnostic Criteria forDiagnostic Criteria forGlycemic AbnormalitiesGlycemic Abnormalities

FPG=Fasting plasma glucose, PG=Plasma glucose, OGTT=Oral glucose tolerance test

To convert mg/dL to mmol/L multiply mg/dl by 0.055

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2001;24:S5-S20American Diabetes Association. Diabetes Care 2010;33:S11-61

FPG

126 mg/dL

100 mg/dL

7.0 mmol/L

5.6 mmol/L

Prediabetes

NormalNormal

Diabetes MellitusDiabetes Mellitus

2-Hour PG on OGTT

200 mg/dL

140 mg/dL

11.1

mmol/L

7.8 mmol/L

Impaired Glucose Tolerance

NormalNormal

Diabetes MellitusDiabetes Mellitus

Hemoglobin A1C

6.5%

6.0%

Prediabetes

NormalNormal

Diabetes MellitusDiabetes Mellitus

Causes of Mortality in Causes of Mortality in Patients With Diabetes Patients With Diabetes

Diabetes and CVDDiabetes and CVD

• Atherosclerotic complications responsible for Atherosclerotic complications responsible for – 80% of mortality among patients with diabetes80% of mortality among patients with diabetes– 75% of cases due to coronary artery disease (CAD)75% of cases due to coronary artery disease (CAD)– Results in >75% of all hospitalizations for diabetic Results in >75% of all hospitalizations for diabetic

complicationscomplications

• 50% of patients with type 2 diabetes have 50% of patients with type 2 diabetes have preexisting CAD. preexisting CAD. (This number may be less now that (This number may be less now that more younger people are diagnosed with diabetes.)  more younger people are diagnosed with diabetes.) 

• 1/3 of patients presenting with myocardial 1/3 of patients presenting with myocardial infarction have undiagnosed diabetes mellitusinfarction have undiagnosed diabetes mellitus

Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28CNorhammar A, et.al. Lancet 2002;359;2140-2144

Most Cardiovascular Patients Have Most Cardiovascular Patients Have Abnormal Glucose MetabolismAbnormal Glucose Metabolism

35% 31%

34%

37%18%

45%

37% 27%

36%

GAMIn = 164

EHSn = 1920

CHSn = 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.

AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease HDL=High-density lipoprotein, HTN=Hypertension, IL-6=Interleukin-6, LDL=Low-density lipoprotein, PAI-1=Plasminogen activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor, TG=Triglycerides, tPA=Tissue plasminogen activator

Subclinical Atherosclerosis

Atherosclerotic Clinical Events

Hyperglycemia

AGE Oxidative

stress

Inflammation

IL-6 CRP SAA

Infection Defense

mechanisms Pathogen burden

Insulin Resistance

HTN Endothelial dysfunction

Dyslipidemia

LDL TG HDL

Thrombosis PAI-1 TF tPA

Disease Progression

Biondi-Zoccai GGL et al. JACC 2003;41:1071-1077.

Mechanisms by which Diabetes Mechanisms by which Diabetes

MellitusMellitusLeads to Coronary Heart DiseaseLeads to Coronary Heart Disease

Risk of Cardiovascular Events in Patients Risk of Cardiovascular Events in Patients withwith Diabetes: Diabetes: Framingham StudyFramingham Study

Age-adjustedAge-adjusted

Biennial Rate Age-Biennial Rate Age-adjustedadjusted

Per 1000Per 1000 Risk RatioRisk RatioCardiovascular EventCardiovascular Event Men WomenMen Women Men WomenMen Women

Coronary DiseaseCoronary Disease 39 2139 21 1.5** 2.2*** 1.5** 2.2***StrokeStroke 15 615 6 2.9*** 2.6*** 2.9*** 2.6***Peripheral Artery Dis. 18 18Peripheral Artery Dis. 18 18 3.4*** 6.4*** 3.4*** 6.4***Cardiac FailureCardiac Failure 23 21 23 21 4.4*** 7.8*** 4.4*** 7.8***All CVD EventsAll CVD Events 76 65 2.2*** 3.7*** 76 65 2.2*** 3.7***

Subjects 35-64 36-year Follow-up **P<.001,***P<.0001Subjects 35-64 36-year Follow-up **P<.001,***P<.0001

_________________________________________________________________

_________________________________________________________________

Cardiovascular Risk Factors are the Top 6 Leading Causes of Death

Metabolic Syndrome: Clustering Metabolic Syndrome: Clustering of of Interconnected Metabolic Risk Interconnected Metabolic Risk FactorsFactors

ObesityInsulin

Resistance+ Hyperglycemia

Hypertension

AtherogenicDyslipidemia

2009 IDF/IAS/NHLBI/AHA/WHF Joint Scientific Statement on Diagnosis of Metabolic Syndrome

(Alberti et al. Circulation 2009) (>=3 criteria required for diagnosis)

Alberti et al. Circulation 2009

Back

Visceral AT

Subcutaneous AT

Front

Intra-abdominal (Visceral) FatIntra-abdominal (Visceral) FatThe dangerous inner fat!The dangerous inner fat!

0

5

10

15

20

25

<28 >28-29 30-31 32-33 34-35 36-37 ≥38

Rel

ativ

e R

isk

of

Dia

bet

es

Waist Circumference (in)

Abdominal Adiposity Is AssociatedAbdominal Adiposity Is Associated With Increased Risk of DiabetesWith Increased Risk of Diabetes

P value for trend <0.001

Carey VJ, et al. Am J Epidemiol. 1997;145:614-619

Metabolic Syndrome and Diabetes in Relation to CHD, CVD, Metabolic Syndrome and Diabetes in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages 30-74and 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.

(Risk-factor Adjusted Cox Regression) NHANES II Follow-up (n=6255)

***

Metabolic Syndrome and CVD Metabolic Syndrome and CVD Risk: Meta-Analysis: Risk: Meta-Analysis: Mottillo et al. JACC 2010Mottillo et al. JACC 2010

• 951,083 pts in 83 studies951,083 pts in 83 studies• Little variation in risk between definitionsLittle variation in risk between definitions• Relative risk:Relative risk:

– 2.35 (2.20-2.73) for CVD events2.35 (2.20-2.73) for CVD events– 2.40 (1.87-3.08) for CVD mortality2.40 (1.87-3.08) for CVD mortality– 1.58 (1.39-1.78) for all-cause mortality1.58 (1.39-1.78) for all-cause mortality– 1.99 (1.61-2.46) for myocardial infarction1.99 (1.61-2.46) for myocardial infarction– 2.27 (1.80-2.85) for stroke2.27 (1.80-2.85) for strokeThose with metabolic syndrome, without Those with metabolic syndrome, without

diabetes, maintained high CVD risk (RR=1.75, diabetes, maintained high CVD risk (RR=1.75, 95% CI=1.19-2.58)95% CI=1.19-2.58)

Type 2 Diabetes and CHD Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI 7-Year Incidence of Fatal/Nonfatal MI (East West Study)(East West Study)

No Diabetes

Diabetes

3.5%

18.8%20.2%

45.0%P<0.001 P<0.001

7-Y

ear

Inci

den

ce R

ate

of

MI

CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitusHaffner SM et al. N Engl J Med. 1998;339:229-234.

Is DM really a CHD Risk Equivalent? Meta-Analysis of 38,578 subjects (Bulugahapitiya et al. Diabetic Med 2008)

DM without prior MI has a 43% lower risk of developing total CHD events compared to those without DM with prior MI, suggesting DM is not a coronary risk equivalent.

Global Risk Assessment in DM: US adults 2003-2006 Global Risk Assessment in DM: US adults 2003-2006 10-year Total CVD Risk by Gender10-year Total CVD Risk by Gender(Wong ND et al., Diab Vas Dis Res 2012)(Wong ND et al., Diab Vas Dis Res 2012)

32% of men and 48% of women are at calculated low to

intermediate risk

2013 Prevention Guidelines 2013 Prevention Guidelines ASCVD Risk EstimatorASCVD Risk Estimator

Available at www.cardiosource.com

Screening for Coronary Disease in Screening for Coronary Disease in Diabetes: When and How Diabetes: When and How (Ali and Maron, Clinical Diabetes (Ali and Maron, Clinical Diabetes 2006)2006)

“ “ Screening patients according to Screening patients according to traditional risk factors and current traditional risk factors and current guidelines alone will frequently fail to guidelines alone will frequently fail to identify CHD, thus losing the opportunity identify CHD, thus losing the opportunity for early diagnosis and intensified for early diagnosis and intensified management”management” “ “A more aggressive approach to A more aggressive approach to identifying asymptomatic coronary identifying asymptomatic coronary disease should therefore be considered disease should therefore be considered in this (diabetic) patient population”in this (diabetic) patient population”

Annual CHD Event Rates (in %) by Calcium Score Events by Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in Subjects with DM, MetS, or Neither DiseaseCAC Categories in Subjects with DM, MetS, or Neither Disease(Malik and Wong et al., Diabetes Care 2011)(Malik and Wong et al., Diabetes Care 2011)

Coronary Heart Disease

Coronary Artery Calcium Score

ACCF/AHA 2010 Guideline: CAC Scoring for CV risk ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in asymptomatic adults aged 40 and over with assessment in asymptomatic adults aged 40 and over with diabetes (Class IIa-B)diabetes (Class IIa-B)

0 1-99 100-399400+

Neither MetS/DM

MetSDM

0.4

1.5 1.9

4

0.20.8

2.1

3.5

0.1 0.41.3

2.2

00.5

11.5

22.5

33.5

4

Annual CHD Event Rate

DIAD Randomized Clinical DIAD Randomized Clinical Trial of Stress MPI Screening Trial of Stress MPI Screening (Young, Inzucchi et al. JAMA 2009)(Young, Inzucchi et al. JAMA 2009)

• Randomized NIH multicenter trial examining whether Randomized NIH multicenter trial examining whether screening for myocardial ischemia using adenosine-screening for myocardial ischemia using adenosine-stress MPI in 1123 persons with type 2 DM and no stress MPI in 1123 persons with type 2 DM and no symptoms of CAD.symptoms of CAD.

• Only 22% were positive for myocardial ischemia with Only 22% were positive for myocardial ischemia with only 6% have moderate or large defectsonly 6% have moderate or large defects

• 5-year 2.9% cumulative event rate (0.6% per year), 5-year 2.9% cumulative event rate (0.6% per year), much lower than expected much lower than expected Event rates similar in those Event rates similar in those screening (2.7%) vs. not screened (3.0%) (p=0.73)screening (2.7%) vs. not screened (3.0%) (p=0.73)

(authors note the study only had 20% power to (authors note the study only had 20% power to detect a 20% difference between groups)detect a 20% difference between groups)

DIAD Study (continued)DIAD Study (continued)• The authors conclude that screening for inducible

ischemia in asymptomatic patients with T2DM cannot be advocated for 4 reasons:• The yield of significant inducible ischemia is very

low• Overall cardiac event rates are low• Routine screening does not appear to affect

overall outcome• Routine screening would be prohibitively

expensiveThe much lower than expected event rates makes

the study inconclusive in demonstrating the lack of efficacy of screening for subclinical CVD

But should we be using stress MPI But should we be using stress MPI to screen for CVD in all pts with to screen for CVD in all pts with DM?DM?• Stress MPI is meant to identify short-Stress MPI is meant to identify short-

term risk due to functional deficit, rather term risk due to functional deficit, rather than long-term prognosis such as that than long-term prognosis such as that identified by a test to quantify identified by a test to quantify atherosclerotic burden such as coronary atherosclerotic burden such as coronary calciumcalcium

• The radiation and costs are much higher The radiation and costs are much higher for MPI as compared to coronary for MPI as compared to coronary calcium, suggesting MPI might be best calcium, suggesting MPI might be best reserved for those DM at highest riskreserved for those DM at highest risk

ADA 2007 Consensus Statement ADA 2007 Consensus Statement (Bax et al. Diab Care 2007)(Bax et al. Diab Care 2007)

““If coronary calcium testing is performed, If coronary calcium testing is performed, it appears reasonable to proceed with it appears reasonable to proceed with further testing in diabetic patients with further testing in diabetic patients with calcium scores >400…….using single calcium scores >400…….using single photon emission tomography to assess photon emission tomography to assess myocardial perfusion or stress myocardial perfusion or stress echocardiography to assess ischemic echocardiography to assess ischemic wall motion abnormalities”wall motion abnormalities”

Prevalence of Inducible Ischemia Associated with Presence Prevalence of Inducible Ischemia Associated with Presence of Metabolic Abnormality and Coronary Calcium Score of Metabolic Abnormality and Coronary Calcium Score (Wong et al., (Wong et al., Diabetes CareDiabetes Care 2005; 28: 1445-50 ) 2005; 28: 1445-50 )

0

5

10

15

20

25%

MP

S p

osit

ive

(SD

S

>=

4)

CCS=0 (192) (90)

CCS 1-99 (156) (75)

CCS 100-399 (168) (54)

CCS 400+ (214) (94)

No Metabolic Abnormality Metabolic Abnormality

P<0.0001 for trend across CCS groups for both metabolic abnormality present and absent; similar relation for those with metabolic syndrome excluding diabetes

P=0.018

P=0.032

ACCF/AHA 2010 Guideline: Stress MPI may be considered for advanced CV risk ACCF/AHA 2010 Guideline: Stress MPI may be considered for advanced CV risk assessment in asymptomatic adults with diabetes or when previous risk assessment assessment in asymptomatic adults with diabetes or when previous risk assessment testing suggests a high risk of CHD, such as a CAC score of 400 or greater (Class IIb – testing suggests a high risk of CHD, such as a CAC score of 400 or greater (Class IIb – Level of Evidence C)Level of Evidence C)

Does Screening for CVD Improve Outcomes?Does Screening for CVD Improve Outcomes?

Beneficial Role of Coronary Multidetector CT Beneficial Role of Coronary Multidetector CT Screening for 5-Year All-Cause Mortality among Screening for 5-Year All-Cause Mortality among Asymptomatic DM Patients Asymptomatic DM Patients (H Kyung Yang et al., ADA 2014)(H Kyung Yang et al., ADA 2014)

1) Asymptomatic T2DM subjects 2) 774 received coronary MDCT and 1548 matched

controls did not get screened3) Groups similar except longer duration DM and

higher A1c in screened group4) After 31 month median follow-up, greater lipid

decreases and statin prescription in screened group5) Coronary angiography and revascularization higher

in MDCT group

Beneficial Role of Coronary Multidetector CT Screening Beneficial Role of Coronary Multidetector CT Screening for 5-Year All-Cause Mortality among Asymptomatic for 5-Year All-Cause Mortality among Asymptomatic DM Patients (Yang et al., ADA 2014)DM Patients (Yang et al., ADA 2014)

All cause mortality at 5 years lower in the MDCT (4.5%) vs. non-MDCT (6.8%) group, p=0.02

Authors conclude “MDCT may play a beneficial role as a screening test to detect advanced macrovascular complications in asymptomatic T2DM patients and to increase survival rate”

April 21, 2023 37

Coronary Artery Calcium and Cardiovascular Events Coronary Artery Calcium and Cardiovascular Events in Diabetes: Implications for Primary Prevention in Diabetes: Implications for Primary Prevention

Therapies:Therapies:The Multi-Ethnic Study of Atherosclerosis (MESA)The Multi-Ethnic Study of Atherosclerosis (MESA)

Presented by: Michael Silverman

Michael G. Silverman1, Michael J. Blaha1, Matthew J. Budoff2, Ron Blankstein3, Roger S. Blumenthal1, Harlan Krumholz4, Juan J. Rivera5, Arthur Agatston6, Nathan D. Wong7, Steven Shea8, John McEvoy1, Khurram Nasir1, 6

1 Johns Hopkins Ciccarone Center for Prevention of Heart Disease, Baltimore, MD2 Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA3 Brigham and Women's Hospital Non-invasive CV Imaging Program, Boston, MA4 Yale University School of Medicine, New Haven, CT5 Division of Cardiology, University of Miami, Miami, FL6 Center for Prevention and Wellness, Baptist Health South Florida, Miami, FL7 UC Irvine Heart Disease Prevention Program, Irvine, CA8 College of Physicians and Surgeons, Columbia University, New York, NY

Presented at AHA 2012

Estimated 5 year NNT with StatinEstimated 5 year NNT with Statin

CAC Group

Estimated CHD event rate at

7.6 years

Estimated CVD event rate at 7.6

years

5-year NNT CHD

5-year NNT CVD

CAC = 0 1.49% 5.47% 486 132

CAC 1-100 12.08% 16.33% 60 44

CAC > 100 18.77% 26.57% 39 27

April 21, 2023 38

NNT calculated using 21% RR reduction

Chen Y-H, Feng R, Chen Z-W. Exp Clin End Diab 2012; 120: 116-120. Cholesterol Treatment Trialists’ Collaboration, Lancet 2008; 371: 117-25

Summary of Care: Summary of Care: ABC's for ProvidersABC's for Providers

A A1c Target Aspirin Daily

B Blood Pressure Control

C Cholesterol ManagementCigarette Smoking Cessation

D Diabetes and Pre-Diabetes Management

E Exercise

F Food Choices

Strategy Strategy ComplicationComplication Reduction of Reduction of ComplicationComplication

Blood glucose control ▪ Heart attack 37%1

Blood pressure control

▪ Cardiovascular disease

▪ Heart failure

▪ Stroke

▪ Diabetes-related deaths

51%2

56%3

44%3

32%3

Lipid control

▪ Coronary heart disease mortality

▪ Major coronary heart disease event

▪ Any atherosclerotic event

▪ Cerebrovascular disease event

35%4

55%5

37%5

53%4

Treating the ABCs Reduces Treating the ABCs Reduces Diabetic ComplicationsDiabetic Complications

1 UKPDS Study Group (UKPDS 33). Lancet. 1998;352:837-853.2 Hansson L, et al. Lancet. 1998;351:1755-1762. 3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:703-713.4 Grover SA, et al. Circulation. 2000;102:722-727.5 Pyŏrälä K, et al. Diabetes Care. 1997;20:614-620.

Benefit of Comprehensive, Intensive Benefit of Comprehensive, Intensive Management: STENO 2 StudyManagement: STENO 2 Study

• Treatment Goals:Treatment Goals:– Intensive TLCIntensive TLC– HgbA1c <6.5%HgbA1c <6.5%– Cholesterol <175Cholesterol <175– Triglycerides <150Triglycerides <150– BP <130/80BP <130/80

0000

1010

2020

4040

5050

6060

Conventional TherapyConventional Therapy

Intensive TherapyIntensive Therapy

3030

Months of Follow UpMonths of Follow Up

Primary End Point=CV events (%)

1212 2424 3636 4848 6060 7272 8484 9696

n =80n =80

n =80n =80

Gaede, P. et al, NEJM 2003;348:390-393

Percent of CHD Events Over 10 Years Prevented in US Adults Percent of CHD Events Over 10 Years Prevented in US Adults with T2DM, According to Individual and Composite Risk Factor with T2DM, According to Individual and Composite Risk Factor Control (Wong ND, et al., Am J Cardiol 2014)Control (Wong ND, et al., Am J Cardiol 2014)

0

10

20

30

40

50

60

HbA1cSystolic Blood PressureTotal CholesterolHDL CholesterolAll Risk Factors

5.1 4.8

18.5

5.1

30.6

Prop

ortio

n of

Eve

nts

Prev

ente

d (%

)Nominal

Goal

Aggressive

Achieving Risk Factor Targets and CVD Event Achieving Risk Factor Targets and CVD Event Risk in Diabetes (Wong et al. ADA 2014)Risk in Diabetes (Wong et al. ADA 2014)

• Potential effects of multifactorial risk factor control are not well-quantitated. • We examined if being at target for LDL-C, HbA1c, and BP, individually and together, is

associated with lower CHD/CVD rates.• 2,160 multiethnic adults with DM without prior CVD from the ARIC, Jackson, and

MESA prospective studies followed for 11 years. • We examined event risk in those at target for LDL-C (<100 mg/dl), HbA1c (<7%), and

blood pressure (BP) (<130/80 mmHg) according to American Diabetes Association guidelines.

• Overall, 39.0%, 42.8%, 30.5%, and 6.8% of subjects were at target for LDL-C, HbA1c, and BP, and all three factors

• Being at composite target (vs one or more factors not at target) was associated with a significantly reduced risk of CHD (HR=0.46, 95% CI = 0.25-0.87) and CVD (HR=0.66, 95% CI=0.45-0.98) events.

• Optimal levels of lipids, blood pressure, and glucose control together are uncommon in persons with DM, but are associated with substantially lower CHD and CVD risks.

Control of DM Risk Factors in a Large Multipayer Outpatient Population in Northern California (n=15,826) (Holland et al., J Diab Complic 2013)

Individual control of HbA1c, BP, and LDL ranged from 42-78% in AsiansComposite control of HbA1c, BP, and LDL ranged from 21-27% in Asians

1. Steering Committee of the Physicians' Health Study Research Group. NEJM 1989;321:129-35

2. ETDRS Investigators. JAMA 1992;268:12923. Antiplatelet Trialists' Collaboration. BMJ

1994; 308:81

0

5

10

15

20

25

PHS ETDRS APT BIP PPP POPADAD JPAD

En

dp

oin

t (%

)No ASA

ASA

n= 533 3711 4502 2368 1031 1276 2539 Endpoint 5 yr MI 7 yr MI 1 yr MCE 5 yr CV Death 4 yr MCE 7yr MCE 4 yr MCE # Events 26 vs 11 283 vs 241 502 vs 415 183 vs 133 20 vs 22 117 vs 116 86 vs 68

Diabetes Mellitus:Diabetes Mellitus:Effect of AspirinEffect of Aspirin

4. Harpaz D et al. Am J Med 1998;105:494

3. Sacco M et al. Diabetes Care 2003;26:3264

4. Belch J et al. BMJ 2008; 337:a18405. Ogawa H et al. JAMA 2008; 300:

2134

p=.04p < 0.001

p<0.002

p=NS

p=NS

p=NS

NS=Not Significant

p<0.05

Recommendations:Recommendations:Antiplatelet Agents (1)Antiplatelet Agents (1)

• Consider aspirin therapy (75–162 mg/day) (C)Consider aspirin therapy (75–162 mg/day) (C)– As a primary prevention strategy in those with type 1 or type 2 As a primary prevention strategy in those with type 1 or type 2

diabetes at increased cardiovascular risk (10-year risk >10%)diabetes at increased cardiovascular risk (10-year risk >10%)– Includes most men >50 years of age or women >60 years of age who Includes most men >50 years of age or women >60 years of age who

have at least one additional major risk factorhave at least one additional major risk factor Family history of CVDFamily history of CVD HypertensionHypertension SmokingSmoking DyslipidemiaDyslipidemia AlbuminuriaAlbuminuria

ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S32-S33.

Recommendations:Recommendations:Antiplatelet Agents (2)Antiplatelet Agents (2)

• Aspirin should not be recommended for CVD prevention Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk, since potential for adults with diabetes at low CVD risk, since potential adverse effects from bleeding likely offset potential adverse effects from bleeding likely offset potential benefits (C)benefits (C)• 10-year CVD risk <5%: men <50 and women <60 years of age 10-year CVD risk <5%: men <50 and women <60 years of age

with no major additional CVD risk factors with no major additional CVD risk factors

• In patients in these age groups with multiple other risk In patients in these age groups with multiple other risk factors (10-year riskfactors (10-year risk55––10%), clinical judgment is required (E)10%), clinical judgment is required (E)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33.

Recommendations:Recommendations:Antiplatelet Agents (3)Antiplatelet Agents (3)

• Use aspirin therapy (75–162 mg/day)Use aspirin therapy (75–162 mg/day)– Secondary prevention strategy in those with diabetes with a Secondary prevention strategy in those with diabetes with a

history of CVD (A)history of CVD (A)• For patients with CVD and documented aspirin allergyFor patients with CVD and documented aspirin allergy

– Clopidogrel (75 mg/day) should be used (B)Clopidogrel (75 mg/day) should be used (B)• Combination therapy with aspirin (75–162 mg/day) and Combination therapy with aspirin (75–162 mg/day) and

clopidogrel (75 mg/day)clopidogrel (75 mg/day)– Reasonable for up to a year after an acute coronary syndrome Reasonable for up to a year after an acute coronary syndrome

(B)(B)

ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33-S34.

United Kingdom Prospective Diabetes Study (UKPDS) 10-Year Follow-Up

Diabetes Mellitus (Type II):Diabetes Mellitus (Type II):Effect of Intensive Glycemic ControlEffect of Intensive Glycemic Control

Sulphonylurea vs. Conventional Therapy

Insulin vs. Conventional Therapy

Holman RR et al. NEJM 2008;359:1577-89

Intensive glycemic control in DM reduces the long-term risk of myocardial infarction

N Engl J Med 2008;359:1577-89.

Glycemic Legacy?

Recent Trials Show No Reduction in CV Events with Recent Trials Show No Reduction in CV Events with More Intensive Glycemic ControlMore Intensive Glycemic Control

1ACCORD Study Group. N Engl J Med. 2008;358:2545-2559.2ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572.

Number at RiskIntensive 5570 5369 5100 4867 4599 1883Standard 5569 5342 5065 4808 4545 1921

25

20

15

10

5

00 12 24 36 48 60

Cu

mu

lati

ve i

nci

de

nce

(%

)

Months of follow-up

Standard therapyIntensive therapy

ADVANCE: Primary Outcome

Number at RiskIntensive 5128 4843 4390 2839 1337 475 448Standard 5123 4827 4262 2702 1186 440 395

Pat

ien

ts w

ith

ev

ents

(%

)

0 1 2 3 4 5 6

25

20

15

10

5

0

Years

Standard therapyIntensive therapy

ACCORD: Primary Outcome

Was Intensive Glycemic Control Harmful? Was Intensive Glycemic Control Harmful? A closer look at ACCORD AND ADVANCEA closer look at ACCORD AND ADVANCE

• ACCORD was discontinued early due to ACCORD was discontinued early due to increased total and CVD mortality in the increased total and CVD mortality in the intensive arm. intensive arm.

• VA Diabetes Trial showed severe hypoglycemia VA Diabetes Trial showed severe hypoglycemia to be a powerful predictor of CVD events.to be a powerful predictor of CVD events.

• A recent analysis of ACCORD (Diabetes Care, A recent analysis of ACCORD (Diabetes Care, May 2010) showed deaths related to May 2010) showed deaths related to unsuccessful intensive therapy where A1c unsuccessful intensive therapy where A1c remained highremained high..

• But in both ACCORD AND ADVANCE, those But in both ACCORD AND ADVANCE, those without macrovascular disease at baseline had without macrovascular disease at baseline had an actual benefit in the primary endpoint.an actual benefit in the primary endpoint.

Metabolic Memory and Glycemic LegacyMetabolic Memory and Glycemic Legacy

Del Prato S. Diabetalogia. 2009;52:1219-1226.

Time Since Diagnosis (years)

A1C

(%

)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

9.5

9.0

8.5

8.0

7.5

7.0

6.5

6.0

Start of intensive therapy Start of intensive therapy in VADT in VADT

Ideal course = Ideal course = early and sustained early and sustained

glycemic controlglycemic control

Bad Bad Glycemic Glycemic LegacyLegacy

Start of intensive therapy Start of intensive therapy in UKPDSin UKPDS

Drives risk of ComplicationsDrives risk of Complications

Risk of complications continues

despite glycemic control

UKPDS vs. VADTUKPDS vs. VADT

American Diabetes Association American Diabetes Association 2012 Standards of Medical Care: 2012 Standards of Medical Care: HbA1c GoalsHbA1c Goals

• A reasonable A1C goal for many nonpregnant adults is <7% A reasonable A1C goal for many nonpregnant adults is <7% due to efficacy in reducing microvascular complications.due to efficacy in reducing microvascular complications.

• Consider more stringent A1C goals (such as <6.5%) for Consider more stringent A1C goals (such as <6.5%) for selected patients, if this can be achieved without significant selected patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment. hypoglycemia or other adverse effects of treatment.

• Less stringent A1C goals (such as <8%) may be appropriate Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular life expectancy, advanced microvascular or macrovascular complications, and extensive comorbid conditions and for complications, and extensive comorbid conditions and for those with longstanding diabetes in whom the general goal those with longstanding diabetes in whom the general goal is difficult to attain.is difficult to attain.

ADA Treatment AlgorithmADA Treatment Algorithm

Effects of α/γ PPAR ActivationEffects of α/γ PPAR ActivationNuclear receptors that function as transcription factors Nuclear receptors that function as transcription factors

regulating the expression of genesregulating the expression of genes

↑ ↑ Insulin Insulin

sensitivitysensitivity

Primary Primary effect is to effect is to improve insulin sensitivityimprove insulin sensitivity

↑ ↑ Fatty acid Fatty acid

oxidationoxidation

↓↓ VLDL-TGVLDL-TG

↑ ↑ Fatty acid Fatty acid uptake uptake

Anti-Anti-inflammatorinflammator

yy

↑ ↑ apo AI, apo AI, HDL HDL

Primary Primary effect is to effect is to improve plasma lipid profileimprove plasma lipid profile

↑ ↑ Beta cellBeta cell

functionfunction

↑ ↑ fatty acid fatty acid uptakeuptake

↑ ↑ Adiponectin Adiponectin

secretion secretion Anti-Anti-inflammatorinflammator

yyheart, heart, liver, liver, muscle, muscle, vasculaturevasculature

AdipocytesAdipocytes

MuscleMuscle

Pioglitazone - PPAR Pioglitazone - PPAR ActivatorActivator

Lincoff et al. JAMA 2007;298:1180-1188.Lincoff et al. JAMA 2007;298:1180-1188.

Meta-AnalysisMeta-AnalysisDeath, MI, or Stroke – 16,390 PtsDeath, MI, or Stroke – 16,390 Pts

00

22

44

66

88

1010

00 2020 4040 6060 8080 100100 120120 140140

WeeksWeeks

Control

Pioglitazone

Estimated Event Rate, (%)Estimated Event Rate, (%)

HR = 0.82 (95% CI, 0.72-0.94)p = 0.005

PERISCOPE TrialCoronary Intravascular Ultrasound

PERISCOPE TrialCoronary Intravascular Ultrasound

Nissen et al. JAMA 2008;299:1561.Nissen et al. JAMA 2008;299:1561.

-0.3-0.3

-0.1-0.1

0.10.1

0.30.3

0.50.5

0.70.7

0.90.9Change in Percent Atheroma Volume (PAV) - %Change in Percent Atheroma Volume (PAV) - %

0.70.7

-0.2-0.2

Glimepiride(n = 181)

Pioglitazone(n = 179)

p <0.001

p = 0.44

p = 0.002 between groups

Aleglitazar - Balanced PPAR Aleglitazar - Balanced PPAR Agonist Agonist

SYNCHRONY Phase 2 TrialSYNCHRONY Phase 2 Trial

Henry R et al. Lancet 2009;374:126.Henry R et al. Lancet 2009;374:126.

HDL-CHDL-C-5-5

00

55

1010

1515

2020

2525

3030

4.44.4

25.125.1

16.516.5

Placebon = 55Placebon = 55

Aleglitazar 150 mcgn = 55Aleglitazar 150 mcgn = 55

Pioglitazone 45 mgn = 57Pioglitazone 45 mgn = 57

p-values vs placebop-values vs placebo

Ab

solu

te c

han

ge f

rom

A

bso

lute

ch

ange

fro

m

bas

elin

eb

asel

ine

TriglyceridesTriglycerides-40-40

-30-30

-20-20

-10-10

00

1010

2020

3030

% C

hang

e Fr

om B

asel

ine

% C

hang

e Fr

om B

asel

ine

13.713.7

-29.7-29.7

-8.6-8.6

p<0.0001p<0.0001

p=0.006p=0.006

HDL-CHDL-C-5-5

00

55

1010

1515

2020

2525

3030

4.44.4

25.125.1

16.516.5

p<0.0001p<0.0001

-0.49

0.35

-0.35

-0.6

-0.4

-0.2

0

0.2

0.4

pp<0.0001<0.0001

HbA1cHbA1c

Aleglitazar in ACS and Aleglitazar in ACS and T2DMT2DM

AleCardio trialAleCardio trial

Study Hypothesis:Study Hypothesis:

Aleglitazar, added to standard of care of pts with T2DM Aleglitazar, added to standard of care of pts with T2DM and recent acute coronary syndrome (ACS), would and recent acute coronary syndrome (ACS), would reduce cardiovascular mortality and morbidity. reduce cardiovascular mortality and morbidity.

phase 3 phase 3

superiority trialsuperiority trial

randomized, placebo-controlled, double-blind, randomized, placebo-controlled, double-blind, multicentermulticenter

Primary Efficacy Primary Efficacy EndpointEndpoint

PlaceboPlacebo 36103610 33943394 32523252 27202720 17061706 773773118118

AleglitazarAleglitazar 36163616 33873387 32493249 27312731 16881688 780780101101

No. at risk:No. at risk:

HR = 0.96 (95% CI, 0.83-1.11)p = 0.57

Cardiovascular Death, Non-Fatal MI, Non-Fatal StrokeCardiovascular Death, Non-Fatal MI, Non-Fatal Stroke

Mechanisms of DPP-4 Mechanisms of DPP-4 Inhibitor and GLP-1Inhibitor and GLP-1

Potential Mechanisms of reducing CV Potential Mechanisms of reducing CV outcomes with DPP-4 inhibitorsoutcomes with DPP-4 inhibitors

Fadini,G, Cardiovascular effects of DPP-4 Inhibition, Vascular Pharm 2011

DPP-4 Inhibitors and CV DPP-4 Inhibitors and CV Events: A Meta-analysisEvents: A Meta-analysis

52% reduction in risk for CV events compared to other oral agents or placebo.52% reduction in risk for CV events compared to other oral agents or placebo.Patil HR, et al. Am J Cardiol. 2012;110(6):826-833.

First AuthorDPP4i Comparator

Risk RatioM-H, Random, 95% CI

Risk RatioM-H, Random, 95% CIEvents Total Events Total Weight

Aschner 1 528 3 522 3.7% 0.33 (0.03, 3.16)

Bosi E 1 300 2 294 3.3% 0.49 (0.04, 5.37)

Chan 10 65 12 26 37.7% 0.33 (0.16, 0.67)

Defronzo 2 264 0 64 2.1% 1.23 (0.06, 25.54)

Foley 0 546 0 546 Not estimable

Foley Je 0 29 0 30 Not estimableNCT00316082 4 291 3 74 8.6% 0.34 (0.08, 1.48)NCT00374907 0 20 1 16 1.9% 0.27 (0.01, 6.21)

NCT00698932 4 284 0 284 2.2% 9.00 (0.49, 166.39)

NCT00918879 0 107 0 106 Not estimable

NCT01263496 5 391 0 83 2.3% 2.36 (0.13, 42.22)

Pfuntzer 2 335 7 328 7.7% 0.28 (0.06, 1.34)

Pi-Sunyer 0 262 0 92 Not estimable

Rosenstock 11 306 3 95 11.9% 1.14 (0.32, 4.00)

Rosenstock J 0 396 0 202 Not estimable

Schweitzer 2 169 2 166 4.9% 0.98 (0.14, 6.89)

Schweitzer A 0 526 2 254 2.0% 0.10 (0.00, 2.01)Williams-Herman 3 179 11 364 11.7% 0.55 (0.16, 1.96)

Total (95% CI) 4998 3546 100.0% 0.48 (0.31,0.75)

Total events 45 46

Heterogeneity: Tau2 = 0.00; Chi2 = 11.22, df = 12 (P = 0.51); I2 = 0%Test for overall effect: Z = 3.28 (P = 0.001)

0.001

DPP4i better0.1 1 10 1000

DPP4i worse

SAVOR-TIMI 53SAVOR-TIMI 53

• Primary endpoint (CV death/MI/stroke) for Primary endpoint (CV death/MI/stroke) for saxagliptin vs. placebo: 7.3% vs. 7.2%; HR saxagliptin vs. placebo: 7.3% vs. 7.2%; HR 1.00, 95% CI 0.89-1.12; p1.00, 95% CI 0.89-1.12; pnoninferiority noninferiority < 0.001 < 0.001 for, pfor, psuperiority superiority = 0.99= 0.99

• CV death: 3.2 vs. 2.9%, p = 0.72; MI: 3.2% CV death: 3.2 vs. 2.9%, p = 0.72; MI: 3.2% vs. 3.4%, p = 0.52; all-cause mortality: vs. 3.4%, p = 0.52; all-cause mortality: 4.9% vs. 4.2%, p = 0.154.9% vs. 4.2%, p = 0.15

• HbAHbA1c1c at 2 years: 7.5% vs. 7.8%, p < 0.001 at 2 years: 7.5% vs. 7.8%, p < 0.001

Trial design: Patients with type 2 diabetes mellitus (DM2) and established CV disease or multiple risk factors were randomized to either saxagliptin 5 mg daily or placebo. Patients were followed for a median of 2.1 years.

Results

Conclusions

Scirica BM. N Engl J Med 2013;Sep 2:[Epub]

Saxagliptin(n = 8,280)

Primary endpoint

• Saxagliptin, a DPP-4 inhibitor, is not associated with an excess of CV events as compared with placebo in patients with DM2 and either established CV disease or risk factors

• The upper margin of 95% CI of 1.12 for the primary endpoint was lower than the threshold set by the FDA (1.3) for postmarketing trial, supporting its CV safety in diabetic patients

0

5

10

7.3 7.2

Placebo(n = 8,212)

%

(pnoninferiority < 0.001)

EXAMINEEXAMINE

• Primary endpoint (CV death/MI/stroke) for Primary endpoint (CV death/MI/stroke) for alogliptin vs. placebo: 11.3% vs. 11.8%; HR alogliptin vs. placebo: 11.3% vs. 11.8%; HR 0.96, upper boundary of 95% CI = 1.16; 0.96, upper boundary of 95% CI = 1.16; ppnoninferiority noninferiority < 0.001; p< 0.001; psuperiority superiority = 0.32= 0.32

• CV death: 3.3% vs. 4.1%, p = 0.10; MI: 6.9% CV death: 3.3% vs. 4.1%, p = 0.10; MI: 6.9% vs. 6.5%, p = 0.47; all-cause mortality: 5.7% vs. 6.5%, p = 0.47; all-cause mortality: 5.7% vs. 6.5%, p = 0.23vs. 6.5%, p = 0.23

• HbAHbA1c1c ↓ at 3 years: -0.33% vs. 0.03%, p < 0.001 ↓ at 3 years: -0.33% vs. 0.03%, p < 0.001

Trial design: Patients with type 2 diabetes mellitus (DM2) and recent ACS were randomized to either alogliptin 25 mg daily or placebo. Patients were followed for 3 years.

Results

Conclusions

White WB. N Engl J Med 2013;Sep 2:[Epub]

Alogliptin(n = 2,701)

Primary endpoint

• Alogliptin, a DPP-4 inhibitor, is not associated with an excess of CV events as compared with placebo in patients with DM2 and recent ACS

• The upper margin of 95% CI of 1.16 for the primary endpoint was lower than the threshold set by the FDA (1.3) for postmarketing trial, supporting its CV safety in diabetic patients

0

10

20

11.3 11.8

Placebo(n = 2,679)

%

(pnoninferiority < 0.001)

67

82 week weight reduction

exenatide

Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1)

Receptor Agonist Exenatide Twice Daily orOther Glucose-Lowering Therapies A retrospective analysis of the LifeLink database

JENNIE H. BEST, PHD, Diabetes Care 34:90–95, 20111

Exenatide and CV outcomes- 430,000 patients-near 40,000 on exenatide

Canagliflozin EfficacyCanagliflozin EfficacyCanaCana

CanaCanaCanaCana

CanaCana

Other Meds with Glycemic Other Meds with Glycemic BenefitBenefit

Fast-acting Bromocryptine- drop 0.5-1%Fast-acting Bromocryptine- drop 0.5-1%central dopaminergic effect oncentral dopaminergic effect on decreasing peripheral sympathetic tone decreasing peripheral sympathetic tone

decreasing insulin resistancedecreasing insulin resistance Decreases CV outcomes 50% in 1 yearDecreases CV outcomes 50% in 1 yearColsevelam- drop 0.5%Colsevelam- drop 0.5% lipid benefitlipid benefit(Ranolazine) drop 0.5-1.0%(Ranolazine) drop 0.5-1.0%

Decrease angina ( or equivalent)Decrease angina ( or equivalent)Decreases arrhythmiaDecreases arrhythmiaImproves diastolic dysfunction, thus-decreases Improves diastolic dysfunction, thus-decreases

edema of Pio-, edema of Pio-, Decreases HgA1c, FBS in glucose dependent Decreases HgA1c, FBS in glucose dependent

fashion , no hypoglycemiafashion , no hypoglycemia

Diabetes Mellitus:Diabetes Mellitus:Effect of Blood Pressure ControlEffect of Blood Pressure Control

Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial

Pat

ien

ts w

ith

Eve

nts

(%

)

0

5

10

15

20

Years Post-Randomization0 1 2 3 4 5 6 7 8

Pat

ien

ts w

ith

Eve

nts

(%

)

0

5

10

15

20

Years Post-Randomization0 1 2 3 4 5 6 7 8

Tota

l S

troke

HR=0.8895% CI (0.73-1.06)

HR=0.5995% CI (0.39-0.89)

4,733 diabetic patients randomized to intensive BP control (target SBP <120 mm Hg) or standard BP control (target SBP <140 mm Hg)

for 4.7 years

Intensive BP control in DM does not reduce a composite of adverse CV events, but does reduce the rate of stroke

Non

fata

l M

I,

non

fata

l str

oke,

or

CV

death

BP=Blood pressure, DM=Diabetes mellitus, HR=Hazard ratio, SBP=Systolic blood pressureACCORD study group. NEJM 2010

Recommendation #5Recommendation #5

5.  In patients aged ≥18 years with diabetes, initiate 5.  In patients aged ≥18 years with diabetes, initiate pharmacologic treatment at systolic BP ≥140mmHg or pharmacologic treatment at systolic BP ≥140mmHg or diastolic BP ≥90mmHg and treat to a goal systolic BP diastolic BP ≥90mmHg and treat to a goal systolic BP <140mmHg and goal diastolic BP <90mmHg. (Expert <140mmHg and goal diastolic BP <90mmHg. (Expert Opinion–Grade E)Opinion–Grade E)

For Adults with diabetes aim for the same BP goals as in the general

population

Treat if BP >140/90; Aim for <140/90

Diabetes Mellitus:Diabetes Mellitus:Effect of an HMG-CoA Reductase InhibitorEffect of an HMG-CoA Reductase Inhibitor

Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet 2008;37:117-25

Meta-analysis of 18,686 patients with DM randomized to treatment with a HMG-CoA Reductase Inhibitor

Statins reduce CV events 21% in diabetics (similar to non-diabetics)

High, Moderate and Low Intensity Statin Dosages

DDiabetes iabetes PPrevention revention PProgram: rogram: Reduction in Diabetes Reduction in Diabetes IncidenceIncidence

Look AHEAD (Action for Health in Diabetes): Look AHEAD (Action for Health in Diabetes): Trial Halted EarlyTrial Halted Early

1, 2. Look AHEAD Research Group. Diabetes Care. 2007;30:1374-1383 and Arch Intern Med.2010;170:1566–1575; http://www.nih.gov/news/health/oct2012/niddk-19.htm.

• Intensive lifestyle Intensive lifestyle intervention resulted inintervention resulted in11

– Average 8.6% weight lossAverage 8.6% weight loss– Significant reduction of Significant reduction of

A1CA1C– Reduction in several CVD Reduction in several CVD

risk factorsrisk factors• However, trial halted However, trial halted

after 11 years of follow-after 11 years of follow-up because there was up because there was no significant no significant difference in primary difference in primary cardiovascular outcome cardiovascular outcome between weight loss, between weight loss, standard care group standard care group HR=0.95 (0.80-1.05),

p=0.51

NEJM June 24, 2013

Look Ahead Trial Risk Factor DifferencesLook Ahead Trial Risk Factor Differences

Diminished differences between groups over time:

1) weight 2) physical fitness, 3) waist circumference 4) HbA1c.

PREDIMED STUDY (n=7447): Primary Prevention of High Risk Pts with DM or 3+ Risk Factors Randomized to Mediterranean Diet with Extra Virgin Olive Oil or Nuts vs. AHA Diet

ADA Dietary ADA Dietary Recommendations 2013Recommendations 2013

1) Individualized medical nutrition therapy (MNT) by 1) Individualized medical nutrition therapy (MNT) by dietitiandietitian2) Balance energy expenditure with intake, reducing 2) Balance energy expenditure with intake, reducing intake to promote weight lossintake to promote weight loss3) Optimal mix of macronutrients with a variety of 3) Optimal mix of macronutrients with a variety of eating patterns acceptable taking into account personal eating patterns acceptable taking into account personal preferences and metabolic goalspreferences and metabolic goals4) Amount of carbohydrates may be most important 4) Amount of carbohydrates may be most important factor influencing glycemic response after eating, so factor influencing glycemic response after eating, so monitoring carbohydrate intake is a key strategy and monitoring carbohydrate intake is a key strategy and choosing intake from vegetables, fruits, whole grains, choosing intake from vegetables, fruits, whole grains, legumes and dairy productslegumes and dairy products5) substitute low-glycemic load foods for higher 5) substitute low-glycemic load foods for higher glycemic load foodsglycemic load foods6) Consumption of fiber and whole grains6) Consumption of fiber and whole grains

Consume a dietary pattern that emphasizes intake of Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, nontropical dairy products, poultry, fish, legumes, nontropical vegetable oils and nuts; and limits intake of sweets, vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages, and red meats.sugar-sweetened beverages, and red meats.

• Adapt this dietary pattern to appropriate calorie Adapt this dietary pattern to appropriate calorie requirements, personal and cultural food requirements, personal and cultural food preferences, and nutrition therapy for other preferences, and nutrition therapy for other medical conditions (including diabetes).medical conditions (including diabetes).

• Achieve this pattern by following plans such as Achieve this pattern by following plans such as the DASH dietary pattern, the U.S. Department of the DASH dietary pattern, the U.S. Department of Agriculture (USDA) Food Pattern, or the AHA Agriculture (USDA) Food Pattern, or the AHA Diet.Diet.

LDL-C: Advise adults who LDL-C: Advise adults who would benefit from LDL-C would benefit from LDL-C lowering* to:lowering* to:

II IIaIIa IIbIIb IIIIII

*Refer to 2013 Blood Cholesterol Guideline for guidance on who *Refer to 2013 Blood Cholesterol Guideline for guidance on who would benefit from LDL-C lowering.would benefit from LDL-C lowering.

AskAsk and document tobacco and document tobacco use statususe status

AdviseAdvise Provide a strong, personalized Provide a strong, personalized message message

AssessAssess Readiness to quit in next Readiness to quit in next 30 days30 days

Prevent RelapsePrevent Relapse Congratulate successesCongratulate successes Encourage Encourage Discuss benefits experienced by Discuss benefits experienced by patientpatient Address weight gain, negative Address weight gain, negative mood, and lack of supportmood, and lack of support

Increase MotivationIncrease Motivation Relevance to personal situationRelevance to personal situation Risks: short and long-term, Risks: short and long-term, environmentalenvironmental Rewards: potential benefits of Rewards: potential benefits of quittingquitting Roadblocks: identify barriers and Roadblocks: identify barriers and solutionssolutions Repetition: repeat motivational Repetition: repeat motivational interventionintervention Reassess readiness to quit Reassess readiness to quit

Assist: Assist: Negotiate plan Negotiate plan STAR**STAR** Discuss pharmacotherapyDiscuss pharmacotherapy Social supportSocial support Provide educational materialsProvide educational materials

ArrangeArrange Follow-up to check plan or adjust Follow-up to check plan or adjust medsmeds Call right before and after quit dateCall right before and after quit date Weekly follow-up x 2 weeks, then monthly Weekly follow-up x 2 weeks, then monthly x 6 monthsx 6 months Ask about difficulties (withdrawal, Ask about difficulties (withdrawal, depressed mood)depressed mood) Build upon successesBuild upon successes Seek commitment to stay tobacco-freeSeek commitment to stay tobacco-free

**STAR**STARSSetet quit datequit dateTTell family, friends, and coworkersell family, friends, and coworkersAAnticipate challenges: withdrawal, nticipate challenges: withdrawal, breaksbreaksRRemoveemove tobacco from the house, tobacco from the house, car etc.car etc.

Recent Recent QuitterQuitter

(<6 months)(<6 months) Current Current UserUser

Not Not ReadyReady

Ready Ready

Tobacco Cessation Algorithm

Recommendations: Physical ActivityRecommendations: Physical Activity

• Advise people with or without diabetes to Advise people with or without diabetes to perform at least 150 min/week of moderate-perform at least 150 min/week of moderate-intensity aerobic physical activity (50intensity aerobic physical activity (50––70% of 70% of maximum heart rate), spread over at least 3 maximum heart rate), spread over at least 3 days per week with no more thandays per week with no more than2 consecutive days without exercise (A)2 consecutive days without exercise (A)

• In absence of contraindications, adults with In absence of contraindications, adults with type 2 diabetes should be encouraged to type 2 diabetes should be encouraged to perform resistance training at least twice per perform resistance training at least twice per week (A)week (A)

ADA. V. Diabetes Care. Diabetes Care 2013;36(suppl 1):S24.

RCT Trial Assessment of Pedometer RCT Trial Assessment of Pedometer InterventionsInterventions

Bravata, DM et al. JAMA 2007; 298:2296-2304

N=277; 8 TrialsPedometer increased steps by 2500/day

• Up to 80% of heart disease, stroke Up to 80% of heart disease, stroke and type 2 diabetes and over a and type 2 diabetes and over a third of the most common cancers third of the most common cancers could be prevented by eliminating could be prevented by eliminating obesity, unhealthy diets and obesity, unhealthy diets and physical inactivityphysical inactivity

• Call for commitments at the global Call for commitments at the global and national level to address these and national level to address these risk factors including:risk factors including:

– Control food supply, food Control food supply, food information and marketing and information and marketing and promotion of energy-dense, promotion of energy-dense, nutrient-poor foods that are high nutrient-poor foods that are high in saturated, trans-fat, salt or in saturated, trans-fat, salt or refined sugarsrefined sugars

Nutrition, physical activity and NCD prevention

SummarySummary• Most persons with diabetes will suffer and die Most persons with diabetes will suffer and die

from cardiovascular consequencesfrom cardiovascular consequences• Few persons with diabetes are appropriately Few persons with diabetes are appropriately

controlled for key measures of A1c, BP, lipids, controlled for key measures of A1c, BP, lipids, and weight.and weight.

• Combined control of risk factors can result in up Combined control of risk factors can result in up to 50% reductions in risk for cardiovascular to 50% reductions in risk for cardiovascular diseasedisease

• Greater adherence to lifestyle modifications and Greater adherence to lifestyle modifications and use of guideline-based and newer therapies can use of guideline-based and newer therapies can help us address remaining residual risks.help us address remaining residual risks.

http://cardiometabolic.cardiosource.org/

American Society for Preventive Cardiology: www.aspconline.org

Now Available

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