1. Metabolic Syndrome, Diabetes and Cardiovascular Disease: Strategies for Management Nathan D. Wong, PhD, FACC, FAHA Professor and Director, Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine Past President, American Society of Preventive Cardiology

2. Global Distribution of Diabetes, WHO 2011

3. Diabetes: A Growing Challenge Prevalence in the United States
Diagnosed Diabetes
% of Population
# of Patients in Millions
Diabetes Mellitus:  Prevalence in the US
Beginning in 1958, the noninstitutionalized United States population has been sampled annually through interviews from 36,000 to 49,000 randomly selected households. Data from the National Health Interview Survey reveal a steady increase in both the prevalence rate and number of people with diabetes. Several explanations to explain this increase in prevalence include: an aging United States population and higher rates of diabetes in older adults; reduction in mortality of people with diabetes; and modifications to the criteria used to diagnose diabetes, which were based on glycosuria prior to the mid-1950’s. These explanations may account for some of the increase in the prevalence rate, however, the growing number of overweight and physically inactive individuals is also likely to contribute to the elevated numbers.
All ages
23.6 million
7.8% of population
17.9 million diagnosed
5.7 million undiagnosed
> 20 years old: 23.5 million
10.7% of age group
> 60 years old: 12.2 million
23.1% of population
Men: 12.0 million
11.2% of those > 20 years old
Women: 11.5 million
10.2% of those > 20 years old
Reference
Kenny SJ, Aubert RE, Geiss LS. Prevalence and incidence of non-insulin-dependent diabetes. In: Diabetes in America. 2nd ed. Bethesda, Md: National Diabetes Data Group, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; 1995: NIH Publication No
Centers for Disease Control and Prevention, Division of Diabetes Translation.
National Diabetes Surveillance System. Available at 3

4. Age-Adjusted Prevalence of Type 2 DM: California Adults Aged >18 Including Hispanic and Asian Subgroups 2009
N.D. Wong, California Health Interview Survey (unpublished)

5. Diabetes Mellitus: Lifetime Risk
Advancing age is a strong predictor of developing diabetes mellitus in men and women alike.
Narayan et al. JAMA 2003;290: 5

6. Microvascular complications Macrovascular complications
Natural History of Type II Diabetes Mellitus
Years from diagnosis
-10 -5 5 10 15
Onset
Diagnosis
Insulin resistance
Postprandial
glucose
Insulin secretion
Type II diabetes mellitus increases the risk of microvascular and macrovascular complications. Improved glycemic control can help to minimize these complications over time.
Fasting glucose
Microvascular complications
Macrovascular complications
Pre-diabetes
Type II diabetes
Ramlo-Halsted BA et al. Prim Care. 1999;26:
Nathan DM et al. NEJM 2002;347:

7. Diagnostic Criteria for Glycemic Abnormalities
FPG
126 mg/dL
100 mg/dL
7.0 mmol/L
5.6 mmol/L
Prediabetes
Normal
Diabetes Mellitus
2-Hour PG on OGTT
200 mg/dL
140 mg/dL
11.1
mmol/L
7.8
Impaired Glucose
Tolerance
Hemoglobin A1C
6.5%
6.0%
Criteria for the diagnosis of diabetes mellitus include: (a) a fasting glucose >126 mg/dl or (b) a two hour plasma glucose of >200mg/dl after a 75 gram oral glucose load. An International Committee recently added the hemoglobin A1C assay as an alternative diagnostic test, with a level ≥6.5% indicating diabetes and a level between 6.0 and 6.5% indicating high risk for progression to diabetes.
To convert mg/dL to mmol/L multiply mg/dl by 0.055
FPG=Fasting plasma glucose, PG=Plasma glucose, OGTT=Oral glucose tolerance test
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2001;24:S5-S20
American Diabetes Association. Diabetes Care 2010;33:S11-61

8. Causes of Mortality in Patients With Diabetes
Cardiovascular disease is the most common cause of death among patients with diabetes, according to data from death certificates. Heart disease accounts for approximately 55% of all deaths and cerebrovascular disease is responsible for another 10% of deaths.
Acute diabetes-related complications are the next most common cause of death, accounting for 13% of deaths. Pneumonia/influenza, malignant neoplasms, and other causes account for the remaining deaths.
Renal disease is not listed as a separate category, because dialysis and transplantation have made renal failure an uncommon immediate cause of death. However, cardiovascular disease is a common cause of death in patients on long-term dialysis.
In patients with type 2 diabetes, the relative contribution of cardiovascular disease as a cause of death is greater in younger-age and younger-age-at-onset patients than in older-age and older-age-at-onset patients.
Geiss LS, et al. Mortality in non-insulin-dependent diabetes. In: Diabetes in America. 2nd ed. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; 1995: NIH Publication No

9. Diabetes and CVD Atherosclerotic complications responsible for
80% of mortality among patients with diabetes
75% of cases due to coronary artery disease (CAD)
Results in >75% of all hospitalizations for diabetic complications
50% of patients with type 2 diabetes have preexisting CAD. (This number may be less now that more younger people are diagnosed with diabetes.) 
1/3 of patients presenting with myocardial infarction have undiagnosed diabetes mellitus
Diabetes: Atherosclerotic Complications
Atherosclerotic cardiovascular disease is the primary cause of death in people with diabetes. In addition, most hospitalizations resulting from diabetes-associated complications are a consequence of atherosclerotic cardiovascular disease. Incidence of atherosclerotic cardiovascular disease is 2- to 4-fold higher in individuals with diabetes than without the disease. A likely explanation for the elevated post-infarction mortality rate among individuals with diabetes is the diffuse pattern of atherosclerosis generally observed in this patient population. .
Dyslipidemia correlates with elevated risk for coronary artery disease (CAD) in patients with and without diabetes. It is therefore suggested that aggressive management of lipid level abnormalities may dramatically decrease the incidence of CAD in the diabetic patient population.
The “50% with CAD” is likely an overestimate, given the prevalence of T2DM now in children and young adults
Reference
Lewis GF. Diabetic dyslipidemia: a case for aggressive intervention in the absence of clinical trial and cost effective data. Can J Cardiol. 1995;11(suppl C):24C-28C.
Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28C
Norhammar A, et.al. Lancet 2002;359; 9

10. Most Cardiovascular Patients Have Abnormal Glucose Metabolism
GAMI
n = 164
EHS
n = 1920
CHS
n = 2263
18%
27%
35%
31%
37%
37%
45%
36%
34%
Prediabetes
Type 2 Diabetes
Normoglycemia
GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction study; EHS = Euro Heart Survey; CHS = China Heart Survey
Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38. 10

11. Subclinical Atherosclerosis Atherosclerotic Clinical Events
Mechanisms by which Diabetes Mellitus
Leads to Coronary Heart Disease
Hyperglycemia
Insulin Resistance
HTN Endothelial dysfunction
Inflammation
Dyslipidemia
 LDL
 TG
 HDL
 AGE
 Oxidative stress
Infection
 IL-6
 CRP
 SAA
Thrombosis
 PAI-1
 TF
 tPA
 Defense mechanisms
 Pathogen burden
Subclinical Atherosclerosis
Disease Progression
Infection, inflammation, hyperglycemia, insulin resistance, dyslipidemia, and thrombosis have all been implicated in the development of atherosclerosis and subsequent adverse CV events in patients with diabetes mellitus.
Atherosclerotic Clinical Events
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
Biondi-Zoccai GGL et al. JACC 2003;41: 11

12. Risk of Cardiovascular Events in Patients with Diabetes: Framingham Study
_________________________________________________________________
Age-adjusted
Biennial Rate Age-adjusted
Per Risk Ratio
Cardiovascular Event Men Women Men Women
Coronary Disease ** ***
Stroke *** 2.6***
Peripheral Artery Dis *** 6.4***
Cardiac Failure *** 7.8***
All CVD Events *** 3.7***
Subjects year Follow-up **P<.001,***P<.0001
_________________________________________________________________ 12

13. Cardiovascular Risk Factors are the Top 6 Leading Causes of Death

15. Metabolic Syndrome: Clustering of Interconnected Metabolic Risk Factors
Insulin
Resistance
+ Hyperglycemia
Obesity
Hypertension
Atherogenic
Dyslipidemia

16. IDF/IAS/NHLBI/AHA/WHF Joint Scientific Statement on Diagnosis of Metabolic Syndrome (Alberti et al. Circulation 2009) (>=3 criteria required for diagnosis)

17. Alberti et al. Circulation 2009

18. Intra-abdominal (Visceral) Fat The dangerous inner fat!
Front
Visceral AT
Subcutaneous AT
Back 3

19. To measure waist circumference, 1) locate the upper hip bone and the top of the right iliac crest, 2) place the measuring tape in a horizontal plane around the abdomen at the iliac crest, 3) ensure that the tape is snug but does not compress the skin, 4) the tape should be parallel to floor, and 5) record the measurement at the end of a normal expiration.
Men are at increased relative risk if they have a waist circumference greater than 40 inches (102 cm); women are at an increased relative risk if they have a waist circumference greater than 35 inches (88 cm).
There are ethnic- and age-related differences in body fat distribution that may affect the predictive validity of waist circumference as a surrogate for abdominal fat.
Heterogeneity of composition of abdominal tissues, in particular adipose tissue and skeletal muscle, and their location-specific and changing relations with metabolic factors and CV risk factors in different ethnic groups do not allow a simple definition of abdominal obesity that could be applied uniformly. In particular, Asians appear to have higher morbidity at lower cutoff points for waist circumference than do white Caucasians.
National Institutes of Health, National Heart, Lung, and Blood Institute, NHLBI Obesity Education Initiative, North American Association for the Study of Obesity. The practical guide to the identification, evaluation, and treatment of overweight and obesity in adults. NIH Publication Number October 2000.
Misra A, Wasir JS, Vikram NK. Waist circumference criteria for the diagnosis of abdominal obesity are not applicable uniformly to all populations and ethnic groups. Nutrition. 2005;21:

20. Abdominal Adiposity Is Associated With Increased Risk of Diabetes
P value for trend <0.001
Relative Risk of Diabetes
Circling back to the discussion of abdominal adiposity, data regarding waist circumference and diabetes illustrate its health impact. These are age-adjusted data from the Nurses’ Health Study, analyzing responses from 43,581 subjects who provided information on weight and body measurements in These subjects had no history of cancer, heart disease, stroke, or any type of diabetes. An 8-year follow-up in this population showed a strong positive association between waist circumference and the incidence of diabetes. At the far end of the spectrum, women with a waist circumference >38 inches had a diabetes risk of 22.4, relative to women in the normal waist circumference range of <28 inches. Other obesity measures studied included body mass index and waist-to-hip ratio; both of these were also found to be independent determinants of type 2 diabetes in this population. The sharpest risk gradient was documented with waist circumference, indicating that it is a powerful independent predictor of type 2 diabetes in women.
(WC was measured at the high point of the iliac crest at minimal respiration to the nearest 0.1 cm.)
Carey VJ, Walters EE, Colditz GA, et al. Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women: the Nurses’ Health Study. Am J Epidemiol. 1997;145:
Waist Circumference (in)
Carey VJ, et al. Am J Epidemiol. 1997;145: 20

21. Metabolic Syndrome and Diabetes in Relation to CHD, CVD, and Total Mortality: U.S. Men and Women Ages 30-74
(Risk-factor Adjusted Cox Regression) NHANES II
Follow-up (n=6255)
***
***
***
***
***
***
***
*** * **
***
***
Malik and Wong, et al., Circulation 2004.
* p<.05, ** p<.01, **** p<.0001 compared to none 21

22. Metabolic Syndrome and CVD Risk: Meta-Analysis: Mottillo et al
Metabolic Syndrome and CVD Risk: Meta-Analysis: Mottillo et al. JACC 2010
951,083 pts in 83 studies
Little variation in risk between definitions
Relative risk:
2.35 ( ) for CVD events
2.40 ( ) for CVD mortality
1.58 ( ) for all-cause mortality
1.99 ( ) for myocardial infarction
2.27 ( ) for stroke
Those with metabolic syndrome, without diabetes, maintained high CVD risk (RR=1.75, 95% CI= )

23. 7-Year Incidence Rate of MI
Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study)
P<0.001
P<0.001
45.0%
20.2%
7-Year Incidence Rate of MI
18.8%
3.5%
Type 2 Diabetes and CHD 7-Year Incidence of Fatal/Nonfatal MI (East West Study)
Prior to completion of this study, little data existed to compare mortality rates from coronary heart disease (CHD) in patients with diabetes, but without prior myocardial infarction (MI), and patients without diabetes, but with a history of MI. To sort out the risks among the groups and determine whether patients with diabetes and no MI history should be treated as aggressively for cardiovascular (CV) risk factors as patients who have had an MI, the 7-year incidence MI in 2432 patients (1059 with diabetes, 1373 without diabetes) was quantified.
Results indicate, the 7-year incidence of MI in patients with diabetes was 45.0% for those with a previous MI, and 20.2% for patients without an MI at baseline (P<0.001). Among patients without diabetes, but with a positive history for prior MI, 7-year incidence of MI was 18.8%. Kaplan-Meier estimates that the probability of death from CHD reveals similar outcomes for patients with diabetes/no history of MI and no diabetes/history of MI. The hazard ratio for death from CHD for the 2 groups was not significantly different from 1.0 (hazard ratio, 1.4; 95% confidence interval [CI]) of 0.7 to 2.6). This hazard ratio remained close to 1.0 even after adjustment for total cholesterol, hypertension, and smoking.
These data support that treatment of CV risk factors in patients with diabetes and no history of MI should be as aggressively treated as with patients without diabetes, but with a history of previous MI.
Reference
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339:
No Diabetes
Diabetes
CHD=coronary heart disease; MI=myocardial infarction; DM=diabetes mellitus
Haffner SM et al. N Engl J Med. 1998;339: 23

25. Is DM really a CHD Risk Equivalent
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.

26. 32% of men and 48% of women are at calculated low to intermediate risk
Global Risk Assessment in DM: US adults year Total CVD Risk by Gender (Wong ND et al., Diab Vas Dis Res 2012)
32% of men and 48% of women are at calculated low to intermediate risk

27. 2013 Prevention Guidelines ASCVD Risk Estimator
Available at

28. Screening for Coronary Disease in Diabetes: When and How (Ali and Maron, Clinical Diabetes 2006)
“ Screening patients according to traditional risk factors and current guidelines alone will frequently fail to identify CHD, thus losing the opportunity for early diagnosis and intensified management” “A more aggressive approach to identifying asymptomatic coronary disease should therefore be considered in this (diabetic) patient population”

29. Coronary Heart Disease
Annual CHD Event Rates (in %) by Calcium Score Events by CAC Categories in Subjects with DM, MetS, or Neither Disease (Malik and Wong et al., Diabetes Care 2011)
Coronary Heart Disease
Coronary Artery Calcium Score
ACCF/AHA 2010 Guideline: CAC Scoring for CV risk assessment in asymptomatic adults aged 40 and over with diabetes (Class IIa-B)

30. DIAD Randomized Clinical Trial of Stress MPI Screening (Young, Inzucchi et al. JAMA 2009)
Randomized NIH multicenter trial examining whether screening for myocardial ischemia using adenosine-stress MPI in 1123 persons with type 2 DM and no symptoms of CAD.
Only 22% were positive for myocardial ischemia with only 6% have moderate or large defects
5-year 2.9% cumulative event rate (0.6% per year), much lower than expected Event rates similar in those screening (2.7%) vs. not screened (3.0%) (p=0.73)
(authors note the study only had 20% power to detect a 20% difference between groups)

31. 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 expensive
The much lower than expected event rates makes the study inconclusive in demonstrating the lack of efficacy of screening for subclinical CVD

32. But should we be using stress MPI to screen for CVD in all pts with DM?
Stress MPI is meant to identify short-term risk due to functional deficit, rather than long-term prognosis such as that identified by a test to quantify atherosclerotic burden such as coronary calcium
The radiation and costs are much higher for MPI as compared to coronary calcium, suggesting MPI might be best reserved for those DM at highest risk

33. ADA 2007 Consensus Statement (Bax et al. Diab Care 2007)
“If coronary calcium testing is performed, it appears reasonable to proceed with further testing in diabetic patients with calcium scores >400…….using single photon emission tomography to assess myocardial perfusion or stress echocardiography to assess ischemic wall motion abnormalities”

34. Prevalence of Inducible Ischemia Associated with Presence of Metabolic Abnormality and Coronary Calcium Score (Wong et al., Diabetes Care 2005; 28: )
P=0.032
P=0.018
P< for trend across CCS groups for both metabolic abnormality present and absent; similar relation for those with metabolic syndrome excluding diabetes
ACCF/AHA 2010 Guideline: Stress MPI may be considered for advanced CV risk 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 – Level of Evidence C)
Lipid Management in Clinical Practice - Section 1

35. Does Screening for CVD Improve Outcomes
Does Screening for CVD Improve Outcomes? Beneficial Role of Coronary Multidetector CT Screening for 5-Year All-Cause Mortality among Asymptomatic DM Patients (H Kyung Yang et al., ADA 2014)
Asymptomatic T2DM subjects
774 received coronary MDCT and 1548 matched controls did not get screened
Groups similar except longer duration DM and higher A1c in screened group
After 31 month median follow-up, greater lipid decreases and statin prescription in screened group
Coronary angiography and revascularization higher in MDCT group

36. Beneficial Role of Coronary Multidetector CT Screening for 5-Year All-Cause Mortality among Asymptomatic 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”

37. Coronary Artery Calcium and Cardiovascular Events in Diabetes: Implications for Primary Prevention Therapies: The Multi-Ethnic Study of Atherosclerosis (MESA)
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, MD
2 Division of Cardiology, Harbor-UCLA Medical Center, Torrance, CA
3 Brigham and Women's Hospital Non-invasive CV Imaging Program, Boston, MA
4 Yale University School of Medicine, New Haven, CT
5 Division of Cardiology, University of Miami, Miami, FL
6 Center for Prevention and Wellness, Baptist Health South Florida, Miami, FL
7 UC Irvine Heart Disease Prevention Program, Irvine, CA
8 College of Physicians and Surgeons, Columbia University, New York, NY
Presented at AHA 2012
Presented by: Michael Silverman
April 20, 2017

38. Estimated 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
NNT calculated using 21% RR reduction
Chen Y-H, Feng R, Chen Z-W. Exp Clin End Diab 2012; 120:
Cholesterol Treatment Trialists’ Collaboration, Lancet 2008; 371:
April 20, 2017

39. Summary of Care: ABC's for Providers
A1c Target
Aspirin Daily B
Blood Pressure Control C
Cholesterol Management
Cigarette Smoking Cessation D
Diabetes and Pre-Diabetes Management E
Exercise F
Food Choices

40. Treating the ABCs Reduces Diabetic Complications
Strategy
Complication
Reduction of Complication
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
1 UKPDS Study Group (UKPDS 33). Lancet. 1998;352:
2 Hansson L, et al. Lancet. 1998;351:
3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:
4 Grover SA, et al. Circulation. 2000;102:
5 Pyŏrälä K, et al. Diabetes Care. 1997;20:

41. Benefit of Comprehensive, Intensive Management: STENO 2 Study
Primary End Point=CV events (%) 60
Treatment Goals:
Intensive TLC
HgbA1c <6.5%
Cholesterol <175
Triglycerides <150
BP <130/80 50
Conventional Therapy
n =80
Intensive Therapy 40 30 20
n =80 10 12 24 36 48 60 72 84 96
Months of Follow Up
Gaede, P. et al, NEJM 2003;348:

42. Percent of CHD Events Over 10 Years Prevented in US Adults with T2DM, According to Individual and Composite Risk Factor Control (Wong ND, et al., Am J Cardiol 2014)
Goal(ADA Guidelines)
Nominal
Aggressive
HbA1C* 7%
1% AR
2% AR
Systolic Blood Pressure
130mmHg
10% RR
20% RR
Total Cholesterol
170mg/dl (4.4mmol/L)
25% RR
50% RR
HDL-Cholesterol
40mg/dl(M), 50 mg/dl(F)
10% relative increase
20% relative increase
RR-Relative Reduction; AR- Absolute Reduction; HbA1C levels were not allowed to be reduced further than 6.5%

43. Achieving Risk Factor Targets and CVD Event 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 = ) and CVD (HR=0.66, 95% CI= ) 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.

44. 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 Asians
Composite control of HbA1c, BP, and LDL ranged from 21-27% in Asians

45. Diabetes Mellitus: Effect of Aspirin NS=Not Significant
Endpoint yr MI yr MI yr MCE yr CV Death 4 yr MCE 7yr MCE yr MCE # Events 26 vs vs vs vs vs vs vs 68
p<0.002
p=NS
p < 0.001
p=.04
p<0.05
p=NS
p=NS
Aspirin provides varying degrees of CV risk reduction in diabetes mellitus.
NS=Not Significant
1. Steering Committee of the Physicians' Health Study Research Group. NEJM 1989;321:129-35
2. ETDRS Investigators. JAMA 1992;268:1292
3. Antiplatelet Trialists' Collaboration. BMJ 1994; 308:81
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:a1840
5. Ogawa H et al. JAMA 2008; 300: 2134

46. Recommendations: Antiplatelet Agents (1)
Consider aspirin therapy (75–162 mg/day) (C)
As a primary prevention strategy in those with type 1 or type 2 diabetes at increased cardiovascular risk (10-year risk >10%)
Includes most men >50 years of age or women >60 years of age who have at least one additional major risk factor
Family history of CVD
Hypertension
Smoking
Dyslipidemia
Albuminuria
Recommendations for the use of antiplatelet agents1 are summarized in three slides
Slide 1 of 3
Low-dose (75–162 mg/day) aspirin use for primary prevention is reasonable for adults with diabetes and no previous history of vascular disease who are at increased CVD risk (10-year risk of CVD events >10%) and who are not at increased risk for bleeding
This generally includes most men over age 50 years and women over age 60 years who also have one or more of the following major risk factors: smoking, hypertension, dyslipidemia, family history of premature CVD, or albuminuria
In 2010, a position statement of the ADA, AHA, and the American College of Cardiology Foundation (ACCF) updated prior joint recommendations for primary prevention2
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S32-S33.
References
Pignone M, Alberts MJ, Colwell JA, et al.; American Diabetes Association; American Heart Association; American College of Cardiology Foundation. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care 2010;33:
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36(suppl 1):S32-S33.

47. Recommendations: Antiplatelet Agents (2)
Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk, since potential adverse effects from bleeding likely offset potential benefits (C)
10-year CVD risk <5%: men <50 and women <60 years of age with no major additional CVD risk factors
In patients in these age groups with multiple other risk factors (10-year risk 5–10%), clinical judgment is required (E)
Recommendations for the use of antiplatelet agents are summarized in three slides
Slide 2 of 3
Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk (10-year CVD risk <5%, such as in men <50 and women <60 years of age with no major additional CVD risk factors), since the potential adverse effects from bleeding likely offset the potential benefits (C)
In patients in these age groups with multiple other risk factors (e.g., 10-year risk 5%-10%) clinical judgment is required (E)
However, aspirin is no longer recommended for those at low CVD risk (women under age 60 years and men under age 50 years with no major CVD risk factors; 10-year CVD risk <5%), as the low benefit is likely to be outweighed by the risks of significant bleeding
Clinical judgment should be used for those at intermediate risk (younger patients with one or more risk factors, or older patients with no risk factors; those with 10-year CVD risk of 5–10%) until further research is available. Use of aspirin in patients under the age of 21 years is contraindicated due to the associated risk of Reye syndrome
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33.
Reference
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36(suppl 1):S33.

48. Recommendations: Antiplatelet Agents (3)
Use aspirin therapy (75–162 mg/day)
Secondary prevention strategy in those with diabetes with a history of CVD (A)
For patients with CVD and documented aspirin allergy
Clopidogrel (75 mg/day) should be used (B)
Combination therapy with aspirin (75–162 mg/day) and clopidogrel (75 mg/day)
Reasonable for up to a year after an acute coronary syndrome (B)
Recommendations for the use of antiplatelet agents1 are summarized in three slides
Slide 3 of 3
Use aspirin therapy ( mg/day) as a secondary prevention strategy in those with diabetes with a history of CVD (A)
For patients with CVD and documented aspirin allergy, clopidogrel (75 mg/day) should be used (B)
Combination therapy with ASA ( mg/day) and clopidogrel (75 mg/day) is reasonable for up to a year after an acute coronary syndrome (B)
Clopidogrel has been demonstrated to reduce CVD events in diabetic individuals2
It is recommended as adjunctive therapy in the first year after an acute coronary syndrome or as alternative therapy in aspirin-intolerant patients
ADA. VI. Prevention, Management of Complications. Diabetes Care 2013;36(suppl 1):S33-S34.
References
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36(suppl 1):S33-S34.
Bhatt DL, Marso SP, Hirsch AT, Ringleb PA, Hacke W, Topol EJ. Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus. Am J Cardiol 2002;90:

49. Diabetes Mellitus (Type II): Effect of Intensive Glycemic Control
United Kingdom Prospective Diabetes Study (UKPDS) Year Follow-Up
Sulphonylurea vs Conventional Therapy
Insulin vs Conventional Therapy
Intensive glycemic control in DM reduces the long-term risk of myocardial infarction
Holman RR et al. NEJM 2008;359:

50. Glycemic Legacy?
N Engl J Med 2008;359:

51. Recent Trials Show No Reduction in CV Events with More Intensive Glycemic Control
ACCORD: Primary Outcome
ADVANCE: Primary Outcome 25 20 15 10 5
Years
Standard therapy
Intensive therapy 25 20 15 10 5
Standard therapy
Intensive therapy
Patients with events (%)
Cumulative incidence (%)
Months of follow-up
Number at Risk
Intensive
Standard
Number at Risk
Intensive
Standard
1ACCORD Study Group. N Engl J Med. 2008;358:
2ADVANCE Collaborative Group. N Engl J Med. 2008;358: 51

52. Was Intensive Glycemic Control Harmful
Was Intensive Glycemic Control Harmful? A closer look at ACCORD AND ADVANCE
ACCORD was discontinued early due to increased total and CVD mortality in the intensive arm.
VA Diabetes Trial showed severe hypoglycemia to be a powerful predictor of CVD events.
A recent analysis of ACCORD (Diabetes Care, May 2010) showed deaths related to unsuccessful intensive therapy where A1c remained high.
But in both ACCORD AND ADVANCE, those without macrovascular disease at baseline had an actual benefit in the primary endpoint.

53. Metabolic Memory and Glycemic Legacy
UKPDS vs. VADT
Start of intensive therapy in VADT
Start of intensive therapy in UKPDS
9.5
Drives risk of Complications
9.0
8.5
8.0
Risk of complications continues
despite glycemic control
A1C (%)
Bad Glycemic Legacy
Reference
Del Prato S. Diabetalogia. 2009;52:
Key Points and Additional Details
This figure is a hypothetical representation of the natural history of patients with T2DM in the VADT study.
The upper dashed line represents the time course of HbA1c estimated by the average glucose profile in the UKPDS, based on the premise that duration of diabetes in VADT would be similar to that in UKPDS.
The lower dashed line represents the ideal time course of glycemic control (early and sustained at time of diagnosis).
The solid line to the right represents the time course of HbA1c in the VADT (mean time between diagnosis and start of intensive treatment in VADT = 11.4 years).
Intensive therapy implemented in VADT resulted in a rapid lowering of plasma glucose levels close to the ideal target.
However, this time course is far from the ideal (ie, the achievement and maintenance of near-normal glycemia from the time of diagnosis).
The difference between the ideal and the actual time course of glycemic control represents a time period that may have had some impact on the effect of subsequent tight glycemic control (ie, the glycemic legacy).
7.5
7.0
Ideal course = early and sustained glycemic control
6.5
6.0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
Time Since Diagnosis (years)
Del Prato S. Diabetalogia. 2009;52:

54. American Diabetes Association 2012 Standards of Medical Care: HbA1c Goals
A reasonable A1C goal for many nonpregnant adults is <7% due to efficacy in reducing microvascular complications.
Consider more stringent A1C goals (such as <6.5%) for selected patients, if this can be achieved without significant hypoglycemia or other adverse effects of treatment.
Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, and extensive comorbid conditions and for those with longstanding diabetes in whom the general goal is difficult to attain.

56. ADA Treatment Algorithm

57. Effects of α/γ PPAR Activation
Nuclear receptors that function as transcription factors regulating the expression of genes
↑ Insulin
sensitivity a
Primary g effect is to improve insulin sensitivity g
↑ Fatty acid oxidation
↓ VLDL-TG
↑ Fatty acid uptake
Anti-inflammatory
↑ apo AI, HDL
Primary a effect is to improve plasma lipid profile
↑ Beta cell
function
↑ fatty acid uptake
↑ Adiponectin secretion
Anti-
inflammatory
heart, liver, muscle, vasculature
Adipocytes
Muscle

58. Pioglitazone - PPAR g Activator
Lincoff et al. JAMA 2007;298:
Meta-Analysis
Death, MI, or Stroke – 16,390 Pts
HR = 0.82 (95% CI, )
p = 0.005
PERISCOPE Trial
Coronary Intravascular Ultrasound
Nissen et al. JAMA 2008;299:1561.
p <0.001
p = 0.44
p = between groups 58

59. Aleglitazar - Balanced PPAR a/g Agonist
SYNCHRONY Phase 2 Trial
p<0.0001
p=0.006
HbA1c
Absolute change from baseline
p-values vs placebo
Henry R et al. Lancet 2009;374:126.

60. Aleglitazar in ACS and T2DM
AleCardio trial
Study Hypothesis:
Aleglitazar, added to standard of care of pts with T2DM and recent acute coronary syndrome (ACS), would reduce cardiovascular mortality and morbidity.
phase 3
superiority trial
randomized, placebo-controlled, double-blind, multicenter

61. Primary Efficacy Endpoint
Cardiovascular Death, Non-Fatal MI, Non-Fatal Stroke
HR = 0.96 (95% CI, )
p = 0.57
No. at risk:
Placebo
Aleglitazar 61

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

63. Potential Mechanisms of reducing CV outcomes with DPP-4 inhibitors
Fadini,G, Cardiovascular effects of DPP-4
Inhibition, Vascular Pharm 2011

64. DPP-4 Inhibitors and CV Events: A Meta-analysis
First Author
DPP4i
Comparator
Risk Ratio
M-H, Random, 95% CI
Events
Total
Weight
Aschner 1
528 3
522
3.7%
0.33 (0.03, 3.16)
Bosi E
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
264 64
2.1%
1.23 (0.06, 25.54)
Foley
546
Not estimable
Foley Je 29 30
NCT 4
291 74
8.6%
0.34 (0.08, 1.48)
NCT 20 16
1.9%
0.27 (0.01, 6.21)
NCT
284
2.2%
9.00 (0.49, )
NCT
107
106
NCT 5
391 83
2.3%
2.36 (0.13, 42.22)
Pfuntzer
335 7
328
7.7%
0.28 (0.06, 1.34)
Pi-Sunyer
262 92
Rosenstock 11
306 95
11.9%
1.14 (0.32, 4.00)
Rosenstock J
396
202
Schweitzer
169
166
4.9%
0.98 (0.14, 6.89)
Schweitzer A
526
254
2.0%
0.10 (0.00, 2.01)
Williams-Herman
179
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
0.1 1 10
1000
DPP4i better
DPP4i worse
52% reduction in risk for CV events compared to other oral agents or placebo.
Patil HR, et al. Am J Cardiol. 2012;110(6):

65. (pnoninferiority < 0.001)
SAVOR-TIMI 53
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
(pnoninferiority < 0.001)
Primary endpoint (CV death/MI/stroke) for saxagliptin vs. placebo: 7.3% vs. 7.2%; HR 1.00, 95% CI ; pnoninferiority < for, psuperiority = 0.99
CV death: 3.2 vs. 2.9%, p = 0.72; MI: 3.2% vs. 3.4%, p = 0.52; all-cause mortality: 4.9% vs. 4.2%, p = 0.15
HbA1c at 2 years: 7.5% vs. 7.8%, p < 0.001 10
7.3
7.2 % 5
Conclusions
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
Primary endpoint
Saxagliptin
(n = 8,280)
Placebo
(n = 8,212)
Scirica BM. N Engl J Med 2013;Sep 2:[Epub]

66. (pnoninferiority < 0.001)
EXAMINE
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
(pnoninferiority < 0.001)
Primary endpoint (CV death/MI/stroke) for alogliptin vs. placebo: 11.3% vs. 11.8%; HR 0.96, upper boundary of 95% CI = 1.16; pnoninferiority < 0.001; psuperiority = 0.32
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 = 0.23
HbA1c ↓ at 3 years: -0.33% vs. 0.03%, p < 0.001 20
11.8
11.3 % 10
Conclusions
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
Primary endpoint
Alogliptin
(n = 2,701)
Placebo
(n = 2,679)
White WB. N Engl J Med 2013;Sep 2:[Epub]

67. week weight reduction exenatide 67 REQUIRED DISCUSSION POINTS:
Weight: 25% of the patients lost on average 26.2 lbs (11.4% of baseline body weight)
Overall, 81% of patients had reductions in body weight
SLIDE BACKGROUND:
Patients in this analysis received either 5 or 10 mcg BYETTA BID in the 30-week placebo- controlled trials, followed by 5 mcg BID for 4 weeks and 10 mcg BID thereafter
All patients continued any pre-existing treatment regimens of MET and/or SFU throughout the trials
The 82-week completer cohort (n = 314) consisted of those patients who were treated with BYETTA for 82 weeks by the time of this analysis
Weight-change quartiles consisted of 4 subgroups with approximately equal numbers of patients (n = 78 or 79) for each treatment arm, with Quartile 1 consisting of the 25% of patients with the greatest weight reductions, Quartile 4 consisting of the 25% of patients with the smallest weight reductions (or weight gains), and Quartiles 2 and 3 consisting of those with intermediate weight changes
Baseline weights: Quartile 1: lbs, Quartile 2: lbs, Quartile 3: lbs, Quartile 4: lbs
week weight reduction 67

68. Exenatide and CV outcomes- 430,000 patients-near 40,000 on 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, 2011 1

70. Canagliflozin Efficacy

71. Other Meds with Glycemic Benefit
Fast-acting Bromocryptine- drop 0.5-1%
central dopaminergic effect on
decreasing peripheral sympathetic tone
decreasing insulin resistance
Decreases CV outcomes 50% in 1 year
Colsevelam- drop 0.5%
lipid benefit
(Ranolazine) drop %
Decrease angina ( or equivalent)
Decreases arrhythmia
Improves diastolic dysfunction, thus-decreases edema of Pio-,
Decreases HgA1c, FBS in glucose dependent fashion , no hypoglycemia

72. Nonfatal MI, nonfatal stroke, or CV death
Diabetes Mellitus:
Effect of Blood Pressure Control
Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial
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
HR=0.88
95% CI ( )
HR=0.59
95% CI ( )
Nonfatal MI, nonfatal stroke, or CV death
Total Stroke
BP=Blood pressure, DM=Diabetes mellitus, HR=Hazard ratio, SBP=Systolic blood pressure
ACCORD study group. NEJM 2010

73. Treat if BP >140/90; Aim for <140/90
Recommendation #5
5.  In patients aged ≥18 years with diabetes, initiate pharmacologic treatment at systolic BP ≥140mmHg or diastolic BP ≥90mmHg and treat to a goal systolic BP <140mmHg and goal diastolic BP <90mmHg. (Expert 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

74. Statins reduce CV events 21% in diabetics (similar to non-diabetics)
Diabetes Mellitus:
Effect of an HMG-CoA Reductase Inhibitor
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)
Cholesterol Treatment Trialists’ (CTT) Collaborators. Lancet 2008;37:117-25

77. High, Moderate and Low Intensity Statin Dosages

78. It has become well accepted that moderate weight loss improves cardiovascular and metabolic risk factors. In a study by Case and colleagues of obese individuals enrolled in a medically supervised rapid weight loss program study, 1 year of consecutive patients’ charts was reviewed to determine the response to diet-induced weight loss. Out of 185 individuals, 125 (68%) met the NCEP definition of the metabolic syndrome.
At 4 weeks, a moderate decrease in weight (6.5%) induced by a very low calorie diet resulted in substantial reductions of systolic (11.1 mm Hg) and diastolic (5.8 mm Hg) blood pressure, glucose (17 mg/dL), triglycerides (94 mg/dL) and total cholesterol (37 mg/dL) (all P<0.001). These improvements were sustained at the end of active weight loss (average 16.7 weeks; total weight loss 15.1%), with further significant reductions in blood pressure and triglycerides. Weight loss was related to the changes in each criterion of the metabolic syndrome.
The authors concluded that moderate weight loss markedly improved all aspects of the metabolic syndrome.
Case CC, Jones PH, Nelson K, O’Brian Smith E, Ballantyne CM. Impact of weight loss on the metabolic syndrome. Diabetes Obes Metab. 2002;4:

79. Diabetes Prevention Program: Reduction in Diabetes Incidence
Lifestyle reduced the incidence of diabetes by 58% (95% CI, 48%-66%) and metformin reduced the incidence by 31% (95% CI, 17%-43%).
The incidence of diabetes was 39% lower (95% CI, 24%-51%) in the lifestyle group than in the metformin group.
Treatment effects did not differ significantly according to sex or to race or ethnic group.
The lifestyle intervention was highly effective in all subgroups. Its effect was significantly greater among persons with lower base-line glucose concentrations two hours after a glucose load than among those with higher base-line glucose values.
The advantage of lifestyle intervention over metformin was greater in older persons and those with a lower body-mass-index than in younger persons and those with a higher body-mass-index.
The effect of metformin was less with a lower body-mass-index or a lower fasting glucose concentration than with higher values for those variables.
The investigators concluded that, compared with placebo, 1 case of diabetes can be prevented for every 7 persons treated with lifestyle changes for 3 years and for every 14 persons treated with metformin for 3 years.
Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:

80. Look AHEAD (Action for Health in Diabetes): Trial Halted Early
Intensive lifestyle intervention resulted in1
Average 8.6% weight loss
Significant reduction of A1C
Reduction in several CVD risk factors
However, trial halted after 11 years of follow-up because there was no significant difference in primary cardiovascular outcome between weight loss, standard care group
Look AHEAD (Action for HEAlth in Diabetes) is a large clinical trial designed to determine whether long-term weight loss will improve glycemia and prevent cardiovascular events in subjects with type 2 diabetes1
One-year results of the intensive lifestyle intervention in this trial show an average of 8.6% weight loss, significant reduction of A1C, and reduction in several cardiovascular disease (CVD) risk factors, with benefits sustained at 4 years2
At the time this article was going to press, the Look AHEAD trial was halted early, after 11 years of follow-up, because there was no significant difference in the primary cardiovascular outcome between the weight loss and standard care group (
Multiple cardiovascular risk factors were improved with weight loss, and those participants on average were on fewer medications to achieve these improvements
HR=0.95 ( ), p=0.51
NEJM June 24, 2013
1, 2. Look AHEAD Research Group. Diabetes Care. 2007;30: and Arch Intern Med. 2010;170:1566–1575;
References
Pi-Sunyer X, Blackburn G, Brancati FL, et al, for the Look AHEAD Research Group. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the Look AHEAD trial. Diabetes Care. 2007;30:
Wing RR, Egan C, Bahnson JL, et al, for the Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med 2010;170:

81. Look Ahead Trial Risk Factor Differences
Diminished differences between groups over time:
1) weight
2) physical fitness,
3) waist circumference ) HbA1c.
This set of six slides summarize recommendations for screening, treatment, and goals for dyslipidemia/lipid management in patients with diabetes
Slide 5 of 6 – Treatment Recommendations and Goals (Slide 4 of 5)
If drug-treated patients do not reach the targets outlined on the previous slide (Slide 3 of 5) on maximal tolerated statin therapy, a reduction in LDL cholesterol of ~30-40% from baseline is an alternative therapeutic goal (A)
Triglyceride levels <150 mg/dl (1.7 mmol/l) and HDL cholesterol >40 mg/dl (1.0 mm/l) in men and >50 mg/dl (1.3 mmol/l) in women, are desirable (C); however, LDL cholesterol-targeting statin therapy remains the preferred strategy (A)
Reference
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36(suppl 1):S31.

82. 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

83. ADA Dietary Recommendations ) Individualized medical nutrition therapy (MNT) by dietitian 2) Balance energy expenditure with intake, reducing intake to promote weight loss 3) Optimal mix of macronutrients with a variety of eating patterns acceptable taking into account personal preferences and metabolic goals 4) Amount of carbohydrates may be most important factor influencing glycemic response after eating, so monitoring carbohydrate intake is a key strategy and choosing intake from vegetables, fruits, whole grains, legumes and dairy products 5) substitute low-glycemic load foods for higher glycemic load foods 6) Consumption of fiber and whole grains

84. LDL-C: Advise adults who would benefit from LDL-C lowering* to:
IIa
IIb
III A
Consume a dietary pattern that emphasizes intake of vegetables, fruits, and whole grains; includes low-fat dairy products, poultry, fish, legumes, nontropical vegetable oils and nuts; and limits intake of sweets, sugar-sweetened beverages, and red meats.
Adapt this dietary pattern to appropriate calorie requirements, personal and cultural food preferences, and nutrition therapy for other medical conditions (including diabetes).
Achieve this pattern by following plans such as the DASH dietary pattern, the U.S. Department of Agriculture (USDA) Food Pattern, or the AHA Diet.
*Refer to 2013 Blood Cholesterol Guideline for guidance on who would benefit from LDL-C lowering.

85. Tobacco Cessation Algorithm
Ask and document tobacco use status
Prevent Relapse
Congratulate successes
Encourage
Discuss benefits experienced by patient
Address weight gain, negative mood, and lack of support
Recent Quitter
(<6 months)
Current User
Advise Provide a strong, personalized message
Assess Readiness to quit in next 30 days
Not Ready
Increase Motivation
Relevance to personal situation
Risks: short and long-term, environmental
Rewards: potential benefits of quitting
Roadblocks: identify barriers and solutions
Repetition: repeat motivational intervention
Reassess readiness to quit
Ready
Assist: Negotiate plan
STAR**
Discuss pharmacotherapy
Social support
Provide educational materials
**STAR
Set quit date
Tell family, friends, and coworkers
Anticipate challenges: withdrawal, breaks
Remove tobacco from the house, car etc.
This slide provides a simple approach to assisting patients with smoking cessation.
Arrange Follow-up to check plan or adjust meds
Call right before and after quit date
Weekly follow-up x 2 weeks, then monthly x 6 months
Ask about difficulties (withdrawal, depressed mood)
Build upon successes
Seek commitment to stay tobacco-free 85

86. Recommendations: Physical Activity
Advise people with or without diabetes to perform at least 150 min/week of moderate-intensity aerobic physical activity (50–70% of maximum heart rate), spread over at least 3 days per week with no more than 2 consecutive days without exercise (A)
In absence of contraindications, adults with type 2 diabetes should be encouraged to perform resistance training at least twice per week (A)
Exercise is an important part of the diabetes management plan
Regular exercise has been shown to improve blood glucose control, reduce cardiovascular risk factors, contribute to weight loss, and improve well being1
Regular exercise may also prevent type 2 diabetes in high-risk individuals2-4
A joint position statement by ADA and the American College of Sports Medicine summarizes the evidence for the benefits of exercise in people with type 2 diabetes5
Recommendations for physical activity for people with diabetes1 are summarized on this slide
People with diabetes should be advised to perform at least 150 minutes per week of moderate-intensity aerobic physical activity (50-70% of maximum heart rate) (A)
In the absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance training three times per week (A)
ADA. V. Diabetes Care. Diabetes Care 2013;36(suppl 1):S24.
References
American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care 2013;36(suppl 1):S24-S25.
Knowler WC, Barrett-Connor E, Fowler SE, et al, for the Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:
Tuomilehto J, Lindström J, Eriksson JG, et al.; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:
Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20:
Colberg SR, Sigal RJ, Fernhall B, et al. Exercise and type 2 diabetes. The American Collegoe of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care 2010;33:

87. RCT Trial Assessment of Pedometer Interventions
N=277; 8 Trials
Pedometer increased steps by 2500/day
Review of 26 studies (n=2767)
8 RCT, 18 obs, mean age 49, 85% female, BMI 30, normotensive, 18 week duration
Inactive at baseline: 1385 steps/day
Use of a pedometer increased PA over baseline by 2183 steps/day or 26.9%
Having a step goal was key predictor of increased activity
Those without a step diary did not increase activity
Decrease BP by 3.8 mm Hg/.3 mm Hg
Bravata, DM et al. JAMA 2007; 298:

88. Nutrition, physical activity and NCD prevention
Up to 80% of heart disease, stroke and type 2 diabetes and over a third of the most common cancers could be prevented by eliminating obesity, unhealthy diets and physical inactivity
Call for commitments at the global and national level to address these risk factors including:
Control food supply, food information and marketing and promotion of energy-dense, nutrient-poor foods that are high in saturated, trans-fat, salt or refined sugars

89. Summary
Most persons with diabetes will suffer and die from cardiovascular consequences
Few persons with diabetes are appropriately controlled for key measures of A1c, BP, lipids, and weight.
Combined control of risk factors can result in up to 50% reductions in risk for cardiovascular disease
Greater adherence to lifestyle modifications and use of guideline-based and newer therapies can help us address remaining residual risks.

90. THANK YOU! Now Available
American Society for Preventive Cardiology: