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Effects of Diabetes, Obesity, Metabolic Syndrome on Cardiovascular Health Filipino American Cardiovascular Health Summit July 9, 2011 Washington, D.C.

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Title: Effects of Diabetes, Obesity, Metabolic Syndrome on Cardiovascular Health Filipino American Cardiovascular Health Summit July 9, 2011 Washington, D.C.


1
Effects of Diabetes, Obesity, Metabolic Syndrome
on Cardiovascular HealthFilipino American
Cardiovascular Health Summit July 9, 2011
Washington, D.C.
  • Socorro Juan Vargas, M.D., F.A.C.P., F.A.C.E
  • Section of Diabetes and Endocrinology
  • St. Francis Hospital and Medical Center
  • Assistant Professor of Medicine
  • University of Connecticut School of Medicine

2
Disclosure of Conflicts of Interest
  • Nothing to disclose

3
Outline
  • Diabetes
  • Definition
  • Complications
  • Burden of disease
  • Cardiometabolic risk factors
  • Metabolic Syndrome
  • Effects of intensive glycemic control on
    cardiovascular risk
  • Primary prevention of cardiovascular risk in
    diabetes patients
  • Treatment goals

4
What is Diabetes?
  • Diabetes is a state characterized by an absolute
    or relative deficiency of insulin relative to the
    physiological needs of a given individual

5
Prevalence and Incidence of Diabetes and
Pre-diabetes in the U.S.A.
  • 25.8 million people have diabetes
  • Diagnosed 18.8 million people
  • Undiagnosed 7.0 million people
  • A total of 1.9 million new cases of diabetes were
    diagnosed in 2010 in the United States among
    people aged 20 years and older
  • 79 million U.S. adults ages 20 and older have
    pre-diabetes

National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm.
6
Diabetes in Asian Americans and Pacific Islanders
  • 8.4 of all Asian Americans have diagnosed
    diabetes
  • Prevalence data for diabetes among Pacific
    Islanders is limited

National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm.
7
Diabetes Care 2001 242054-2058
8
Diagnostic Criteria for Pre-diabetes and Diabetes
Category A1C Fasting Plasma Glucose Test (FPG) 2-Hour Oral Glucose Challenge
Acceptable N/A Below 100 mg/dl Below 140 mg/dl
Pre-diabetes 5.7 - 6.4 100-125 mg/dl (IFG) 140-199 mg/dl (IGT)
Diabetes 6.5 126 mg/dl or above 200 mg/dl or above
American Diabetes Association. Diabetes Care
2011 34(Suppl.1)S11-61.
9
Diabetes Complications
  • Diabetes is the leading cause of
  • kidney failure
  • 48,374 people with diabetes began treatment for
    end stage kidney disease in 2008
  • new cases of adult blindness
  • 4.2 million people with diabetes aged 40 and
    older had diabetic retinopathy in 2005-2008
  • nontraumatic lower-limb amputations
  • Over 65,000 nontraumatic lower-limb amputations
    were performed in people with diabetes in 2006

National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm.-
10
Diabetes Complications
  • The risk of periodontal disease is two to three
    times higher in adults with diabetes
  • About one-third of people with diabetes have
    severe periodontal disease
  • 60 to 70 of people with diabetes have mild to
    severe nervous system damage
  • Almost 30 of people with diabetes aged 40 years
    and older have impaired sensation in the feet
  • People with diabetes are twice as likely to have
    depression

National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm.
11
Cardiovascular disease is leading cause of death
in patients with Type 1 and Type 2 Diabetes
  • Framingham study CVD incidence in diabetics 1
  • Males 2-fold increase
  • Females 3-fold increase
  • Women had greater cardiovascular mortality
  • CVD morbidity and mortality greater for diabetic
    women than non-diabetic men 2
  • MRFIT Absolute risk of CVD death 3X higher in
    diabetic men at every age, race, income,
    cholesterol and blood pressure 3

1 Kannel WB, McGee DL. Diabetes Care 1979
2120-126 2 Lee WL et al. Diabetes Care 2000
23962-968 3 Stamler J et al. Diabetes Care
199316434-444
12
Diabetes is a CVD Risk Equivalent
  • Subjects with diabetes have the same 7-year risk
    for future MI as nondiabetic individuals who have
    had a previous MI

Haffner SM et al. N Engl J Med 1998339229-234
13
Diabetes and Risk for Cardiovascular Disease (CVD)
  • Cardiovascular disease (CVD) a major complication
    of diabetes and leading cause of death in
    patients with diabetes
  • In adults with diabetes
  • 68 die of heart disease or stroke
  • the risk for stroke is 2 to 4 times higher
  • 67 have high blood pressure
  • smoking doubles the risk for heart disease

National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm.
14
Type 1 Diabetes and CVD
  • The prevalence of coronary artery disease is 10
    times greater among patients with Type 1 diabetes
    than age- and gender-matched individuals without
    diabetes
  • Insulin resistance is not a characteristic
    feature of T1DM
  • Is hyperglycemia a direct risk mediator?

15
Estimated Costs of Diabetes and CVDin the U.S.
Estimated Direct Medical Costs Estimated Indirect Costs TOTAL
Cardiovascular disease 324 B 179 B 503 B
Diabetes 116 B 58 B 174 B
TOTAL 440 B 237 B 677 B
Disability, work loss, premature mortality
Totals do not add up because of rounding and
overlap
National Diabetes Fact Sheet, CDC,
2011. http//www.cdc.gov/diabetes/pubs/factsheet11
.htm. American Heart Association. Circulation
2010 121e46-e215
16
The Evolution of Mankind
17
The Evolution of Mankind
18
Age-adjusted Percentage of U.S. Adults Who Were
Obese or Who Had Diagnosed Diabetes
Obesity BMI 30 kg/m2
1994
2000
2008
Diabetes
1994
2000
2008
Centers for Disease Control and Prevention
National Diabetes Surveillance System http//www.c
dc.gov/diabetes/statistics
19
(No Transcript)
20
Definitions of Metabolic Syndrome
Clinical Measure AHA/NHLBI Any 3 of 5 features IDF
Waist circumference Non-Asian Men 102 cm Women 88 cm Europid, Sub-Saharan Africans, Middle Eastern Men 94 cm Women 80 cm
Waist circumference East Asian South Asians Men 90 cm Women 80 cm East Asian South Asians South Central Americans Men 90 cm Women 80 cm
Waist circumference Japanese Men 85 cm Women 90 cm
Triglycerides 150 mg/dl or on drug therapy for high triglycerides 150 mg/dl or on drug therapy for high triglycerides
HDL-C Men lt40 mg/dl, Women lt50 mg/dL or on drug therapy for low HDL-C Men lt40 mg/dl, Women lt50 mg/dL or on drug therapy for low HDL-C
Blood pressure Systolic 130 mmHg Diastolic 85 mmHg or on drug therapy for hypertension Systolic 130 mmHg Diastolic 85 mmHg or on drug therapy for hypertension
Fasting glucose 100 mg/dl or on drug therapy for elevated glucose 100 mg/dl (includes diabetes)
AHA/NHLBI Circulation 20051122735-2752
IDF Lancet 20053661059-1062
21
Glycemic Control and CV RiskClinical Trials
  • Hypothesis Treatment that normalizes blood
    glucose will prevent or delay the long term
    complications of diabetes mellitus

TYPE CLINICAL TRIAL
DCCT T1DM Diabetes Control and Complications Trial
EDIC T1DM Epidemiology of Diabetes Interventions and Complications
UKPDS T2DM United Kingdom Prospective Diabetes Study
ACCORD T2DM Action to Control Cardiovascular Risk in Diabetes Study Group
ADVANCE T2DM Action in Diabetes and Vascular Disease Preterax and Diamicron Controlled Evaluation
VADT T2DM Veterans Diabetes Trial
22
Diabetes Control and Complications Trial (DCCT)
  • Improved control of blood glucose reduced the
    risk of clinically meaningful

Retinopathy 76 P0.002
Nephropathy 54 Plt0.04
Neuropathy 60 P0.002
Cardiovascular endpoint 57 P0.007
DCCT. N Engl J Med 1993 329 977-986 DCCT/EDIC.
N Engl J Med 20053532643-2653
23
EDIC Findings Cardiovascular Events
Cumulative Incidence of First of Any Event
0.12
0.10
Risk reduction 42 95 CI 9 to 63 P 0.02
Conventional
0.08
0.06
Cumulative Incidence
0.04
Intensive
0.02
0.00
0 1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21
Non-Fatal MI, Stroke, or CVD Death
0.12
0.10
Risk reduction 57 95 CI 12 to 79 P 0.02
0.08
0.06
Conventional
0.04
Cumulative Incidence
0.02
Intensive
0.00
0 1 2 3 4 5
6 7 8 9 10 11 12
13 14 15 16 17 18
19 20 21
Years from Study Entry
DCCT/EDIC N Engl J Med 20053532643-2653
24
United Kingdom Prospective Diabetes Study (UKPDS)
Risk reduction with 1 decline in annual mean A1C
P lt.0001
P .035
P .021
P .0001
0
15
30
45
UKPDS. BMJ 2000321405-412
25
UKPDS Follow-Up Study
Differences in A1C between intensive standard
glycemia control treatment groups were lost after
one year
Relative Risk Reductions Relative Risk Reductions Relative Risk Reductions Relative Risk Reductions
Intensive Insulin/Sulfonylurea Intensive Insulin/Sulfonylurea Intensive Metformin Intensive Metformin
Any DM endpoint 9 P0.04 21 P0.01
Microvascular disease 24 P0.001
Myocardial Infarction 15 P0.01 33 P0.005
Death from any cause 13 P0.007 21 P0.002
UKPDS. N Engl J Med 20083591577-1589
26
ACCORD, ADVANCE and VADT
Characteristic ACCORD ADVANCE VADT
N 10,251 11,140 1,791
Mean age 62 66 60
Duration of T2DM 10 yr 8 yr 11.5 yr
History of CVD 35 32 40
BMI 32 28 31
Baseline A1c 8.3 7.5 9.4
A1c achieved 6.4 vs 7.5 6.3 vs 7.0 6.9 vs 8.5
HR CVD Events 0.9 (0.78-1.04) 0.94 (0.84-1.06) 0.88 (0.74-1.05)
HR Mortality 1.22 (1.01-1.46) 0.93 (0.83-1.06) 1.07 (0.81-1.42)
ACCORD Study Group. N Engl J Med
20083582545-2559 ADVANCE Collaborative Group. N
Engl J Med 20083582560-2572 VADT. N Engl J Med
2009360129-139
27
Effects of Intensive Glycemic Control
Study Microvascular Disease Microvascular Disease Macrovascular Disease Macrovascular Disease Mortality Mortality
UKPDS
DCCT/EDIC
ACCORD ? ?
ADVANCE
VADT
UKPDS. Lancet 1998 352837-853 UKPDS. N Engl J
Med 2008 3591577-1589 DCCT. N Engl J Med 1993
329 977-986 DCCT/EDIC. N Engl J Med
20053532643-2653 ACCORD. N Engl J Med 2008
358(24)2545-59 ADVANCE. N Engl J Med 2008 358
(24) 2560-72 VADT. N Engl J Med 2009360129-139
28
Effects of Intensive Glycemic Control
  • Benefit from intensive therapy when initiated
    earlier in the course of disease
  • CV benefit may be evident only after an extended
    period of time
  • Effect may be sustained for period longer than 10
    years after intensive therapy is discontinued

29
Intensive Glycemic Control in DiabetesImplicatio
ns of ACCORD, ADVANCE and VADT
  • Clinical implication individualized goals and
    care
  • General A1c goal of lt7
  • For microvascular disease prevention
  • Reasonable for macrovascular risk reduction,
    pending more evidence
  • A1c goals closer to normal for some patients
  • Short duration of diabetes, long life expectancy,
    no significant CVD
  • Levels reached without significant adverse
    treatment effects

ADA/ACC/AHA Position Statement. Diabetes Care
200932187-192
30
Intensive Glycemic Control in DiabetesImplicatio
ns of ACCORD, ADVANCE and VADT
  • Less stringent goals for some patients
  • History of severe hypoglycemia
  • Limited life expectancy
  • Advanced micro- or macrovascular complications
  • Extensive comorbid conditions
  • Long-standing diabetes with difficulty achieving
    glycemic goals

ADA/ACC/AHA Position Statement. Diabetes Care
200932187-192
31
Targets for Glycemic, Blood Pressure and Lipid
Control
ADA AACE
HbA1c lt7.0 6.5
Premeal PG 70-130 mg/dL lt110 mg/dL
Postmeal PG lt180 mg/dL lt140 mg/dL
BP lt 130/80 mmHg lt 130/80 mmHg
Lipids
LDL-C lt100 mg/dL lt70 (CVD) lt100 mg/dL lt70 (CVD)
HDL-C gt40 mg/dL (M) gt50 mg/dL (F) gt40 mg/dL (M) gt50 mg/dL (F)
Triglycerides lt150 mg/dL lt150 mg/dL
American Diabetes Association. Diabetes Care.
201134(suppl 1)S11-S61 American College of
Endocrinology. Endocr Pract. 200713(suppl 1)1-68
32
Recommendations Individualize Goals
  • Individualize goals based on
  • Duration of diabetes
  • Age/life expectancy
  • Comorbid conditions
  • Known CVD or advanced microvascular complications
  • Individual patient considerations

American Diabetes Association. Diabetes Care.
201134(suppl 1)S11-S61
33
HYPERGLYCEMIA
34
Primary Prevention of CVD in People with Type 1
and Type 2 Diabetes
Intervention Recommended Goals Recommended Agents
Weight Moderate weight loss (5-7 of starting weight)
Medical nutrition therapy Saturated fat lt7 of energy intake Dietary cholesterol lt200 mg/day Trans-unsaturated fats lt1 of energy intake
Physical activity 150 min moderate intensity aerobic activity or 90 minutes vigorous aerobic activity Distributed over at least 3 days/wk
Tobacco Tobacco cessation
AHA/ADA Circulation 2007115114-126
35
Primary Prevention of CVD in People with Type 1
and Type 2 Diabetes
Intervention Recommended Goals Recommended Agents
Blood pressure lt130/80 mmHg ACE-I, ARB (ß-blockers, thiazides, CCB added as needed)
Lipids LDL lt 100 mg/dL If TG 200-499 mg/dL Non-HDL target 130 mg/dL If TG 500 mg/dL Treat prior to LDL reduction TG 150 mg/dL HDL men gt40 mg/dL Women gt50 mg/dL
Antiplatelets gt 40 yrs of age or if increased CV risk Aspirin 75-162 mg/day
Glycemic control HgbA1c lt7
AHA/ADA Circulation 2007115114-126
36
Summary
  • A comprehensive approach to the prevention and
    management of cardiovascular disease in diabetes
    patients is best accomplished through a
    combination of lifestyle modification and
    targeting of multiple cardiometabolic risk
    factors and comorbidities
  • Focus on individualizing therapy choose the
    appropriate A1c target, cardiometabolic goals and
    proper drug regimen for each patient

37
THANK YOU
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