Post on 05-Jun-2020
1
Diabetes
and
Cardiovascular Disease
Satellite Conference and Live WebcastWednesday, March 5, 2008
2:00-4:00 p.m. (Central Time)
Produced by the Alabama Department of Public HealthVideo Communications and Distance Learning Division
Beverly Stoudemire-Howlett, M.D.Cardiologist
Montgomery CardiovascularAssociates &
Montgomery Links Incorporated
Faculty
Diabetes• 21 million Americans have diabetes and
284,000 die from it each year.
• 65% of the deaths are related tocardiovascular causes.
• Type 2 diabetes increases the risk forheart disease 2 to 4 times.
• The Diabetes Education Grouprecommends a HgAlC 7% for Type 2Diabetes.
What is Diabetes?
• Diabetes is a group of diseasescharacterized by high levels of bloodglucose (blood sugar).
• Diabetes can lead to serious healthproblems and premature death.
Diabetes Complications• 2 in 3 people with diabetes die of heart
disease or stroke.
• Diabetes is the #1 cause of adultblindness.
• Diabetes is the #1 cause of kidneyfailure.
• Diabetes causes more than 60% of non-traumatic lower-limb amputations eachyear.
Common Types of Diabetes
Type 1 diabetes
• 5% to 10% of diagnosed cases ofdiabetes.
Type 2 diabetes
• 90% to 95% diagnosed cases ofdiabetes.
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Obesity Trends1990 2001
20011990 Diabetes Trends
U.S. Diabetes PrevalenceAll Ages, 2005
20.8 million people have diabetes.
• Diagnosed: 14.6 million people
• Type 1 diabetes accounts for 5 –10%
• Type 2 diabetes accounts for 90 –95%
• Undiagnosed: 6.2 million people
U.S. Diabetes Prevalence20 Years or Older, 2005
25
20
15
10
5
0
Percent
Age Group20-39 40-59 60+
U.S. Diabetes Prevalence20 Years or Older, by Race/Ethnicity, 2005
0 4 8 1 2 1 6 2 0
American Indians and AlaskaNatives and Diabetes
• 12.8 percent of American Indians and
Alaska Natives had diabetes in 2003.
• 2.2 times as likely to have diabetes as
non-Hispanic whites.
African Americansand Diabetes
• 13.3 percent of all African Americans
have diabetes.
• African Americans are 1.8 times as
likely to have diabetes as non-Hispanic
whites.
3
Hispanic/Latino Americansand Diabetes
• 9.5 percent of all Hispanic/Latino
Americans have diabetes.
• Mexican Americans are 1.7 times as
likely to have diabetes as non-Hispanic
whites.
Preventing DiabetesComplications
• Glucose control
• Blood pressure control
• Blood lipid control
• Preventive care practices for eyes,
kidneys, feet, teeth and gums
• Aspirin as directed by physician
What is Pre-Diabetes?• People with pre-diabetes have blood
glucose levels higher than normal butnot high enough to be diagnosed withdiabetes.
• People with pre-diabetes can prevent ordelay the onset of type 2 diabetesthrough lifestyle change and/ormedication - though none are approvedfor diabetes prevention.
Pre-Diabetes
• At least 54 million U.S. adults age 20
and older have pre-diabetes—which
raises their risk for type 2 diabetes and
cardiovascular disease.
Other Factors for Pre-Diabetes• Hypertension• Abnormal lipid levels• Family history of
diabetes• Race/ethnicity• History of
gestational diabetes• History of vascular
disease• Signs of insulin
resistance
• PCOS
• Previous IGT orIFG
• Inactive lifestyle
Metabolic Syndrome
• Also termed Insulin Resistance - The
concurrence of multiple metabolic
abnormalities associated with
cardiovascular disease.
• 1/3 of US Adults have Metabolic
Syndrome.
4
Definition of MetabolicSyndrome
• Hyperglycemia (Glucose intolerance)
• Abdominal Obesity (Central Obesity)
• Hypertriglyceridemia (Dyslipidemia)
• Low High Density Lipoproteincholesterol
• Hypertension
• Increased Prothrombotic andAntifibrinolytics (Lp(a), Lp-PLA2)
Risk of CV Events
• 3 or more Coronary Risk Fators.
• Evaluation of several large longitudinal
studies suggest increased risk of CV
events and death in people with
MetSyn.
• CV risk conferred by MetSyn is a third
higher in women than men.
Alabama vs Nation Adult RiskFactor Data
30.5
10
31.2
38.3
25.1
7.5
25.5
35.6
05
1015202530354045
Obe
sity
Diabe
tes
Hyper
tens
ion
High
Cholest
erol
Perc
en
t
AlabamaNation
30.5
10
31.2
38.3
25.1
7.5
25.5
35.6
05
1015202530354045
Obe
sity
Diabe
tes
Hyper
tens
ion
High
Cholest
erol
Perc
en
t
AlabamaNation
Alabama vs Nation Adult RiskFactor Data
29.7
20.123.8 23.2
0
5
10
15
20
25
30
35
Physically Inactive Consume fruits orvegetables 5 or more
time daily
Pe
rce
nt
AlabamaColumn 2
29.7
20.123.8 23.2
0
5
10
15
20
25
30
35
Physically Inactive Consume fruits orvegetables 5 or more
time daily
Pe
rce
nt
AlabamaColumn 2
Treatment
• Target individualrisk factors
• Primary prevention
trials of aggressive
• Dietary
• Lifestyle
• Pharmocologic
interventions
Risk Factors for Diabetes• Older age
• Overweight (BMI ≥ 25)
• Hypertension
• Abnormal lipid levels
• Family history of diabetes
• Race/ethnicity
• History of gestational diabetes
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Risk Factors for Diabetes
• History of vascular disease
• Signs of insulin resistance
• PCOS
• Previous IGT or IFG
• Inactive lifestyle
Diabetes Control andComplications Trial (DCCT)
• Compared effects of two diabetes
treatment regimens – standard
therapy and intensive control – on the
complications of diabetes.
• Glucose control is key to preventing or
delaying complications of diabetes.
• Any sustained lowering of blood
glucose helps, even if the person has a
history of poor control.
DCCT Findings DCCT Findings
Lowering blood glucose reduced risk of:
• Eye disease by 76%
• Kidney disease by 50%
• Nerve disease by 60%
United Kingdom ProspectiveDiabetes Study (UKPDS)
Clinical Trial
Looked at intensive management ofblood glucose levels and long termrisk-factors for diabetes complications.
• Mirrored the findings of DCCT in people with type 2 diabetes—better glucose control reduced development of microvascular complications.
• Demonstrated the need for management of high blood pressure and cholesterol as well as blood glucose levels (the ABCs of diabetes).
UKPDS Findings
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UKPDS Findings
P <.0001 P = .035 P = .021P =
.0001
Risk reduction with 1% decline in annualmean A1C
Micro-vascularDisease
37%
PVD
43%
StrokeMI
14% 12%
HeartFailure
CataractExtraction
16% 19%
0%
15%
30%
45%
Epidemiology of DiabetesInterventions and
Complications Study (EDIC)
• Observational study
• DCCT participants
• Looked at risk factors for long-term
complications
• Participants continue to benefit frommetabolic memory of intense glucose control
• Intensive therapy aimed at achievingnear normoglycemia:
• Reduces CVD events by more than half
• Should be implemented as earlyas possible
EDIC Findings: IntensiveTherapy and Diabetes
Complications
EDIC Findings: Cardiovascular EventsC
um
ula
tive
Inci
den
ce
Years from Study Entry
Cumulative Incidence of First of Any Event
0 2 4 6 8 10 12 14 16 18 20
Risk reduction 42%95% CI: 9% to 63%P = 0.02
0.12
0.10
0.08
0.06
0.04
0.02
0.00
Conventional
Intensive
EDIC Findings: Cardiovascular Events
Conventional
Intensive
Non-Fatal MI, Stroke, or CVD Death
0 2 4 6 8 10 12 14 16 18 20Years from Study Entry
0.00
0.02
0.04
0.06
0.08
0.10
0.12
Cu
mu
lati
ve In
cid
ence
Risk reduction 57%95% CI: 12% to 79%P = 0.02
• The DPP was a major clinical trial to
determine whether diet and
exercise or the oral diabetes drug
metformin could prevent or delay
the onset of type 2 diabetes.
Diabetes Prevention Program(DPP)
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DPP ParticipantsAdults at high risk for type 2 diabetes• Presence of IGT• Mean age 51 years• Mean body mass index (BMI) 34• 68% women• 45% minority groups:
• African Americans• Hispanic and Latino Americans• American Indians• Asian Americans and Pacific
Islanders
DPP Methods• Lifestyle intervention
- 5% to 7% weight reduction- Healthy low-calorie, low-fat diet- 30 min. of physical activity,
5 days/week
• Metformin- Oral diabetes drug
• Placebo
DPP Methods• DPP Curriculum:
– Diet
– Exercise
– Behavior change modification
• Taught one-on-one by case managers
Incidence of Diabetes
0 1 2 3 4
0
10
20
30
40Placebo (n=1082)Metformin (n=1073, p<0.001 vs. Plac)Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Percent developing diabetes
All participants
All participants
Years from randomization
Cu
mu
lative
in
cid
en
ce
(%
)
0 1 2 3 4
0
10
20
30
40Placebo (n=1082)Metformin (n=1073, p<0.001 vs. Plac)Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
Percent developing diabetes
All participants
All participants
Years from randomization
Cu
mu
lative
in
cid
en
ce
(%
)
Placebo (n=1082)
Metformin (n=1073, p<0.001 vs. Placebo)Lifestyle (n=1079, p<0.001 vs. Metformin, p<0.001 vs. Placebo)
Incidence of Diabetes
Risk reduction31% by metformin58% by lifestyle
Diabetes Prevention
• Type 2 diabetes prevention is:
– PROVEN
– POSSIBLE, and
– POWERFUL
Testing Recommendations forPeople at High Risk
• Consider testing plasma glucose if aperson is:
– Age 45 or older and overweight.
– Younger than 45, overweight, withany additional risk factor.
• Repeat testing at 3-year intervals.
• Obtain FPG or 2-hour plasma glucosepost 75-g glucose challenge after overnight 8 to 12 hr fast.
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Diagnostic Criteria forPre-diabetes and Diabetes
Fasting PlasmaGlucose Test
(FPG)
2-Hour OralGlucose
Tolerance Test(OGTT)
Normal Below 100 mg/dl Below 140 mg/dl
Pre-diabetes
100-125 mg/dl (IFG) 140-199 mg/dl (IGT)
Diabetes 126 mg/dl or above 200 mg/dl or above
ACCORD• 10,251 Participants.
• 257 in the intensive treatment groupdied. HgbAlc less than 6.
• 203 in the standard treatment group.
• Trial end June 2009 now the intensiveand standard tx groups will be thesame.
ACCORD
• Intensively reducing blood sugar belowguidelines causes harm in high risktype 2 diabetes patients.
• Standard tx arm will continue.
• Seek answer for cause of death in theintense group.
The standard treatment arm
Effects of treatments for blood pressure
Effects of treatments for blood lipids
The results of ACCORD does not apply
to patients with type I Diabetes
Unclear if applies to recently
diagnosed type 2
Action to ControlCardiovascular Disease in
Diabetes
Diminished Benefit of LoweringLDL-C Substantially Below 100
mg/dL in High-Risk Patients
22% RiskReduction 32% Risk
Reduction
25.1
0
5
10
15
20
25
30
Placebo Simvastatin
13.4
ResidualCVD Risk Residual
CVD Risk
20.2
9.4
0
2
4
6
8
10
12
14
16
Placebo Atorvastatin
Acu
te C
VD
Eve
nt
Rat
e, %
Residual CVD Risk in DiabeticPatients Treated With Statins
CARDSN = 2838
HPS: Patients With Diabetesn = 5963
Maj
or
Vas
cula
r E
ven
t R
ate,
%
9
Diabetic Patients Have Particularly HighResidual CVD Risk After Statin Treatment
17.9%13.8%9.7%7.8%TNT6_
OnPlacebo
On StatinOn PlaceboOn Statin
11.4%9.6%8.7%4.9%ASCOT-LLA5‡
18.4%23.1% 16.0%13.1%PROSPER4§
22.8%19.2%15.2%11.7%LIPID3‡
36.8%28.7%24.6%19.4%CARE2†
37.8%25.7%19.8%HPS1* (CHDpatients) 33.4%
Event Rate(Diabetes)
Event Rate (NoDiabetes)
Residual CVD Risk in Patients TreatedWith Intensive Statin Therapy
Pat
ien
ts E
xper
ien
cin
g
Maj
or
CV
D
Eve
nts
, % Standard statin therapy
Intensive high-dose statin therapy
PROVE IT-TIMI 222 IDEAL3 TNT4
N
LDL-C,*mg/dL
4162 8888 10 001
95 62 104 81 101 77
Statistically significant, but clinically inadequate CVD reduction1
The Role of ElevatedTriglycerides and LowHDL-C in Residual CVD
Risk
VisceralAdiposopathy
FFA
Fatty LiverCholesterol
Ester
TG CETP
CETP
CholesterolEster
Lipases
Lipases
TG
Renal Clearance
Small, Dense LDL
Small,Dense HDL
TG
TG
TG
HDL
LDL
VLDL
Dyslipidemia and Particle Size:Role of CETP
0
1
2
3
100 160 220 8565
4525
0
1
2
3
100 160 220 8565
4525
HDL-C Is a Modifier of Riskat All Levels of LDL-C
The Framingham Study*
LDL-C, mg/dL HDL-C, mg/dL
Ris
k o
f C
HD
*Men 50 to 70 years of age
3
21
4Equivalent Risk
Patient 1LDL-C 100 mg/dLHDL-C 65 mg/dLRisk level 0.4
Patient 2LDL-C 100 mg/dLHDL-C 45 mg/dLRisk level 0.6
Patient 3LDL-C 100 mg/dLHDL-C 25 mg/dLRisk level 1.2
Patient 4LDL-C 220 mg/dLHDL-C 45 mg/dLRisk level 1.2
HDL
HDL and Reverse CholesterolTransport
Pre-β-HDL is
produced by
the liver
Benefits in Reducing Atherosclerosis
10
ADA/AHA 2007 Scientific Statement:Primary Prevention of CVD in Patients With
Diabetes• Elevated LDL-C is primary target of
lipid-lowering therapy
• LDL-C goal <100 mg/dL
• TG-rich lipoproteins, especially VLDL,are often elevated in patients withdiabetes, appear to be atherogenic, andrepresent a secondary target of lipid-lowering therapy.
ADA/AHA 2007 Scientific Statement:Primary Prevention of CVD in Patients With
Diabetes• TG goal <150 mg/dL; HDL-C goal >40
mg/dL*
• If TG are 200-499 mg/dL, non–HDL-Cgoal ≤130 mg/dL
• If TG are ≥500 mg/dL, lowering TG isprimary target
• Combination therapy of LDL-cholesterollowering drugs (statins) with fibrates orniacin may be necessary to achieve lipidtargets
ADA
AHA
HDL-C
Raising
Goal: >40
mg/dL†
LDL-C
Lowering
Goal:
<100mg/dL*
Second Priority
•Niacin‡ or fibrates•TLC
•Niacin, ezetimibe, bile
acid sequestrants, or
fenofibrate
•TLC
•Statins
First Priority
American Diabetes AssociationStandards of Medical Care in Diabetes:
Dyslipidemia Management
•Glycemic control + statin+ fibrate
•Glycemic control + statin+ niacin‡
•Glycemiccontrol +high-dosestatin
Combined
Hyperlipidma
•Fibrates (fenofibrate,gemfibrozil)
•Niacin‡
•Statins (if also have highLDL-C)
•TLC
•Glycemiccontrol
TG Lowering
Goal: <150mg/dL
Second PriorityFirst Priority
American Diabetes AssociationStandards of Medical Care in Diabetes:
Dyslipidemia Management
National Guidelines:Niacin Therapy
NCEP ATP III Guidelines1
• “Among lipid-lowering agents, nicotinicacid appears to be the most effectivefor favorably modifying all of thelipoprotein abnormalities associatedwith atherogenic dyslipidemia.”
ADA/AHA 2007 Scientific Statement2
• “The most effective available drug forraising HDL-cholesterol levels isnicotinic acid.”
Summary
• Diabetes is preventable.
• Cornary Artery Disease is preventable.
• Decrease the incidence ofcardiovascular events.
• Decrease the incidence of stroke.
• Decrease the incidence of severity ofcongestive heart failure.
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Summary
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Thursday, March 27, 200812:00 - 1:30 p.m. (Central Time)
Generation Rx: The Adolescent“Pharming” Phenomenon
Thursday, April 3, 200811:00 - 1:00 p.m. (Central Time)
HIV/AIDS Update 2008 forHome Health Aides & Attendants
Wednesday April 30, 200812:00 - 1:30 p.m. (Central Time)
For complete list of upcoming programsvisit: www.adph.org/alphtn