Special Diabetes Program for Indians: Competitive Grant
Program
Treatment of Cardiovascular Risks in Patients with Diabetes:
Reaching Goals
Objectives:
• Review the pharmacologic treatment of hyperglycemia, hypertension and high cholesterol in patients with type 2 diabetes.
• Appreciate the benefits of good control on risk factors for cardiovascular outcomes.
Modifiable CHD Risk FactorsModifiable CHD Risk Factors
High blood pressureHigh blood pressure
DyslipidemiaDyslipidemia
Elevated total cholesterol and LDL-C Elevated total cholesterol and LDL-C Elevated triglycerides Elevated triglycerides Low HDL-CLow HDL-C
Tobacco smokeTobacco smoke
ObesityObesity
Physical inactivityPhysical inactivity
Diabetes mellitusDiabetes mellitus
CVD Risk
Reduction
Hyperglycemia
Hypertension Control
Lipid Control
Daily AspirinLifestyle ChangesWeight loss, healthy foods,Increased activity
Smoking Cessation
A1c < 7%
Medications
Healthy Food Choices Increased Physical Activity
HYPERGLYCEMIA
Impact on Complication with Glucose Control
0102030405060708090
100
5 6 7 8 9 10 11
Updated Mean Hgb A1c
Co
mp
lic
ati
on
Ra
te %
pe
r 1
00
0
pe
rso
n-y
ea
rs
Macrovascular
Microvascular
Other factors must be targeted
Statton IM et al. BMJ 2000; 321: 405-412
ADA and ACE Glycemic Goals
American Diabetes Association. Diabetes Care. 2004;26:S33-S50.American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control
6.5 < 7.0< 6.0HgbA1c (%)
TargetGoalNormalBiochemical Index
ACEADA
ADA Updated recommendations: "more stringent goals (i.e., a normal A1C, <6%) can
be considered in individual patients"
2004 AI/AN Diabetic Patients with HbA1c < 7%
33
25
44
36 36 37 3633
42
31
39
27
0
5
10
15
20
25
30
35
40
45
50
ABD ABQ AK BEM BIL CAL NAV NSH OKL PHX POR TUC
IHS Standards of Care Audit Data 2004
IHS 2003Average
34%
Minneapolis, International Diabetes Center, 2000.
Can the Course of Type 2 Diabetes Be Altered?
Glucose(mg/dL)
RelativeFunction
(%)
Years of Diabetes
UncontrolledHyperglycemia
50 –
100 –
150 –
200 –
250 –
300 –
350 –
0 –
50 –
100 –
150 –
200 –
250 –
-10 -5 0 5 10 15 20 25 30
Fasting Glucose
Post-meal Glucose
Obesity IFG* Diabetes
Insulin Resistance
-cell Failure
Type 2 Diabetes:Who Is Your Typical Patient?
• Patients typically present with:
– A1c? _____________
– Approximately _______ % reduction in
beta-cell function?
– Degree of Insulin Resistance? ________
– Complications? _____________
– Other conditions? _____________
Hyperglycemia
*Primary site(s) of action.
DeFronzo RA. Ann Intern Med. 1999;131(4):281-303.
Inzucchi SE. JAMA. 2002;287(3):360-372.
Pancreas• Sulfonylureas• Repaglinide• Nateglinide
Liver• Metformin*• Rosiglitazone• Pioglitazone
Adipose Tissue• Rosiglitazone*• Pioglitazone* Gut
• Acarbose• Miglitol
Muscle• Rosiglitazone*• Pioglitazone*• Metformin
Oral Therapy for Type 2 Diabetes: Sites of Action
Choosing An Oral Agent
1. What is the current degree of control?
2. How long has the patient been diagnosed?
3. Is the patient overweight?
4. Does the patient have dyslipidemia?
Choosing An Oral Agent5. What is the kidney and liver function
like?
6. Does the patient have known heart disease?
7. How does the patient feel about taking meds?
B B LL DD HSHS BB
MealsMeals
NPH/LantusNPH/LantusInsulin EffectInsulin Effect
ADDING INSULIN
Bedtime intermediate or long acting insulin plus oral agent(s)
premixed 70/30premixed 70/30
B B LL DD HSHS BB
MealsMeals
Insulin EffectInsulin Effect
Rapid-acting mixture (NPH/R or lispro) before dinner plus oral agent(s)
Combination Therapy With Insulin
• 1 injection a day
• Convenience (usually given at night)
• Slow, safe, and simple titration
• Low dosage compared to a full insulin regimen
• Limited weight gain
• Effective improvement in glycemic control by suppressing hepatic glucose production
BP< 130/80
Medications
Healthy Food Choices Increased Physical Activity
HYPERTENSION
Goals for Control
• ADA:Target Blood Pressure is < 130/80
• IHS: Target Blood Pressure is 130/80
• Additional protection against complications, including renal failure, may be obtained by lowering BP further to 125/75
2004 AI/AN Diabetic Patients with BP < 130/80
33
39
3431
43
32
3834
3234
36 35
0
5
10
15
20
25
30
35
40
45
50
ABD ABQ AK BEM BIL CAL NAV NSH OKL PHX POR TUC
IHS Standards of Care Audit Data 2004
IHS 2003Average
34%
Average Number of Antihypertensive Agents Needed Per Diabetic Patient to Achieve Target BP
UKPDS DBP<85
ABCD DBP<75
VDRD MAP<92
HOT DBP<80
AASK MAP<92
1 2 3 4
Number of Antihypertensive AgentsTrail Target BP mm Hg
JNC-7 Algorithm for the treatment of hypertension in patients with diabetes
Lifestyle Modifications: Weight reduction, diet high in fruits & vegetables, low fat dairy produces,
and decreased total and saturated fats;Na+ restriction to 2gr/day;
regular aerobic exercise; and moderation of alcohol intake
Drug Monotherapy:Consider ACE or ARB as first line
Compelling indications for individual classes:ACEs, ARBs, thiazides, -blockers, CCBs
Optimize dosing or add additional agents until BP goal achieved
NOT AT BP GOAL < 130/80
NOT AT BP GOAL < 130/80
ACE & ARBSLimits nephropathy and
Lower CVD risk
Thiazide -Blocker* Blocker Ca++CB
Step-wise progression to controlling Blood pressure
Thiazide Diuretics
• ALLHATT Study
• Excellent second agent in patient’s with diabetes
• Start at 12.5 mg/day and increase to 25 mg/day if needed
• No benefit of a higher dose
ß-blockers
• Used in patients with known cardiovascular disease
• Risk of masking hypoglycemia
• Side effect can be limiting factor, taper down slowly if needed
Calcium Channel Blocker
• May add reno-protective benefit
• Syst-Euro study, HOT study showed a reduction in cardiovascular events in hypertensive diabetic patients
• Offers elderly patients with isolated systolic hypertension good protection against cardiovascular events
SUMMARYTreatment of Hypertension in Diabetes
• Blood pressure goal in diabetes < 130/80– Level of blood pressure more important that type
of therapy– Reduces rates of both micro and macrovascular
disease
• ACE/ARB based therapies: 1st Line Choice– Reduces CVD complication and offers reno-
protection
• Multi-drug therapy often needed• Aggressive treat essential, if CVD present
ideal goal is lower: 125/75
Arch Intern Med, Vol 160, Sep 11, 2000, 2447-2452
LDL < 100TR < 150
HDL: Men >45 Women > 55
Medications
Healthy Food Choices Increased Physical Activity
HYPERLIPIDEMA
Treatment Decisions Based on LDL Cholesterol Levels in Adults With
Diabetes
Medical
Therapy Nutrition Drug Therapy
Initiation Level
LDL Goal
Initiation Level
LDL Goal
CVD Risk Equivalence
>100 100 >100 100
Very high risk >100 70 100 70
Diabetes Care, Volume 28, Supplement 1, January 2005
*
Goals for Control• LDL < 100 mg/dL, 70 mg/dL for patients
at high risk
• HDL**: Men > 45 mg/dL
• HDL**: Women > 55 mg/dL
• Triglycerides < 150 mg/dL
**There is no clear consensus on the use of drug therapy to raise HDL
Considerations in Therapy
• Diet and exercise are key• Hyperglycemia itself will lead to increased TG:
try to improve sugars first• Metformin will decrease LDL• Glitazones will decrease TG, increase HDL• Check TFTs in initial work-up• Metamucil, increased dietary fiber
Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults:
1. LDL cholesterol lowering1. LDL cholesterol lowering
- Lifestyle interventions
- HMG CoA reductase inhibitor (statin)
- Cholesterol absorption inhibitior (ezetimibe)
- Bile acid binding resin or fenofibrate
2. HDL cholesterol raising2. HDL cholesterol raising
- Lifestyle interventions (weight loss, physical activity, smoking cessation)
- Nicotinic acid or fibratesAdapted from ADA. Diabetes Care 2004;27(suppl 1):S68
3.3. Triglyceride loweringTriglyceride lowering - Lifestyle interventions - Glycemic control - Fibric acid derivative (gemfibrozil, fenofibrate) - Niacin - High-dose statin therapy (in those who have high
LDL-C)
4. Combined hyperlipidemia
- First choice: Improved glycemic control plus high dose statin
- Second choice:Improved glycemic control plus statin plus fibrate
- Third choice: Improved glycemic control plus statin plus nicotinic acid
Adapted from ADA. Diabetes Care 2004;27(suppl 1):S68
Testing• Lipid panel annually, more often is
medication adjustments are made
• Consider direct LDL if TG >250 mg/dL or if specimen is non-fasting
• All diabetic patients with LDL > 100 mg/dL need medical, dietary and lifestyle intervention
First Line Therapy: Statins
• Effect in lowering LDL
• Marginal benefit on HDL and TG
• Generally well tolerated, mild GI side effects
• May potentiate effect of oral anticoagulation
• In high doses with other meds, may cause myalgia
Fibrates
• Best for lowering TG
• May increase LDL is TG very high
• May increase incidence of choleilithiasis
• Generally well tolerated with some GI side effects
• May potentiate the effects of oral anticogaulants
2004 AI/AN Diabetic Patients LDL Tested LDL < 100
6962
79
65
7567
60
7377
71
62
39
21
323542
3730
353631
41
3235
0
10
20
30
40
50
60
70
80
90
ABD ABQ AK BEM BIL CAL NAV NSH OKL PHX POR TUC
IHS Standards of Care Audit Data 2004
IHS 2003Average
35%
Procoagulant State in Patients with Diabetes
• Platelets are overly sensitive to platelet aggregating agents
• High levels of Thromboxane, a potent vasoconstrictor
• Decreased fibrinolytic activity• Increased levels of Plasminogen Activitor
Inhibitor-1• Clot lysis cannot precede normally
Aspirin Therapy in Diabetes
“Aspirin - the poor man’s statin”
• Reduces risk of MI by ~ 15-60%
• Treat all high risk patients with diabetes over the age of 35
• Use 162 – 325 mg/day
The Lancet
IHS Standards of Care for Patients with Type 2 Diabetes
2004 AI/AN Diabetic Patients prescribed Aspirin
65 63
7569
52
7266 67
57
6861
65
0
10
20
30
40
50
60
70
80
90
ABD ABQ AK BEM BIL CAL NAV NSH OKL PHX POR TUC
IHS Standards of Care Audit Data 2004
IHS 2003Average
65%
Smoking Cessation
• Smoking doubles the risk of CVD in patients with diabetes
• Attenuates the benefit of gained from modifying other risks
• MRFIT: independent and ing risk of CVD based on the # cigarettes/day
Putting It All Together
Updating the Approach to Treatment to Improve Cardiovascular Risks
The Traditional Treatment: “Treatment to Failure Approach”• Treatment is initiated with a trial of diet
and exercise• If glycemic control not achieved, start
mono-therapy• Maximize therapy • If glycemic control not achieved, start 2nd
agent: repeat pattern• Little if no attention paid to cardiovascular
risk
Updated Approach to Treatment
• Goal: to help patients achieve earlier and better control
• Initiation of medical nutritional therapy, increased activity, diabetes self-management
• Evaluate other cardiovascular risk factors: hypertension, cholesterol, smoking, aspirin use.
Updated Approach to Glycemic Treatment
• Early initiation on monotherapy
• Rapid progression to combination therapy when glycemic control not attained or maintained
• Therapy directed at multiple defects
• Self glucose monitoring and frequent HgbA1c checks (Q 3 months) while gaining control
Putting It All Together:• Address other aspects of CVD risk at each
visit
• Multiple approaches to treatment
• GOAL: pushes the plan forward quickly and consistantly
How Can We Help Improve Cardiovascular Outcomes?
1. Improve patient’s awareness of risks
2. Address emotional barriers
3. Empower the patient through education, motivation, and self advocacy
Thank you