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