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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.
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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 Factors High blood pressure Dyslipidemia Elevated total cholesterol and LDL-C Elevated triglycerides Low HDL-C Tobacco smoke Obesity Physical inactivity Diabetes mellitus
Smoking Cessation Hyperglycemia CVD Risk Reduction Lifestyle Changes Weight loss, healthy foods, Increased activity Daily Aspirin Lipid Control Hypertension Control
HYPERGLYCEMIA Medications A1c < 7% Increased Physical Activity Healthy Food Choices
Impact on Complication with Glucose Control Microvascular Macrovascular Other factors must be targeted Statton IM et al. BMJ 2000; 321: 405-412
HgbA1c (%) < 6.0 < 7.0 6.5 ADA and ACE Glycemic Goals ADA ACE Biochemical Index Normal Goal Target • ADA Updatedrecommendations: "more stringentgoals (i.e., a normal A1C, <6%) canbe considered in individualpatients" American Diabetes Association. Diabetes Care. 2004;26:S33-S50.American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control
2004 AI/AN Diabetic Patients with HbA1c < 7% IHS 2003 Average 34% IHS Standards of Care Audit Data 2004
Can the Course of Type 2 Diabetes Be Altered? Obesity IFG* Diabetes UncontrolledHyperglycemia 350– Post-meal Glucose 300 – 250 – Fasting Glucose 200 – Glucose (mg/dL) 150 – 100 – 50 – 250 – Insulin Resistance 200 – RelativeFunction(%) 150 – 100 – -cell Failure 50 – 0 – -10 -5 0 5 10 15 20 25 30 Years of Diabetes Minneapolis, International Diabetes Center, 2000.
Type 2 Diabetes:Who Is Your Typical Patient? • Patients typically present with: • A1c? _____________ • Approximately _______ % reduction inbeta-cell function? • Degree of Insulin Resistance? ________ • Complications? _____________ • Other conditions? _____________
Oral Therapy for Type 2 Diabetes: Sites of Action • Pancreas • Sulfonylureas • Repaglinide • Nateglinide • Adipose Tissue • Rosiglitazone* • Pioglitazone* • Gut • Acarbose • Miglitol Hyperglycemia • Liver • Metformin* • Rosiglitazone • Pioglitazone • Muscle • Rosiglitazone* • Pioglitazone* • Metformin *Primary site(s) of action. DeFronzo RA. Ann Intern Med. 1999;131(4):281-303. Inzucchi SE. JAMA. 2002;287(3):360-372.
Choosing An Oral Agent What is the current degree of control? How long has the patient been diagnosed? Is the patient overweight? 4. Does the patient have dyslipidemia?
Choosing An Oral Agent What is the kidney and liver function like? Does the patient have known heart disease? How does the patient feel about taking meds?
ADDING INSULINBedtime intermediate or long acting insulin plus oral agent(s) NPH/Lantus Insulin Effect B L D HS B Meals
Rapid-acting mixture (NPH/R or lispro) before dinner plus oral agent(s) premixed 70/30 Insulin Effect B L D HS B Meals
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
HYPERTENSION Medications BP< 130/80 Increased Physical Activity Healthy Food Choices
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 IHS 2003 Average 34% IHS Standards of Care Audit Data 2004
Average Number of Antihypertensive Agents Needed Per Diabetic Patient to Achieve Target BP Number of Antihypertensive Agents Trail Target BP mm Hg UKPDS DBP<85 ABCD DBP<75 VDRD MAP<92 HOT DBP<80 AASK MAP<92
JNC-7 Algorithm for the treatment of hypertension in patients with diabetes NOT AT BP GOAL < 130/80 NOT AT BP GOAL < 130/80
Step-wise progression to controlling Blood pressure ACE & ARBS Limits nephropathy and Lower CVD risk Blocker Ca++CB Thiazide -Blocker*
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
HYPERLIPIDEMA Medications LDL < 100 TR < 150 HDL: Men >45 Women > 55 Increased Physical Activity Healthy Food Choices
Treatment Decisions Based on LDL Cholesterol Levels in Adults With Diabetes * 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 lowering - Lifestyle interventions - HMG CoA reductase inhibitor (statin) - Cholesterol absorption inhibitior (ezetimibe) - Bile acid binding resin or fenofibrate 2. HDL cholesterol raising - Lifestyle interventions (weight loss, physical activity, smoking cessation) - Nicotinic acid or fibrates Adapted from ADA. Diabetes Care 2004;27(suppl 1):S68
Triglyceride 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 IHS 2003 Average 35% IHS Standards of Care Audit Data 2004
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 IHS 2003 Average 65% IHS Standards of Care Audit Data 2004
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? Improve patient’s awareness of risks Address emotional barriers Empower the patient through education, motivation, and self advocacy