Getting to Goal:‘Practical Tricks of the trade‘

How to Achieve the ABCs

Robert Gabbay MD, PhDDirector

Penn State Hershey Diabetes InstitutePenn State College of Medicine

rgabbay@psu.edu

The ‘ABCs’

• A1C

• BP < 130/80

• Cholesterol (LDL<100, if CAD <70)

Evidence based interventions that reduce morbidly and mortality

• HbA1C < 7• BP < 130/80• LDL cholesterol < 100 (or <70 if CAD) • Aspirin age > 50 men, 60 women with 1 risk factor• ACE -age >55• Statin use- age >40• Yearly screen for nephropathy, feet, and eye exams

Current Diabetes Care in US• 71 % < 1 A1c measurements per year

– 18 % A1C > 9.5– ½ A1C > 7

• ~64% blood pressure above goal• 89 % LDL > 100• 37 % no dilated eye exam• 45 % no yearly foot exam

How Low to Go?

What’s the Problem?

• Not Bad Patients or Bad Doctors• It’s the System• Acute Care vs. Chronic Care

–Self-management• Clinical Inertia

A1C < 7Why?How?

6

6.5

7

7.5

8

8.5

9

Conventional Intensive

7.9

UKPDS: Hemoglobin A1C (HbA1C)

MedianHbA1C (%)

7.0

-50-45-40-35-30-25-20-15-10

-50

% Risk Reduction

UKPDS: Risk ReductionsAny Diabetes-

relatedEndpoint

MicrovascularEndpoints

Laser Rx Cataract Albuminuria

But I thought it was Bad to Lower A1C too Much

• All recent studies aimed at A1C = 6.5 or lower• No evidence that A1C = 7 is bad• Data says to reduce CVD- its not so much

about Glucose• It’s the Blood Pressure and Cholesterol

Really really important points:

1. Aggressive control early prevents complications.2. Because of the log-linear relationship between control

and complications, absolute benefits are greatest at high HbA1c values.

3. Pushing patients with advanced disease (particularly macrovascular complications) to ‘tight’ control that they cannot achieve probably increases mortality

• attention to hypoglycemia and particularly nocturnal hypoglycemia

Sites of Drug ActionCarbohydrate

DIGESTIVE ENZYMES

Glucose

Defectiveb-cell secretion

Excessglucoseproduction

Resistance to the action of insulin

Reduced glucoseuptake

Excessivelipolysis

Dinneen SF. Diabet Med. 1997; 14 (Suppl 3): S19-24.

Sulfonlyureas MeglitinidesIncretinsInsulin

Alpha-glucosidaseInhibitors, Incretins

MetforminTZDIncretins TZD, Metformin

How to choose?• Pathophysiology – I resist or I secretion?• Cost• Rapid onset- avoid TZD• Co-morbidities

– Renal – no metformin– Liver –no TZD– CHF – no TZD– CAD? – avoid TZD?– Weight- favor metformin, incretins– Concern hypo- avoid SU

Points to remember

• Each oral agent lower A1C 1-2• If A1C >9, start two agents• Follow SMBG, A1C, and Titrate!!!!!

T2DM treatment strategies revisited

7

9

HbA 1

c (%

)

8

Diagnosis

Target-driven therapy*

Adapted from Riddle M. Endo Metab Clin NA 1997;26:659―77.Riddle M. Am J Med 2004;116:35―95.

*Individualise

STEP 1

STEP 2

STEP 4

OHA monotherapy

OHA combinations

STEP 3

Lifestyle modification

Basal insulin

Basal plus prandial

20 10 0 10 20 30

Natural History of Type 2 Diabetes

Adapted from International Diabetes Center (IDC). Minneapolis, Minnesota.

Years of Diabetes

Relative b-Cell Function

PlasmaGlucose

Insulin resistance

Insulin secretion

126 mg/dL Fasting glucose

Postmeal glucose

6-6

TYPE 2 DIABETES . . . A PROGRESSIVE DISEASE

Over time,most patients will need

insulinto control glucose

6-7

Correcting Fasting Hyperglycemia…

100

200

300

Normal A1C 5%–6%

PG (

mg/

dL)

0800 1200 1800 0800Time of Day

Uncontrolled A1C ~9%

A1C ~6%

Is Usually the First Task!!

…then, Tackle Postprandial Hyperglycemia if A1C still >7%!

“Controlled” A1C <7%

Adapted with permission from Cefalu WT. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:1

2003 Aventis Pharmaceuticals Inc

Titrating Glargine or Detemir

2 units q 3 days until FPG < 100

Its that easy and it works!

50

4:00

25

75

8:00 12:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

PlasmaInsulin ( µU/mL)

Time8:00

Physiologic Serum Insulin Secretion Profile

Blood Pressure<130/80

Why?How?

Benefits of tight vs less tight BP control

Ris

k R

educ

tion

(%)

AnyDiabetes-

relatedEndpoint

Diabetes-relatedDeath Retinopathy Stroke HF

24P=.0046

32 P=.019

34 P=.0038

44 P=.013

56 P=.0043

-70

-20

0

-10

-50

-60

-30

-40

UKPDS: Effect of Intensive BP Lowering on Risk of Micro- and Macrovascular

ComplicationsMI

21P=.13

RenalFailure

42 P=.29

47 P=.0036

Vision Deterioration

UKPDS 36. BMJ. 2000;321:412-419. UKPDS 38. BMJ. 1998;317:703-713.

UKPDS (United Kingdom Prospective Diabetes Study) was a randomized, prospective trial in which 1,148 hypertensive patients with type 2 diabetes were allocated to tight (<150/<85 mm Hg, n=758) or less tight (<180/<105 mm Hg, n=390) BP control and followed for a median of 8.4 years. Microvascular endpoints included retionpathy requiring photocoagulation, vitreous hemorrhage, and fatal or nonfatal renal failure.

Consistency Across Guidelines on BP Goal in Patients With Diabetes

• JNC 7:

• ADA: BP Goal Is <130/80 mm Hg

• NKF:Adapted from American Diabetes Association. Diabetes Care. 2003;26(suppl 1):S33-S50; NHBPEPCC. JNC 7 Express. 2003. NIH Publication No. 03-5233; NKF. Available at: www.kidney.org/general/news/diabetic.cfm?id=64. Accessed March 9, 2004.

ABCD2,3 (132 mm Hg)

AASK1 (134 mm Hg)

High-Risk Hypertensive Patients Require Multiple Agents to Achieve Goal

1Wright JT et al. JAMA. 2002;288:2421-2431. 2Bakris GL. J Clin Hypertens. 1999;1:141-147. 3Estacio RO et al. N Engl J Med. 1998;338:645-652. 4The ALLHAT Officers and Coordinators. JAMA. 2002;288:2981-2997. 5Hansson L et al. Lancet. 1998;351:1755-1762. 6Lewis EJ et al. N Engl J Med. 2001;345:851-860. 7Bakris GL et al. Arch Intern Med. 2003;163:1555-1565. 8UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.

1 2 3 4Number of BP Medications

ALLHAT4 (135 mm Hg)

RENAAL7 (140 mm Hg)

IDNT6 (140 mm Hg)

UKPDS2,8 (144 mm Hg)

HOT2,5 (141 mm Hg)

AchievedSystolic BP

Evidence Based Guidelines

• < 130/80 (you will report <140/90)• How about LOWER???• ACCORD looked at lower (120)- no better• What is the first line medication?

– Who cares?

20

0 1 2 3 4 5 6 7

Cum

ulat

ive

Even

t Rat

e (%

)

0

4

8

12

16

ChlorthalidoneAmlodipineLisinopril

ALLHAT (The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack) participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n=15,255); amlodipine, 2.5 to 10 mg/d (n=9,048); or lisinopril, 10 to 40 mg/d (n=9,054) for planned follow-up of approximately 4 to 8 years, mean follow-up 4.9 years.ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997.

ALLHAT: Cumulative Event Rates for Fatal CHD or Nonfatal MI by Treatment

Years to EventNumber at Risk:Chlorthalidone 15,255 14,477 13,820 13,102 11,362 6,340 2,956 209Amlodipine 9,048 8,576 8,218 7,843 6,824 3,870 1,878 215Lisinopril 9,054 8,535 8,123 7,711 6,662 3,832 1,770 195

Medication Treatment Algorithm?

• Start with ACE or ARB and/or HCTZ– Either one - best might be early combo since all

will likely need it • Third agent based on co-morbidity

– Beta blocker and/or Ca channel• Add the 4th and hopefully you’ve reached goal-

if not call an expert +/- alpha blocker?

Tashko and Gabbay, Integrated Blood Pressure Control (2010)

Practical: What can I do on when I get back to work?

• Track BP• Don’t miss an opportunity to escalate• Shared goals• Standing Orders?

Cholesterol LDL control <100

If CVD <70

LDLTreat the water supply?

%

Follow-up (years)

Placebo

Simvastatin

Benefit/1,000 -1 13 34 47 51 58

P<0.0001

0 1 2 3 4 5 60

5

10

15

20

25

30

HPS Collaborative Group. Lancet. 2003;361:2005-2016.

HPS Substudy: First Major Vascular Event in Patients With Diabetes

22 %

Follow-up (yr)

Cumulativeincidence

(%)

0

1

2

3

4

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5

Atorvastatin 10 mgPlacebo

Number of events: 100Number of events: 154

HR=0.64 (0.50-0.83) P=0.0005

36%reduction

Nonfatal MI (including silent MI) and fatal CHD.Sever PS et al. Lancet. 2003;361:1149-1158.

ASCOT-LLA: Primary End Point

Statins for DM

The question is:Who do we NOT treat?

Putting it All together

The Chronic Care Model

36

Informed,ActivatedPatient

ProductiveInteractions

Prepared,ProactivePractice Team

DeliverySystemDesign

DecisionSupport

ClinicalInfo

Systems

Self-Management

Support

Health SystemResources and Policies

Community Health Care Organization

Improved Outcomes

Self-management support

Increase adherence• Education but most important

SUPPORT• Use handouts, share goals• Combo Rx for pill burden

– Who else on the team can help?– Use Diabetes Educators where available

Delivery System Design

• Distribute tasks amongst team– It takes a TEAM to manage a Chronic disease

• Care management of high risk– Stratifying your population

• Regular f/u by team• Planned Visits• Dealing with CLINICLA INERTIA

The Chronic Care Model

39

Informed,ActivatedPatient

ProductiveInteractions

Prepared,ProactivePractice Team

DeliverySystemDesign

DecisionSupport

ClinicalInfo

Systems

Self-Management

Support

Health SystemResources and Policies

Community Health Care Organization

Improved Outcomes

Decision support

–Evidence based guidelines (ADA)–SHARE WITH YOUR PATIENTS

41

42

Clinical Information systems

Registry!!!!Track outcomes and ID those not at goal with a plan for intensification

Evidence based interventions that reduce morbidly and mortality

• HbA1C < 7• BP < 130/80• LDL cholesterol < 100 (or <70 if CAD) • Aspirin age > 50 men, 60 women with 1 risk factor• ACE -age >55• Statin use- age >40• Yearly screen for nephropathy, feet, and eye exams

QUESTIONS?