Jay Shubrook DO FACOFP, FAAFPAssociate Professor of Family

MedicineDirector, Diabetes Fellowship

Ohio University College of Osteopathic Medicine

Improving Medical Management of Diabetes

Diabetes in the US24 million American with diabetes

90%-95% have type 2>1 million more per year57 million Americans have pre-DM$170 billion dollars

Estimated 25% of adults > 60 y/o have DM1 in 5 Medicare dollars

CDC Fact Sheet

Diabetes in the US Children can have type 2

SEARCH trial20% of children with DM have type 2 DMSome have estimated 7% of children and

adolescents have pre-DM

CDC predicts people born in 20001 in 3 will develop DM40% risk in at risk populations50% or 1 in 2 in Hispanic population

Natural History of DM-2

0

100

200

300

-10 -5 0 5 10 15 20 25 30

50

150

250

350

At risk for Diabetes

Glucose

Relative Function

Post Meal Glucose

Fasting Glucose

Insulin Resistance

Insulin LevelBeta Cell Failure

Years of Diabetes

Bergenstal, ©2000 International Diabetes Center Used with permission.

Diabetes is progressiveAt diagnosis 50% of functional beta cells

lostUKPDS results

No slowing of progressionLifestyle or metformin

Typically we start low and go slowLike the old rheumatoid arthritis treatment

algorithms

NORMAL IFG or IGT DIABETES

FPG < 100 mg/dl

IFG FPG > 100 - 125 mg/dl

FPG > 126 mg/dl

2-h PG < 140 mg/dl

IGT2-h PG > 140 -

199 mg/dl

2-h PG > 200 mg

Random PG > 200 +

symptoms

A1C 5.7% to 6.4% ≥ 6.5%

2010 Diagnosis of Diabetes and Categories of Increased Risk for

Diabetes

ADA, Diabetes Care 33: Suppl. 1, S11-S61, 2010

International Expert Committee Report on A1C in the Diagnosis of Diabetes

6.5%

THE INTERNATIONAL EXPERT COMMITTEE. Diabetes Care 2009;32:1327

Rate

/100 P

ers

on

-Years

24

20

16

12

8

4

09876543210

Mean HbA1c = 11%

10%9%

8%

7%

Conventional treatment

Time During Study (y)

DCCT Research Group. Diabetes 1995;44:968-983.

DCCT: Absolute Risk of Sustained Retinopathy Progression by HbA1c

and Years of Follow-up

Clinical Efficacy of Oral Hypoglycemic Agents

Class of hypoglycemic Class of hypoglycemic agentsagents

Reduction in HbAReduction in HbA1c1c (%)(%)

Reduction in Reduction in FPG (mg per dl)FPG (mg per dl)

SulfonylureasMeglitinides

BiguanidesThiazolidinedion

esAlpha-

glucosidase inhibitors

DPP-4 inhibitor

0.8 to 2.00.5 to 2.01.5 to 2.00.5 to 1.50.7 to 1.0

0.5 to 0.9

60 to 70 65 to 7550 to 70 25 to 50 35 to 40

20 to 30

Adapted from University Educators MD-PhD

Probability of events of non-fatal myocardial infarction with intensive glucose-lowering vs. standard treatment

Ray et al, Lancet 2009; 373: 1765–72

ACCORD – Primary Outcome by Subgroup

Protocol Defined Subgroups

n Events

Overall 10251 723

Primary Prevention 6643 330

Secondary Prevention 3608 393

Women 3952 212

Men 6299 511

Baseline Age < 65 677 383

Baseline Age ≥ 65 3472 340

Baseline A1C ≤ 8.0 4868 284

Baseline A1C > 8.0 5360 438

Non White

White

3647

6604

222

501

0.6 1.0 1.4HR (Intensive vs. Standard)

Interaction P- value

0.04

0.74

0.65

0.03

0.29

UKPDS: 10 yr Follow up

HbA1c difference disappearedOutcome reduction with intensive control

Any DM end point 9% p= 0.04Myocardial infarction 15% p=0.01Death overall 13% p=0.005

If on metforminMI 33% p=0.005Death 27% p=0.002

Intensive Glycemic Control in Diabetes:

Implications of ACCORD, ADVANCE and VADT• A1C targets for diabetesA1C targets for diabetes

– Lowering A1C to < 7% has been shown to Lowering A1C to < 7% has been shown to significantly reduce the risk of microvascular significantly reduce the risk of microvascular complications in both type 1 and type 2 diabetescomplications in both type 1 and type 2 diabetes

– Controlled trials of Controlled trials of more intensive glycemic more intensive glycemic controlcontrol have not shown a decrease in CVD have not shown a decrease in CVD mortality mortality

– Long-term follow-up suggests that A1C < 7% in Long-term follow-up suggests that A1C < 7% in the years following diagnosis is associated with a the years following diagnosis is associated with a reduction in CVD risk reduction in CVD risk

– Until more evidence becomes available, the Until more evidence becomes available, the general A1C target of < 7% appears reasonable general A1C target of < 7% appears reasonable

A position statement of the ADA and a scientific statement of the ACC and the AHA. A position statement of the ADA and a scientific statement of the ACC and the AHA. Diabetes CareDiabetes Care 32; 2009; 187-192 32; 2009; 187-192

Early treatment=greater successMarch 2010 Diabetes Care

If metformin started with in 3 months of diagnosis

Worked for twice as long12% vs 21% failure rate per year

Brown JB . Secondary Failure of Metformin Monotherapy in Clinical Practice. Diabetes Care March 2010

Tips to get controlLifestyle should be used in all patients but

only as part of the treatmentStart aggressively and back offAssume each medication will improve

HgA1c 1%Never substitute meds

Always add new agent first Titrate to get control Then stop first agent

Ask the patient what they wantShots may be better than more pills

Develop a plan that prevents hypoglycemia

Lifestyle + MET + PIO + SFU

Lifestyle + MET + PIO + SFU

STEP 1

At diagnosis: Lifestyle + MET

STEP 2 Tier 1: Well-validated core therapies*

STEP 3 Lifestyle + MET + Intensive Insulin

OR

If A1C If A1C ≥7%≥7%

CHF, chronic heart failureMET, metformin PIO, pioglitazone SFU, sulfonylurea

*Validation based on clinical trials and clinical judgment. Adapted from Nathan DM, et al. Diabetes Care. 2008;31(1):173-175.

Lifestyle + MET + Basal Insulin

Lifestyle + MET + Basal Insulin

Lifestyle + MET + SFU

Lifestyle + MET + SFU

Lifestyle + MET + Basal Insulin

Lifestyle + MET + Basal Insulin

Tier 2: Less-well-validated therapies*

Lifestyle + MET + PIO

Lifestyle + MET + PIO

Lifestyle + MET + GLP-1 Agonist

Lifestyle + MET + GLP-1 Agonist

ADA Consensus Statement for the Management of Type 2 Diabetes

AACE Guidelines

What about special populations?

Glucose control for special populations

Children with type 1A1c <8% and limit hypoglycemiaGlucose variability may be important

Children with type 2No guidelinesSame goals as adults

Older adultsBased upon life expectancyTime to benefit for glucose vs. BP and lipids

ADA – Summary of Recommendations for Adults with Diabetes

Goals

Glycemic control: A1C* < 7%

Preprandial BG 90 – 130 mg/dl

Peak postprandial BG <180 mg/dl

ADA. Diabetes Care, 2010.

Blood Pressure: < 130/80

mm HgLipids: LDL < 100 mg/dl Triglycerides <150 mg/dl HDL > 40 mg/dl

* Death due to MI, sudden death, stroke, peripheral vascular disease, renal disease, hyperglycemia, or hypoglycemia. † Fatal or nonfatal.‡ Retinopathy requiring photocoagulation, vitreous hemorrhage and fatal or nonfatal renal failure. Mean BP : 144/82 mm Hg (tight BP control) vs 154/87 mm Hg (less tight BP control).UK Prospective Diabetes Study Group. BMJ. 1998;317:703-713.

Risk Reduction of Diabetes-RelatedEnd Points with Tight BP Control

Ris

k R

educt

ion (

%)

Diabetes-related

Mortality* Stroke†Microvascular

End Points‡

Myocardial Infarction

0

10

20

30

40

50

32

44

37

21

Lipid lowering: Heart Protection Study

LDL lowering

resulted in 22%

reduction in CVD events

across all categories

of LDL

Antiplatelet Agents in Diabetes, 2010

Primary Prevention (75–162 mg/day):Type 1 or type 2 diabetes at increased CV risk (10 yr

risk > 10%), men > 50 yr or women >60 yr who have at least one additional major risk factor (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria)

There is not sufficient evidence to recommend aspirin for primary prevention in lower risk individuals

Secondary prevention (75–162 mg/day):Use aspirin therapy as a secondary prevention

strategy in those with diabetes with a history of CVD

ADA Clinical Practice Recommendations, Diabetes Care, January 2010

Multifactorial intervention and CVD in type 2 diabetes: STENO 2

Gaede P, Gaede P, et alet al. . N Engl J MedN Engl J Med 2008;358:580–91.2008;358:580–91.

11 22 33 44 55 66 8877 99 1010 1111 1212 1313

00

44

55

66

77

88

99

1010

1111

Conventional Conventional therapytherapy

Intensive Intensive therapytherapy

Gly

cate

d h

em

og

lob

in (

%)

Gly

cate

d h

em

og

lob

in (

%)

Follow-up time Follow-up time (years)(years)

00

STENO 2 - Risk of Death from Any Cause

00

1010

2020

3030

4040

5050

6060

7070

8080

Follow-up time Follow-up time (years)(years)

11 22 33 44 55 66 8877 99 1010 1111 1212 131300

No. at riskNo. at riskIntensiveIntensive 8080 78 78 75 75 72 72 65 62 65 62

57 3957 39ConventionalConventional 8080 80 80 77 77 69 69 63 63 51 51

43 3043 30

Cu

mu

lati

ve I

ncid

en

ce o

f d

eath

(%

)C

um

ula

tive I

ncid

en

ce o

f d

eath

(%

)

p = 0.02p = 0.02

Conventional Conventional therapytherapy

Intensive Intensive therapytherapy

Gaede P, Gaede P, et alet al. . N Engl J MedN Engl J Med 2008;358:580–91.2008;358:580–91.

ADA – Summary of Recommendations for Adults with Diabetes

Goals

Glycemic control: A1C* < 7%

Preprandial BG 90 – 130 mg/dl

Peak postprandial BG <180 mg/dl

ADA. Diabetes Care, 2010.

Blood Pressure: < 130/80

mm HgLipids: LDL < 100 mg/dl Triglycerides <150 mg/dl HDL > 40 mg/dl

Managing Diabetes Most psychologically and behavior mod.

challenging disease to manage95% of care is self-careOffice visits have 3 agendas:

PatientPhysicianInsurer

Cultural and social influences are strong

Results: T2DM Survey Adults

HGM 11 Records 9 Oral meds 8 Foot care 6 Oral care 8 Problem sol 13 Ob. supplies 11 Support groups

13 Sch. Med appts

9

88 minutes

Common needs Meal planning 21 Shopping 23 Exercise 32 Preparing meals

54 Stress manage

16

146 minutes

Total 234 minutes 3 hours and 54 minutes!!

Shubrook et al. In press

Keys to Managing DiabetesAddress the 3 agendasBuild efficiencies into your careMeasure your care (others already are)

Celebrate small successesFocus on the positiveDispel myths- be an accurate source

Work as a team and re-enforce messages

Glucose monitoringGlucose measurement should match the

intensity of treatmentRare checks if no meds3-7 checks per week on insulin sensitizers

onlyIf on insulin:

FSG for each time injecting insulinAVOID sliding scale insulin loneaAVOID insulin that have variable absorption

SummaryDiabetes is common and will get more

commonEarly aggressive treatment may be our best

bet at preventing burden of diseaseStart low and go slow does not workAssume 1% reduction in A1c for each

medicationGuidelines exist to help direct treatmentRemember the 3 agendasThis is the patient’s disease process not yours

It will be a lifetime so pace yourself as well