Biotechnology:Its Promises and PathwaysSpring 2006 Series

The InnovatorsDiabetes: How Sweet It Isn’t!R. Keith Campbell, RPh, CDEFosberg Distinguished Professor of Pharmacy Department of PharmacotherapyCollege of Pharmacy

Diabetes Facts:Scary but True…

• Over 6.8% of U.S. Population has diabetes• 20.8 million people with diabetes in the U.S.• 1 of every 3 babies born today will develop

diabetes in his/her lifetime• 1 in every 5 dollars spent on health care

is for diabetes: $134 billion/year

Diabetes Facts:Scary but True…

• Fastest growing segments of the populationare people 30-39 years old and adolescentsdeveloping type 2 diabetes

• Diabetes in Washington State affects 1.3 million patients/family; kills 4000/year; is a factorin 67,000 hospitalizations & accountsfor > $1 Billion just in hospitalizations

• Number of diabetes patients will doublein the world within 10 years

Status of Diabetes Management• Majority of patients with type 2 diabetes have

only fair to poor metabolic control§ Fasting serum glucose levels of ≥ 200 mg/dL § HbA1c levels of > 9%

• Postprandial blood glucose levels average~300 mg/dL

• < 2% of American adults with diabetesreceive optimal quality of care

Beckles GLA et al. Diabetes Care. 1998;21:1432-1438.American Diabetes Association. Diabetes Care. 1998;21(Suppl 1).Colwell JA. Ann Intern Med. 1996;124(1pt2):131-135.Abraira C et al. Diabetes Care. 1992;15:1560-1571.Klein R et al. Am J Epidemiol. 1987;126:415-428.Cowie CC et al. Diabetes in America. 2nd ed.

Diabetes Healthcare System ProblemsManaged Care Places Barriers to Optimal Care

• Greater than 90% of patients are seenonly by primary care physicians

• 70% of patients receive no diabetes education

• 70% of patients do not receive annualeye exams

• Less than half of all patients performSMBG appropriately

Harris MI et al. Ann Intern Med 1996 Jan 1;124(1 Pt 2):117-22

ADA Standards of Care• Physician Visits 2-4 per year• HbA1c Measurement 2-4 per year• Fasting Glucose Measurement / (SMBG) 4-6 per year/daily• Foot Exams Every Visit• Aspirin Daily• Urine Protein Measurements Yearly• Blood Pressure As needed to achieve goals

• Lipid Levels As needed to achieve goals• Dilated Pupil Eye Exam Yearly• Flu and Pneumovax As needed

Prevalence of GlucoseIntolerance in the United States

0

5

10

15

20

25

30

35

40

45

50

0 20-44 45-54 55-64 65-74

Age

% o

f Pop

ulat

ion

Diabetes

Undiagnosed diabetes

Impaired glucose tolerance

Kenny SJ et al. In: Diabetes in America. 2nd ed. 1995;chap 4.

Patients with diabetes are impacted by many groups and health care providers including:

Physicians

Nurses

RD’s

Pharmacists

Eye docs

Podiatrists

Physician Assistants

Dermatologists

The Amer. Diabetes Assoc.

Managed care organizations

Government & private health care programs

AADE

Center For Disease Control

The NIH

State diabetes control projects

Pharmaceutical manufacturers

Universities’ research and education programs

Local hospital patient support groups

Other diabetes patients

Insulin Resistance

• A core defect in type 2 diabetes- 92% of patients with type 2 diabeteshave insulin resistance

• Definition: Impaired response to thephysiological effects of insulin

• Deterioration of the beta cell over time

Haffner SM et al. Diabetes Care 1999;22:562-568.Consensus Development Conference of the American

Diabetes Association. Diabetes Care 1998;21:310-314.

The Metabolic Syndromeof Insulin Resistance

EndothelialDysfunction Systemic

InflammationComplex

DyslipidemiaInc TG, sdLDL

Dec HDL

InsulinResistance

Type 2Diabetes

AtherosclerosisDisorderedFibrinolysis

Hypertension VisceralObesity

Adapted from the Consensus Development Conference of theAmerican Diabetes Association. Diabetes Care 1998;21:310-314.

Pradhan AD et al. JAMA 2001;286:327-334.

© International Diabetes Center. From Kendall D, Bergenstal R.

Timeline forUtilization of Therapies

Glucose

Relative Function

050

100150200250

-10 -5 0 5 10 15 20 25 30

50100150200250300350

Years of Diabetes

Insulin Resistance

Insulin Level

Fasting Glucose

Beta cell failure

Post Meal Glucose

At riskfor Diabetes

Lifestyle InsulinMetformin, TZD, AGI, Incretins

SUMeglitinide

Priorities of Care for Adults with Diabetes

© 2005 International Diabetes Center. All rights reserved.

Hemoglobin A1C Target < 7.0%

SMBGPre 70-140 mg/dLPost <160 mg/dL

(~ 50% of readings)Combination RxInsulin therapy

Insulin sensitizers

Annual Lipid ProfileLDL < 100HDL > 40

Trigs < 150

Statin FibrateNiacin TZD Ezetimibe

Combination Rx

Blood Pressure(every visit)

Dx and Rx = 130/80

ACEI or Thiazidebased-Rx

Combo therapy

Annual ScreeningNephropathy

Microalbumin screening

RetinopathyDilated retinal exam

NeuropathyNeuro and foot exam

Sexual heath

Hospital care Gestational DM

Foot careDental care

Immunizations

CVD RiskASA, Tobacco, ACEI/ARB, Statin

Diagnosis and PreventionPrediabetes (IFG -IGT) - Metabolic Syndrome

HypertensionGlucoseInsulin resistance

Microvascular Complications

Other Essentialsof CareLipids

Diabetes Self-Management SkillsLifestyle• Patient education• BG monitoring• Medical nutrition• Physical activity

Behavioral Health• Emotional assessmentdistress, depression, complications

• Support needsfamily, peers, medical

Diabetes = Cardiovascular Disease

• Up to 70 % of diabetes patients diefrom heart disease or stroke

• Diabetes is a cardiovascular risk factor• Diabetes treatment must include treatment

of blood pressure, blood fats, blood sugarand coagulation factors

Treating the Metabolic Syndrome

• Stop smoking• Eat less• Exercise more• Take magnesium• Take aspirin• Take an ace inhibitor or an arb• Take a statin• Take pioglitazone, metformin

to reduce insulin resistance

Treatment Options: Needs

• Nutrition• Education• Exercise• Drug therapy• Self-monitoring

Matching Pharmacologyto Pathophysiology

↑HepaticGlucose Output

↓PeripheralGlucose Uptake

Glucose Influx

↓InsulinSecretionHyperglycemia

Biguanides(TZD)

Insulin TZD(Biguanides)

Insulin

SulfonylureasMeglitinides

Insulin

AGIIncretins

Prototype Pulmonary InsulinDelivery System: Exubera

www.PDC-USA.com

PDC Technosphere™/Insulin

• Fastest onset of anyinsulin-mimics firstphase insulin release

• Highest bioavailability(40-50%)

• Initial studies suggestless variable absorption

Generex: Buccal Insulin Delivery

• Oral-Lyn: Absorbed directlyvia the oral mucosa

• Aminopeptidase inhibitorsmay need to be added

FDA Approved CGM Devices

Device GlucoWatch CGMs Gold Guardian 1

Invasive? No? Yes Yes

Real-time/Retrospective? Real-time Retrospective Real-time

Frequency of Data?Every 10 minutes

up to 13 hoursEvery 5 minutes up

to 72 hours Alarm only

Alarm?• Low, high

• Pending lowNo Low, high

Investigational Devices

Device Navigator DesCom Guardian RealTime

Invasive? Yes Yes Yes

Real-time/Retrospective? Real-time Real-time Real-time

Frequency of Data? Every minute Every 5minutes

Every 5minutes

Alarm?Low, high

Pending low/highLow, high

Pending low/highLow, high

FreeStyle Navigator™ Continuous Glucose Monitor

TransmitterSensor/Sensor Mount

Receiver

Investigational Device

Experimental but Promising New Medications to Treat Diabetes

• Ruboxistaurin (Arxxant) preventseye and kidney disease

• Rimonabant (Acomplia) inhibits theeffects of cannabis and results in weightloss, smoking cessation and improvedinsulin resistance

• Adiponectin type products

VEGF and PKC-ß Inhibition

VEGF VEGF+PKCßi

Diabetes and WSU• The Diabetes Initiative• Educational programs from Pharmacy,

Nursing, Extension, FSHN and others• Clinical research from Pharmacy, Nursing,

FSHN, Health Care Policy Administrationand other departments

• Basic science research from Biochemistry,Veterinary Medicine, Pharmacy

Conclusions

Questions and comments

Thank you so much for your timeand attention; it is much appreciated.

rkcamp@wsu.edu

Coming UpThe Innovators lecture series in Seattle

The InnovatorsEpigenetics, Heredity, and the Environment:The Ghost in Your GenesMichael K. Skinner, Ph.D. Director and Professor, Center for Reproductive BiologyCenter for Integrated BiotechnologySchool of Molecular Biosciences

The InnovatorsWhy Diseases Emerge:The World of Surveillance, Risk, and Response

Guy H. Palmer, DVM, Ph.D.Diplomate, American College of Veterinary PathologistsProfessor of Microbiology and PathologyCollege of Veterinary Medicine

For more information:www.wsu.edu/theinnovatorsToll free 1-877-978-3868