MANAGEMENT OF MANAGEMENT OF

DIABETES MELLITUSDIABETES MELLITUS

BYBY

Dr. Dr. Mohammed Gameil Mohammed Gameil MDMD..

Lecturer of internal medicineLecturer of internal medicineDiabetes & endocrine deptDiabetes & endocrine dept..

Mansoura universityMansoura university

Why are We Concerned about Why are We Concerned about DiabetesDiabetes??

Every 24 hours...Every 24 hours...

3,600 new cases of diabetes are diagnosed3,600 new cases of diabetes are diagnosed 580 people die of diabetes-related 580 people die of diabetes-related

complicationscomplications 225 people have a diabetes-related amputation225 people have a diabetes-related amputation 120 people with diabetes progress to end-stage 120 people with diabetes progress to end-stage

renal diseaserenal disease 55 people with diabetes become blind55 people with diabetes become blind

Goals of treatmentGoals of treatment

Complete elemenation of overt clinical Complete elemenation of overt clinical

manifestationmanifestation

Prevention of ketoacidosisPrevention of ketoacidosis

Prevention and treatment of hypoglycemiaPrevention and treatment of hypoglycemia

Control if hyperglycemia and glucosuria to Control if hyperglycemia and glucosuria to

minimize the caloric loss minimize the caloric loss

Maintenance of high levels of physical Maintenance of high levels of physical

fitnessfitness

GOALSGOALS

Achievement of normal growth including Achievement of normal growth including

proper timing of puberty.proper timing of puberty.

Encourage the patient for full participation Encourage the patient for full participation

in all activities appropriate for his age.in all activities appropriate for his age.

Education of patient and his families Education of patient and his families

regarding diabetic process.regarding diabetic process.

Prevention of complication.Prevention of complication.

Specific Goals in Specific Goals in Management of DiabetesManagement of Diabetes

Fasting < 110 mg/dL Fasting < 110 mg/dL

Post-meal < 140 mg/dLPost-meal < 140 mg/dL

A1C < 6.5%A1C < 6.5%

Blood Pressure < 130/80Blood Pressure < 130/80

LDL < 100 mg/dL; HDL > 45 mg/dLLDL < 100 mg/dL; HDL > 45 mg/dL

Triglycerides < 150 mg/dLTriglycerides < 150 mg/dL

Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2001;24(Suppl 1):S5-S20.

FPG

126 mg/dL

100 mg/dL

7.0 mmol/L

5.6 mmol/L

Prediabetes

NormalNormal

2-Hour PG on OGTT

200 mg/dL

140 mg/dL

11.1 mmol/L

7.8 mmol/L

Diabetes MellitusDiabetes Mellitus

Impaired Glucose Tolerance

NormalNormal

Diabetes MellitusDiabetes Mellitus

Diagnostic Criteria Diagnostic Criteria Associated with Glucose Associated with Glucose

AbnormalitiesAbnormalities

Treatment of diabetes Treatment of diabetes mellitusmellitus

EducationEducation

DietDiet

Physical exercisePhysical exercise

Peroral antidiabetic drugsPeroral antidiabetic drugs

InsuliInsulinn

Islet call transplantationIslet call transplantation

ADA RecommendationsADA Recommendations

Glycemic goals should be individualizedGlycemic goals should be individualized

Certain populations (children, pregnant women, and Certain populations (children, pregnant women, and

elderly) require special considerationselderly) require special considerations

Less intensive glycemic goals may be indicated in patients Less intensive glycemic goals may be indicated in patients

with severe or frequent hypoglycemiawith severe or frequent hypoglycemia

More stringent glycemic goals (i.e. a normal A1C, 6%) may More stringent glycemic goals (i.e. a normal A1C, 6%) may

further reduce complications at the cost of increased risk further reduce complications at the cost of increased risk

of hypoglycemia.of hypoglycemia.

Postprandial glucose may be targeted if A1C goals are not Postprandial glucose may be targeted if A1C goals are not

met despite reaching pre-prandial glucose goals.met despite reaching pre-prandial glucose goals.

Non-pharmacological Medical Non-pharmacological Medical Therapy Therapy

for Type 2 Diabetesfor Type 2 Diabetes

Optimize BG Control Improve blood lipids Control blood pressure

Consistent carbohydrate intake

Monitor blood glucose to adjust therapy

Moderate weight loss

Increase physical activity

Space meals

Modify fat and calorie content

EDUCATIONEDUCATION

Pathophysiology of diabetes and its Pathophysiology of diabetes and its

complicationcomplication

Diet educationDiet education

Monitoring of blood glucose at home Monitoring of blood glucose at home

(clinical ,biochemical).(clinical ,biochemical).

Monitoring Parameters for Monitoring Parameters for Control of ComplicationsControl of Complications

Every visitEvery visitBlood PressureBlood PressureFoot Exam (55% achieve goal)Foot Exam (55% achieve goal)

3-63-6 monthsmonthsA1CA1C- Every 3 months if treatment changes or - Every 3 months if treatment changes or not meeting goalsnot meeting goals- Every 6 months if stable- Every 6 months if stable

AnnualAnnualDilated Eye ExaminationDilated Eye Examination (63% achieve goal)(63% achieve goal)Lipid Levels*Lipid Levels*MicroalbuminMicroalbumin

*Every 2 years if levels fall in lower risk categories*Every 2 years if levels fall in lower risk categories

DIETDIETLower caloric.Lower caloric.

Fewer foods of Fewer foods of ““high glycemic high glycemic

indexindex””

Spread meals .Spread meals .

Caloric need of the body (ideal body Caloric need of the body (ideal body

weight in pound X 10) OR 30- 50 weight in pound X 10) OR 30- 50

calories for each k gm according to calories for each k gm according to

activity which may reach 60 cal/kg activity which may reach 60 cal/kg

in high active person.in high active person.

EXERCISEEXERCISE

Under physician supervisionUnder physician supervision

Check glucose priorCheck glucose prior

Regular physical exercise Regular physical exercise

decrease vascular decrease vascular

complications and dyslipidemia complications and dyslipidemia

associated with diabetesassociated with diabetes

Strategies to Improve Strategies to Improve Glycemic Control: Type 2 Glycemic Control: Type 2

DiabetesDiabetes Monitor glycemic targets Monitor glycemic targets –– Fasting Fasting

and postprandial glucose, A1Cand postprandial glucose, A1C

Nutrition and activity are Nutrition and activity are

cornerstones of therapycornerstones of therapy

Treatment of both insulin resistance Treatment of both insulin resistance

and insulin deficiency is often and insulin deficiency is often

necessary to achieve glycemic necessary to achieve glycemic

targetstargets

ORAL ANTIBIABETICSORAL ANTIBIABETICS

SulfonylureasSulfonylureas

ThiazolidinedionesThiazolidinediones

BiguanidesBiguanides

Alpha-glucosidase inhibitorsAlpha-glucosidase inhibitors

D-phenylalinine derivativesD-phenylalinine derivatives

CombinationsCombinations

Insulin secretagoguesInsulin secretagogues

Benefits :Benefits :Risks :Risks :A1C reduced 1A1C reduced 1––1.5% 1.5% Rare hypoglycemiaRare hypoglycemiaHigh initial response High initial response raterateEstablished safety Established safety profileprofileNo weight gainNo weight gainFavourable lipid profileFavourable lipid profileDecreased Decreased macrovascular macrovascular complications with complications with monotherapy: UKPDmonotherapy: UKPD

All have some risk All have some risk

of hypoglycemia of hypoglycemia

(higher with (higher with

glyburide)glyburide)

Weight gainWeight gain

Earlier loss of Earlier loss of

control than control than

metformin or TZDs metformin or TZDs

(ADOPT)(ADOPT)

SulfonylureasSulfonylureas

Stimulate pancreas to secrete insulin Stimulate pancreas to secrete insulin (in T2DM) :(in T2DM) :

GlibenclamideGlibenclamide GliclazideGliclazide GlipizdeGlipizde gilmepridegilmepride

Adverse reactions :Adverse reactions : HypoglycemiaHypoglycemia Chloretic jaundiceChloretic jaundice Hypersensitivity reactionsHypersensitivity reactions

Drug Interactions with sulphonylurea

Increased

Hypoglycemia :

Anticoagulants

Salicylates

Sulfonamides

MAO Inhibitors

Tricyclic

antidepressants

Azole antifungals

Decreased Action : Beta Blockers,

Diuretics, Ca2t Blockers Corticosteroids, Estrogens, Thyroid Hormones Sympathomimetics, Phenothiazines Isoniazid, Phenytoin, Nicotinic Acid

BiguanidesBiguanides

Decreases liver production of glucoseDecreases liver production of glucose

Decreases intestinal absorption of glucoseDecreases intestinal absorption of glucose

Improves cell sensitivity to insulinImproves cell sensitivity to insulin

Example: MetforminExample: Metformin

GI upset, flatulenceGI upset, flatulence

Cardiac (CHF, MI)Cardiac (CHF, MI)

Biguanides: MetforminBiguanides: Metformin

BenefitsBenefits A1C reduced 1A1C reduced 1––1.5% 1.5% Rare hypoglycemiaRare hypoglycemia High initial response rateHigh initial response rate Established safety profileEstablished safety profile No weight gainNo weight gain Favourable lipid profileFavourable lipid profile Decreased Decreased

macrovascular macrovascular complications with complications with monotherapy: UKPDSmonotherapy: UKPDS

RisksRisks GI side effects in up to GI side effects in up to

50%50% Not tolerated in up to 20%Not tolerated in up to 20% Earlier loss of glucose Earlier loss of glucose

control than TZDscontrol than TZDs Caution or contraindication Caution or contraindication

if CrCl < 60 mL/minif CrCl < 60 mL/min Lactic acidosis: very rare Lactic acidosis: very rare Discontinued at or prior to Discontinued at or prior to

IV contrast and withheld IV contrast and withheld for 48for 48  hours post IV hours post IV contrastcontrast

ThiazolidinedionesThiazolidinediones

Increase cellular sensitivity to Increase cellular sensitivity to insulininsulinPioglitazone Pioglitazone Rosiglitazone (Avandia)Rosiglitazone (Avandia)

Client should have liver enzymes Client should have liver enzymes

checked periodicallychecked periodically

Thiazolidinediones (TZDs)Thiazolidinediones (TZDs)

Benefits :Benefits :

A1C lowering 1A1C lowering 1––1.5%1.5%

Hypoglycemia rareHypoglycemia rare

High initial response High initial response

raterate

Most durable glycemic Most durable glycemic

effect in ADOPTeffect in ADOPT

Risks :Risks : Slow onset of actionSlow onset of action Weight gain Weight gain Peripheral edema (3-5%)Peripheral edema (3-5%) Incidence of CHF < 1% Incidence of CHF < 1%

with monotherapywith monotherapy Macular edema: rareMacular edema: rare Not tolerated in up to 4%Not tolerated in up to 4% Increased distal Increased distal

fractures in women, fractures in women, decreased BMDdecreased BMD

Contraindications: Contraindications: - Serious hepatic Serious hepatic

impairmentimpairment- CHFCHF

Kahn SE, et al; ADOPT Study Group. N Engl J Med 2006;355:2427-43.CDA Clinical Practice Guidelines Expert Committee. Can J Diabetes 2003;27(Suppl 2):S1-S152.

Alpha-Glucosidase Alpha-Glucosidase InhibitorsInhibitors

Competitive inhibitor of alpha glucosidase Competitive inhibitor of alpha glucosidase enzymes in small intestines; taken before enzymes in small intestines; taken before mealsmeals

Efficacy :Efficacy :

- decrease fasting plasma glucose 20-30 mg/dl- decrease fasting plasma glucose 20-30 mg/dl

- decrease peak postprandial glucose - decrease peak postprandial glucose 40-50 mg/dl40-50 mg/dl

- no specific effect on lipids or blood pressure- no specific effect on lipids or blood pressure

- reduce HbA1c 0.5-1.0%- reduce HbA1c 0.5-1.0% Other Effects :Other Effects :

- abdominal discomfort and flatulence- abdominal discomfort and flatulence

- contraindicated with inflammatory bowel disease or - contraindicated with inflammatory bowel disease or cirrhosis cirrhosis

D-Phenylalanine D-Phenylalanine derivativesderivatives

Repaglinide ( Novonorm ):Repaglinide ( Novonorm ):

- short pulse duration of action- short pulse duration of action

- give after meal with capricious appetite- give after meal with capricious appetite

- full dose range (0.5-4 mg) with meals taken- full dose range (0.5-4 mg) with meals taken

Nateglinide (Starlix) :Nateglinide (Starlix) :- Rapid onset, short half-lifeRapid onset, short half-life- Good for those with rapid post prandial rise in Good for those with rapid post prandial rise in

blood glucoseblood glucose

CombinationsCombinations

Glucovance or diavaceGlucovance or diavace

Glebenclamide and MetforminGlebenclamide and Metformin

AvandametAvandamet

Avandia and MetforminAvandia and Metformin

GLUCOSE ABSORPTION

GLUCOSE PRODUCTION

Metformin Thiazolidinediones

MUSCLE

PERIPHERAL GLUCOSE UPTAKE Thiazolidinediones Metformin

PANCREAS

INSULIN SECRETION Sulfonylureas: Glyburide, Gliclazide, Glimepiride Non-SU Secretagogues: Repaglinide, Nateglinide

ADIPOSE TISSUELIVER

Alpha-glucosidase inhibitors

INTESTINE

Sites of Action of Currently Sites of Action of Currently Available Therapeutic OptionsAvailable Therapeutic Options

Hyperglycaemia Treatment Hyperglycaemia Treatment AlgorithmAlgorithm

Success: satisfactory glycaemiccontrol (usually HbA1c < 7%) and absence of symptoms; continue regular review of control, targets and complications; re-enter algorithm if subequent treatment failure

Failure: success targets not achieved after at least 3 months of particular intervention titrated to maximum tolerated dosage

Blood glucose > 20mmol/l

Diagnosis Type 2 Diabetes

Lifestyle intervention + Metformin

Failure

Add Sulphonylurea or Glitazone Insulin + Metformin

Failure Failure

Add third oral agent Intensify insulin therapy

Failure

Insulin + Metformin + Glitazone

Failure

Titration: oral agents 2 weekly, insulin every 3 days

Metformin: continue at each stage if tolerated and creatinine < 150 micromol/l

Glitazones: combination with insulin unlicensed at present so refer to secondary care if considering final combination

Based on ADA/EASD guideline 2006

ADA/ADA/EASDEASD 20122012

IDFIDF 20122012

Impact of Therapies on A1C Impact of Therapies on A1C LevelsLevels

TherapyTherapy A1C A1C ReductionReduction

Diet and ExerciseDiet and Exercise 0.5 - 2.0%0.5 - 2.0% Sulfonylureas and GlitinidesSulfonylureas and Glitinides 1.0 - 2.0%1.0 - 2.0% MetforminMetformin 1.0 - 2.0%1.0 - 2.0% -Glycosidase Inhibitors-Glycosidase Inhibitors 0.5 - 1.0 %0.5 - 1.0 % ThiazolidinedioneThiazolidinedione 0.5- 1.0%0.5- 1.0% InsulinInsulin >5.0% >5.0%

Nathan, D. Oct 2002. N Engl J Med, Vol. 347, Nathan, D. Oct 2002. N Engl J Med, Vol. 347, No.17No.17

Evidence based Evidence based recommendationsrecommendations

Aspirin: 81-325 mgAspirin: 81-325 mg Smoking: importance of stoppingSmoking: importance of stopping Hypertension: < 130/80 if toleratedHypertension: < 130/80 if tolerated Diuretic: monitor electrolytesDiuretic: monitor electrolytes ACE-I or ARB: monitor K & creatinineACE-I or ARB: monitor K & creatinine CCBCCB’’s: edema, heart block s: edema, heart block Lipids: statins to LDL less than 100 mg/dlLipids: statins to LDL less than 100 mg/dl Rosuvastatin or atorvastatin first choiceRosuvastatin or atorvastatin first choice Ezitimide and low dose statin for myalgiaEzitimide and low dose statin for myalgia Ie, simvastatin 10-20 mg AC supperIe, simvastatin 10-20 mg AC supper

Decisions Regarding Therapy are Decisions Regarding Therapy are Driven by Benefit-Risk Driven by Benefit-Risk

ConsiderationsConsiderations

Disadvantages

Advantages

Insulin TherapyInsulin Therapy

Understanding the Potential Understanding the Potential

Application of New Application of New

Analogue InsulinsAnalogue Insulins

InsulinInsulin

Made in Made in betabeta cells of the cells of the

pancreaspancreas

Moves glucose into cells Moves glucose into cells

Moves potassium into cells Moves potassium into cells

Banting and BestBanting and Best

First Human PatientFirst Human Patient

On Jan. 11, 1922, 14-year-old Leonard Thompson was the first human patient to receive insulin made by Banting and Best.

The initial test failed, causing only slight reductions in blood glucose levels.

A second series of "purified" insulin injections, produced by J.B. Collip, achieved the desired results.

Leonard's blood glucose dropped to normal, and he began to gain weight.

Banting and BestBanting and Best

Marjorie

The Miracle of InsulinThe Miracle of Insulin

Patient J.L., December 15, 1922

February 15, 1923

The Miracle of The Miracle of InsulinInsulin

When to initiate insulinWhen to initiate insulin In people with type 2 diabetes, if individual In people with type 2 diabetes, if individual

treatment goals have not been reached with a treatment goals have not been reached with a

regimen of nutrition therapy, physical activity regimen of nutrition therapy, physical activity

and appropriate oral agents, insulin therapy and appropriate oral agents, insulin therapy

should be initiated to improve glycemic should be initiated to improve glycemic

control.control.

Insulin may be used as initial therapy in Type 2 Insulin may be used as initial therapy in Type 2

Diabetes, especially in cases of marked Diabetes, especially in cases of marked

hyperglycemia (A1C ≥9.0%), and always in hyperglycemia (A1C ≥9.0%), and always in

Gestational DiabetesGestational Diabetes CDA 2003 CPG, Can J Diabetes 27(Suppl 2)

A Failing Pancreas is not A Failing Pancreas is not the Fault of the Patient or the Fault of the Patient or

DoctorDoctor!!

Z Z Z Z Z Z Z Z z z z !

A “pooped-out” pancreas

-Cell Failure is -Cell Failure is ProgressiveProgressive

-Cellfunction

(%)25

100

75

0

50

-12 -10 -6 -2 0 2 6 10 14

Years from diagnosis

Diagnosis

Dashed line shows extrapolation forward and backward from years 0 to 6 based on HOMA data from UKPDS.

Lebovitz H. Diabetes Rev 1999;7:139–153.Holman RR. Diabetes Res Clin Pract 1998;40(suppl):S21-

S25.

Indications Of InsulinIndications Of Insulin

Type 1 DMType 1 DM

Type2 DMType2 DM

Failed oral therapyFailed oral therapy

Acute diabetic complicationsAcute diabetic complications

Stressful conditions ( Surgery )Stressful conditions ( Surgery )

PregnancyPregnancy

Medical illness Medical illness

(infections, infarction, renal and hepatic (infections, infarction, renal and hepatic

insufficiency)insufficiency)

4:004:00

2525

5050

7575

8:008:00 12:0012:00 16:0016:00 20:00 20:00 24:0024:00 4:004:00

BreakfastBreakfast LunchLunch DinnerDinner

Pla

sma

insu

lin

(P

lasm

a in

suli

n (µ U

/ml)

U

/ml)

TimeTime

8:008:00

Physiological Serum Insulin Physiological Serum Insulin Secretion ProfileSecretion Profile

Normal Pancreatic Normal Pancreatic FunctionFunction

Meal Meal Meal

Bolus: At mealtime, insulin is rapidly released in response to food.

Basal: Beta cells secrete small amounts of insulinthroughout the day.

Basal Insulin

Bolus Insulin

•Expected insulin changes during the dayExpected insulin changes during the day •for individuals with a healthy pancreasfor individuals with a healthy pancreas..

*Insulin effect images are theoretical representations and are not derived from clinical trial data.

Rapid Acting InsulinRapid Acting Insulin

Lispro , aspart, glulisine Lispro , aspart, glulisine Onset of actionOnset of action

““15-3015-30”” minutes [may come on in 5 minutes [may come on in 5 minutesminutes……]]

Peak of actionPeak of action1 - 2 hours1 - 2 hours

DurationDuration3 3 –– 4 hours 4 hours

Short Acting InsulinsShort Acting Insulins

Regular (clear so can be given IV)Regular (clear so can be given IV)Onset of actionOnset of action

0.5 to 1 hour0.5 to 1 hour

Peak of actionPeak of action2 2 –– 4 hours 4 hours

Duration of actionDuration of action6 6 –– 8 hours 8 hours

Prefilled Syringe withPrefilled Syringe with Flexible Dosing Flexible Dosing

Lilly Insulin PensLilly Insulin Pens

Intermediate Acting Intermediate Acting InsulinsInsulins

NPH, Lente (chemicals added. Cloudy) :NPH, Lente (chemicals added. Cloudy) :Onset of actionOnset of action

1 1 –– 4 hours 4 hours

Peak of actionPeak of action4 4 –– 12 hours 12 hours

Duration of actionDuration of action18 18 –– 24 hours 24 hours

Once a day insulinOnce a day insulin

Glargine/Lantus or detemir/levemir :Glargine/Lantus or detemir/levemir :

Cannot be diluted or mixed in Cannot be diluted or mixed in

syringe with any other insulinsyringe with any other insulin

Slow, steady releaseSlow, steady release

Daily dosing [usually at bedtime .Daily dosing [usually at bedtime .

Treatment to Target Study: Treatment to Target Study: NPH vs Glargine in DM2 NPH vs Glargine in DM2

patients on OHApatients on OHA Add 10 units Basal insulin at bedtime Add 10 units Basal insulin at bedtime

(NPH or Glargine) (NPH or Glargine) Continue current oral agentsContinue current oral agents Titrate insulin weekly to fasting BG < Titrate insulin weekly to fasting BG <

100 mg/dL100 mg/dL

- if 100-120 mg/dL, increase 2 units- if 100-120 mg/dL, increase 2 units

- if 120-140 mg/dL, increase 4 units- if 120-140 mg/dL, increase 4 units

- if 140-180 mg/dL, increase 6 units- if 140-180 mg/dL, increase 6 units

- if >180 mg/dL, increase 8 units- if >180 mg/dL, increase 8 units

Combination insulinsCombination insulins

70/30 (70% NPH and 30% regular)70/30 (70% NPH and 30% regular)

Fewer injectionsFewer injections

Rotate sites to decrease Rotate sites to decrease

lipodystrophylipodystrophy

The Basal/Bolus Insulin The Basal/Bolus Insulin ConceptConcept

Basal insulin :Basal insulin :

Suppresses glucose production between Suppresses glucose production between

meals and overnightmeals and overnight

40% to 50% of daily needs40% to 50% of daily needs

Bolus insulin (mealtime) :Bolus insulin (mealtime) :

Limits hyperglycemia after mealsLimits hyperglycemia after meals

Immediate rise and sharp peak at 1 hour Immediate rise and sharp peak at 1 hour

10% to 20% of total daily insulin 10% to 20% of total daily insulin

requirement at each meal requirement at each meal

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Glargine

Lispro Lispro Lispro

Aspart Aspart Aspartor oror

Pla

sma

insu

lin

Basal/Bolus Treatment Program withBasal/Bolus Treatment Program withRapid-acting and Long-acting AnalogsRapid-acting and Long-acting Analogs

Starting MDIStarting MDI

Starting insulin dose is based on weight Starting insulin dose is based on weight

0.2 x wgt. in lbs. or 0.45 x wgt. in kg0.2 x wgt. in lbs. or 0.45 x wgt. in kg

Bolus dose (aspart/lispro) = 20% of Bolus dose (aspart/lispro) = 20% of

starting dose at each mealstarting dose at each meal

Basal dose (glargine/NPH) = 40% of Basal dose (glargine/NPH) = 40% of

starting dose at bedtimestarting dose at bedtime

Starting MDI in 80 kgm Starting MDI in 80 kgm personperson

Starting dose = 0.45 x wgt. in kgm. Starting dose = 0.45 x wgt. in kgm.

0.45 x 80 kgm. = 36 units0.45 x 80 kgm. = 36 unitsBolus dose = 20% of starting dose at Bolus dose = 20% of starting dose at

each mealeach meal

20% of 36 units = 7 units ac (tid)20% of 36 units = 7 units ac (tid)Basal dose = 40% of starting dose at Basal dose = 40% of starting dose at

bedtimebedtime

40% of 36 units = 14 units at HS 40% of 36 units = 14 units at HS

Misperceptions About Misperceptions About Insulin TherapyInsulin Therapy

STEP 1STEP 1Add metformin or insulin secretagogueAdd metformin or insulin secretagogue

STEP 2STEP 2If on metformin, add insulin secretagogueIf on metformin, add insulin secretagogueIf on insulin secretagogue, add TZDs or If on insulin secretagogue, add TZDs or

metformin metformin

continued ;continued ;

Pharmacologic TherapyPharmacologic TherapyPossible Treatment StepsPossible Treatment StepsPharmacologic TherapyPharmacologic Therapy

Possible Treatment StepsPossible Treatment Steps

STEP 3STEP 3Add insulinAdd insulin

Switch to insulinSwitch to insulin

Add a thiazolidinedione Add a thiazolidinedione

STEP 4STEP 4Add an oral drug to insulinAdd an oral drug to insulin

Use multiple component insulin Use multiple component insulin

therapytherapy

Pharmacologic TherapyPharmacologic TherapyPossible Treatment StepsPossible Treatment StepsPharmacologic TherapyPharmacologic Therapy

Possible Treatment StepsPossible Treatment Steps

Anticipated Response to Anticipated Response to TreatmentTreatment

Agent Time to Response SMBG Indicator

Secretatogogues Long-acting Rapid-acting

7 – 10 days Immediate

Fasting Postprandial

Metformin 2 – 3 weeks Fasting

Glitazones 6 – 8 weeks AGIs Immediate Postprandial

Insulin Rapid Acting Long-acting

Immediate Immediate

Postprandial Fasting

Future ofFuture ofDiabetes ManagementDiabetes Management

Dosing Tools: The FUTUREDosing Tools: The FUTURE

Monitor sends BG value to pump via Monitor sends BG value to pump via radio waves : No transcribing error radio waves : No transcribing error

Enter carbohydrate intake into pumpEnter carbohydrate intake into pump ““Bolus WizardBolus Wizard”” calculates suggested calculates suggested

dose dose

Paradigm Link™

Paradigm 512™) ) ) ) ) ) ) ) ) )

) ) )

Bolus Wizard Calculator : meter-Bolus Wizard Calculator : meter-enteredentered

Pump Infusion Pump Infusion SetsSets

CGMS

GlucoWatchGlucoWatch®® Biographer Biographer

GLUCOSE MONITORING GLUCOSE MONITORING SYSTEMS - TelemetrySYSTEMS - Telemetry

““Real timeReal time”” glucose glucose readingsreadings

Wireless Wireless communication communication from sensor to from sensor to monitormonitor

High and low High and low glucose alarmsglucose alarms

FDA panel pendingFDA panel pending

Consumer Product

FreeStyle NavigatorFreeStyle NavigatorTheraSense Continuous Glucose TheraSense Continuous Glucose

MonitorMonitor

• Patient Inserted Sensor

• “On demand” glucose and trend arrow

• User-configurable Low Glucose and High Glucose Alarms

• Projected alarms give advance warning of glucose excursions

• Integrated FreeStyle blood glucose meter

• (3) BG calibrations for each 3-day sensor

• Wireless sensor-to-Meter path (10 foot operating range)

Pulmonary InsulinPulmonary Insulin

Implantable Implantable PumpPump

Average Average HbAHbA1c1c 7.1% 7.1%

HypoglycemHypoglycemicic events events reduce to 4 reduce to 4 episodes per episodes per 100 pt-years100 pt-years

Implantable Insulin Pump Placement

Implantable Biomechanical Beta Implantable Biomechanical Beta CellCell

Decisions Regarding Therapy are Decisions Regarding Therapy are

Driven by Benefit-Risk ConsiderationsDriven by Benefit-Risk Considerations

DisadvantagesAdvantages