lecture teraphy diabetes

7/29/2019 lecture teraphy diabetes

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Slide 1

Insulin Initiation and Monitoring

Lecture:

30 minutes


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The Usage of InsulinLecture

Main Learning Points

Understand the insulin mechanism ofaction and its relationship to bloodglucose

Understand the current usage ofInsulin in Indonesia

Understand the different types ofinsulin, when to use insulin and thedifferent insulin regiments

Understand the relationship betweeninsulin dosage and blood glucose

measurements

Slide 2


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3

ADA/EASD consensus algorithm

At diagnosis:Lifestyle +Metformin

Lifestyle + Metformin+ Basal insulin

Lifestyle + Metformin

+ Sulfonylurea

Lifestyle + Metformin+ Intensive insulin

Tier 1:well-validated therapies

STEP 1 STEP 2 STEP 3

Call to action if HbA1c is 7%

Tier 2:Less well validatedtherapies

Lifestyle + Metformin+ PioglitazoneNo hypoglycaemiaOedema/CHFBone loss

Lifestyle + Metformin

+ Pioglitazone+ Sulfonylurea

Lifestyle + metformin+ Basal insulin

Lifestyle + metformin+ GLP-1 agonistNo hypoglycaemiaWeight loss

Nausea/vomitingNathan DM, et al. Diabetes Care2009;32 193-203.


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Slide 5

Treatment therapies for Type 2 diabetesWhen and How to start treatment

Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.

Lifestyle +Metformin

+-other OADor GLP-1agonists

HbA1c7.0%

Basal

BasalInsulin

PremixInsulin

Basal +Bolus

Insulin

START TREATMENT OAD TREATMENT START INSULIN INSULIN INTENSIFICATION


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Slide 6

Insulin remains the most efficacious glucoselowering agent

Decrease in HbA1c: Potency of monotherapy

Hb

A1c

%

Nathan et al., Diabetes Care 2009;32:193-203.


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Slide 7

What is Insulin

After a meal carbohydratesare digested and enter theblood system, which transportsthem to the cells

INSULINis needed

for glucose uptakeand storage

Some cells (those ofmuscles and fat tissue) needassistance to have bloodsugar enter into them and tobe used for energy production

The liver needs assistance tostart the process of storage ofglucose in the form ofglycogen


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Slide 8

Insulin secretion is delayed and blunted inType 2 Diabetes

Adapted from: Polonsky KS, et al. N Engl J Med. 1996 Mar 21;334(12):777-783.

Normal

Type 2 diabetes

Time (24 hours)

800

600

400

200

0

InsulinSecretion

(pmol/min)

Meal Meal Meal

The goal of insulin therapy is to restore normal insulinsecretion

Gap that needsto be covered


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Slide 9

How Insulin acts in the body

Insulin

Insulin binds to the insulin receptors on the cell membranes of thetarget cells in the liver, muscles and adipose tissue

LiverAdiposeTissue

Muscles

Inhibits glucoseproduction Promotes formation ofglycogen and its storage

Promotes uptake andutilization of glucose

Promotes uptake ofglucoseSuppresses lipolysis


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Slide 10

Maintain blood glucose levels between 80-140 mg/dl:

1. By promoting uptake of glucose by target cells

subsequent breakdown into energy (glycolysis)

storage as glycogen (glycogenesis)

2. By inhibiting new glucose formation from non carbohydrate

source (gluconeogenesis) or production of glucose by liver

3. By suppressing lipolysis (breakdown of fat)

Objectives of Insulin Treatment


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Slide 11

Most people with type 2 diabetes will, in time,need insulin therapy because

Wright A et al. Diabetes Care 2002;25:3306

(Patients treated with chlorpropramide)

Years from start of UKPDS

Patientsreq

uiring

additionalinsulin(%)

0

10

20

30

40

50

60

1 2 3 4 5 6


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The Natural History of Type 2 Diabetes

Progressive decline of-cell function


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Slide 13

diabetes Patients will eventually fail on OADs

6.2% upper limit of normal range

MedianHbA1c(%

)

UKPDS

6

7

8

9

Years from randomisation

Conventional*

GlibenclamideMetforminInsulin

2 4 6 8 100

7.5

8.5

6.5

Recommendedtreatment

target 15 mmol/L; ADA clinical practicerecommendations. UKPDS 34, n=1704

UKPDS 34. Lancet 1998:352:85465; Kahn et al (ADOPT). NEJM 2006;355(23):242743


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Slide 14

Insulin can be initiated at any time

Traditionally, insulin has been reserved as the last line oftherapy

However, considering the benefits of normal glycemic

status, Insulin can be initiated earlier and as soon as

possible

InadequateLifestyle

+ 1 OAD + 2 OAD + 3 OAD

INITIATE INSULIN


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Slide 15

IMS Full year 2011 Data. CIA World Factbook

29

67

92

Malaysia

Thailand

Vietnam

Philippines 104

Bangladesh 161

Indonesia 248

Population

Million People Mega Units

Total Insulin Used

2,029

3,258

417

982

3,097

694

70

49

5

9

19

3

Insulin Usage per Capita

Insulin Units / Capita

but Insulin usage is currently very low inIndonesia compared to its neighbouring countries


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Absolut Indication

Type 1 Diabetes

Relative Indication

Patients who fail to reach target with OAD optimal dosage

(3-6 months)

Type 2 DM Outpatient with:Pregnancy not controlled with diet

Infected Diabetes Feet

High Blood Glucose Fluctuations

Repeated History of Ketoacidosis

History of Pankreotomi

Besides the above, there are a number of conditions

where insulin is required, e.g. chronic liver, kidney

function interruption and high dosage steroid therapy

Slide 16

Insulin Indications


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Slide 17

Three Types of InsulinSchematic Representation Only

GIR(mg/kg/min)

Time (h)

0 4 8 12 16 20 24

BASAL INSULIN

PRE-MIX INSULIN

FAST-ACTING INSULIN


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Slide 18

Three Types of Insulin

1. Hompesch M. Diabetes Obes Metab 2006; 8:568; 2. Weyer et al. Diabetes Care 1997;10:16121614.; 3. 1. Heinemann et al.Diabetes Care. 1998;21:19104

Basal Insulin provides asteady concentration of

insulin in the bloodstreamover 24 hours. Initially,basal insulin should be

given at 10 units per dayat night time or in the

morning1

Time (h)

Premixed insulins containa mixture of rapid-actingand intermediate-acting

insulin in a fixedcombination to provide

coverage of prandial andbasal insulin

requirements2

Fast-acting insulinsinclude single amino acidreplacement that reduce

their ability to self-associate into dimers and

hexamers. This meansthat they are quickly

absorbed into thebloodstream, following

subcutaneous injection.3

FAST-ACTINGPRE-MIXBASAL

GIR(mg/kg/min)

0 8 16 20 244 12

Time (h)

GIR(mg/kg/min)

0 8 16 20 244 12

Time (h)

GIR(mg/kg/min)

0 8 16 20 244 12


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Pharmacokinetics of the different Types of Insulinavailable in Indonesia

Slide 19

Profile

Type of Insulin Insulin Name Onset(hours) Peak(hours)

Fast-acting Analogue Insulin Insulin Aspart (NovoRapid) 0.2 0.5 0.5 - 2

Insulin Lispro (HumaLog) 0.2 0.5 0.5 - 2

Insulin Gluisine (Apidra) 0.2 0.5 0.5 - 2

Fast-acting Human Insulin ActRapid 0.5 1 0.5 - 1

Humulin R 0.5 1 0.5 - 1

Intermediate Human Insulin Insulatard 1.5 4 4 - 10

Humulin N 1.5 4 4 - 10

Long-acting Analogue Insulin Insulin Detemir (Levemir) 1 - 3

Insulin Glargine (Lantus) 1 - 3

Pre-mix Analogue Insulin Insulin Aspart (NovoMix) 0.2 0.5 1 - 4

Insulin NPL (HumaLog) 0.2 0.5 1 - 4

Pre-mix Human Insulin Mixtard 0.5 1 3 - 12

Humulin Mix 0.5 1 3 - 12

Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34


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Slide 20

Basic Insulin Start Recommendation

If Fasting Blood Glucose is elevated Start with Basal Insulin

If both Fasting and Prandial BloodGlucose are elevated

Start with Premix Insulin OR add Basal Insulin to OAD

OR Start Basal/Bolus Therapy

Source: ADA Guidelines

N l I li S i


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B DL HS

Insulin

Effect

Bolus Insulin

Basal Insulin

Endogenous Insulin

B, breakfast; L, lunch; D, dinner; HS, bedtime.Adapted from:

1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.

Normal Insulin Secretion

The Basal-Bolus Insulin Concept

Time of Administration


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Start one injection long-acting analogue

Insulin after oral failure

Insulin by night tablet(s) by day


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Oral


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Starting Basal Insulin

Start dose around 10

Ajust Long-acting analogue dose by fasting

SMBG

Increaseinsulin dose every 3 to 5days asneeded (2 4 )

Treat to target basal (fasting)< 130 mg%)


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Slide 25

Insulin Titration schemesBasal and Fast-Acting Insulin

Fasting Blood GlucoseContent (mg/dl)

Basal Insulin Titration

180 mg/dl Increase dosage 4 units per 3 days

Once titrated, continue to monitor HbA1c every 3 months

BASALINSULIN

Fasting Blood GlucoseContent (mg/dl) Fast-acting Insulin Titration

Start with 4 units / day Increase by 2 units every 3 daysuntil target is reached

When starting Fast-acting Insulin, secretagogues should bediscontinued

FAST-

ACTINGINSULIN

Source: KONSENSUS: Insulin Treatment 2011

Slid 26


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Slide 26

Insulin Treatment OptimizationHow to Optimize Treatment after Initiation

Basal Insulin OnlyUsually with OAD

Start with Basal Insulin10u / daily with mealor before bedtime.Same injection timeevery day

If glycemic target is notreached within 2-3 months,intensify Insulin treatment

If glycemic target is notreached titrate according toBasal Titration Scheme

Basal Insulin OnlyUsually with OAD

Basal with

PrandialUsually keep OAD

Premix InsulinUsually keep OAD

Basal BolusUsually keep OAD

Add Prandial startingwith 4u / day either

once or twice-daily andtitrate accordingly

Switch to Premix twice-daily.Start with equal basal dose,but give 50% per injection

and titrate accordingly

Switch to Basal Bolus(3 daily prandial) start

with 4u / day andtitrate accordingly)

Source: PERKENI Insulin Guidelines 2011


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The Basal Plus Concept

When basal insulin added to oral agentsdoes not sustain target A1c

Add mealtime insulin stepwise: Basal +12nd injection before the largest

meal Basal +2 3rd injection before 2nd largest

meal

Basal +3 4th injection before 3rd meal

(basal bolus)

Meal related insulin (short-/rapid-acting insulin)


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Add mealtime insulin stepwise: Basal +1 2nd injection before the largest

meal

Basal +2 3rd injection before 2nd largest

meal Basal +3 4th injection before 3rd meal

(basal bolus)



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Add mealtime insulin stepwise: Basal +1 2nd injection before the largest

meal

Basal +2 3rd injection before 2nd largest

meal Basal +34th injection before 3rd meal

(basal bolus)



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Basal + 3 (Basal - Bolus)


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The New Paradigm of Diabetes

Treatment

Aggressive treatment driven by target

(AIC < 7%)

Early combination

Oral agents oral agents

Oral agents insulin

Early and aggressive treatment withinsulin

Slide 34


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Slide 34

Primarily one type of Insulin device available in Indonesia

Disposable disposed ofonce empty

Less teaching time required

Primarily plastic

Easy and Convenient forPatients

Prefilled devices

Slide 35


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Slide 35

WE WILL COVER HOW TO START A

PATIENT ON INSULIN ANDINJECTION TECHNIQUES IN ASEPARATE WORKSHOP

lecture teraphy diabetes

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