Slide 1

Lecture:
Insulin Initiation and Monitoring

30 minutes

Slide 2

The Usage of Insulin Lecture Main Learning Points

Understand the insulin mechanism of action and its relationship to blood glucose Understand the current usage of Insulin in Indonesia Understand the different types of insulin, when to use insulin and the different insulin regiments Understand the relationship between insulin dosage and blood glucose measurements

ADA/EASD consensus algorithm

Tier 1:
well-validated therapies Call to action if HbA1c is 7% Lifestyle + Metformin + Basal insulin At diagnosis: Lifestyle + Metformin Lifestyle + Metformin + Intensive insulin

Lifestyle + Metformin + Sulfonylurea

STEP 2 STEP 3

STEP 1

Tier 2:
Less well validated therapies Lifestyle + Metformin + Pioglitazone
No hypoglycaemia Oedema/CHF Bone loss

Lifestyle + Metformin + Pioglitazone + Sulfonylurea

Lifestyle + metformin + GLP-1 agonist

No hypoglycaemia Weight loss Nausea/vomiting
Nathan DM, et al. Diabetes Care 2009;32 193-203.

Lifestyle + metformin + Basal insulin

Slide 5

Treatment therapies for Type 2 diabetes

When and How to start treatment

START TREATMENT

OAD TREATMENT

START INSULIN

INSULIN INTENSIFICATION

Lifestyle + Metformin

+-other OAD or GLP-1 agonists

Basal
Basal Insulin Premix Insulin

Basal + Bolus Insulin

HbA1c 7.0%

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

Slide 6

Insulin remains the most efficacious glucose lowering agent

Decrease in HbA1c: Potency of monotherapy

HbA1c %
Nathan et al., Diabetes Care 2009;32:193-203.

Slide 7

What is Insulin

After a meal carbohydrates are digested and enter the blood system, which transports them to the cells

Some cells (those of muscles and fat tissue) need assistance to have blood sugar enter into them and to be used for energy production

INSULIN is needed for glucose uptake and storage

The liver needs assistance to start the process of storage of glucose in the form of glycogen

Slide 8

Insulin secretion is delayed and blunted in Type 2 Diabetes

The goal of insulin therapy is to restore normal insulin secretion
800

Meal

Meal

Meal

Gap that needs to be covered Normal

600

Type 2 diabetes

Insulin Secretion 400 (pmol/min)

200

Time (24 hours)

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

Slide 9

How Insulin acts in the body

Insulin

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

Liver

Muscles

Adipose Tissue

Inhibits glucose production Promotes formation of glycogen and its storage

Promotes uptake and utilization of glucose

Promotes uptake of glucose Suppresses lipolysis

Slide 10

Objectives of Insulin Treatment

Maintain blood glucose levels between 80-140 mg/dl: 1. By promoting uptake of glucose by target cells 2. subsequent breakdown into energy (glycolysis) storage as glycogen (glycogenesis)

By inhibiting new glucose formation from non carbohydrate source (gluconeogenesis) or production of glucose by liver

3.

By suppressing lipolysis (breakdown of fat)

Slide 11

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

60

Patients requiring additional insulin (%)

50 40 30 20 10 0 1 2 3 4 5 6

Years from start of UKPDS (Patients treated with chlorpropramide)

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

The Natural History of Type 2 Diabetes

Progressive decline of -cell function

Slide 13

diabetes Patients will eventually fail on OADs

UKPDS
9 8.5
Median HbA1c (%) 8

Conventional* Glibenclamide Metformin Insulin

ADOPT
8

Rosiglitazone Metformin Glibenclamide

7.5

7.5 7 Recommended treatment target <7.0% 6.2% upper limit of normal range 0 2 4 6 8 Years from randomisation 10

6.5 6

6.5

6 0 1 2 3 Time (years) 4 5

*Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L; ADA clinical practice recommendations. UKPDS 34, n=1704

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

Slide 14

Insulin can be initiated at any time Traditionally, insulin has been reserved as the last line of therapy However, considering the benefits of normal glycemic status, Insulin can be initiated earlier and as soon as possible
Inadequate Lifestyle + 1 OAD + 2 OAD + 3 OAD

INITIATE INSULIN

Slide 15

but Insulin usage is currently very low in Indonesia compared to its neighbouring countries
Population Indonesia Bangladesh Philippines Vietnam Thailand Malaysia 104 161 982 417 3,258 2,029 Mega Units Insulin Units / Capita 248 Total Insulin Used 694 3,097 Insulin Usage per Capita

3 19 9 5 49 70

92 67 29

Million People

IMS Full year 2011 Data. CIA World Factbook

Slide 16

Insulin Indications
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 17

Three Types of Insulin

Schematic Representation Only

BASAL INSULIN PRE-MIX INSULIN

GIR (mg/kg/min)

FAST-ACTING INSULIN

12
Time (h)

16

20

24

Slide 18

Three Types of Insulin

BASAL
GIR (mg/kg/min)
GIR (mg/kg/min)

PRE-MIX
GIR (mg/kg/min)

FAST-ACTING

0 4

8 12 16 20 24
Time (h)

0 4

8 12 16 20 24
Time (h)

0 4

8 12 16 20 24
Time (h)

Basal Insulin provides a steady concentration of insulin in the bloodstream over 24 hours. Initially, basal insulin should be given at 10 units per day at night time or in the morning1

Premixed insulins contain a mixture of rapid-acting and intermediate-acting insulin in a fixed combination to provide coverage of prandial and basal insulin requirements2

Fast-acting insulins include single amino acid replacement that reduce their ability to selfassociate into dimers and hexamers. This means that they are quickly absorbed into the bloodstream, following subcutaneous injection.3

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

Slide 19

Pharmacokinetics of the different Types of Insulin available in Indonesia

Profile

Type of Insulin
Fast-acting Analogue Insulin

Insulin Name
Insulin Aspart (NovoRapid) Insulin Lispro (HumaLog) Insulin Gluisine (Apidra)

Onset (hours) 0.2 0.5 0.2 0.5 0.2 0.5 0.5 1 0.5 1 1.5 4 1.5 4 1-3

Peak (hours) 0.5 - 2 0.5 - 2 0.5 - 2 0.5 - 1 0.5 - 1 4 - 10 4 - 10

Fast-acting Human Insulin

ActRapid Humulin R

Intermediate Human Insulin

Insulatard Humulin N

Long-acting Analogue Insulin

Insulin Detemir (Levemir)

Insulin Glargine (Lantus)

Pre-mix Analogue Insulin Insulin Aspart (NovoMix) Insulin NPL (HumaLog)

1-3
0.2 0.5 0.2 0.5 1-4 1-4

Pre-mix Human Insulin

Mixtard
Humulin Mix

0.5 1
0.5 1

3 - 12
3 - 12

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

Slide 20

Basic Insulin Start Recommendation

If Fasting Blood Glucose is elevated

Start with Basal Insulin

If both Fasting and Prandial Blood Glucose are elevated

Start with Premix Insulin OR add Basal Insulin to OAD OR Start Basal/Bolus Therapy

Source: ADA Guidelines

Normal Insulin Secretion The Basal-Bolus Insulin Concept

Endogenous Insulin

Bolus Insulin

Insulin Effect

Basal Insulin

D
Time of Administration

HS

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.

Insulin after oral failure

Start one injection long-acting analogue

Insulin by night tablet(s) by day

Oral

Starting Basal Insulin

Start dose around 10 Ajust Long-acting analogue dose by fasting SMBG Increase insulin dose every 3 to 5 days as needed (2 4 ) Treat to target basal (fasting)< 130 mg%)

Slide 25

Insulin Titration schemes Basal and Fast-Acting Insulin

Fasting Blood Glucose Content (mg/dl) <70 mg/dl Basal Insulin Titration Reduce dosage with 2 units Maintain dosage Increase dosage 2 units per 3 days Increase dosage 4 units per 3 days

BASAL INSULIN

70-130 mg/dl 130-180 mg/dl >180 mg/dl

Once titrated, continue to monitor HbA1c every 3 months

FASTACTING INSULIN

Fasting Blood Glucose Content (mg/dl) Start with 4 units / day

Fast-acting Insulin Titration

Increase by 2 units every 3 days until target is reached

When starting Fast-acting Insulin, secretagogues should be discontinued

Source: KONSENSUS: Insulin Treatment 2011

Slide 26

Insulin Treatment Optimization

How to Optimize Treatment after Initiation

Start with Basal Insulin 10u / daily with meal or before bedtime. Same injection time every day

Basal Insulin Only Usually with OAD

If glycemic target is not reached titrate according to Basal Titration Scheme

Basal Insulin Only Usually with OAD

If glycemic target is not reached within 2-3 months, intensify Insulin treatment
Premix Insulin Usually keep OAD Basal with Prandial Usually keep OAD Basal Bolus Usually keep OAD

Switch to Premix twice-daily. Add Prandial starting Start with equal basal dose, with 4u / day either but give 50% per injection once or twice-daily and and titrate accordingly titrate accordingly
Source: PERKENI Insulin Guidelines 2011

Switch to Basal Bolus (3 daily prandial) start with 4u / day and titrate accordingly)

The Basal Plus Concept

When basal insulin added to oral agents does not sustain target A1c 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)
Meal related insulin (short-/rapid-acting insulin)

The Basal Plus Concept

When basal insulin added to oral agents does not sustain target A1c 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)
Meal related insulin (short-/rapid-acting insulin)

The Basal Plus Concept

When basal insulin added to oral agents does not sustain target A1c 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)
Meal related insulin (short-/rapid-acting insulin)

Basal + 3 (Basal - Bolus)

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 with insulin

Slide 34

Primarily one type of Insulin device available in Indonesia

Prefilled devices

Disposable disposed of once empty Less teaching time required Primarily plastic Easy and Convenient for Patients

Slide 35

WE WILL COVER HOW TO START A PATIENT ON INSULIN AND INJECTION TECHNIQUES IN A SEPARATE WORKSHOP