Post on 04-Apr-2018
transcript
7/29/2019 lecture teraphy diabetes
1/35
Slide 1
Insulin Initiation and Monitoring
Lecture:
30 minutes
7/29/2019 lecture teraphy diabetes
2/35
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
7/29/2019 lecture teraphy diabetes
3/35
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.
7/29/2019 lecture teraphy diabetes
4/35
7/29/2019 lecture teraphy diabetes
5/35
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
7/29/2019 lecture teraphy diabetes
6/35
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.
7/29/2019 lecture teraphy diabetes
7/35
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
7/29/2019 lecture teraphy diabetes
8/35
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
7/29/2019 lecture teraphy diabetes
9/35
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
7/29/2019 lecture teraphy diabetes
10/35
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
7/29/2019 lecture teraphy diabetes
11/35
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
7/29/2019 lecture teraphy diabetes
12/35
The Natural History of Type 2 Diabetes
Progressive decline of-cell function
7/29/2019 lecture teraphy diabetes
13/35
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
7/29/2019 lecture teraphy diabetes
14/35
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
7/29/2019 lecture teraphy diabetes
15/35
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
7/29/2019 lecture teraphy diabetes
16/35
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
7/29/2019 lecture teraphy diabetes
17/35
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
7/29/2019 lecture teraphy diabetes
18/35
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
7/29/2019 lecture teraphy diabetes
19/35
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
7/29/2019 lecture teraphy diabetes
20/35
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
7/29/2019 lecture teraphy diabetes
21/35
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
7/29/2019 lecture teraphy diabetes
22/35
Start one injection long-acting analogue
Insulin after oral failure
Insulin by night tablet(s) by day
7/29/2019 lecture teraphy diabetes
23/35
Oral
7/29/2019 lecture teraphy diabetes
24/35
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%)
7/29/2019 lecture teraphy diabetes
25/35
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
7/29/2019 lecture teraphy diabetes
26/35
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
7/29/2019 lecture teraphy diabetes
27/35
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)
7/29/2019 lecture teraphy diabetes
28/35
7/29/2019 lecture teraphy diabetes
29/35
The Basal Plus Concept
When basal insulin added to oral agentsdoes 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)
7/29/2019 lecture teraphy diabetes
30/35
7/29/2019 lecture teraphy diabetes
31/35
The Basal Plus Concept
When basal insulin added to oral agentsdoes 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 +34th injection before 3rd meal
(basal bolus)
Meal related insulin (short-/rapid-acting insulin)
7/29/2019 lecture teraphy diabetes
32/35
Basal + 3 (Basal - Bolus)
7/29/2019 lecture teraphy diabetes
33/35
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
7/29/2019 lecture teraphy diabetes
34/35
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
7/29/2019 lecture teraphy diabetes
35/35
Slide 35
WE WILL COVER HOW TO START A
PATIENT ON INSULIN ANDINJECTION TECHNIQUES IN ASEPARATE WORKSHOP