Initiation and Titration o Insulin Neurotransmitter in ... · Subcutaneous insulin injection for...

Initiation and Titration of Insulin

in Outpatient Setting

Dr. WS Chow & Ms. Karen Wong

Department of Medicine

Queen Mary Hospital

Decreased glucose uptake

Neurotransmitter

dysfunction Decreased incretin

effect

Increased lipolysis

Increased glucagon

secretion

Decreased insulin

secretionIncreased HGP

Increased glucose

reabsorbtion

Adipose

tissue

Liver

Muscle

Pancreas

Hyperglycemia

Type 2 Diabetes: The Ominous Octet

Intestine

BrainKidney

β and α-cell dysfunction

Adapted from R.DeFronzo

M Prentki. J Clin Invest. 2006; 116(7): 1802–1812.

Glycaemic Control Deteriorates across Time

UKPDS 34 Study. Lancet. 1998:352:854–865.

FPG = fasting plasma glucose; UKPDS = United Kingdom Prospective Diabetes Study

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

Me

dia

n H

bA

1c

(%)

6

7

8

9

Years from randomisation

2 4 6 8 100

7.5

8.5

6.5

Recommended

treatment target < 7.0%†

Conventional* (n = 411)

Glibenclamide (n = 277)

Insulin (n = 409)

Metformin (n = 342)

UKPDS 34 Study

Who will benefit from insulin therapy ?

• Type 1 DM• Life-saving, hence essential

• Type 2 DM • with inadequate glycaemic control

• with pancreatic insufficiency• UKPDS reveals annual failure rate of 7 %

• with decompensation eg sepsis, AMI

• Acute hyperglycaemia / hyperosmolar coma

• with significant renal impairment

• Gestational DM

Standard of Medical Cares in diabetes 2015

SE Inzucchi et al. Diabetes Care 2015;38:140–149

Sharing of

DM Management in HKWC

Case Illustrations – Case 1 & 2

Patient-Identified Barriers to Insulin

Therapy

personal failure

not effective

painful

causes complications

or death

too expensive

Change in lifestyle

Fear of hypoglycemia weight gain

Diabetes Care. 2005 Oct;28(10):2543-5.

Clinical Diabetes Vol 25(1) 2007: 36-38

28.2% reported being unwilling

to take insulin if prescribed

Overcoming Barriers to Insulin Initiation

Initiate prescribed

Insulin

Insulin Self-Management

Training

Shared Decision Making

Better provider communication regarding risks

Karter, el tal (2010) Diabetes Care, Vol 33, no. 4


Enhancing Positive Beliefs:

• Health Care Provider:

recommend insulin therapy and explain risks

• Good short term outcomes:

lower blood glucose, improve symptoms, feel better

• Long term benefits:

prolonged life, reduce risk of complications

• Natural disease progression

• Easy insulin delivery devices


• Refer patients to diabetes educator for Diabetes Self-Management Education (DSME)

motivate patient, education, insulin dose titration

• Provide ongoing self-management supportsustain gains in diabetes self-care behaviours

• Adopt successful strategies follow up of blood glucose (in person/telephone)

• Address emotional issues thoughts and feelings about insulin

Funnell (2007) Overcoming Barriers to the Initiation of Insulin Therapy

Clinical Diabetes vol 25, No. 1

Sharing of

DM Management in HKWC

Case Illustrations – Case 3 & 4

Insulin secretion in T2 diabetes

Polonsky KS et al. NEJM 1996 334 (12):777-83

0 2 4 6 8 10 12 14 16 18 20 22 24

Hours

Pla

sma

In

suli

n L

eve

ls

Human Insulins and Analogues

Aspart, Lispro, Apidra (4 to 6 hrs)

Regular (6 to 10 hrs)

NPH (12 to 20 hrs)

Detemir, Glargine (20 to 26 hrs)

Basal Insulins

Prandial Insulins

Insulin Therapy in Clinical Practice

General Principles

• Start Low and Go slow

• Titration Frequency – Ideal : twice weekly – Practical : depend on manpower esp. diabetic nurse

specialist, every 1-2 weeks seems reasonable

• Don’t titrate up if hypoglycemia (unexplained) occurs

• Intensify treatment regimens if control (HbA1c) remains suboptimal in 6 months

• No limitation on total insulin dose – Workup for causes of insulin resistance if >1.5 u/kg

Insulin Therapy in Clinical Practice

• Insulin therapy ought to be tailor-made to suit individual’s needs, taking into account :

• Patient’s lifestyle & habits

• Glycaemic profile

• Education and independence

• Motivation and compliance

• Age, existing complications and risks of hypoglycaemia

Adapted from Hirsch I, et al. Clin Diabetes 2005;23:78–86.

Time of day (hours)

400

300

200

100

0

06.00 06.0010.00 14.00 18.00 22.00 02.00

Plasm

a glucose (mg/dl)

Normal

Meal Meal Meal

20

15

10

5

0

Plasm

a glucose (m

mol/l)

Treating fasting hyperglycaemia lowers the entire 24-hour plasma glucose profile

Hyperglycaemia due to an increase in fasting glucose

T2DM

• Less insulin required

• Less weight gain

• More acceptable to patient

Initiation and Titration with

Daily Dose Basal Insulin

25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time

DinnerLunchBreakfast

NPH

Detemir

/Glargine

25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


NPH

Initiation : 10 U or 0.2 U/kg

0.1U/kg for patients with risk for

hypoglycemia

Detemir

/Glargine



25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


NPH



hypoglycemia

Target :

Pre-breakfast BG

Target 4-7 mmol/L

Detemir

/Glargine



25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


NPH



hypoglycemia

Target :

Pre-breakfast BG

Target 4-7 mmol/L

Titration :

< 4 => reduce dose by 2-4 units

> 4-7 => maintain current dose

> 7 => increase by 2 units

> 10 => increase by 4 units

Watch for nocturnal hypoglycemia

If happens, consider basal insulin

analogue

Detemir

/Glargine



Riddle M, et al. Diabetes Care 2003;26(11):3080–3086

Treat-to-Target: Insulin Glargine reduces the risk of hypoglycaemia compared

with NPH when initiating insulin in Type 2 diabetes

N: 756 insulin-naïve T2DM patients, added insulin Glargine or NPH daily for 24-week

Similar glycaemic control

Less hypoglycaemia: 21–48% lower with Insulin Glargine

Almost 25% more patients (Insulin Glargine) achieved HbA1c target of 7% without documented

nocturnal hypoglycaemia, than patients treated with NPH

Teaching Insulin Injection

International Labeling for Insulin

http://www.idf.org/insulin-colour-code

Jun 2015

Dept of Pharmacy

QMH HKWC

Insulin Storage

• All unopened insulin

should be kept refrigerated 2-8ºC until the expiry date

• Opened insulin

can be kept at room temp < 25 to < 30ºC for 4 to 6 weeks

• Insulin should be stored according to the manufacturers’ instructions

Injection Devices: Syringes

• Insulin syringes: 0.3, 0.5 and 1ml capacity

• Needle length: 6, 8, 12.7mm

• Increment: 1 or 2 units / division

Injection Devices: Insulin Pen

Disposable Insulin Pen

4mm 5mm 8mm 12.7mm

Reusable Injection Pen

Pen Needles

Insulin Pump

Pump Accessories

Evidence-based Clinical Guideline:

Subcutaneous insulin injection for people

with Diabetes Mellitus

(www.ahkdn.com) The Association of Hong Kong Diabetes Nurses 2014/1 (English); 2015/11(Chinese)

Preparation for insulin injection

• Ensure cleanliness of the skin

• Cloudy insulin must be well mixed before injection

• Air should be removed before injection

• Pen devices must be primed before each injection

Injection Technique

• Insulin injection should be made into subcutaneous tissue

• Intramuscular injection is not recommended for routine injection

• Adults and children using an 8mm needle should lift a skin fold and inject at a 45 to 90 degree angle to the skin surface

• The desired length of a pen needle should be individually defined within the range of 4, 5, 6mm.

Injection Site Pinching

Fold the top layers

Not pull muscle into the fold

Inject straight into the skin fold or at an angle

to avoid injecting into the muscle

Injection Sites

• Arm: Upper lateral and posterior aspect

• Abdomen: Avoiding umbilicus

• Thigh: Upper lateral and anterior aspect

• Buttock: Upper lateral quadrant

When combination of bedtime

insulin daytime & anti-DM drugs fails

• HbA1c > 7% and FBG at

goal

• Basal Insulin dose

>0.5U/kg

Sequential Insulin Strategies

v. 2013….SE Inzucchi et al. Diabetes Care 2015;38:140–149

25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


Initiation :

Total dose transfer

2/3 pre-breakfast

(PB)

1/3 pre-dinner

(PD)

Monitoring PB BG determine PD dose

PD BG determine PB dose

Target 4-7 mmol/L

Dose Titration reduce by 2-4 units

- 4-7 => maintain current

dose

�7 => increase by 2 units

�10=>increase by 4 units

Change from daily Basal to Twice daily

Basal Insulin/Premixed human insulin

Humulin N , Protaphane HM

Humulin 70/30, Mixtard 30HM

Off SUs

25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


Initiation :

Total dose transfer

2/3 pre-breakfast

(PB)

1/3 pre-dinner

(PD)



Target 4-7 mmol/L

Dose Titration reduce by 2 units


dose



HYPOGLYCEMIA

Humulin N , Protaphane HM

Humulin 70/30, Mixtard 30HM

Change from daily Basal to Twice daily

Basal Insulin/Premixed human insulin

Change from Premixed human to Premixed

insulin analogues before breakfast & dinner

25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


e.g. Humulin 70/30 =>Humalog Mix,

Mixtard 30HM to NovoMix

Initiation :

Total dose transfer 1:1 ratio



Target 4-7 mmol/L



dose



25

75

50

4:00 8:00 12:00 16:00 20:00 24:00 4:00

Pla

sma

In

suli

n (

uU

/mL)

Time


e.g. Humalog mix

75/25, Humalog mix

50/50, Novomix 30

Initiation :

Total dose transfer 1/2 pre-breakfast (PB) 1/2 pre-dinner (PD)



Target 4-7 mmol/L



dose



Change from Premixed human to Premixed

insulin analogues before breakfast & dinner

Premixed Human insulin vs Premixed

Analogue

Adapted from Rehan Qayyum et al. Ann Int Med. 2008;149:549-559

Strength of

evidence

Pre-mix insulin analogues vs

Pre-mix human insulin

Fasting glucose level Moderate Suggests similar effectiveness

Posprandial glucose

level

High Favors insulin analogues

HbA1c High Suggests similar effectiveness

Hypoglycemia High Suggests similar effectiveness

Weight gain Moderate Suggests similar effectiveness

CVD mortality and

morbidity

Low Cannot make a conclusion

Trouble Shooting for Insulin Injection

• Skin Problem of Injection Site

Lipohypertrophy

Lipoatrophy

Bleeding and Bruising

Local Allergy

• Glucose Monitoring:

Hypoglycaemia / hyperglycaemia

• Needle Phobia

• Adherence Problem

Skin Problem of Injection Site

Lipoatrophy(Loss of fat)

Lipohypertrophy(Lumps at injection site)

Lipodystrophy

Skin Problem of Injection Site

Right Thigh Left Thigh

Bleeding and Bruising

Reuse of Injection Needle

• Avoid reuse of needle: dull or bend the tip, causing bleeding, bruising or

lipodystrophy / increase risk of

infection

Injection Site Rotation

• Injection points should be rotated in the same area

regularly when using the same type of insulin

• Patient should be taught a systematic rotation

scheme

• Examine injection site and avoid injection into the

hypertrophic and atrophic areas

Site Rotation Grip

Education Pamphlets Skin Problem of Injection Site

• Local Skin Allergy

• Erythema, pruritis and induration

• May be due to insulin, additives, disinfectant

• Cool boiled water for skin cleansing

• Trying a different type of insulin

• Desensitization

Glucose Monitoring

• Self Monitoring of Blood Glucose (SMBG)

• To evaluate the efficacy of insulin regimen

• To enhance self care

(diet/ exercise / medication)

• Identify and treat hypoglycaemia

Frequency of Monitoring

Continuous Glucose Monitoring (CGM)

7 Days CGM

• A “sensor” is inserted subcutaneously

• records glucose concentration in interstitial fluid every 5 minutes

• Results need finger stick blood sugar readings for calibration

• Insulin, exercise, and meals or snacks are entered into a paper-based "diary" and recorded into the monitor

• After completion, the result is downloaded into a computer


7 Days CGM


7 Days CGM

www.medtronic.com

Hypoglycaemia unawareness

Nocturnal hypoglycaemia

Dawn phenomenon

Post-prandial hyperglycaemia


Real Time CGM

www.dexcom.com


Real Time CGM

www.abbottnextfrontier.us

Insulin pump with CGM

A. Insulin pump

B. Insulin delivery set

C. Glucose sensor

D. Continuous Glucose monitoring System - CGMS

Needle Phobia

• Needle phobia affects up to 10% of the general

population

• Upsetting experience of needles when young

e.g. painful procedure at hospital

• Anxiety → Avoidance

Nash. J. Needle Phobia-Overcoming Fear of Needles & Needle Phobia Symptoms

www.diabetes.co.uk

Needle Phobia

Coping with Needle Phobia

Hold the insulin syringe /pen in hand

Practice drawing insulin

Act ‘as if’ going to inject

Inject over abdomen; alternate site testing

Inject in different geographical locations

• Gaining skills of relaxation and confidence

• Relaxation exercise

• Establish own Fear Hierarchy steps:

(series of steps of actions to overcome fear of injection)

Nash. J. Needle Phobia-Overcoming Fear of Needles & Needle Phobia Symptoms

www.diabetes.co.uk

Injection Aids for Needle Phobia

Adherence Problem:

Insulin Injection Omission

• Intentional insulin omission in Type 1 and Type 2 DM was

reported by more than 50% of respondents; regular omission

was reported by 20% (A survey in U.S., n=502)

• Risk Factors:

Youngage

Pain & Embarrassment

Multiple injections

Type 2 Diabetes

Low Income &

High Education

Not follow

healthy diet

Interference with daily activities

Peyrot, et al., 2010, Correlates of insulin injection omission, Diabetes Care, vol 33, no.2

Adherence Problem: Insulin-taking

behavior and memory problems

• A web survey:

• Insulin-taking behavior and memory problems

among people with diabetes in 5 countries

• USA, UK, Canada, Germany & China

• Type 1 and Type 2 patients

• n= 1,754

Brod et al. (2014) Patient Intelligence: Insulin-taking behavior and memory problems among people with diabetes in five countries: findings from a web survey

Brod et al. (2014) Patient Intelligence: Insulin-taking behavior and memory problems among people with diabetes in five countries: findings from a web survey

Injection Assistance Devices

To Enhance Insulin Injection Adherence

• Be aware of the potential risk factors and injection-related problems

• need to work out with patient to identify the specific issues and develop solutions that will

work for them

• Use device-related strategies

• To alleviate the emotional burden of injection and enhance psychological well-being

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