Insulin and Insulin Pumps - PowerPoint Presentation

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Insulin and Insulin Pumps

Dr

Waqar

Malik

Consultant

Diabetologist

Blakesley

Hall,

Blakesley

Road, Birmingham

9

th

Jan. 2017

Slide3

Lay Out

Why glycaemic control is important and what role insulin plays

Different insulins old and new

Some tips about dose titration

Different devices

Continuous subcutaneous insulin infusion (CSII or 'insulin pump')

Slide4

Relative Risk of Progression of Diabetes Complications (DCCT)

DCCT Research Group,

N Engl J Med

1993, 329:977-986.

RELATIVE

RISK

Mean A1C

Slide5

Lifetime Benefits of

Intensive Therapy (DCCT)

Gain of

15.3 years

of complication free living compared to conventional therapy

Gain of

5.1 years of life compared to conventional therapy

DCCT Study Group, JAMA 1996, 276:1409-1415.

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Effect of A1C On Complications in the UKPDS Study

A1C

Stratton IM et al. BMJ 2000;321:405

0

10

20

30

40

50

60

Myocardial Infarction

Microvasc Disease

5.5%

6.5%

7.5%

8.5%

9.5%

10.5%

Slide7

Lessons from the DCCT and UKPDS:

Sustained Intensification of Therapy is Difficult

DCCT

EDIC

(Type 1)

UKPDS (Type 2),

Insulin Group

DCCT/EDIC Research Group.

New Engl J Med

2000; 342:381-389

Steffes M et al.

Diabetes

2001; 50 (suppl 2):A63

UK Prospective Diabetes Study Group (UKPDS) 33

Lancet

1998; 352:837-853

4

6

8

10

9.0

8.1

7.3

7.9

0

6.5

+ 4

+ 6 yrs

DCCT

EDIC

0

6

7

8

0

2

4

6

8

10 yrs

A1C (%)

Normal

Baseline

A1C (%)

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Mortality of DM Patients Undergoing CABG

Furnary et al J Thorac Cardiovasc Surg 2003;123:1007-21

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P=0.0009

P=0.026

BG<110

110<BG<150

BG>150

Surgical ICU Mortality

Effect of Average BG

Van den Berghe et al (Crit Care Med 2003; 31:359-366)

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Hyperglycemia and Hospital Mortality

1826 consecutive ICU patients 10/99 thru 4/02, Stamford CT

Krinsley JS: Mayo Clin Proc 78: 1471-1478, 2003

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Insulin

The most powerful agent we have

to control glucose

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Patient J.L., December 15, 1922

February 15, 1923

The Miracle of Insulin

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Progression of Type 1 Diabetes

Adapted from: Atkinson.

Lancet.

2002;358:221-229.

Age (y)

Precipitating Event

Beta-cell mass

Genetic

predisposition

Normal insulin

release

Glucose

normal

Overt diabetes

No C-peptide

present

Progressive loss

of insulin release

C-peptide

present

Antibody

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Options in Insulin Therapy for Type 1 Diabetes

Current

Multiple injections

Insulin pump (CSII)

artificial pancreas

Implant Transplant (pancreas; islet cells)

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Type 2 Diabetes …

A Progressive Disease

Over time,

most patients will need insulin

to control glucose

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Multiple factors may drive progressive decline of

b

-cell function

b

-cell

(genetic background)

Hyperglycaemia

(glucose toxicity)

Protein

glycationAmyloiddeposition

Insulin resistance

“lipotoxicity”

elevated FFA,TG

Slide17

Algorithm for blood glucose lowering therapy

Adapted from

Type 2 diabetes in adults: management. NICE Clinical guideline update (NG28)

2015 [Accessed Dec 2015].

When prescribing pioglitazone, exercise particular caution if the person is at high risk of the adverse effects of the drug. Pioglitazone is associated with an increased risk of heart failure, bladder cancer and bone fracture. Known risk factors for these conditions, including increased age, should be carefully evaluated before treatment: see the manufacturers’ summaries of product characteristics for details. Medicines and Healthcare products Regulatory Agency (MHRA) guidance (2011) advises that ‘prescribers should review the safety and efficacy of pioglitazone in individuals after 3–6 months of treatment to ensure that only patients who are deriving benefit continue to be treated’.

Treatment with combinations of drugs including sodium–glucose cotransporter 2 inhibitors may be appropriate for some people at first and second intensification; see NICE technology appraisal guidance 288, 315 and 336 on

dapagliflozin

,

canagliflozin

and

empagliflozin

respectively. All three SGLT-2 inhibitors are recommended as options in dual therapy regimens with metformin under certain conditions. All three are also recommended as options in combination with insulin. At the time of publication, only

canagliflozin

and

empagliflozin

are recommended as options in triple therapy regimens. The role of

dapagliflozin

in triple therapy will be reassessed by NICE in a partial update of TA288. Serious and life-threatening cases of diabetic ketoacidosis have been reported in people taking SGLT-2 inhibitors (

canagliflozin

,

dapagliflozin

or

empagliflozin

) or shortly after stopping the SGLT-2 inhibitor. MHRA guidance (2015) advises testing for raised ketones in people with symptoms of diabetic ketoacidosis, even if plasma glucose levels are near normal.

Only continue GLP-1 mimetic therapy if the person has a beneficial metabolic response (a reduction of HbA1c by at least 11 mmol/mol [1.0%] and a weight loss of at least 3% of initial body weight in 6 months).

Be aware that, if metformin is contraindicated or not tolerated,

repaglinide

is both clinically effective and cost effective in adults with type 2 diabetes. However, discuss with any person for whom repaglinide is being considered, that there is no licensed non-metformin-based combination containing repaglinide that can be offered at first intensification. Be aware that the drugs in dual therapy should be introduced in a stepwise manner, checking for tolerability and effectiveness of each drug. MHRA guidance (2011) notes that cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for the development of cardiac failure. It advises that if the combination is used, people should be observed for signs and symptoms of heart failure, weight gain, and oedema. Pioglitazone should be discontinued if any deterioration in cardiac status occurs.

The recommendations in this guideline also apply to any current and future biosimilar product(s) of insulin glargine that have an appropriate Marketing Authorisation that allows the use of the biosimilar(s) in the same indication. A consultant-led multidisciplinary team may include a wide range of staff based in primary, secondary and community care.

Recommendations that cover

dipeptidyl

peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 (GLP-1)

mimetics and sulfonylureas (SUs) refer to these groups of drugs at a class levelSGLT-2, sodium-glucose cotransporter-2

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Vocabulary

Target Range:

A range of numbers that represents an individual’s ideal blood glucose level; determined by health care team with the individual (child with diabetes and parent/guardian)

Basal Insulin:

Sometimes called "background" insulin, the insulin working steadily throughout the day

Bolus Insulin

:

a single dose of insulin, given for one of two reasons:

Carb or Meal/Snack Bolus: Insulin dosed when food is eaten Correction Bolus: Insulin dosed when blood glucose level is too high and needs to be corrected (made lower)18

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19

Insulin Delivery Methods

Insulin Syringe

Insulin Pen

Insulin Pump

Jet Injector

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Dissociation & Absorption of Aspart / Lispro

Insulin

Aspart or

Lispro

Regular

Human

Insulin

Peak Time = 80-120 min

Peak Time = 40-50 min

Capillary

Membrane

Subcutaneous Tissue

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400

350

300

250

200

150

100

Meal

SC injection

50

0

0

30

60

Time (min)

90

120

180

210

150

240

Regular

Lispro

500

450

400

350

300

250

150

50

200

100

0

0

50

100

Time (min)

150

200

300

250

Plasma insulin (pmol/L)

Plasma insulin (pmol/L)

Meal

SC injection

Heinemann, et al.

Diabet Med

. 1996;13:625–629; Mudaliar, et al.

Diabetes Care

. 1999;22:1501–1506.

Short-Acting Insulin Analogs

Lispro and Aspart Plasma Insulin Profiles

Regular

Aspart

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Lepore, et al.

Diabetes

. 1999;48(suppl 1):A97.

6

5

4

3

2

1

0

0

10

Time (h) after SC injection

End of observation period

20

30

Glargine

NPH

Glucose utilization rate

(mg/kg/h)

Glargine vs NPH Insulin in Type 1 Diabetes

Action Profiles by Glucose Clamp

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4:00

25

50

75

8:00

12:00

16:00

20:00

24:00

4:00

Breakfast

Lunch

Dinner

Plasma insulin (

µ

U/ml)

Time

8:00

Physiological Serum Insulin Secretion Profile

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4:00

16:00

20:00

24:00

4:00

Breakfast

Lunch

Dinner

8:00

12:00

8:00

Time

Glargine

Lispro Lispro Lispro

Aspart Aspart Aspart

or

or

or

Plasma insulin

Basal/Bolus Treatment Program with

Rapid-acting and Long-acting Analogs

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The Basal/Bolus Insulin Concept

Basal insulin

Suppresses glucose production between meals and overnight

40% to 50% of daily needs

Bolus insulin (mealtime)

Limits hyperglycemia after meals

Immediate rise and sharp peak at 1 hour

10% to 20% of total daily insulin requirement at each meal

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Insulin Therapy in Type 2 Diabetes

Indications

Significant hyperglycemia at presentation

Hyperglycemia on maximal doses of oral agents

Decompensation

Acute injury, stress, infection, myocardial ischemia

Severe hyperglycemia with ketonemia and/or ketonuria

Uncontrolled weight loss

Use of diabetogenic medications (eg, corticosteroids) Surgery Pregnancy

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Starting With Basal Insulin in DM 2

Advantages

1 injection with no mixing

Insulin pens for increased acceptance

Slow, safe, and simple titration

Low dosage

Effective improvement in glycemic control

Limited weight gain

6-37

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Starting MDI

Starting insulin dose is based on weight

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

Bolus dose (aspart/lispro) = 20% of starting dose at each meal

Basal dose (glargine/NPH) = 40% of starting dose at bedtime

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Starting MDI in 70Kg person

Starting dose = 0.45 x

wgt

. in Kg.

.45 x 70. = 32 units

Bolus dose = 20% of starting dose at each meal

20% of 32 units = 6 units ac (

tid

)Basal dose = 40% of starting dose at bedtime 40% of 32 units = 12 units at HS

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Treat to Target Study: Glargine vs NPH Added to Oral Therapy of Type 2 Diabetes

Type 2 DM on 1 or 2 oral agents (SU, MET, TZD)

Age 30 to 70

BMI 26 to 40

A1C 7.5 to 10% and FPG > 140 mg/

dL

(7.8mmol/L)

Anti GAD negative

Willing to enter a 24 week randomized, open labeled study

Riddle et al, Diabetes June 2002, Abstract 457-p

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Treatment to Target Study: NPH vs Glargine in DM2 patients on OHA

Add 10 units Basal insulin at bedtime (NPH or Glargine)

Continue current oral agents

Titrate insulin weekly to fasting BG < 100 mg/

dL

(5.6mmol/L)

- if 100-120 mg/

dL

, increase 2 units (5.6-6.7) - if 120-140 mg/dL, increase 4 units (6.8-7.8) - if 140-180 mg/dL, increase 6 units(7.8-10) - if >180 mg/dL, increase 8 units >10

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Treatment to Target Study: % at Goal

57% of patients in both groups reached A1C



7%

At wk 24, mean insulin glargine dose was higher than mean NPH insulin dose:

Insulin glargine NPH insulin

48.8 IU/day 42.4 IU/day ,

P<0.001

Rosenstock J, Riddle M, HOE901/4002 Study Group. Diabetes 2002;51(suppl 2):A482. Abstract 1982-POResults

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Treat to Target Study: Glargine vs NPH Added to Oral Therapy of Type 2 Diabetes

Nocturnal Hypoglycemia reduced by 40% in the Glargine group (532 events) vs NPH group (886 events)

Riddle et al,

Diabetes

June 2002, Abstract 457-p

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Why NICE/Med management want us to

use Human insulin

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Morning vs Bedtime Insulin

Baseline: 9.1

1.0

Morning

Glargine

Bedtime

Glargine

Bedtime

NPH

-2

-1

0

A1C Change From

Baseline (%)

–

1.24

–

0.96

–

0.84

P<

0.001

P

=0.008

Adapted from Fritsche A et al, and the 4001 Study Group.

Ann Intern Med.

2003:138:952

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Advancing Basal/Bolus Insulin

Indicated when FBG acceptable but

A1C > 7% or > 6.5%

and/or

SMBG before dinner > 7.8mmol/L

Insulin options

To glargine or NPH, add mealtime

aspart

/ lisproTo suppertime 70/30, add morning 70/30Oral agent optionsUsually stop sulfonylureaContinue metformin for weight control

Continue glitazone for glycemic stability?

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Devices

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Novo Innolet

®

Large push button with low

resistance

Large-scale numbers

1 unit increments

Support shoulder

Maximum dose 50 units

Clear & uncomplicated dial,

dials forward and back

Contains 300 units Novolin

®

70/30, NPH, or R

Audible clicks

NovoFine

®

disposable needle

Needle storage compartment

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NEW INSULINS

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INSULIN PUMP

Slide49

Human Insulin Time-action Patterns

Time (h)

Baseline

level

Regular insulin

Premix 70/30

SC injection

Normal insulin secretion

at mealtime

NPH insulin

Change in serum insulin

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Analog Mix 70/30:

Serum Insulin Levels in Type 2 Diabetes

Breakfast

Lunch

0

6

:00

PM

10

:00

PM

8:00

AM

6

:00

PM

1:00

PM

Dinner

C

max

Serum insulin (mU/

L

)

100

Time

80

40

20

60

*

*

NovoLog

®

Mix 70/30

70/30 Premix

McSorley.

Clin Ther.

2002;24(4):530-539.

*

P

<0.05.

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Analog Mix 70/30 vs 75/25 vs 70/30 Premix:

Serum Insulin Levels in Type 2 Diabetes

Lispro Mix 75/25

70/30 Premix

Aspart Mix 70/30

0

1

2

3

4

5

0

80

Time (h)

Serum insulin (mU/L)

60

40

20

Hermansen.

Diabetes Care.

2002;25(5):883-888.

Slide52

Aspart Mix 70/30:

Serum Glucose Levels in Type 2 Diabetes

Aspart Mix 70/30

70/30 Premix

Dinner

Breakfast

Lunch

*

0

300

200

150

250

Serum glucose

(

m

g

/d

L

)

6

:00

PM

10

:00

PM

8:00

AM

6

:00

PM

1

:00

PM

*

*

*Glucose excursions 0-4 h,

P

<0.05.

McSorley.

Clin Ther.

2002;24(4):530-539.

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4:00

16:00

20:00

24:00

4:00

Breakfast

Lunch

Dinner

8:00

12:00

8:00

Time

Basal infusion

Bolus

Bolus

Bolus

Plasma insulin

Variable Basal Rate: CSII Program

Slide54

Photograph reproduced with permission of manufacturer

.

Slide55

Pump Infusion Sets

Slide56

CSII vs MDI in 100 DM 1 Patients

Bode, et al.

Diabetes

52,(Suppl 1), 2003 Abstract 438.

Mean

± 2 SEM

200

160

140

120

100

180

Self-

monitored

BG (mg/dL)

BB

AB

BL

AL

BD

AD

Midnight

3

AM

CSII (n=93)

MDI (n=91)

Slide57

n=63 in each treatment

0

500

1000

1500

2000

2500

3000

CSII

MDI

p = 0.0027

Novo Nordisk, data on file (Study 2155/US)

Aspart (CSII) vs Aspart/Insulin glargine (MDI)

Glucose Exposure During CGMS

Measurement of AUC

(glu)

≥80 mg/dL during the 48-hour continuous glucose monitoring period

†

AUC

glu

(mg

•

hr/dL

)

†

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6

6.5

7

7.5

8

8.5

9

Baseline

4 weeks

8 weeks

12 weeks

16 weeks

Glargine (n=16)

CSII (n=14)

CSII vs. MDI with Glargine in Children (Preliminary Data)

Boland, E.

Diabetes

52,(Suppl 1), 2003 Abstract 192.

A1c

Slide59

Continuous subcutaneous insulin infusion (CSII or 'insulin pump') therapy is recommended as a treatment option for adults and children 12 years and older with type 1 diabetes mellitus provided that:

attempts to achieve target haemoglobin A1c (HbA1c) levels with multiple daily injections (MDIs) result in the person experiencing disabling hypoglycaemia. For the purpose of this guidance, disabling hypoglycaemia is defined as the repeated and unpredictable occurrence of hypoglycaemia that results in persistent anxiety about recurrence and is associated with a significant adverse effect on quality of life

or

HbA1c levels have remained high (that is, at 8.5% [69

mmol

/

mol

] or above) on MDI therapy (including, if appropriate, the use of long-acting insulin analogues) despite a high level of care.

NICE GUIDANCE

Slide60

Children

CSII therapy is recommended as a treatment option for children younger than 12 years with type 1 diabetes mellitus provided that:

MDI therapy is considered to be impractical or inappropriate, and

children on insulin pumps would be expected to undergo a trial of MDI therapy between the ages of 12 and 18 years.

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Person has to look after pump rather than other way

need for having back up insulin

What do you need to know as GP

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