UC201001158EE 1 CSII-related studies presented during diabetes conferences in 2008 Compiled by Dr Andreas Thomas, Germany DDG Munich ADA San Francisco.

1UC201001158EE

CSII-related studies presented during

diabetes conferences in 2008

Compiled byDr Andreas Thomas, Germany

DDG Munich DDG Munich

ADA San Francisco ADA San Francisco

EASD RomeEASD Rome

ISPAD Durban, South AfricaISPAD Durban, South Africa

ATTD PragueATTD Prague

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Studies using CSII (1):

Use made of available insulin pump functions

Duration of insulin action following basal rate suspension in insulin pump therapy

Comparison of CSII and MDI in treatment of patients with type 1 diabetes

Comparison of CSII and MDI in pregnant women with type 1 diabetes

Effect of CSII on glycemic control and quality of life in patients with type 1 diabetes

Impact of CSII treatment of inflammatoric parameter hs CRP on children with type 1 diabetes

Success of CSII in children of different ages with type 1 diabetes

Contents: studies from 2008 diabetes conferences

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Insulin pump therapy in children with type 1 diabetes

CSII in toddlers from the onset of type 1 diabetes: a five-year follow up study

Bolus management in pediatric patients on insulin pump therapy

Effects of CSII on long-term glycemia in children and adolescents with type 1 diabetes

Impact of bolus management of glycemic control on children with type 1 diabetes

Optimum bolus management following a pizza meal in children and adolescents with type 1 diabetes


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Algorithm for diabetes management based on real-time continuous glucose monitoring

Cost-effectiveness analysis of CSII and MDI in patients with type 1 diabetes

Comparison of subcutaneous and intraperitoneal insulin infusion in patients with type 1 diabetes

Short-term use of CSII after type 2 diabetes has been diagnosed

Quality of life and treatment satisfaction with CSII

Fulfilment of expectations with CSII therapy

Impact of CSII on cost of treating pediatric patients with type 1 diabetes


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Aim of study:

Compare glycemic control, frequency and severity of hypoglycemic episodes and quality of life achieved by two modes of insulin delivery (i.e. CSII and MDI) in ‘clinical practice’ conditions.


Myneni, A. et al.: Comparison of insulin infusion pumps versus basal/bolus insulin injections for treatment of type 1 diabetes mellitus in clinical practice. 68th ADA Scientific Session 2008, San Francisco, 2016-PO, Diabetes 2008; 57 (Suppl. 1), A556

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Myneni, A. et al.: ADA 2008

Method and study group: • Randomized, controlled trial over a two-year period after an initial period

of six months to allow stability for each regimen: CSII with Lispro or Aspart and MDI with Lispro / Glargine or Aspart / Glargine.

• Study parameters in a ‘clinical practice’ setting: - glycemic control (HbA1c)

- hypoglycemic episodes (mild or severe) - Life satisfaction, impact and diabetes-related worries*

• 107 patients with type 1 diabetes:

*Based on DQOL diabetes quality of life questionnaire

Group CSII (n = 53) MDI (n = 54)

Gender 34 f / 19 m 16 f / 38 m

Age (years) 43.2 + 4.2 46.6 + 3.6

Duration of diabetes (years)

23.5 + 3.3 20.7 + 3.6


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Findings after two years:

7.45 + 0.25

8.14 + 0.36

6

7

8

9

Hb

A1c

(%)

Comparison of HbA1c Frequency of severe hypoglycemia*

*Assistance required

MDI CSII

0.49 + 0.14

0.25 + 0.12

0

0.2

0.4

0.6

Hy

po

gl.

rate

(p

er

pa

t. y

ea

r)

MDI CSII

p = 0.003 p = 0.013


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Findings after two years:

DQOL score (safety of treatment)

MDI CSII

2.54 + 1.44

2.06 + 1.18

0

1

2

3

DQ

OL

sco

re

be

tte

r


Lower score indicates higher life satisfaction

DQOL: Diabetes quality of life questionnaire

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Myneni A et al.: ADA 2008

Conclusions:

CSII therapy is associated with improved glycemic control, fewer episodes of severe hypoglycemia and greater life satisfaction as compared with MDI in a routine clinical practice. Patients using CSII are less worried about their treatment.


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Aim of study:

Verify CSII-treated patients’ awareness of the potential of modern insulin pumps. Assess the frequency of use of individual functions in a diabetes centre.

Jankovec, Z. et al.: Frequency of available insulin pump functions use by patients with diabetes mellitus. Abstract 112, 1st ATTD Meeting, Prague 2008

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Jankovec Z et al.: Abstract 112, 1st ATTD Meeting, Prague 2008

Method and study group: • Survey of CSII-treated patients in a diabetological center treating 100

patients with the aid of CSII• Respondents asked about their knowledge of available CSII functions

and frequency of use of the following functions:- temporary basal rate- various basal profiles- extended Bolus- Bolus calculator - remote control

• Questionnaires completed for 87 patients; (43% f / 57% m)• Age: 44.4 + 14.84 years

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Jankovec, Z. et al.: Abstract 112, 1st ATTD Meeting, Prague 2008

Findings: frequency of use of functions

Function Frequency % of patients using function

Average frequency of insulin bolus administration

4.06 + 1.09 per 24 hrs 100%

Extended bolus 19.38 + 32.38 per month 44%

Insulin bolus calculation 5.33 + 3.06 per week 54%

Selection from two or more basal profiles

6.38 + 4.17 per month 49%

Temporary adjustments to basal increment

11.75 + 21.65 per month 57%

Display backlight 11.31 + 21.65 per week 86%

Remote control 18.39 + 18.93 per week 41%

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Findings:

Satisfaction with insulin pump

0% 9% 1% 3% 2%

85%

Dissatisfied, considering ending treatment

Partially satisfied

Dissatisfied, considering switching to different pump

Dissatisfied, but pump is essential for diabetes control

Satisfied, would like insulin pen treatment

Entirely satisfied

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17% 21%

26%

6%

30%

10% 16%

28%

4%

42%



Findings:

Temporary basal ratenon-user, Function not known or not learnt

non-user, Function not known or not learnt

frequent application, very helpful

non-user, function not important

Intermittent use, very helpfuluser, function

not necessary


non-user, function not important

Intermittent use, very helpfuluser, function

not necessary

Various basal profiles

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20%

13%

38%

8%21%

0% 22%0%

35%43%



Findings:

Extended bolus

non-user, Function not knownor not learnt


non-user, Function not necessary

intermittent application, very helpfuluser,

function not necessary

non-user, Function not known or notlearnt


non-user, FunctionNot necessary

intermittent application, very helpful

user, function not necessary

Bolus calculator

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Findings:

Watertight / splash-resistant pump

10% 8%

57%8%

17%

non-user, unknown function


non-user, unimportant function

intermittent application, very helpful

user, unnecessary function

11%

46%

13%

30%

non-user, unknown / unlearned function

user, very helpful

non-user, unimportant function

user, unnecessary function

Remote control

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Jankovec Z et al.: Abstract 112, 1st ATTD Meeting, Prague 2008

Conclusions:

Patients welcome technically advanced insulin pumps and most of them use the additional functions. Patients should be taught to use the additional functions; they should also be advised about the use of additional functions as a matter of routine during the management of problems arising during treatment with insulin pumps.

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Aim of study:

Investigate the time taken to observe a change in glucose concentration following modification of the basal rate. The study has a bearing on predictive pump suspension with the aim of preventing hypoglycemia.


Buckingham, B. et al.: Duration of insulin action following pump suspension. 68th ADA Scientific Session 2008, San Francisco, 2019-PO, Diabetes 2008; 57 (Suppl. 1), A557

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19UC201001158EEBuckingham, B. et al.: ADA 2008

Method and study group: • Determine rate of change (ROC) in blood glucose levels

(mg/dl/min) following discontinuation of basal insulin infusion:

- initial increase in basal rate

- target: glucose level of 80 mg/dl within 30-45 mins

- subsequently suspend basal insulin infusion for 90 mins• Measure rate of change in blood glucose level with FreeStyle

meter (every 10 minutes) and CGM (FS Navigator) • 7 patients with type 1 diabetes

- average age: 27 (range 11-38 years)


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Findings: Rate of change of glucose levels following pump shut-off

Buckingham, B. et al.: ADA 2008

High basalrate

Pump off Normal basal rate

Rat

e o

f ch

ang

e in

glu

cose

(m

g/d

l/m

in)

Time from start of pump shut-off (min)

Basal insulin infusion rates rose by 212% (mean increase) until projected alarm, based on a glucose threshold of 80 mg/dl and a projection horizon of 30-45 mins.


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Conclusions:

The study showed that it takes at least 75 minutes for any change in basal insulin to have a full impact. This is a key factor that needs to be taken into account not just whenever an insulin pump is switched off temporarily, but also for developing algorithms for automated sensor-augmented pump therapy.

Buckingham, B. et al.: ADA 2008


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Aim of study:

Compare effectiveness of CSII and MDI and pregnancy outcomes in pregnant women with type 1 diabetes.

Cyganek, K. et al.: Assessment of continuous subcutaneous insulin infusion versus multiple daily injections of insulin in pregnant women with type 1 diabetes. 68th ADA Scientific Session 2008, San Francisco, 1844-P, Diabetes 2008; 57 (Suppl. 1), A512 and: Hebda-Szydło, A. et al.: The efficacy of continuous subcutaneous insulin infusion and multiple daily injections of insulin in pregnant women with type 1 diabetes. 44th Annual Meeting of EASD 2008, Rome, 1121, Diabetologia 2008; 51 (Suppl. 1), S456-S457


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Cyganek, K. et al.: ADA 2008, Hebda-Szydło, A. et al.: EASD 2008

Method and study group: • Controlled observational study

• Measure average blood glucose and HbA1c in each trimester of pregnancy

• Analysis of pregnancy outcomes for both groups • 216 pregnant women with type 1 diabetes:

• MDI: 142 women, age: 28.4 + 6.0 years, duration of diabetes: 11.2 + 7.3 years, proportion of planned pregnancies: 31%

• CSII: 74 women, age: 28.9 + 4.4 years, duration of diabetes: 12.2 + 6.9 years, proportion of planned pregnancies: 59.5 %


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Findings:

Change in HbA1c values during pregnancy

5,7 + 1,15,7 + 0,7

6,9 + 1,2 7,0 + 1,6

6,0 + 1,0 5,9 + 0,9

4

4,5

5

5,5

6

6,5

7

7,5

8

Hb

A1c

(%

)

1st trimester 2nd trimester 3rd trimester

p = 0.7 p = 0.03 p = 0.2

CSII MDI

Cyganek, K. et al.: ADA 2008, Hebda-Szydło, A. et al.: EASD 2008


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Findings: ComplicationsWeight at birth

Cyganek, K. et al.: ADA 2008, Hebda-Szydło A et al.: EASD 2008


CSII MDI

3355+725

3437+642

3000

3200

3400

3600

3800

4000

Geb

urt

sgew

ich

t (g

)

Wei

gh

t at

bir

th (

g)

5,6

4,6

1,4

6,3

8,5

4,2

01

23

45

67

89

10

An

teil

(%

)

CSII MDI

n: 1 6 4 12 4 7 Infant death Still birth Congenital malformation

Rat

io w

ith

co

mp

licat

ion

s (%

)

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Conclusions:

This large observational study produced evidence that the CSII model is superior to an MDI regimen in terms of metabolic control and pregnancy outcomes in women with type 1 diabetes. The slightly better glycemic control significantly decreased the risk of complications for both mother and infant.


Cyganek, K. et al.: ADA 2008, Hebda-Szydło A et al.: EASD 2008

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Aim of study:

Ascertain whether the use of CSII in patients with type 1 diabetes managed by multiple daily injections improves glycemia and meets quality of life (QOL) expectations.

O'Neal, D.N. et al.: Insulin pump therapy (CSII) improves glycaemic control and quality of life in type 1 diabetes. Abstract 153, 1st ATTD Meeting, Prague 2008 UC201001158EE

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O'Neal, D.N. et al.: Abstract 153, 1st ATTD Meeting, Prague 2008

Method and study group: • Assessment of patients with type 1 diabetes (St. Vincent’s Hospital,

University of Melbourne Department of Medicine)

• Analysis of glycemic control (HbA1c)

• Continuous glucose monitoring and analysis of CGM profiles before and after pump initiation

• Measurement of quality of life (QoL) by a diabetes-specific scale after pump initiation

• 44 patients (33 female / 11 male) with type 1 diabetes• Age: 39 + 12 years• Duration of diabetes: 15 + 11 years• BMI: 27.6 + 0.9 kg/m2

• Diabetes complications pre-CSII: 8.9%

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Findings: Change in HbA1c

Pre- 0-4 4-8 8-12 12-16 16-18 18-24 weeks CSIIpump

Hb

A1c

(%)

Ch

ang

e in

Hb

A1c

(%)

fr

om

bas

elin

e

0

-0.2

-0.4

-0.6

-0.8

-1.0

-1.2

8.0

7.5

7.0

7.9 + 1.4 %

7.1 + 1.0 %

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Findings: Proportion of glucose values in various glycemic ranges, measured with CGMS

Hypoglycemia (< 4 mmo/l) Euglycemia (4 - 10 mmo/l) Hyperglycemia (> 10 mmo/l)

Pre- 0-4 4-8 8-12 12-16 16-18 18-24 weeks CSIIpump

Pro

po

rtio

n o

f g

luco

se v

alu

es (%

)

100

80

60

40

20

0

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Findings: patient expectations of CSII

0

10

20

30

40

50

60

70

80

90

100

Part

of

pati

en

ts (

%)

Glucose < 8 mmo/l

Glucose variability

Prevent mildhypo

Prevent severe hypo

PreventDKA

Mealtime flexibility

Physical fitness

Expected Achieved

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Conclusions:

Improved glycemia was observed in patients with type 1 diabetes commencing CSII with CGM, without any increased incidence of hypoglycemia. The quality of life improved with CSII in line with patients’ expectations.

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Aim of study:

Extensive study of highly sensitive C-reactive protein (hs-CRP) as a marker of chronic inflammation. Plasma levels of over 1 mg/l are considered to represent sub-clinical vasculitis promoting chronic complications. Apart from lowering hyperglycemia, it is important to identify treatment conditions in young patients with type 1 diabetes that could cause CRP to fall below this critical level.

Nuboer, R. et al.: Gradual decrease in hs-CRP during prospective study comparing continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDII). 34th Annual Meeting ISPAD 2008, Durban, WED03, Pediatric Diabetes 2008, 9 (Suppl. 10), 19-20

Impact of CSII treatment of inflammatoric parameter hs-CRP on children with type 1

diabetes

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Method and study group: • Open, parallel, randomized, controlled, prospective comparative study of

MDII and CSII over a period of 10.5 months:

• 38 pediatric patients with type 1 diabetes• Age: 9.5 ± 3.3 years• Duration of diabetes: 4.4 ± 2.9 years

CSII (n =19) CSII Preference phase

0 3.5 7 10.5 month

Run-in

MDI(n = 38)

MDI (n =19) switch CSII Preference phase

Impact of CSII treatment of inflammatoric parameter hs-CRP on children with type 1 diabetes

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Findings:

Change in HbA1c

Nuboer, R. et al.: ISPAD 2008

8.34 + 0.93

7.80 + 0.70

7.65 + 0.88

6

7

8

9

Hb

A1c

(%

)

Baseline (MDI) At start of CSII After CSII (3 and 5-7 months) (final MDI values)

p < 0.001

Impact of CSII treatment of inflammatoric parameter hs-CRP on children with type 1

diabetes

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Findings:


Change in insulin requirement Change in hs-CRP

1.03 + 1.06 0.94 + 0.98

0.76 + 0.86

0

0.5

1

1.5

hs-

CR

P (

mg

/l)

Baseline At start After CSII (MDI) of CSII

p = 0.035


1,04+0,351,04+0,29

0,74+0,18

0

0,5

1

1,5

Insu

lin

bed

arf

(IE

/kg

KG

/T

ag)

Baseline At start After CSII (MDI) of CSII

Insu

lin r

equ

irem

ent

(IU

/kg

BW

/day

)

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Conclusions:

A gradual decrease in CRP was observed during an intensive insulin treatment study, the greatest decrease occurring during CSII. Obviously, CSII also has an effect on CRP levels in patients with type 1 diabetes. Further research is needed.

Comment:The decline in the HbA1c value caused by the use of CSII is not highly significant in comparison with the effects of optimised MDI. The question is, what is the main reason for the decline in hs CRP levels during treatment with CSII? This effect may well be caused by a lower level of glycemic variability. Unfortunately, this was not investigated.



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Aim of study:

Investigate how pump therapy helps to improve the condition of children with type 1 diabetes, even in those cases in which disease control was poor prior to the use of pump therapy.

Petryaykina, E. et al.: Improvement in HbA1c levels in children and adolescents in the Moscow region with type 1 diabetes after CSII therapy, Abstract 162, 1st ATTD Meeting, Prague 2008and 34th Annual Meeting ISPAD 2008 Durban, WED 37, Pediatric Diabetes 2008, 9 (Suppl. 10), 34

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Method and study group:• Switch to CSII in children with poor glycemic control (during

MDI: failure to adhere to diet and insulin therapy regime and also failure to follow doctor’s recommendations)

• Observe glycemic control (change in HbA1c)

• Measure insulin requirement (insulin/body weight) • 85 children with type 1 diabetes (65% female, 35% male)• subdivided into three age groups:

- pre-school age (2-6): n = 11 - primary-school age (7-11): n = 31 - adolescents (12-18): n = 43

• Duration of diabetes: 4.5 + 1.24 years• Average duration of CSII treatment: 1.3 ± 0.25 years

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Findings:

Change in HbA1c

2–6 years

9.3 + 1.4

10.7 +0.5

9.7 + 0.6 9.8 + 0.8

8.1 + 0.4

7.6 + 0.67.8 + 0.4 7.8 + 0.5

6

8

10

12

Hb

A1c

(%)

Before CSII

With CSII

Before CSII

With CSII

Before CSII

With CSII

Before CSII

With CSII

7–11 years 12–18 years All

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Findings:

Change in daily insulin requirement

2–6 years

Before CSII

CSII Before CSII

CSII Before CSII

CSII Before CSII

CSII

7–11 years 12–18 years All

Petryaykina, E. et al.: 1st ATTD Meeting, Prague 2008 and ISPAD 2008

0,8

1,1

0,60,7

0,80,7

0,9 0,9

0

0,5

1

1,5

Insu

lin

/ k

g b

od

y w

eig

ht

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Conclusions:

The prolonged use of pump therapy in children with a poor record of control helps significantly to improve carbohydrate metabolism and to reduce the insulin dosage per weight ratio.

Petryaykina, E. et al.: 1st ATTD Meeting, Prague 2008 and ISPAD 2008 UC201001158EE

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Bolotova, N.V. et al.: Insulin pump therapy in children with type 1 diabetes. Abstract 67, 1st ATTD Meeting, Prague 2008

Aim of study:

Evaluate the effectiveness of insulin pump therapy in children with type 1 diabetes.

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Bolotova, N.V. et al.: Abstract 67, 1st ATTD Meeting, Prague 2008

Method and study group:• Two-year observation in an endocrinological centre• Measure glycemic control (i.e. average glucose values,

glucose fluctuations, hypoglycemia rate and insulin requirement)

• 19 children with type 1 diabetes (12 female, 7 male)• Age range: 9-15 years• Duration of diabetes: 1-15 years• Complications: neuropathy: n = 7

angiopathy: n = 4nephropathy: n = 3cardioneuropathy: n = 3retinopathy: n = 1

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Findings:

Glycemic control

9.4 +2.9

11.8 +3.1

7.1 +1.87.7 +2.7

0

2

4

6

8

10

12

14

16

Ave

rag

e b

loo

d s

ug

ar (

mm

ol/l

)

Average morning glucose

Before CSII With CSII

Average bedtime glucose

Variability: • morning glucose

Before CSII: 7.0-16.9 mmol/l

With CSII: 6.0-10.0 mmol/l • bedtime glucose

Before CSII: 5.0-13.2 mmol/l

With CSII: 5.0-10.4 mmol/l

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Findings:

Insulin requirement

Before CSII

With CSII

• Variability of insulin requirement:

Before CSII: 0.42 –1.07 IU/kg BW

With CSII: 0.34-0.86 IU/kg BW

0.78 + 0.34

0.57 + 0.41

0

0.2

0.4

0.6

0.8

1

Da

ily in

su

lin d

os

e (

IU)

• Patients with severe hypoglycemias (2-3 per week):

Before CSII: 4

With CSII: 1

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Conclusions:

For children with type 1 diabetes, CSII is a highly effective therapy with a high level of user satisfaction, improved glycemic control and reduced insulin dosage. All patients commented on the ease of pump use and increased mobility.

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Aim of study:

Longitudinal assessment (five-year follow-up) of metabolic control in children under the age of six treated with CSII from the onset of type 1 diabetes.

CSII in toddlers from the onset of type 1 diabetes: a five-year follow-up study

Szypowska, A. et al.: Insulin pump therapy in children under the age of 6 from the onset of type 1 diabetes. A five-year follow-up study. 68th ADA Scientific Session 2008, San Francisco, 1800-P, Diabetes 2008; 57 (Suppl. 1), A499 and Groele, L. et al.: Insulin requirement in children under the age of 6 treated with insulin pumps from the onset of type 1 diabetes mellitus: a five-year follow-up study. 44th Annual Meeting of EASD 2008, Rome, 0989, Diabetologia 2008; 51 (Suppl. 1), S398-S399

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49UC201001158EESzypowska, A. et al.: ADA 2008, and Groele, L. et al.: EASD 2008

Method and study group : • Insulin pump therapy started within two months of onset of

type 1 diabetes• Measure metabolic parameters every sixth months and after

five years: HbA1c, daily insulin requirement, share of basal rate in daily insulin requirement, and frequency of episodes of diabetic ketoacidosis and severe hypoglycemia

• 58 children (31 girls), under the age of 6 at time of diabetes manifestation (age: 3.3 ± 1.5 years)


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Findings:

Change in HbA1c

Average frequency of episodes of:

• severe hypoglycemia:0.6/100 pat. years• diabetic ketoacidosis:0.6/100 pat. years

ONSET months

3 6 12 18 24 30 36 42 48 54 60

12

10

8

6

4

2

0

Hb

A1

c (

%)

9,6

6,7 7,26,97,3

Szypowska, A. et al.: ADA 2008, and Groele, L. et al.: EASD 2008


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Findings:

month

3 6 12 18 24 30 36 42 48 54 60

30

25

20

15

10

5

0

Pro

po

rtio

n o

f b

asal

rat

e in

DIR

(%

)

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0 Insu

lin

re

qu

irem

ent

(IU

/kg

BW

)

Proportion of basal rate in

daily insulin requirement (DIR )

months

3 6 12 18 24 36 48 54 60

100

80

60

40

20

0

Pro

po

tio

n o

f p

atie

nts

(%

)

Proportion of patients with corresponding share of basal rate in DIR*

Proportion of basal rate: > 35% 25-35% <25% 0%



*Daily insulin requirement

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Conclusions:

Initiating insulin pump therapy at recognition of type 1 diabetes in children under the age of six results in sustained metabolic control, with a minimal risk of severe hypoglycemia and diabetic ketoacidosis and without any increase in the body mass index. The daily insulin dose increases during type 1 diabetes follow-up to 0.7U/kg BW/d, with 25% basal insulin in total insulin dose.



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Aim of study:

Determine the long-term effect of insulin pump therapy (CSII) on glycemia in children and adolescents with type 1 diabetes.

Quinn, M. et al.: Impact of pump therapy on long-term glycemia in children and adolescents with type 1 diabetes. 34th Annual Meeting ISPAD 2008, Durban, THU44, Pediatric Diabetes 2008, 9 (Suppl. 10), 56


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Method and study group :

• Examine the intra-individual changes in mean annual HbA1c in pediatric patients with type 1 diabetes who had used pump therapy for at least two years as part of the Diabetes Programme at the Boston Children’s Hospital

• Observe proportion of patients attaining ADA goals:

<6 years: 7.5-8.5%, 6-12 years: <8%, >13 years: <7.5%• 209 patients (47% girls)

- Age: 11.7 + 4.4 years

- Duration of diabetes: 4.2 + 3.4 years

- Baseline HbA1c: 7.9 + 0.9%

- Number injections during MDI treatment: 30 + 2.7/day


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Findings:

Change in HbA1c before and during CSII treatment

Quinn, M. et al.: ISPAD 2008

- 2 years - 1 year Start of CSII + 1 year + 2 years

Time

8.5

8.0

7.5

7.0

Hb

A1c

(%

)


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Findings:

Proportion of patients (in age groups) attaining ADA goals for HbA1c



- 2 years - 1 year + 1 year of CSII + 2 years of CSII

0

10

20

30

40

50

60

70

80

90

100

An

teil

Pa

tie

nte

n (

%)

Age: <6 years 6-12 years 13-17 years >18 years All

39 29 15 12 109 102 78 65 59 69 88 84 2 9 28 48 119 122 145 129 n

Pro

po

rtio

n o

f p

atie

nts

(%

)

UC201001158EE

57UC201001158EE

Conclusions:

Pump therapy enabled 43/210 (= 20%) children and adolescents whose HbA1c exceeded target levels on multiple injection therapy to achieve and maintain age-specific HbA1c targets. Optimising the bolus to basal dose ratios is a major contributory factor in achieving the target HbA1c.



58UC201001158EE

Aim of study:

Investigate effect of meals with different glycemic index on postprandial glucose excursions by varying meal bolus.


O'Connell, M.A. et al.: Optimising glycaemic control in pediatric patients on insulin pump therapy: the impact of glycaemic index and bolus wave type on postprandial glycaemia. Abstract 152, 1st ATTD Meeting, Prague 2008 and: Optimizing postprandial glycemia in pediatric patients with type 1 diabetes using insulin pump therapy. Diabetes Care 2008; 31 (8): 1491-1495

59UC201001158EE

O'Connell, M.A. et al.: Abstract 152, 1st ATTD Meeting, Prague 2008

Method:

Meals with a high and low glycemic index (GI) have distinct effects on post-prandial glycemia (PPG). PPG excursions may contribute to changes in diabetes-related complications. Insulin pump therapy enables insulin delivery to be tailored to meal composition. Optimum bolus types for meals of varying GI were not defined, however.


60UC201001158EEO'Connell, M.A. et al.: Abstract 152, 1st ATTD Meeting, Prague 2008

Method and study group:• Test meals with equal macronutrient (CHO, fat, protein), fiber and

energy composition, but opposing GI levels, i.e. 34 v. 76, low GI and high GI

• Subjects eat meals of the same GI on consecutive days. Study group randomized to receive either standard (100%) or dual-wave (50:50 over 2 hours) pre-meal bolus each day

• Measure glucose profiles (CGMS)• 20 children and adolescents with type 1 diabetes and CSII diabetic

patients• Age: 11.3 + 1.8 years (2.3-17.1 years) • Duration of diabetes: 4.9 + 1.9 years (2.1-8.9 years) • Experience of CSII: 0.8 + 0.4 years (0.3-1.8 years)• HbA1c: 7.5 + 0.6% (5.9-8.5%)

• Control group: 10 healthy adults


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61UC201001158EE


Findings: Postprandial glucose profiles after different meals and using different

bolus options (mean deviation in sensor glucose values from baseline)

Low glycemic index

10

5

0

-5-30 0 30 60 90 120 150 180

Time (min.)

Glu

cose

dev

. b

ase

lin

e (m

mo

l/l)

10

5

0

-5-30 0 30 60 90 120 150 180

Time (min.)

Glu

cose

dev

. b

ase

lin

e (m

mo

l/l)

High glycemic index

Standard bolus

Dual bolus

Control


62UC201001158EE


Conclusions:

The use of a dual-wave bolus for meals of low glycemic index is associated with significantly less postprandial glycemic excursion than any other meal-bolus combination (45% reduction in postprandial AUC). Hyperglycemic excursions were common after high glycemic index meals. This data supports the use of a dual-wave bolus with low glycemic index meals to optimize postprandial glucose in children with type 1 diabetes on insulin pump therapy.


63UC201001158EE

Aim of study:

Assess impact of use of dual-wave and square-wave bolus on metabolic control. Estimate ability of pediatric patients to use this system in real life.

Impact of bolus management of glycemic controlon children with type 1 diabetes

Pankowska, E. et al.: Three kinds of mealtime insulin administration and metabolic control in diabetic children on insulin pumps. 44th Annual Meeting of EASD 2008 Rome, 0948, Diabetologia 2008; 51 (Suppl. 1), S381

64UC201001158EEPankowska, E. et al.: EASD 2008

Method: • Cross-sectional prospective study in real-life conditions over two-week

period: • Teach patients to calculate insulin dose per carbohydrate unit (1 CU =

10g CU) and fat-protein unit (1 FPU = 100 kcal fat/protein) with following bolus management:

- normal bolus = insulin ratio x CU- square-wave bolus = insulin ratio x FPU

- prolongation times for FPUs: 1 1 FPU: 3 hours, 2 FPUs: 4 hours, 3 FPU: 5 hours, >3 FPUs: 8 hours

• Measure frequency of dual-wave or square-wave bolus, daily insulin requirement and HbA1c.



Study group: • 499 children with type 1 diabetes (246 f / 253 m)• Age: 10.60 + 4.14 years• Duration of diabetes: 4.34 + 2.95 years• Age at onset of diabetes: 6.16 + 6.15 years• HbA1c: 7.42 + 1.47%

• Daily insulin requirement: 0.74 + 0.22 IE/day• Share of basal rate in daily insulin requirement:

31.95 + 14.18%



Findings:

Frequency of dual-wave or square-wave bolus in relation to HbA1c

Average frequency of dual-wave or square-wave bolus: 1.19 + 0.06 per day


0,89+0,16

1,39+0,15

0

0,5

1

1,5

2

An

zah

l ve

rl B

oli/

Du

alb

oli

(/T

ag

)

HbA1c < 7.5% HbA1c > 7.5%Fre

qu

ency

of

d-w

or

s-w

bo

lus

/ day

67UC201001158EE

7.82 + 1.69

7.61 + 1.307.42 + 1.47

6

7

8

9

Hb

A1c

(%

)

Pankowska, E. et al.: EASD 2008

Findings:

HbA1c value in relation to frequency of dual-wave or square-wave bolus

0-1 / day 2-3 / day > 3 / day

p < 0.001 p < 0.001


68UC201001158EE

Pankowska, E. et al.: EASD 2008

Conclusions: The HbA1c level in patients using at least one dual-wave or square-wave bolus per day is equivalent to the recommended level. Pediatric patients on CSII are able to use dual-wave or square-wave boluses in real-life situations. 18.8% of patients did not use dual-wave or square-wave boluses during the two-week study and had a higher level of HbA1c (7.82% as opposed to 7.32%).


69UC201001158EE

Aim of study:

Identify optimum insulin pump meal bolus by comparing postprandial blood sugar levels using six methods of insulin pump meal blousing for a consistent pizza meal.


Scaramuzza, A.E. et al.: The optimum type of bolus following a pizza meal in children and adolescents with type 1 diabetes. 44th Annual Meeting of EASD 2008, Rome, 0949, Diabetologia 2008; 51 (Suppl. 1), S381-S382

70UC201001158EEScaramuzza, A.E. et al.: EASD 2008 Rome

Method: • Use bolus management for pizza meals (with the same CHU* value)

on consecutive days:a) Margherita Pizza: Dual-Wave Bolus (30% insulin immediately, 70% over 6-hr

period), given 15 min. prior to meal (GPM)b) Margherita Pizza: Dual-Bolus (30% insulin immediately, 70% over 6-hr period),

given 0 min. prior to meal c) Margherita Pizza: normal bolus (100% insulin immediately),

given 15 min. prior to meal d) Margherita Pizza: normal bolus (100% insulin immediately),

given 0 min. prior to meal e) Vegetable Pizza: Dual-Bolus (30% Insulin immediately, 70% over 6-hr period),

given 15 min. prior to meal f) Vegetable Pizza: Dual-Bolus (30% insulin immediately, 70% over 6-hr period),

given 0 min. prior to meal

• Measure glucose profiles over 6-hr period by measuring blood glucose (SMBG, 30-min. frequency)

• Aspart insulin


*Carbohydrate unit

71UC201001158EEScaramuzza, A.E. et al.: EASD 2008 Rome

Study group: • 26 children and adolescents with type 1 diabetes,

treated with CSII • Age: 14.81 + 4.28 (range: 4-22) years• Duration of diabetes: 8.23 + 4.41 (range: 1-19) years• Daily insulin requirement: 0.44 + 0.32 IU /day• BMI: 22.16 + 4.28 kg/m2


72UC201001158EE

60

80

100

120

140

160

180

200

220

time (min)

Glu

cose

(m

g/d

l)

0 30 60 90 120 180 240 360

Scaramuzza, A.E. et al.: EASD 2008 Rome

Findings:

Glycemic values following various types of bolus

Dual-Wave 6 hrs, 15 min. prior to Margherita

Dual-Wave 6 hrs, 0 min. prior to MargheritaNormal bolus 15 min. prior to MargheritaNormal bolus 0 min. prior to MargheritaDual-Wave 6 hrs, 15 min. prior to VegetableDual-Wave 0 min prior to Vegetable


73UC201001158EE

Scaramuzza, A.E. et al.: EASD 2008 Rome

Conclusions:

The use of a dual-wave bolus during a six-hour period following a pizza meal resulted in significantly less postprandial hyperglycemia during this period, provided that it was given 15 minutes in advance. A normal bolus could be used only if given 15 minutes before consumption of a vegetable pizza. This is despite the fact that a rise in glycemic values was observed during the final two hours of the study.

Optimum bolus management following a pizza meal in children and adolescents with type 1

diabetes

74UC201001158EE

Aim of study:

Identify preconceptions of CSII and their impact on outcomes.

Barnard, K.D. et al.: Do prior expectations affect perceived success/satisfaction with CSII therapy? 68th ADA Scientific Session 2008, San Francisco, 1865-P, Diabetes 2008; 57 (Suppl. 1), A518

Fulfillment of expectations with CSII therapy

75UC201001158EEBarnard, K.D. et al.: ADA 2008

Method and study group: • Participants were recruited via the website of the University

of Southampton’s School of Psychology during a six-month period

• Participants completed a brief web-based questionnaire about their expectations of CSII

• Where their expectations had been met, they were asked what was better and worse about CSII than previous insulin regimens, and any other issues

• 184 participants



Findings:

Proportion of patients whose expectations of CSII were met


80,0 96,7 76,1

0

20

40

60

80

100

An

teil

Pat

ien

ten

(%

)

All prior expectations

met

CSII significantly better than previous

regimen

CSII exceeded prior expectations

Pro

po

rtio

n o

f p

atie

nts

(%

)


Findings:

Proportion of patients with concerns before start of CSII therapy


Concerns about insertion

of canula / infusion set

Concerns about psychological implications of being

permanently attached to pump No concerns

49

41

49

0

20

40

60

80

100

An

teil

Pat

ien

ten

(%

)

Pro

po

rtio

n o

f p

atie

nts

(%

)


Findings:

Number of patients citing disadvantages of CSII

Number of patients citing advantages of CSII


Permanent attachment

to pump

Appea-rance/

visibility of device

Increased blood

glucose testing

16

4335

0

20

40

60

An

zah

l P

atie

nte

n

Nu

mb

er

of

pa

tie

nts

Greater flexibility / improved lifestyle

Better blood

glucose values

Fewer hypo-glycemias

21

110100

0

20

40

60

80

100

120

An

zah

l P

atie

nte

n

Nu

mb

er

of

pa

tie

nts

79UC201001158EE


Barnard, K.D. et al.: ADA 2008

Conclusions:

Despite the quality-of-life benefits said to be associated with CSII therapy, the majority of participants chose CSII for its perceived biomedical benefits e.g. improved diabetes control. A number of participants expected to experience psychosocial benefits, e.g. improved quality of life, greater lifestyle flexibility and greater overall control of their lives as well as biomedical benefits. Very few participants chose CSII purely for psychosocial reasons. Differences in the rationale for choosing CSII, i.e. for the perceived biomedical or psychosocial benefits, did not affect the participants’ degree of satisfaction with CSII, however.

80UC201001158EE

Aim of study:

Compare quality of life and treatment satisfaction among adults with type 1 diabetes, according to the main indication for CSII treatment.


Franciose, M. et al.: Correlates of quality of life in adults with type 1 diabetes treated with continuous subcutaneous insulin injection. 68th ADA Scientific Session 2008, San Francisco, 0419-P, Diabetes 2008; 57 (Suppl. 1), A125

81UC201001158EEFranciose, M. et al.: ADA 2008

Method and study group:• Patients treated with CSII recruited in 43 Italian diabetes clinics • Patients completed various questionnaires during routine visits:

• DSQOLS (Diabetes-Specific Quality of Life Scale)• DTSQ (Diabetes Treatment Satisfaction Questionnaire )• SF-36 (Health Survey )

• Patients categorised in three groups according to indications for CSII• Group A: poor glycemic control (n = 158)• Group B: unstable glycemia (n = 197)• Group C: others (i.e. dawn phenomenon, desire for greater lifestyle

flexibility, pregnancy, n = 122) • 477 consecutive patients, aged 18-55


82UC201001158EE

Responses to questionnaires:

Franciose, M. et al.: ADA 2008



Study group:

Indication for CSII Unstable diabetes Poor glyc. control Other

Age (years) 37.0 + 10.8 35.0 + 11.0 32.2 + 10.2

Gender (%) 61.5 f / 38.5 m 60.6 f / 39.2 m 46.7 f / 53.3 m

Duration of diabetes (years) 19.8 + 10.5 18.4 + 9.8 15.9 + 9.5

HbA1c (%) 7.9 + 5.5 8.0 + 1.3 7.1 + 1.1

Complications: 0 1 2 >3

55.1%27.0%11.2%6.6%

54.4%24.7%13.3%7.6%

81.2%15.6%2.5%0.8%

Incidence of severe hypoglycemia / year: 0 1 > 1

73.9%11.1%15.0%

89.9%3.4%6.8%

83.9%7.1%8.9%

Incidence of ketoacidosis / year: 0 > 1

84.3%15.7%

91.1%8.9%

93.4%6.6%


84UC201001158EE

Findings: Correlation between DSQOLS score and indication for CSII

40

60

80

100

Wer

t

Social

relat

ionsh

ips

Leisu

re tim

e

flexib

ility

Physic

al

com

plaint

s

Wor

ries a

bout

futu

re

Unstable diabetes

Diet re

strict

ions

Day-to

-day

hass

lesCon

cern

s

abou

t

hypo

glyce

mia

Sco

re

Poor glycemic control Other indications

Franciose, M. et al.: ADA 2008

be

tte

rQuality of life and treatment satisfaction with CSII


Findings of multivariate linear regression analyses:Comparison between groups*

QoL aspects A v. B (p value)

B v. C (p value)

QoL aspects A v. B (p value)

B v. C (p value)

DSQOLS: social relationships

- 5.1 (0.028)

- 11.1 (<0.0001)

SF-36: physical well-being

--- - 9.2 (0.0027)

DSQOLS: leisure time flexibility

- 7.7 (0.004)

- 10.5 (<0.0001

SF-36: emotional well-being

--- - 14.4 (0.0008)

DSQOLS: physical complaints

- 5.39 (0.016)

- 8.8 (0.0002)

SF-36: energy-vitality

--- - 4.3 (0.018)

DSQOLS: worries about future

- 7.1 (0.02)

- 8.6 (0.004)

SF-36: mental health

--- - 5.97 (0.0013)

DSQOLS: diet restrictions .

--- - 7.0 (0.006)

SF-36:bodily pain - 8.9 (0.0033)

- 7.25 (0.012)

DSQOLS: concerns about hypoglycemia

--- - 7.3 (0.008)

SF-36: social functioning

- 5.7 (0.06)

- 10.9 (0.0002)

SF-36: physical functioning

--- - 2.8 (0.03)

SF-36: mental com-ponent summary

--- - 5.9 (0.0002)

*Group A: poor glycemic control; group B: unstable diabetes; group C: other indications.



Conclusions:

Patients with unstable diabetes, and to a lesser extent those with poor metabolic control, report a particularly poor QoL. They require patient-tailored education and psychological support.


87UC201001158EE

Approach:

A plausible mechanism to induce long-term remission of patients newly diagnosed with type 2 diabetes after short-term CSII is that the normalization of plasma glucose leads to relief of glucose toxicity and improved pancreatic insulin secretion.

Aim of study:

Determine the impact of short-term CSII on insulin sensitivity and first phase of insulin secretion in newly diagnosed patients with type 2 diabetes.

Yang, Z. et al.: Impact of short-term continuous subcutaneous insulin infusion therapy on insulin sensitivity and insulin secretion in newly diagnosed type 2 diabetes patients. 68th ADA Scientific Session 2008, San Francisco, 0349-OR, Diabetes 2008; 57 (Suppl. 1), A86-A87


Tony Parr:

This paragraph does not make sense in English. Can we take a look at it together?

Tony Parr:

This paragraph does not make sense in English. Can we take a look at it together?

88UC201001158EEYang, Z. et al.: ADA 2008

Method: • Prospective investigation with healthy persons and new

diagnosed patients with type 2 diabetes • Realization of hyperinsulinemia euglycemia clamp test

(determination insulin sensitivity, time: 150 min, insulin infusion rate: 1 mU/ kg BW/min, goal: 5 mmol/l) and intravenous glucose tolerance test (determination insulin secretion) before using CSII and follow-up



Study group:

Group Type 2 diabetes (n = 10)

Control (n = 9)

Gender 3 f / 7 m 5 f / 4 mAge (years) 42.7 + 11.3 35.3 + 5.3FBG (mmol/l) 13.5 + 2.9 4.7 + 0.5BMI (kg /m2) 28.8 + 5.6 22.8 + 2.6



Findings in patients with diabetes:

Plasma glucose in IVGTT before and after CSII

Time (min.)

0 1 2 3 5 10

35

30

25

20

15

10

5

0

Glu

cose

(m

mo

l/l)

Time (min.)

0 1 2 3 5 10

35

30

25

20

15

10

5

0

Glu

cose

(m

mo

l/l)

Before CSII After CSII



Findings in patients with diabetes:

Plasma insulin level in IVGTT before and after CSII

Time (min.)

0 1 2 3 5 10

35

30

25

20

15

10

5

0In

suli

n (

mU

/l)

Time (min.)

0 1 2 3 5 10

35

30

25

20

15

10

5

0

Insu

lin

(m

U/l

)




Findings:

Change in AIR

7.63 + 4.73

0.83 + 1.96

0

2

4

6

8

10

12

AIR

(mU

/min

)

AIR: Acute Insulin Response


GIR: Glucose Infusion Rate

5.33 + 1.43

8.26 + 2.48

2.30 + 0.81

0

2

4

6

8

10

12

GIR

(mg

/kg

//min

)

Before CSII After CSII Control

Change in GIR



Conclusions:

The normalization of blood glucose levels by transient intensive CSII therapy can improve pancreas ß cell function and insulin sensitivity, both of which may contribute to long-term diabetic remission.


94UC201001158EE

Aim of study:

Examine outcomes and cost of continuous subcutaneous insulin infusion (CSII) therapy in pediatric patients with type 1 diabetes.


Feltbower, R. et al.: Using insulin pump therapy in the management of insulin-dependent diabetes in childhood: the Leeds, UK, Experience, 34th Annual Meeting ISPAD 2008, Durban, WED34, Pediatric Diabetes 2008, 9 (Suppl. 10), 33

95UC201001158EE

Method and study group: • Examination of data in a pediatric diabetic center (Leeds,

UK): situation 12 months before treatment compared with situation 12 months after start of CSII treatment (2002-2007):

- glycemic parameter (HbA1c)

- frequency of hypoglycemias- frequency of hospitalizations - accumulated cost of treatment

• 83 patients (54% female) with type 1 diabetes • Age 0-18 years • average age: 12 (range 0.3–17.0 years)

Feltbower, R. et al.: ISPAD 2008


96UC201001158EEFeltbower, R. et al.: ISPAD 2008

Findings:

Change in HbA1c

8,9+1,5

9,4+1,7

6

7

8

9

10

Hb

A1c

(%

)

Baseline 12 months before CSII after start

of CSII

Age-specific proportion of patients with better HbA1c


88

36

77

0

20

40

60

80

100

120

An

teil

Pat

ien

ten

(%

)

<12 years 12-15 years >16 years

Pro

po

tio

n o

f p

atie

nts

(%

)


Findings:

HospitalizationCost reduction during

CSII treatment


7,59

8,80

7,30

2,40

0

2

4

6

8

10

Ho

spit

alis

ieru

ng

srat

e/10

0 P

J

MDI CSII MDI CSII

Severe Severe hypoglycemia hyperglycemia

Fre

quen

cy o

f ho

spita

liza

tion/

100

PY

-9106

-639

-10000

-8000

-6000

-4000

-2000

0

Ko

sten

sen

kun

g (

bri

t. P

fun

d/1

00P

J)

Severe Severe hypoglyc. hyperglyc.

Dec

reas

e in

cos

t (G

BP

/100

PY

)


Conclusions:

Compared with MDI, CSII not only resulted in an improved HbA1c value, but also lowered the cost of treatment. The main reason is a lower frequency of hospitalization due to complications (especially hypoglycemias). The study showed that CSII is a cost-effective treatment option for pediatric patients.


99UC201001158EE

Aim of study:

Calculate long-term cost and outcomes of CSII compared with MDI in adult patients with type 1 diabetes, using clinical and cost data published in the USA.


Meaghan, S.C. et al.: A cost-effectiveness analysis of continuous subcutaneous insulin injection v. multiple daily injections in type 1 diabetes patients: a third party USA payer perspective. 68th ADA Scientific Session 2008, San Francisco, 1182-P, Diabetes 2008; 57 (Suppl. 1), A337

100UC201001158EE

Method: • Clinical and cost data published in the USA • Calculate the incremental cost-effectiveness ratio (ICER*) of CSII as compared with

MDI among adult and adolescent patients by using a valid health economic model (CORE model)

• Simulate the progression of diabetes-related complications by using the Markov model

• Characteristics of study group:

Meaghan, S.C. et al.: ADA 2008

Adults Adolescents

MDI CSII MDI CSII

Age (years) 27 27 13 13

Gender (% female) 53.5 53.5 50 50

Diabetes duration (years) 9.0 9.0 5.6 5.6

HbA1c (%) 8.95 8.95 8.2 8.2

BMI (kg/m2) 23.75 23.75 23.75 23.75

*ICER = costsCSII-costsMDI

profitCSII-profitMDI


101UC201001158EE

Underlying assumptions (based on study data):

• Change in HbA1c value with CSII as compared with MDI:

- 0.9% in adolescents1 and - 1.2% in adults2

• Reduction in severe hypoglycemias: 50% with CSII as compared with MDI3

• Average cost per annum of treatment options (assuming a seven-year pump life in the case of CSII):

• Prospective time horizon: 60 years, with costs and clinical outcomes discounted at a rate of 3.0% per annum


Adults Adolescents

MDI USD 3,776.33 USD 3,501.35

CSII USD 5,358.42 USD 5,167.46

1 Doyle et al., Diabetes Care 20042 Weissberg-Benchell et al., Diabetes Care 20033 Bruttomesso et al., Diabetic Med 2002


102UC201001158EE

Findings: • CSII treatment is associated with an improvement in quality-adjusted

life years (QALYs) gained, viz. of 1.061 v. MDI for adults and 0.799 v. MDI for adolescents

• ICER of CSII v. MDI: - USD 16,992/QALY* in adults- USD 27,195/QALY in adolescents

• Factors possibly affecting values:


*Quality-adjusted life year

- change in HbA1c value

- reduced frequency of hypoglycemias- economic life of insulin pump (e.g. four years)


103UC201001158EE

Findings:

Improved glycemic control resulting from CSII treatment led to a lower incidence of complications:


- cumulative incidence of proliferative diabetic retinopathy (- 29%, NNT: 9)

- peripheral vascular disease (- 16%, NNT: 41)- end-stage renal disease (- 20%, NNT: 19)- mortality caused by nephropathy (- 22%, NNT: 21)

NNT – number needed to treat


104UC201001158EE

Conclusions:

If the willingness to pay is set at USD 50,000/QALY, the study showed that CSII is a cost-effective treatment option compared with MDI for both adult and adolescent patients with type 1 diabetes in the USA.



105UC201001158EE

Aim of study: Investigate whether continuous intraperitoneal insulin infusion (CIPII) delivered with an implantable pump is safe and provides equal or superior glycemic control with fewer episodes of hypoglycemia as compared with intensive subcutaneous insulin therapy (SC), multiple dose injections (MDI) and continuous subcutaneous insulin infusion (CSII)) in poorly controlled type 1 diabetes patients.


Lotgenberg, S.J. et al.: Marked improvement in glycaemic control, and more time in euglycaemia without increase in hypoglycaemia with CIPII compared to CSII in type 1 diabetes. 44th Annual Meeting of EASD 2008, Rome, 0182, Diabetologia 2008; 51 (Suppl. 1), S81-S82

106UC201001158EE

Method: Continuous intraperitoneal insulin infusion (CIPII) using MIP 2007 C implantable pump (Medtronic)

- Surgery required for implantation- Transdermal insulin refills (concentration:

U400)- No. of worldwide implantations:

approximately 1,000 (including re-explants)


107UC201001158EE

Method: • Open-label, randomized, controlled, cross-over trial during 16-month

period: three-month run-in for optimization of insulin therapy Randomization of patients:- six months on either CSII or CIPII - wash-out phase between both options (max. 4 weeks)

• Inclusion criteria: HbA1c >7.5% and/or >5 hypoglycemic events per week

• Outcomes: - HbA1c, value after 3 and 6 months in both phases

- time spent in euglycemia range (4.0–10.0 mmol/l), as measured with CGM

- frequency of hypoglycemias

Lotgenberg, S.J. et al.: EASD


108UC201001158EE

Study group: • 24 patients with type 1 diabetes (13 f and 11 m)• Baseline therapy: 21 CSII, 3 MDI • Age: 43.6 + 11.8 years• Duration of diabetes: 22.6 + 10.6 years• Baseline HbA1c: 8.6 + 1.1 %

• Baseline for inclusion criteria:- 20 patients with HbA1c >7.5%

- 14 patients with > 5 hypoglycemic events per week



109UC201001158EE

Findings:

HbA1c (%) at different points for both groups


start IP, following CSII

start CSII, following IP


110UC201001158EE

Findings:

HbA1c values with both therapeutic options

8,5 8,5

8,1

7,47,6

8,58,4

6

7

8

9

10

Hb

A1

c (

%)

Baseline month 0 month 3 month 6 month 0 month 3 month 6

CIPIICSII



111UC201001158EE

Findings:

Time spent in euglycemia (4.0–10.0 mmol/l)

41

5953

48

41

0

20

40

60

80

Sh

are

of

tim

e p

er

da

y (

%)

Baseline month 3 month 6 month 3 month 6

CIPIICSII



112UC201001158EE

Findings:

Frequency of hypoglycemic events



2,70

3,94

2,07

3,11

0

1

2

3

4

5

Hyp

og

l. /W

och

e

CSII CIPII CSII CIPII

<4.0 mmo/l <3.5 mmol/l

Hyp

og

lyce

mic

eve

nts

(p

er w

eek)

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Conclusion:

CIPII improved glycemic control without increasing the incidence of hypoglycemic events (trend toward decrease) or increasing the amount of time spent in euglycemia. CIPII will therefore be of value for selected subjects with type 1 diabetes who do not attain acceptable levels of glycemic control on MDI or CSII.



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Aim of study:

Investigate acceptance, safety and effectiveness of a comprehensive diabetes treatment algorithm based on recommendations using glucose values, trends and alerts from real-time continuous glucose monitoring.


Deiss, D. et al.: Evaluation of a standardized algorithm for diabetes management decisions based on real-time continuous glucose monitoring in pediatric patients with CSII. Abstract 21, 1st ATTD Meeting, Prague 2008 and: Standardized treatment algorithm for diabetes management decisions based on real-time continuous glucose monitoring, 68th ADA Scientific Session 2008, San Francisco, 2006-PO, Diabetes 2008; 57 (Suppl. 1), A554

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Method and study group:• Algorithm used for four-week period• Algorithm contains following types of behavior:

hypoglycemia (daytime, bedtime and overnight), hyperglycemia and correction rules, postprandial hyperglycemia, exercise

• 20 patients with type 1 diabetes (10 female and 10 male)• Age: 11.3 (range: 2.3-17.1 years ) • Therapy: CSII with Paradigm®REAL-Time system


Deiss, D. et al.: Abstract 21, 1st ATTD Meeting, Prague 2008

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Findings: Application rate of guideline rules according to baseline HbA1c

Hypoglycemiaevents

p < .001

p = 0.034n. s.

HbA1c <7.5%

HbA1c ≥7.5%

Gu

idel

ine

rule

ap

plie

d (

%)

100

80

60

40

20

0

64%

37%

89%

78%

94%92%

Hyperglycemiatrend events

Normoglycemiatrend events



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Findings: Effect of RT algorithm on blood glucose

Event category Rules applied/ not appl.

(number)

Success rate

(percent)

Hypo event 116 115 68.5* 62.5

Hypo trend 45 58 79.1* 66.7

Hypo sport 17 23 64.7* 60.9

Hyper trend 159 28 52.6 46.2

Normo trend 53 4 81.1 50.0

Total 390 228 64.8 61.3

*Success rate more pronounced in patients with HbA1c <7.5%



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Findings: Change in HbA1c during study (using algorithm) and at follow-up (without algorithm)

N = 20

Follow-up

Studyend

Studybegin

HbA

1c (

%)

11.0

10.0

9.0

8.0

7.0

6.0

5.020 19

p =.024 p <.001

Study begin 7.6%

End of study 7.3%

Follow-up 7.9%at 3 months

MeanHbA1c



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Findings: End-of-study questionnaire ratings on guideline use and efficacy



54321

For bolus

After alarm

At arrow-up

At arrow-down

During sport

Never used

54321

Frequently Ineffective Effective

Guidelines used Efficacy

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Conclusions:

The RT guidelines are a safe and effective tool that patients can use to process new information on glucose trends obtained from RT-CGM. Using the guidelines may increase glycemic stability.


UC201001158EE 1 CSII-related studies presented during diabetes conferences in 2008 Compiled by Dr Andreas Thomas, Germany DDG Munich ADA San Francisco.

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