Utilizing Insulin Pump Therapy in Challenging Populations

Bruce W. Bode, MD, FACE

Atlanta Diabetes Associates

Atlanta, Georgia

ACE / AACE Targets for Glycemic Control

A1C (HbA1c ) < 6.5 %

Fasting/preprandial glucose < 110 mg/dL

Postprandial glucose < 140 mg/dL

ACE / AACE Consensus Conference, Washington DC August 2001

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6 7 8 9 10 11 12

Retinop

Neph

Neurop

Microalb

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LA

TIV

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RIS

K

HbA1cSkyler, Endo Met Cl N Am 1996

Relative Risk of Progression of Diabetic Complications by Mean A1CBased on DCCT Data

HbA1c and Plasma Glucose

26,056 data points (A1c and 7-point glucose profiles) from the DCCT

Mean plasma glucose = (A1c x 35.6) – 77.3

Post-lunch, pre-dinner, post-dinner, and bedtime correlated better with A1c than fasting, post-breakfast, or pre-lunch

Rohlfing et al, Diabetes Care 25 (2) Feb 2002

Insulin

The most powerful agent we have

to control glucose

Patient J.L., December 15, 1922 February 15, 1923

The Miracle of Insulin

4:00 16:00 20:00 24:00 4:00

Breakfast Lunch Dinner

8:0012:008:00

Time

Pla

sma

insu

lin

Ideal Basal/Bolus Insulin Absorption Pattern

Glargine

Plasma Glucose

Time (hours)

220

200

180

160

140

120

12

11

10

9

8

7

0 4 8 12 16 20 24

mg

/dL

mm

ol/L

Lepore M, et al. Diabetes. 2000;49:2142–2148.

n = 20 T1DMMean ± SEM

SC insulin

NPH

Ultralente

CSII

Lauritzen. Diabetologia. 1983;24:326–329.

Fast (n = 12)

Semilente (n = 9)

Intermediate (n = 36)

Fra

ctio

n a

t in

j. si

te

1.00

0.75

0.50

0.25

06 12 18 24 36 42 4830

Hours after single SC injectionsFemoral region

Variability of Insulin Absorption

CSII <2.8%

SubcutaneousInjectable10% to 52%

Pump TherapyBasal & Bolus Short-Acting Insulin

Pump TherapyBasal & Bolus Short-Acting Insulin

Pump TherapyBasal & Bolus Short-Acting Insulin

Combined with SMBG, physiologic insulin requirements can be achieved more closely

Flexibility in lifestyle

History of Pumps

PARADIGM PUMP

Paradigm. Simple. Easy.

Paradigm Pump: Advantages

29% smaller, water resistant

Menu driven:

bolus, suspend, basal, prime, utilities

Reservoir based (easier to fill)

Silent motor

AAA batteries

Paradigm Pump: Advantages

Various bolus options

normal, square, dual, and “easy bolus”

Enhanced memory

Enhanced safety features

(low reservoir alarm, auto off, etc.)

Pump Infusion Sets

Softset QR Silhouette

Lauritzen. Diabetologia. 1983;24:326–329.

Pharmacokinetic Advantages CSII vs MDI

Uses only regular or very rapid insulin

– More predictable absorption than modified insulins (variation 3% vs 25 to 52%)

Uses 1 injection site

– Reduces variations in absorption due to site rotation

Eliminates most of the subcutaneous insulin depot

Programmable delivery simulates normal pancreatic function

Metabolic Advantages with CSII

Improved glycemic control

Better pharmacokinetic delivery of insulin

– Less hypoglycemia

– Less insulin required

Improved quality of life

Case 1: DM 1 not at goal A1C

35 year old female physician presents with Type 1 Diabetes since age 7

Control suboptimal (A1C 8.7%) on MDI with Regular AC and NPH HS.

SMBG 5/day with CHO counting

Complications: mild retinopathy and neuropathy, and hypoglycemia induced migraines

Case 1: DM 1 not at goal A1C

Recommend CSII but refuses; Does not want to be attached to something

Ask her to record, monitor 6 to 7 times per day, fax readings, and try lispro

She complies with minimal change in A1C falling to 8.4% at 3 months and 7.7% at 6 months

Still refuses CSII

Recommend a sensor (CGMS)

Case 1: DM 1 not at goal A1C

CGMS confirms a dawn rise

Try giving NPH later but no help; Try lente and ultralente but no help; Glargine only available in Germany

Patient gets married and desires children

Attempt to get Glargine from Germany but my contacts say no one uses glargine in pregnancy. Put her on a pump

Case 1: DM 1 Agrees to CSII

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5.5

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6.5

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7.5

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8.5

Nov-00 Feb-01 May-01 Aug-01 Nov-01 Feb-02

A1C

Case 1: DM 1 Agrees to CSII

Patient loves the pump

No more migraines from hypoglycemia

Patient now 13 weeks pregnant with A1C at 5.7%

CSII Reduces HbA1c

5.05.56.06.57.07.58.08.5.099.5

10.0

n = 58 n = 107 n = 116 n = 50 n = 25 n = 56Mean dur. = 36

Adolescents Adults

Mean dur. = 36 Mean dur. = 54 Mean dur. = 42 Mean dur. = 12 Mean dur. = 12

Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327;Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Bell DSH, et al. Endocrine Practice. 2000;6:357–360;Chase HP, et al. Pediatrics. 2001;107:351–356.

Bell Rudolph Chanteleau Bode Boland Chase

Pre-pump Post-pump

Hb

A1

c

CSII Reduces Hypoglycemia

0

20

40

60

80

100

120

140

160

n = 55Mean age 42

n = 107Mean age 36

n = 116Mean age 29

n = 25Mean age 14

n = 56Mean age 17

Eve

nts

per

hu

nd

red

p

atie

nt

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s

Chantelau E, et al. Diabetologia. 1989;32:421–426; Bode BW, et al. Diabetes Care. 1996;19:324–327;Boland EA, et al. Diabetes Care. 1999;22:1779–1784; Chase HP, et al. Pediatrics. 2001;107:351–356.

Bode Rudolph Chanteleau Boland Chase

Pre-pump Post-pump

Monitoring

–HbA1c = 8.3 - (0.21 x BG per day)

Recording 7.4 vs 7.8

Diet practiced–CHO: 7.2–Fixed: 7.5–Other: 8.0

CSIIFactors Affecting HbA1c

Bode et al, Diabetes 1997;46:143

Case 2: New Onset Diabetes

45 year old male lawyer presents with polys and weight loss

Sees internist who recommends metformin (blood glucose 500, urine ketones small, BMI 26)

The lawyer does some internet reading and seeks a second opinion from diabetes specialist who was a high school classmate he has not seen for 27 years

Case 2: New Onset Diabetes

Sees myself the following am (BG 514, urine ketones small)

I concur with him he has Type 1 Diabetes and metformin is not the treatment, insulin is.

He asks about insulin pump therapy instead of multiple injections.

I hospitalized him and told him I would get back to him the following am.

Case 2: New Onset Diabetes

I see him in the am and tell him that 8 out of 10 CSII patients polled yesterday would have started CSII at onset if offered the choice.

Dr. Pozzilli, an expert in DM 1 prevention, also recommended CSII at onset if it was him or a close relative

Patient opted for CSII

Case 2: New Onset Diabetes on CSII: A1C Results

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Nov-99

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Jul-0

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Sep-0

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May

-01

Jul-0

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Sep-0

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Nov-01

A1C

Case 2: New Onset Diabetes on CSII

Patient extremely satisfied with his care

C-peptide 0.9 to 0.8 at 1 year

Does not understand why everyone is not on CSII with optimal control

Case 3: DM 2 Poorly Controlled

58 year old female presented with a 12 year history of poorly controlled, insulin treated diabetes

Ht 66’’, Wt 174#, BMI 28, C-peptide 2.1

A1C 10.4% on 165 units per day (70/30 BID)

Added troglitazone, metformin, glimepiride to MDI insulin

A1C range 7.7 to 12.6% over 3 years

Case 3: DM 2 Poorly Controlled

Admitted twice for IV insulin and fasting with short lived success (A1C to 7.6% but back up to 12.6%)

Tried weight watchers and appetite suppressants; no help

Decided to try CSII

Case 3: DM 2 on CSII, A1C Results

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A1C

Case 3: DM 2 Poorly Controlled

Patient loves the pump

On 110 units per day consuming 2 meals only per day (1.4 units per kg or 0.6 units per lbs)

Also on rosiglitazone 4 mg/day

7.197.57

9.2

5.00

6.00

7.00

8.00

9.00

10.00

Baseline 6 months 18 months

P = 0.026 P = 0.040

N = 11

CSII Usage in Type 2 PatientsAtlanta Diabetes Experience

Mean HbA1c (%)

Davidson et al, Diabetologia 1999; 42: 796

Glycemic Control in Type 2 DM: CSII vs MDI in 127 patients

A1C

7.0

7.2

7.4

7.6

7.8

8.0

8.2

8.4

CSII MDI

Baseline

End of Study (24 wks)

Raskin, Diabetes 2001; 50(S2):A106

DM 2 Study: CSII vs MDI

Overall treatment satisfaction improved in the CSII group: 59% pre to 79% at 24 weeks

93% in the CSII group preferred the pump to their prior regiment (insulin +/- OHA)

CSII group had less hyperglycemic episodes (3 subjects, 6 episodes vs. 11 subjects, 26 episodes in the MDI group) p<0.01

Normalization of Lifestyle

Liberalization of diet — timing & amount

Increased control with exercise

Able to work shifts & through lunch

Less hassle with travel — time zones

Weight control

Less anxiety in trying to keep on schedule

N = 165Average Duration = 3.6 yearsAverage Discontinuation <1%/yr

Continued 97%

Discontinued 3%

Current Continuation RateContinuous Subcutaneous Insulin Infusion (CSII)

Bode BW, et al. Diabetes. 1998;47(suppl 1):392.

6,600 8,700 11,40015,000

20,00026,500

35,00043,000

60,000

81,000

120,000

162,000

0

50,000

100,000

150,000

'90 '91 '92 '93 '94 '95 '96 '97 '98 '99 2000 2001

U.S. Pump UsageTotal Patients Using Insulin Pumps

Pump Therapy Indications

HbA1c >6.5%

Frequent hypoglycemia

Dawn phenomenon

Exercise

Pediatrics

Pregnancy

Gastroparesis

Hectic lifestyle

Shift work

Type 2

Marcus. Postgrad Med. 1995.

Current Candidate Selection

Patient Requirements

–Willing to monitor and record BG

–Motivated to take insulin

–Willing to quantify food intake

–Willing to follow-up

Meal bolus

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12 am 12 pm 12 am

Time of day

Basal rate

Pump Therapy

Units

Meal boluses Insulin needed pre-meal

– Pre-meal BG– Carbohydrates in meal– Activity level

Correction bolus for high BG

Basal rate Continuous flow of

insulin Takes the place of NPH

or glargine insulin

If A1C Not to Goal

SMBG frequency and recording

Diet practiced

– Do they know what they are eating?

– Do they bolus for all food and snacks?

Infusion site areas– Are they in areas of

lipohypertrophy?

Other factors:– Fear of low BG– Overtreatment of low BG

Must look at:

If A1C Not to Goal and No Reason Identified

Place on a continuous glucose monitoring system (CGMS) to determine the cause

Summary

Insulin pump therapy offers improvement in glycemic control with less major hypoglycemia and greater flexibility in lifestyle

Insulin pump therapy should be considered in all DM 1 patients and DM 2 patients failing conventional insulin therapy (basal insulin)

QUESTIONS

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