Transcript Review of Continuous Subcutaneous Insulin Infusion

Review of Continuous Subcutaneous
Insulin Infusion (Insulin pump)
Therapy
Endocrine Morning Rounds
October 8, 2008
Arthur Chung PGY-3
Introduction
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Insulin pumps: how it works
Insulin pumps in Diabetes Mellitus, type 1
advantages
 disadvantages
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Insulin pumps in Diabetes Mellitus, type 2
Insulin pumps in pregnancy
Insulin pumps in perioperative care
What is insulin pump therapy?
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The device includes:
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The pump itself (including controls, processing module, and
batteries)
A disposable reservoir for insulin (inside the pump)
A disposable infusion set, including a cannula for
subcutaneous insertion (under the skin) and a tubing system
to interface the insulin reservoir to the cannula.
With pump therapy, basal insulin is supplied in the
form of a continuous infusion (comprising between 40
and 60 percent of the total daily dose) with pre-meal
bolus doses given to minimize postprandial glucose
excursions.
Good candidates:
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Patients must monitor their blood glucose at least 4 times daily
learn to carbohydrate count
have a “rescue algorithm” (eg, a correction factor)
be sufficiently motivated
have an appropriate support system
possess problem-solving skills.
Choice of insulin:
 Only short-acting insulin (regular), or rapid-acting insulins are used.
 A double-blind crossover trial, insulin lispro, compared to regular insulin,
resulted in greater reduction in postprandial blood glucose concentrations (by
25 mg/dL [1.4 mmol/L]), lower A1C (by 0.3 percent), fewer episodes of
hypoglycemia, and less weight gain (Diabetes 1997 Mar;46(3):440-3). Similar results have
been seen with insulin aspart (Diabetes Care 2002 Mar;25(3):439-44).
Getting started:
 Convert a patient from an MDI regimen to insulin pump therapy based on
pre-pump level of chronic glycemia and total daily dose of insulin.
 Eg. If previously well controlled with A1C <7.0 percent, the initial total daily
dose of insulin administered by pump may be 10 to 20 percent less than the
total daily dose of the previous regimen.
 Approximately ½ of total daily dose = basal rate.
 Eg. basal rates are in the range of 0.01 to 0.015 units per kg per hour (ie, for a
60 kg woman approximately 0.6 to 0.9 units per hour). The basal rates are
adjusted empirically based on glucose monitoring results.
 Infusion rates depending on individual factors including life-style and the
"dawn phenomenon" which often occurs between 2 AM and 8 AM.
 Most pumps allow for pre-programmed changes in basal rate to
accommodate these requirements.
Insulin pump therapy in DM 1
What are the advantages of insulin pump therapy?
1) Improved glycemic control and less hypoglycemic events
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Numerous trials have been done comparing glycemic control and
hypoglycemia with CSII vs. MDI.
Using an insulin pump eliminates unpredictable effects of
intermediate- or long-acting insulin.
Insulin absorption is less variable from day to day. Both the small
subcutaneous depot, and the constancy of the injection site and
depth for the two to three days with each catheter, contribute to
the relative consistency of absorption.
Jeitler et al. 2008. Comparing CSII vs. MDI in DMI and DMII.
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Methods: A meta-analysis of RCTs up to March 2007.
22 trials: 17 on type 1 diabetes mellitus (908 patients), two on type 2 diabetes
mellitus (234 patients), three on children (74 patients).
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Adult DM I: 12 studies were used for the meta-analysis.
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In 6 studies using HbA1c  −0.4% WMD in favour of CSII therapy over
MDI.
In 6 studies using HbA1  - 0.6% WMD (not statistically significant)
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No meta-analysis was performed on hypoglycemic events.
Mild or overall hypoglycemic events were comparable between the two
groups:
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CSII group: 1.9 [0.9–3.1] events per patient per week
MDI group: 1.7 [1.1–3.3] events per patient per week
No overall conclusions were possible for severe hypoglycaemia and adverse
events for any of the different patient groups due to rareness of such events,
different definitions and insufficient reporting.
Jeitler et al. Diabetologia (2008) 51:941–951.
Pickup and Sutton 2008 meta-analysis of CSII vs. MDI in DMI
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Reviewed the frequency of severe hypoglycemia in CSII vs. MDI
Studied more recent trials because of poor quality of earlier trials
Analyzed the idea that CSII may be more beneficial in DMI patients who fail
to achieve glycemic control on MDI.
Method:
 Databases and literature (1996–2006) were searched for randomized
controlled trials (RCTs) and before/after studies of ≥ 6 months duration
CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient
years on MDI.
Results:
22 studies (21 reports). 1414 DMI patients for mean CSII duration of 6 – 28
months.
 Severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038)
and was greater in adults than children (100 vs. 36 events/100 patient years, P
= 0.036).
Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89
(95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19
(2.86 to 6.13) for all studies].
The mean difference in glycated haemoglobin (HbA1c) between treatments was less for RCTs
[0.21% (0.13–0.30%)] than in before/after studies [0.72% (0.55–0.90%)] but strongly related to
the initial HbA1c on MDI (P < 0.001).
The worse controlled subject on MDI injections enjoyed the most improvement on the insulin
pump therapy.
Pickup et al. 2002 meta-analysis of CSII and MDI in DMI
Method: Metaanalysis of 12 randomised controlled trials (1975 -2000). 301
people with DMI allocated to insulin infusion and 299 allocated to
insulin injections for between 2.5 and 24 months.
Results: Glycated haemoglobin was also lower in people receiving insulin
infusion (0.44, 0.20 to 0.69), equivalent to a difference of 0.51%.
BMJ 2002 Mar
23;324(7339):705
Blood glucose variability is less in CSII compared to MDI
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Bruttomeso et al. 2007.
Method: Randomized cross-over study. Compared CSII and MDI in patients
with DM I.
39 DM I patients with previously well controlled diabetes on CSII for at least
6 months were randomly assigned to continue CSII with lispro or switch to
MDI with lispro and glargine.
After 4 months they were switched to the alternative treatment.
Primary end-points:
Blood glucose variability was analysed using various measurements: glucose
standard deviation, mean amplitude of glycaemic excursions (MAGE), lability
index and average daily risk range (ADRR).
Secondary end-points: blood glucose profile, HbA1c, number of episodes of
hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth
hormone and treatment satisfaction.
Results:
 Overall, CSII glucose variability was 5–12% lower than during MDI with
glargine.
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The difference was significant only before breakfast considering glucose
standard deviation (P = 0.011), significant overall using MAGE (P = 0.016)
and lability index (P = 0.005) and not significant using ADRR.
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Although HbA1c was similar during both treatments, during CSII blood
glucose levels were significantly lower, hyperglycaemic episodes were fewer,
daily insulin dose was less,
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FFA were lower and treatment satisfaction was greater than during MDI with
glargine. The frequency of hypoglycaemic episodes was similar during both
treatments.
Diabet. Med. 25, 326–332 (2008).
Improved Quality of Life with CSII vs. MDI
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Flexibility in the timing of meals:
Ability to use bolus insulin (rapid-acting insulin)
whenever needed.
Ideal for patients who eat often or erratically or for
patients who want the flexibility to eat what and when
they want without compromising glycemic control.
Using an insulin pump means eliminating individual
insulin injections
Insulin pumps allow you to exercise without having to
eat large amounts of carbohydrate
Scheidegger et al. 2007. CSII: effects on quality of life.
Methods:
 Diabetes-specific quality of life was measured with the DSQOLSQuestionnaire in 81 adult subjects with DM I on MDI and 78 subjects on
CSII (cross-sectional study).
 19 subjects were followed prospectively, measuring their quality of life before
and after switching from MDI to CSII (longitudinal study).
Results:
 Patients on CSII were more satisfied with their treatment in respect to:
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their metabolic goals, psychosocial factors, physical performance, protection from
long-term complications and hypoglycaemia.
Furthermore, the subjects on CSII experience greater flexibility in their daily
routines, leisure time and diet than the subjects on MDI.
Overall quality of life (+29 points, 95%CI 3 to 54) were significantly better in
CSII compared to MDI only in the longitudinal study.
Swiss Med Wkly 2007;137:476–482.
Hoogma et al. Comparison of CSII and MDI on quality of life
Methods:
 The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11
European centres.
 272 patients were treated with CSII  MDI or MDI  CSII x 6 months.
 3 questionnaires: DQofL, SF-12 health survey questionnaire, Lifestyle and
manageability of disease
Results:
 The overall DQoL score was significantly higher for CSII at the end of treatment
compared with MDI (75 vs. 71, P < 0.001), indicating a positive impact on QoL.
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Improvements in treatment satisfaction (P < 0.001), treatment impact (P < 0.001) and
a significant reduction in diabetes related worry (P < 0.01) when using CSII compared
with MDI.
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SF-12 questionnaire: improvements in perception of mental health when using CSII
compared with MDI (P < 0.05).
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Lifestyle and manageability questionnaire: more flexibility with regard to eating habits
(P < 0.001) and lifestyle flexibility and sleep patterns (P < 0.001) when using CSII
compared with MDI.
Insulin Pump Therapy in DM2
1) Glycemic control in DM 2 with insulin pump therapy
Herman et al. CSII vs MDI in older adults (> 60 years) with DMII
and marked obesity:
Method: 2-center, 12-month, prospective, randomized, controlled
clinical trial compared the efficacy and safety of CSII with that
of MDI
In this population, patients treated with both CSII and MDI
achieved excellent glycemic control with good safety and patient
satisfaction.
CSII group: HbA1c 6.6% (Mean A1c fell by 1.7 ± 1.0%)
MDI group: HbA1c 6.4% (Mean A1c fell by 1.6 ± 1.2%)
Diabetes Care. 2005;28:1568-1573.
There was no statistically significant difference in hypoglycemic events or severe
hypoglycemic events between treatment groups; however, there was a trend
for less hypoglycemic events with CSII.
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CSII group: minor (self-treated) hypoglycemia 81%.
MDI group: minor (self-treated) hypoglycemia 90%. (P = 0.17)
CSII group: severe hypoglycemia 3 / 48
MDI group: severe hypoglycemia 6 / 50. (P = 0.49)
It is not clear if this study of elderly patients can be extrapolated to most patients
with type 2 diabetes. Moreover, it suggests that MDI should be attempted in
elderly patients with marked obesity before considering insulin pump therapy.
Jeiter et al. meta-analysis of 2 randomized control trials:
 In patients with type 2 diabetes mellitus, CSII and MDI treatment showed no
statistically significant difference for HbA1c.
Cross-over trial of CSII and MDI:
 Method: 40 obese, insulin-treated patients with type 2 diabetes were
randomized to treatment with CSII or MDI therapy.
 At the end of the first 18-week treat treatment period, patients underwent a
12-week washout period during which they were treated with MDI plus
metformin.
 They were then crossed over to the alternate treatment for an 18-week
follow-up period.
 Results of the intention-to-treat analysis showed that CSII was superior to
MDI in reducing A1C values. There was no significant change in weight or
insulin dosage.
Diabet Med. 2005;22:1037-1046.
Quality of Life improved with CSII compared to MDI in DM2
Method: 132 CSII naive patients with type 2 diabetes were randomly assigned (1:1) to CSII
(insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin).
 Multicenter, open-label, randomized, parallel-group, 24-week study.
 A total of 93% of CSII-treated patients preferred the pump to their previous
injectable insulin regimen for reasons of convenience, flexibility, ease of use, and
overall preference.
Diabetes Care.
2003;26:2598-2603.
What are the disadvantages of insulin pumps?
1) Expensive cost of insulin pump therapy:
 The costs of the pump and supplies are higher than those of
ordinary syringes and needles.
 Cost of pump: $3000 - 5000. Insulin infusion lines, syringes,
tapes, batteries can add extra $40 – 50 / month.
2) Complications:
 Moreover, approximately 40 percent of patients in one large
study had one or more acute complications (such as infection at
the site of needle insertion) during 3000 patient-months of
treatment. (JAMA 1984 Dec 21;252(23):3265-9.)
 A second study found that 86 percent of patients had at least
one infusion-system failure in a 12-month period. (Diabetes Care 1986 JulAug;9(4):351-5.)
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Blockage or leakage in the syringe or the infusion set or
connectors, causing an interruption of infusion flow. These
issues now occur less commonly with more modern pumps and
supplies.
Any interruption in continuous flow can lead very quickly to
hypoinsulinemia, hyperglycemia, and possibly diabetic
ketoacidosis.
3) Bothersome to wear an insulin pump:
 Patients may feel "tethered" to the pump at all times.
 Complaints that the treatment is awkward, uncomfortable,
embarrassing, or unpleasant, particularly when bathing or having
sexual intercourse.
Can insulin pump therapy be used in
pregnancy?
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A 2008 Cochrane review to compare CSII with MDI of insulin
for pregnant women with diabetes.
Search strategy: Articles were searched from the Cochrane
Pregnancy and Childbirth Group’s Trials Register (November
2006).
Selection criteria: Randomised controlled trials comparing CSII
with MDI for pregnant women with diabetes.
Primary outcome: 1) perinatal mortality 2) fetal anomaly 3)
hypoglycemia/hyperglycemic episodes requiring intervention 4)
admission and length of stay
Secondary outcomes: multiple additional outcomes for the
mother and baby
Results:
 Two studies (60 women with 61 pregnancies) were included.
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There was a significant increase in mean birthweight associated with
CSII as opposed to MDI (WMD 220.56, 95% confidence interval (CI)
-2.09 to 443.20; two trials, 61 participants).
BUT lack of significant difference in rate of macrosomia (birthweight
greater than 4000 g) (relative risk (RR) 3.20, 95% CI 0.14 to 72.62; two
trials, 61 participants).
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No significant differences were found in any other outcomes
measured, which may reflect the small number of trials suitable for
metaanalysis and the small number of participants in the included
studies.
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No significant differences were found in:
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perinatal mortality (RR 2.00, 95% CI 0.20 to 19.91)
fetal anomaly (RR 1.07, 95% CI 0.07 to 15.54)
maternal hypoglycaemia (RR 3.00, 95% CI 0.35 to 25.87)
maternal hyperglycaemia (RR 7.00, 95% CI 0.39 to 125.44).
Cochrane Conclusion
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There is a dearth of robust evidence to support the use of one
particular form of insulin administration over another for
pregnant women with diabetes.
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The data are limited because of the small number of trials
appropriate for meta-analysis, small study sample size and
questionable generalisability of the trial population.
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Conclusions cannot be made from the data available and
therefore a robust randomised trial is needed. The trial should be
adequately powered to assess the efficacy of continuous
subcutaneous insulin infusion versus multiple daily injections in
terms of appropriate outcomes for women with diabetes.
Can insulin be used perioperatively?
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Little evidence regarding CSII and perioperative management
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2 case studies. No randomized controlled trials available.
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First case study: DM I who wore his continuous subcutaneous insulin
infusion (CSII) pump during general anesthesia for surgical repair of a
herniated lumbar disk. Blood glucose levels were stable throughout the
perioperative period. Little or no extra work was required of the CRNA.
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Second case study: A 61-year-old male, while recovering from a Whipple's
procedure for pancreatic carcinoma, was treated for 13 days with an insulin
infusion pump for diabetes exacerbated by enteral hyperalimentation.
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Treatment with continuous subcutaneous insulin infusion resulted in
improved blood glucose control. Associated with this improvement was a
reduction in plasma cholesterol, triglyceride and free fatty acid levels. Plasma
epinephrine, norepinephrine, glucagon and cortisol concentrations were also
lowered although growth hormone levels remained unchanged.
Take Home Message
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Insulin pump therapy is an alternative to MDI in diabetic
patients
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In DM 1, insulin pump therapy compared to MDI may lead to
improvements in glycemic control with less frequent episodes of
hypoglycemia, less glucose variability, and improved quality of
life.
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There is less evidence available in DM 2, but current trials
suggest no additional benefit in glycemic control with CSII
compared to MDI. However, CSII may be associated with
improved quality of life.
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There is currently very little evidence for the benefit of insulin
pump therapy in pregnancy or perioperative management of
diabetes.
Thank you