Review of Continuous Review of Continuous Subcutaneous Insulin Subcutaneous Insulin

Infusion (Insulin pump) Infusion (Insulin pump) TherapyTherapy

Endocrine Morning RoundsEndocrine Morning Rounds

October 8, 2008October 8, 2008

Arthur Chung PGY-3Arthur Chung PGY-3

IntroductionIntroduction

Insulin pumps: how it worksInsulin pumps: how it works Insulin pumps in Diabetes Mellitus, Insulin pumps in Diabetes Mellitus,

type 1type 1 advantagesadvantages disadvantagesdisadvantages

Insulin pumps in Diabetes Mellitus, Insulin pumps in Diabetes Mellitus, type 2type 2

Insulin pumps in pregnancyInsulin pumps in pregnancy Insulin pumps in perioperative careInsulin pumps in perioperative care

What is insulin pump What is insulin pump therapy?therapy?

The device includes:The device includes: 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 With pump therapy, basal insulin is supplied in the form of a continuous infusion in the form of a continuous infusion (comprising between 40 and 60 percent of the (comprising between 40 and 60 percent of the total daily dose) with pre-meal bolus doses total daily dose) with pre-meal bolus doses given to minimize postprandial glucose given to minimize postprandial glucose excursions. excursions.

Good candidates: Good candidates: Patients must monitor their blood glucose at least 4 times dailyPatients must monitor their blood glucose at least 4 times daily learn to carbohydrate countlearn to carbohydrate count have a “rescue algorithm” (eg, a correction factor)have a “rescue algorithm” (eg, a correction factor) be sufficiently motivatedbe sufficiently motivated have an appropriate support systemhave an appropriate support system possess problem-solving skills. possess problem-solving skills.

Choice of insulin: Choice of insulin:  Only short-acting insulin (regular), or rapid-acting insulins Only short-acting insulin (regular), or rapid-acting insulins

are used. are used. A double-blind crossover trial, insulin lispro, compared to A double-blind crossover trial, insulin lispro, compared to

regular insulin, resulted in greater reduction in postprandial regular insulin, resulted in greater reduction in postprandial blood glucose concentrations (by 25 mg/dL [1.4 mmol/L]), blood glucose concentrations (by 25 mg/dL [1.4 mmol/L]), lower A1C (by 0.3 percent), fewer episodes of hypoglycemia, lower A1C (by 0.3 percent), fewer episodes of hypoglycemia, and less weight gain and less weight gain ((Diabetes 1997 Mar;46(3):440-3)Diabetes 1997 Mar;46(3):440-3). Similar results . Similar results have been seen with insulin aspart have been seen with insulin aspart (Diabetes Care 2002 Mar;25(3):439-44)(Diabetes Care 2002 Mar;25(3):439-44)..

Getting started: Getting started:  Convert a patient from an MDI regimen to insulin pump Convert a patient from an MDI regimen to insulin pump

therapy based on pre-pump level of chronic glycemia and therapy based on pre-pump level of chronic glycemia and total daily dose of insulin.total daily dose of insulin.

Eg. If previously well controlled with A1C <7.0 percent, the Eg. If previously well controlled with A1C <7.0 percent, the initial total daily dose of insulin administered by pump may initial total daily dose of insulin administered by pump may be 10 to 20 percent less than the total daily dose of the be 10 to 20 percent less than the total daily dose of the previous regimen. previous regimen.

Approximately ½ of total daily dose = basal rate. Approximately ½ of total daily dose = basal rate. Eg. basal rates are in the range of 0.01 to 0.015 units per kg 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 per hour (ie, for a 60 kg woman approximately 0.6 to 0.9 units per hour). The basal rates are adjusted empirically units per hour). The basal rates are adjusted empirically based on glucose monitoring results.based on glucose monitoring results.

Infusion rates depending on individual factors including life-Infusion rates depending on individual factors including life-style and the "dawn phenomenon" which often occurs style and the "dawn phenomenon" which often occurs between 2 AM and 8 AM. between 2 AM and 8 AM.

Most pumps allow for pre-programmed changes in basal rate Most pumps allow for pre-programmed changes in basal rate to accommodate these requirements. to accommodate these requirements.

Insulin pump therapy in DM Insulin pump therapy in DM 11

What are the advantages of insulin pump therapy?What are the advantages of insulin pump therapy?

1) Improved glycemic control and less 1) Improved glycemic control and less hypoglycemic eventshypoglycemic events

Numerous trials have been done comparing glycemic Numerous trials have been done comparing glycemic control and hypoglycemia with CSII vs. MDI.control and hypoglycemia with CSII vs. MDI.

Using an insulin pump eliminates unpredictable Using an insulin pump eliminates unpredictable effects of intermediate- or long-acting insulin.effects of intermediate- or long-acting insulin.

Insulin absorption is less variable from day to day. Insulin absorption is less variable from day to day. Both the small subcutaneous depot, and the Both the small subcutaneous depot, and the constancy of the injection site and depth for the two constancy of the injection site and depth for the two to three days with each catheter, contribute to the to three days with each catheter, contribute to the relative consistency of absorption.relative consistency of absorption.

Jeitler et al. 2008. Comparing CSII vs. MDI in DMI and Jeitler et al. 2008. Comparing CSII vs. MDI in DMI and DMII.DMII.

Methods: A meta-analysis of RCTs up to March 2007. Methods: A meta-analysis of RCTs up to March 2007. 22 trials: 17 on type 1 diabetes mellitus (908 patients), two 22 trials: 17 on type 1 diabetes mellitus (908 patients), two

on type 2 diabetes mellitus (234 patients), three on on type 2 diabetes mellitus (234 patients), three on children (74 patients). children (74 patients).

Adult DM I: 12 studies were used for the meta-analysis. Adult DM I: 12 studies were used for the meta-analysis.

In 6 studies using HbA1c In 6 studies using HbA1c −0.4% WMD in favour of CSII −0.4% WMD in favour of CSII therapy over MDI.therapy over MDI.

In 6 studies using HbA1 In 6 studies using HbA1 - 0.6% WMD (not statistically - 0.6% WMD (not statistically significant) significant)

No meta-analysis was performed on hypoglycemic events. No meta-analysis was performed on hypoglycemic events. Mild or overall hypoglycemic events were comparable Mild or overall hypoglycemic events were comparable

between the two groups: between the two groups: CSII group: 1.9 [0.9–3.1] events per patient per weekCSII group: 1.9 [0.9–3.1] events per patient per week MDI group: 1.7 [1.1–3.3] events per patient per weekMDI group: 1.7 [1.1–3.3] events per patient per week

No overall conclusions were possible for severe No overall conclusions were possible for severe hypoglycaemia and adverse events for any of the different hypoglycaemia and adverse events for any of the different patient groups due to rareness of such events, different patient groups due to rareness of such events, different definitions and insufficient reporting.definitions and insufficient reporting.

Jeitler et al. Diabetologia (2008) 51:941–951.

Pickup and Sutton 2008 meta-analysis of CSII vs. MDI Pickup and Sutton 2008 meta-analysis of CSII vs. MDI

in DMIin DMI Reviewed the frequency of severe hypoglycemia in CSII vs. Reviewed the frequency of severe hypoglycemia in CSII vs.

MDIMDI Studied more recent trials because of poor quality of earlier Studied more recent trials because of poor quality of earlier

trialstrials Analyzed the idea that CSII may be more beneficial in DMI Analyzed the idea that CSII may be more beneficial in DMI

patients who fail to achieve glycemic control on MDI.patients who fail to achieve glycemic control on MDI.

Method:Method: Databases and literature (1996Databases and literature (1996–2006) were searched for –2006) were searched for

randomized controlled trials (RCTs) and before/after randomized controlled trials (RCTs) and before/after studies of ≥ 6 months duration CSII and with severe studies of ≥ 6 months duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years hypoglycaemia frequency > 10 episodes/100 patient years on MDI.on MDI.

Results: Results: 22 studies (21 reports). 1414 DMI patients for mean CSII 22 studies (21 reports). 1414 DMI patients for mean CSII

duration of 6 – 28 months.duration of 6 – 28 months. Severe hypoglycaemia during MDI was related to diabetes Severe hypoglycaemia during MDI was related to diabetes

duration (duration (P P = 0.038) and was greater in adults than = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, children (100 vs. 36 events/100 patient years, P P = 0.036). = 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 Pickup et al. 2002 meta-analysis of CSII and

MDI in DMIMDI in DMI Method: Meta analysis of 12 randomised controlled Method: Meta analysis of 12 randomised controlled

trials (1975 -2000). 301 people with DMI allocated to trials (1975 -2000). 301 people with DMI allocated to insulin infusion and 299 allocated to insulin insulin infusion and 299 allocated to insulin injections for between 2.5 and 24 months.injections for between 2.5 and 24 months.

Results: Glycated haemoglobin was also lower in people Results: Glycated haemoglobin was also lower in people receiving insulin infusion (0.44, 0.20 to 0.69), receiving insulin infusion (0.44, 0.20 to 0.69), equivalent to a difference of 0.51%.equivalent to a difference of 0.51%.

BMJ 2002 Mar 23;324(7339):705

Blood glucose variability is less in CSII Blood glucose variability is less in CSII

compared to MDIcompared to MDI Bruttomeso et al. 2007.Bruttomeso et al. 2007. Method: Randomized cross-over study. Compared CSII and Method: Randomized cross-over study. Compared CSII and

MDI in patients with DM I.MDI in patients with DM I. 39 DM I patients with previously well controlled diabetes on 39 DM I patients with previously well controlled diabetes on

CSII for at least 6 months were randomly assigned to continue CSII for at least 6 months were randomly assigned to continue CSII with lispro or switch to MDI with lispro and glargine. CSII with lispro or switch to MDI with lispro and glargine.

After 4 months they were switched to the alternative After 4 months they were switched to the alternative treatment. treatment.

Primary end-points: Primary end-points: Blood glucose variability was analysed using various Blood glucose variability was analysed using various

measurements: glucose standard deviation, mean amplitude of measurements: glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). risk range (ADRR).

Secondary end-points: blood glucose profile, HbA1c, number of Secondary end-points: blood glucose profile, HbA1c, number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction.acids (FFA), growth hormone and treatment satisfaction.

Results: Results: Overall, CSII glucose variability was 5Overall, CSII glucose variability was 5–12% lower than –12% lower than

during MDI with glargine. during MDI with glargine.

The difference was significant only before breakfast The difference was significant only before breakfast considering glucose standard deviation (considering glucose standard deviation (PP = 0.011), = 0.011), significant overall using MAGE (significant overall using MAGE (PP = 0.016) and lability index = 0.016) and lability index ((P P = 0.005) and not significant using ADRR. = 0.005) and not significant using ADRR.

Although HbA1c was similar during both treatments, during Although HbA1c was similar during both treatments, during CSII blood glucose levels were significantly lower, CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was hyperglycaemic episodes were fewer, daily insulin dose was less,less,

FFA were lower and treatment satisfaction was greater than FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments.episodes was similar during both treatments.

Diabet. Med. 25, 326–332 (2008).

Improved Quality of Life with CSII vs. Improved Quality of Life with CSII vs. MDIMDI

Flexibility in the timing of meals:Flexibility in the timing of meals: Ability to use bolus insulin (rapid-acting Ability to use bolus insulin (rapid-acting

insulin) whenever needed.insulin) whenever needed. Ideal for patients who eat often or Ideal for patients who eat often or

erratically or for patients who want the erratically or for patients who want the flexibility to eat what and when they want flexibility to eat what and when they want without compromising glycemic control.without compromising glycemic control.

Using an insulin pump means eliminating Using an insulin pump means eliminating individual insulin injectionsindividual insulin injections

Insulin pumps allow you to exercise without Insulin pumps allow you to exercise without having to eat large amounts of carbohydratehaving to eat large amounts of carbohydrate

Scheidegger et al. 2007. CSII: effects on Scheidegger et al. 2007. CSII: effects on

quality of life.quality of life. Methods: Methods: Diabetes-specific quality of life was measured with the DSQOLS-Diabetes-specific quality of life was measured with the DSQOLS-

Questionnaire in 81 adult subjects with DM I on MDI and 78 Questionnaire in 81 adult subjects with DM I on MDI and 78 subjects on CSII (cross-sectional study). subjects on CSII (cross-sectional study).

19 subjects were followed prospectively, measuring their quality 19 subjects were followed prospectively, measuring their quality of life before and after switching from MDI to CSII (longitudinal of life before and after switching from MDI to CSII (longitudinal study).study).

Results: Results: Patients on CSII were more satisfied with their treatment in Patients on CSII were more satisfied with their treatment in

respect to:respect to: their metabolic goals, psychosocial factors, physical performance, their metabolic goals, psychosocial factors, physical performance,

protection from long-term complications and hypoglycaemia. protection from long-term complications and hypoglycaemia. Furthermore, the subjects on CSII experience greater flexibility in Furthermore, the subjects on CSII experience greater flexibility in

their daily routines, leisure time and diet than the subjects on their daily routines, leisure time and diet than the subjects on MDI.MDI.

Overall quality of life (+29 points, 95%CI 3 to 54) were Overall quality of life (+29 points, 95%CI 3 to 54) were significantly better in CSII compared to MDI only in the significantly better in CSII compared to MDI only in the longitudinal study. longitudinal study.

Swiss Med Wkly 2007;137:476–482.

Hoogma et al. Comparison of CSII and MDI on quality Hoogma et al. Comparison of CSII and MDI on quality of lifeof life

Methods: Methods: The 5-Nations trial was a randomized, controlled, crossover trial The 5-Nations trial was a randomized, controlled, crossover trial

conducted in 11 European centres. conducted in 11 European centres. 272 patients were treated with CSII 272 patients were treated with CSII MDI or MDI MDI or MDI CSII x 6 CSII x 6

months.months. 3 questionnaires: DQofL, SF-12 health survey questionnaire, Lifestyle 3 questionnaires: DQofL, SF-12 health survey questionnaire, Lifestyle

and manageability of diseaseand manageability of disease

Results: Results: The overall DQoL score was significantly higher for CSII at the end of The overall DQoL score was significantly higher for CSII at the end of

treatment compared with MDI (75 vs. 71, treatment compared with MDI (75 vs. 71, P P < 0.001),< 0.001), indicating a indicating a positive impact on QoL. positive impact on QoL.

Improvements in treatment satisfaction (Improvements in treatment satisfaction (P < P < 0.001), treatment impact 0.001), treatment impact ((P < P < 0.001) and a significant reduction in diabetes related worry (0.001) and a significant reduction in diabetes related worry (P < P < 0.01) when using CSII compared with MDI. 0.01) when using CSII compared with MDI.

SF-12 questionnaire: improvements in perception of mental health SF-12 questionnaire: improvements in perception of mental health when using CSII compared with MDI (when using CSII compared with MDI (P < P < 0.05).0.05).

Lifestyle and manageability questionnaire: more flexibility with regard Lifestyle and manageability questionnaire: more flexibility with regard to eating habits (to eating habits (P < P < 0.001) and lifestyle flexibility and sleep patterns 0.001) and lifestyle flexibility and sleep patterns ((P < P < 0.001) when using CSII compared with MDI.0.001) when using CSII compared with MDI.

Insulin Pump Therapy in DM2Insulin Pump Therapy in DM2

1) Glycemic control in DM 2 with insulin pump 1) Glycemic control in DM 2 with insulin pump therapytherapy

Herman et al. CSII vs MDI in older adults (> 60 Herman et al. CSII vs MDI in older adults (> 60 years) with DMII and marked obesity:years) with DMII and marked obesity:

Method: 2-center, 12-month, prospective, Method: 2-center, 12-month, prospective, randomized, controlled clinical trial compared the randomized, controlled clinical trial compared the efficacy and safety of CSII with that of MDIefficacy and safety of CSII with that of MDI

In this population, patients treated with both CSII In this population, patients treated with both CSII and MDI achieved excellent glycemic control with and MDI achieved excellent glycemic control with good safety and patient satisfaction.good safety and patient satisfaction.

CSII group: HbA1c 6.6% (Mean A1c fell by CSII group: HbA1c 6.6% (Mean A1c fell by 1.7 ± 1.0%)1.7 ± 1.0%)MDI group: HbA1c 6.4% (Mean A1c fell by MDI group: HbA1c 6.4% (Mean A1c fell by 1.6 ± 1.2%)1.6 ± 1.2%) Diabetes Care. 2005;28:1568-1573.

There was no statistically significant difference in hypoglycemic There was no statistically significant difference in hypoglycemic events or severe hypoglycemic events between treatment events or severe hypoglycemic events between treatment groups; however, there was a trend for less hypoglycemic groups; however, there was a trend for less hypoglycemic events with CSII. events with CSII.

CSII group: minor (self-treated) hypoglycemia 81%.CSII group: minor (self-treated) hypoglycemia 81%. MDI group: minor (self-treated) hypoglycemia 90%. (P = MDI group: minor (self-treated) hypoglycemia 90%. (P =

0.17)0.17) CSII group: severe hypoglycemia 3 / 48 CSII group: severe hypoglycemia 3 / 48 MDI group: severe hypoglycemia 6 / 50. (P = 0.49)MDI group: severe hypoglycemia 6 / 50. (P = 0.49)

It is not clear if this study of elderly patients can be It is not clear if this study of elderly patients can be extrapolated to most patients with type 2 diabetes. extrapolated to most patients with type 2 diabetes. Moreover, it suggests that MDI should be attempted in Moreover, it suggests that MDI should be attempted in elderly patients with marked obesity before considering elderly patients with marked obesity before considering insulin pump therapy.insulin pump therapy.

Jeiter et al. meta-analysis of 2 randomized control trials:Jeiter et al. meta-analysis of 2 randomized control trials: In patients with type 2 diabetes mellitus, CSII and MDI In patients with type 2 diabetes mellitus, CSII and MDI

treatment showed no statistically significant difference for treatment showed no statistically significant difference for HbA1c.HbA1c.

Cross-over trial of CSII and MDI: Cross-over trial of CSII and MDI: Method: 40 obese, insulin-treated patients with type 2 Method: 40 obese, insulin-treated patients with type 2

diabetes were randomized to treatment with CSII or MDI diabetes were randomized to treatment with CSII or MDI therapy. therapy.

At the end of the first 18-week treat treatment period, At the end of the first 18-week treat treatment period, patients underwent a 12-week washout period during patients underwent a 12-week washout period during which they were treated with MDI plus metformin. which they were treated with MDI plus metformin.

They were then crossed over to the alternate treatment for They were then crossed over to the alternate treatment for an 18-week follow-up period. an 18-week follow-up period.

Results of the intention-to-treat analysis showed that CSII Results of the intention-to-treat analysis showed that CSII was superior to MDI in reducing A1C values. There was no was superior to MDI in reducing A1C values. There was no significant change in weight or insulin dosage.significant change in weight or insulin dosage.

Diabet Med. 2005;22:1037-1046.

Quality of Life improved with CSII compared to Quality of Life improved with CSII compared to

MDI in DM2MDI in DM2 Method: 132 CSII naive patients with type 2 diabetes were randomly Method: 132 CSII naive patients with type 2 diabetes were randomly

assigned (1:1) to CSII (insulin aspart) or MDI therapy (bolus assigned (1:1) to CSII (insulin aspart) or MDI therapy (bolus insulin aspart and basal NPH insulin).insulin aspart and basal NPH insulin).

Multicenter, open-label, randomized, parallel-group, 24-week Multicenter, open-label, randomized, parallel-group, 24-week study. study.

A total of 93% of CSII-treated patients preferred the pump to A total of 93% of CSII-treated patients preferred the pump to their previous injectable insulin regimen for reasons of their previous injectable insulin regimen for reasons of convenience, flexibility, ease of use, and overall preference.convenience, flexibility, ease of use, and overall preference.

Diabetes Care. 2003;26:2598-2603.

What are the disadvantages of What are the disadvantages of

insulin pumps?insulin pumps? 1) Expensive cost of insulin pump therapy:1) Expensive cost of insulin pump therapy: The costs of the pump and supplies are higher The costs of the pump and supplies are higher

than those of ordinary syringes and needles. than those of ordinary syringes and needles. Cost of pump: $3000 - 5000. Insulin infusion Cost of pump: $3000 - 5000. Insulin infusion

lines, syringes, tapes, batteries can add extra lines, syringes, tapes, batteries can add extra $40 – 50 / month.$40 – 50 / month.

2) Complications:2) Complications: Moreover, approximately 40 percent of patients Moreover, approximately 40 percent of patients

in one large study had one or more acute in one large study had one or more acute complications (such as infection at the site of complications (such as infection at the site of needle insertion) during 3000 patient-months of needle insertion) during 3000 patient-months of treatment. treatment. (JAMA 1984 Dec 21;252(23):3265-9.)(JAMA 1984 Dec 21;252(23):3265-9.)

A second study found that 86 percent of patients A second study found that 86 percent of patients had at least one infusion-system failure in a 12-had at least one infusion-system failure in a 12-month period. month period. (Diabetes Care 1986 Jul-Aug;9(4):351-5.)(Diabetes Care 1986 Jul-Aug;9(4):351-5.)

Blockage or leakage in the syringe or the infusion Blockage or leakage in the syringe or the infusion set or connectors, causing an interruption of set or connectors, causing an interruption of infusion flow. These issues now occur less infusion flow. These issues now occur less commonly with more modern pumps and supplies.commonly with more modern pumps and supplies.

Any interruption in continuous flow can lead very Any interruption in continuous flow can lead very quickly to hypoinsulinemia, hyperglycemia, and quickly to hypoinsulinemia, hyperglycemia, and possibly diabetic ketoacidosis.possibly diabetic ketoacidosis.

3) Bothersome to wear an insulin pump:3) Bothersome to wear an insulin pump: Patients may feel "tethered" to the pump at all Patients may feel "tethered" to the pump at all

times. times. Complaints that the treatment is awkward, Complaints that the treatment is awkward,

uncomfortable, embarrassing, or unpleasant, uncomfortable, embarrassing, or unpleasant, particularly when bathing or having sexual particularly when bathing or having sexual intercourse. intercourse.

Can insulin pump therapy be used Can insulin pump therapy be used in pregnancy?in pregnancy?

A 2008 Cochrane review to compare CSII with MDI A 2008 Cochrane review to compare CSII with MDI of insulin for pregnant women with diabetes. of insulin for pregnant women with diabetes.

Search strategy: Articles were searched from the Search strategy: Articles were searched from the Cochrane Pregnancy and Childbirth Group’s Trials Cochrane Pregnancy and Childbirth Group’s Trials Register (November 2006).Register (November 2006).

Selection criteria:Selection criteria: Randomised controlled trials Randomised controlled trials comparing CSII with MDI for pregnant women with comparing CSII with MDI for pregnant women with diabetes.diabetes.

Primary outcome: 1) perinatal mortality 2) fetal Primary outcome: 1) perinatal mortality 2) fetal anomaly 3) hypoglycemia/hyperglycemic episodes anomaly 3) hypoglycemia/hyperglycemic episodes requiring intervention 4) admission and length of stay requiring intervention 4) admission and length of stay

Secondary outcomes: multiple additional outcomes Secondary outcomes: multiple additional outcomes for the mother and babyfor the mother and baby

Results: Results: Two studies (60 women with 61 pregnancies) were included. Two studies (60 women with 61 pregnancies) were included.

There was a significant increase in mean birthweight associated There was a significant increase in mean birthweight associated with CSII as opposed to MDI (WMD 220.56, 95% confidence with CSII as opposed to MDI (WMD 220.56, 95% confidence interval (CI) -2.09 to 443.20; two trials, 61 participants).interval (CI) -2.09 to 443.20; two trials, 61 participants).

BUT lack of significant difference in rate of macrosomia BUT lack of significant difference in rate of macrosomia (birthweight greater than 4000 g) (relative risk (RR) 3.20, 95% (birthweight greater than 4000 g) (relative risk (RR) 3.20, 95% CI 0.14 to 72.62; two trials, 61 participants). CI 0.14 to 72.62; two trials, 61 participants).

No significant differences were found in any other outcomes No significant differences were found in any other outcomes measured, which may reflect the small number of trials suitable measured, which may reflect the small number of trials suitable for metaanalysis and the small number of participants in the for metaanalysis and the small number of participants in the included studies. included studies.

No significant differences were found in:No significant differences were found in: perinatal mortality (RR 2.00, 95% CI 0.20 to 19.91)perinatal mortality (RR 2.00, 95% CI 0.20 to 19.91) fetal anomaly (RR 1.07, 95% CI 0.07 to 15.54)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 hypoglycaemia (RR 3.00, 95% CI 0.35 to 25.87) maternal hyperglycaemia (RR 7.00, 95% CI 0.39 to 125.44).maternal hyperglycaemia (RR 7.00, 95% CI 0.39 to 125.44).

Cochrane ConclusionCochrane Conclusion There is a dearth of robust evidence to support the There is a dearth of robust evidence to support the

use of one particular form of insulin administration use of one particular form of insulin administration over another for pregnant women with diabetes. over another for pregnant women with diabetes.

The data are limited because of the small number of The data are limited because of the small number of trials appropriate for meta-analysis, small study trials appropriate for meta-analysis, small study sample size and questionable generalisability of the sample size and questionable generalisability of the trial population. trial population.

Conclusions cannot be made from the data available Conclusions cannot be made from the data available and therefore a robust randomised trial is needed. and therefore a robust randomised trial is needed. The trial should be adequately powered to assess The trial should be adequately powered to assess the efficacy of continuous subcutaneous insulin the efficacy of continuous subcutaneous insulin infusion versus multiple daily injections in terms of infusion versus multiple daily injections in terms of appropriate outcomes for women with diabetes.appropriate outcomes for women with diabetes.

Can insulin be used Can insulin be used

perioperatively?perioperatively? Little evidence regarding CSII and perioperative managementLittle evidence regarding CSII and perioperative management

2 case studies. No randomized controlled trials available.2 case studies. No randomized controlled trials available.

First case study: DM I who wore his continuous subcutaneous First case study: DM I who wore his continuous subcutaneous insulin infusion (CSII) pump during general anesthesia for insulin infusion (CSII) pump during general anesthesia for surgical repair of a herniated lumbar disk. Blood glucose levels surgical repair of a herniated lumbar disk. Blood glucose levels were stable throughout the perioperative period. Little or no were stable throughout the perioperative period. Little or no extra work was required of the CRNA.extra work was required of the CRNA.

Second case study: A 61-year-old male, while recovering from a Second case study: A 61-year-old male, while recovering from a Whipple's procedure for pancreatic carcinoma, was treated for Whipple's procedure for pancreatic carcinoma, was treated for 13 days with an insulin infusion pump for diabetes exacerbated 13 days with an insulin infusion pump for diabetes exacerbated by enteral hyperalimentation. by enteral hyperalimentation.

Treatment with continuous subcutaneous insulin infusion Treatment with continuous subcutaneous insulin infusion resulted in improved blood glucose control. Associated with this resulted in improved blood glucose control. Associated with this improvement was a reduction in plasma cholesterol, triglyceride improvement was a reduction in plasma cholesterol, triglyceride and free fatty acid levels. Plasma epinephrine, norepinephrine, and free fatty acid levels. Plasma epinephrine, norepinephrine, glucagon and cortisol concentrations were also lowered glucagon and cortisol concentrations were also lowered although growth hormone levels remained unchanged. although growth hormone levels remained unchanged.

Take Home MessageTake Home Message Insulin pump therapy is an alternative to MDI in Insulin pump therapy is an alternative to MDI in

diabetic patientsdiabetic patients

In DM 1, insulin pump therapy compared to MDI In DM 1, insulin pump therapy compared to MDI may lead to improvements in glycemic control may lead to improvements in glycemic control with less frequent episodes of hypoglycemia, less with less frequent episodes of hypoglycemia, less glucose variability, and improved quality of life.glucose variability, and improved quality of life.

There is less evidence available in DM 2, but There is less evidence available in DM 2, but current trials suggest no additional benefit in current trials suggest no additional benefit in glycemic control with CSII compared to MDI. glycemic control with CSII compared to MDI. However, CSII may be associated with improved However, CSII may be associated with improved quality of life.quality of life.

There is currently very little evidence for the There is currently very little evidence for the benefit of insulin pump therapy in pregnancy or benefit of insulin pump therapy in pregnancy or perioperative management of diabetes.perioperative management of diabetes.

Thank youThank you