THE EXTERNAL PUMP IN THE EXTERNAL PUMP IN PRACTICEPRACTICE

Predrag B. Djordjevic

Academy, US Medical School, Belgrade, Serbia

10th Meeting of the MGSD

26-29 April, 2007

Istanbul, Turkey

• In 1993, the Diabetes Control and Complications Trial In 1993, the Diabetes Control and Complications Trial (DCCT) definitively showed that, in people with type 1 (DCCT) definitively showed that, in people with type 1 diabetes, a good metabolic control, meaning long-term diabetes, a good metabolic control, meaning long-term glucose values as close to normal as possible, (mean glucose values as close to normal as possible, (mean HbA1c - 7.2 % in the intensive treatment group, HbA1c - 7.2 % in the intensive treatment group, compared to conventional treatment, with a mean compared to conventional treatment, with a mean HbA1c - 9.0 %) is associated with a significant HbA1c - 9.0 %) is associated with a significant reduction in the risk for retinopathy (76 %), reduction in the risk for retinopathy (76 %), nephropathy (50%) and neuropathy (60%). nephropathy (50%) and neuropathy (60%).

• Further on, the DCCT / EDIC study (Epidemiology of Further on, the DCCT / EDIC study (Epidemiology of Diabetes Interventions and Complications) has Diabetes Interventions and Complications) has demonstrated the sustained benefits of good metabolic demonstrated the sustained benefits of good metabolic control through intensive insulin therapy: the former control through intensive insulin therapy: the former intensive treatment group continues to exhibit the intensive treatment group continues to exhibit the same reduction in the risks of diabetic retinopathy (75 same reduction in the risks of diabetic retinopathy (75 %), nephropathy (75 %) and neuropathy, starting %), nephropathy (75 %) and neuropathy, starting from a new baseline status at the beginning of EDIC.from a new baseline status at the beginning of EDIC.

• Also cardiovascular events have been Also cardiovascular events have been reduced by 42 % and the major reduced by 42 % and the major cardiovascular events (non-fatal MI, cardiovascular events (non-fatal MI, stroke, death), by 57 %. stroke, death), by 57 %.

• The EDIC study has demonstrated the The EDIC study has demonstrated the concept and the importance of the concept and the importance of the “metabolic memory” in preventing the “metabolic memory” in preventing the later course of complications. later course of complications.

• The release of DCCT and UKPDS has The release of DCCT and UKPDS has definitively demonstrated the importance to definitively demonstrated the importance to optimize glycemic control, either through optimize glycemic control, either through multiple daily injection or continuous multiple daily injection or continuous subcutaneous insulin infusion (CSII or insulin subcutaneous insulin infusion (CSII or insulin pump therapy) and also has renewed interest in pump therapy) and also has renewed interest in the role of CSII therapy in improving metabolic the role of CSII therapy in improving metabolic outcomes, because it offers a more precise outcomes, because it offers a more precise physiological method of insulin administration.physiological method of insulin administration.

• Figure 3. Basal-bolus insulin regimenFigure 3. Basal-bolus insulin regimen

•H

•ui •Bolus (prandial) insulin

•22.00 3.00 6.00 14.00 18.00 22.00

•NPH ( )•Glargine ( )•Short-acting insulin ( )

• The use of insulin glargine as basal insulin The use of insulin glargine as basal insulin therapy has significantly improved the therapy has significantly improved the glycaemic control, with a lower rate of glycaemic control, with a lower rate of hypoglycaemia. Its flat profile of action, the hypoglycaemia. Its flat profile of action, the 24 hours duration and a more predictable 24 hours duration and a more predictable absorption are important advantages. absorption are important advantages. However, multiple daily injection treatment However, multiple daily injection treatment still has some limitsstill has some limits

Insufficient cover of “dawn” phenomenonInsufficient cover of “dawn” phenomenon

• Insufficient cover of “dusk” phenomenonInsufficient cover of “dusk” phenomenon

Excessive insulin during the night, when the high Excessive insulin during the night, when the high insulin sensitivity may predispose to hypoglycaemiainsulin sensitivity may predispose to hypoglycaemia

Delayed action of basal insulin in the morningDelayed action of basal insulin in the morning

Variable absorption of insulin, ranging from 19% Variable absorption of insulin, ranging from 19% to 55%, leading to glycaemic fluctuationsto 55%, leading to glycaemic fluctuations

• Flexible lifestyle can be maintained under certain Flexible lifestyle can be maintained under certain circumstancescircumstances

• Increased number of injections.Increased number of injections.

• A quarter of a century after its A quarter of a century after its introduction, insulin pumps are widely introduction, insulin pumps are widely used in clinical practice, there are now used in clinical practice, there are now estimated to be >300,000, with estimated to be >300,000, with approximately 250,000 in the U.S. approximately 250,000 in the U.S.

• For CSII as a form of IIT external insulin pumps are For CSII as a form of IIT external insulin pumps are used. These operate with the help of short acting used. These operate with the help of short acting (regular) or rapid acting insulin analogues. The insulin (regular) or rapid acting insulin analogues. The insulin is delivered trough a catheter inserted subcutaneously is delivered trough a catheter inserted subcutaneously (the abdomen is preferred site). Basal Rate (BR) of (the abdomen is preferred site). Basal Rate (BR) of insulin infusion (24h) and insulin boluses (BS) are insulin infusion (24h) and insulin boluses (BS) are delivered automatically using the individual programs. delivered automatically using the individual programs.

Insulin pump therapy: technical Insulin pump therapy: technical data data

Modern insulin pump is a pager-size compact, computerized device, Modern insulin pump is a pager-size compact, computerized device, which contains a small vial of regular insulin or short-acting insulin which contains a small vial of regular insulin or short-acting insulin analogue (lispro, aspart, glulisine) or a syringe to be filled with analogue (lispro, aspart, glulisine) or a syringe to be filled with insulin.insulin.

It is attached by a catheter inserted under the skin,It is attached by a catheter inserted under the skin, using a small using a small needle, which is removed. Every two to three days, the catheter needle, which is removed. Every two to three days, the catheter must be changed. must be changed.

• Recent advances also include quick release tubing to enable patients Recent advances also include quick release tubing to enable patients to easily disconnect from the pump during activities such as to easily disconnect from the pump during activities such as showering, swimming, and intimacy. showering, swimming, and intimacy.

The pump continuously and automatically delivers small amounts The pump continuously and automatically delivers small amounts of regular or short acting insulin every few minutes. of regular or short acting insulin every few minutes.

This is called the basal rate.This is called the basal rate.

• Figure 4. “Physiological” insulin pump therapy

•0

•0,2

•0,4

•0,6

•0,8

•1

•1,2

•1,4

•0 •1 •2 •3 •4 •5 •6 •7 •8 •9 •10 •11 •12 •13 •14 •15 •16 •17 •18 •19 •20 •21 •22 •23 H

•Physiological basal insulin •requirement

•Basal rate settled through insulin pump

•ui

Basal insulin doseBasal insulin dose

• Serve to maintain glycemia in target range over night and in Serve to maintain glycemia in target range over night and in the absence of meals or change in daily activities. The Total the absence of meals or change in daily activities. The Total Daily Basal Dose (TDBD) needs to be up to 60% of the Total Daily Basal Dose (TDBD) needs to be up to 60% of the Total Insulin Daily Dose (TIDD). BS of short-acting insulin are Insulin Daily Dose (TIDD). BS of short-acting insulin are given 30min and rapid-acting insulin 5-15min before meal. given 30min and rapid-acting insulin 5-15min before meal. Adjustment of nighttime basal dose is based on 3 a.m and Adjustment of nighttime basal dose is based on 3 a.m and fasting Blood Glucose (BG) and daytime basal dose according fasting Blood Glucose (BG) and daytime basal dose according BG levels when meals are skipped or delayed. Adjustment of BG levels when meals are skipped or delayed. Adjustment of boluses is based on 2-hours postprandial and than pre-meal boluses is based on 2-hours postprandial and than pre-meal BG levels.BG levels.

MAIN ADVANTAGES MAIN ADVANTAGES

• Maximum flexibility; meals can be skipped Maximum flexibility; meals can be skipped or delayed; no peak insulin activity such as or delayed; no peak insulin activity such as intermediate and long-acting insulin; intermediate and long-acting insulin; insulin infusion set needs to be changed insulin infusion set needs to be changed every 2-3 days instead of 4 daily injections every 2-3 days instead of 4 daily injections (MDII); can be disconnected for specific (MDII); can be disconnected for specific activities and substitute with MDII for activities and substitute with MDII for short periods. short periods.

Other advantages Other advantages

• More constant and predictable insulin absorption, with a variability less than 3 %. Both regular insulin and short-acting analogues appear to provide a more consistent, reproducible absorption pattern than intermediate insulin suspensions. Insulin administered by an insulin pump provides the greatest day-to-day reproducibility and insulin availability, and the least unexpected fluctuations in glycaemia control,

• Reduced risk of severe and exercise induced hypoglycaemia due to fact that there is minimal subcutaneous insulin depot, and a lower temporary basal rate can be settled,

• Improvement or slowing of other metabolic factors and diabetes complications: diabetic nephropathy, peripheral and autonomic neuropathy, retinopathy, hypertriglyceridemia and hypoalphalipoproteinemia, and diabetic changes in transplanted kidneys.

• An indirect prove of the certain advantages of insulin pump therapy might be that more than 50% of healthcare professionals with type 1 diabetes who are members of the ADA and American Association of Diabetes Educators as well as many professional athletes(?), use insulin pumps.

MAIN DISADVANTAGES MAIN DISADVANTAGES

• High price; wear pump 24h/day; interruption High price; wear pump 24h/day; interruption of insulin infusion due to the pump or infusion of insulin infusion due to the pump or infusion system malfunction cause hiperglycemia and system malfunction cause hiperglycemia and Diabetic KetoAcidosis (DKA) within hours; Diabetic KetoAcidosis (DKA) within hours; infection at infusion cite.infection at infusion cite.

MAIN FEATURES IMPORTANT FOR MAIN FEATURES IMPORTANT FOR SELECTING OF PUMP TYPE SELECTING OF PUMP TYPE

• Size; type of infusion set; BS and Size; type of infusion set; BS and temporary BR options; display; resistance temporary BR options; display; resistance to moisture; communication with BG to moisture; communication with BG meter with automatic calculation of BS; meter with automatic calculation of BS; availability of 24h technical assistance and availability of 24h technical assistance and record of reliability.record of reliability.

Simplicity in your lifeSimplicity in your life

• A great body of evidence proved that insulin pump therapy is associated with significant improvement in glycaemia control, by reducing the extreme high and low blood glucose values, and the fasting hyperglycaemia (“dawn” phenomenon). In the DCCT, 42% of subjects used CSII during their last full year of study treatment. They achieved a further reduction of HbA1C with 0.2% to 0.4% and a significant improvement in lifestyle flexibility. CSII-treated patients maintained a mean HbA1c of 6.8 % vs. 7.0 % in MDI-treated subjects during the trial (p < 0.05).

• Insulin requirements significantly decreased after switching on insulin pump therapy (pre-CSII: 53.69 ± 0.11 iu/day, or 0.74 ± 0.04 iu / kg / day and post-CSII: 44.19 ± 0.07 iu/day, or 0.62 ± 0.02 iu / kg / day; p < 0.001).

Most of the studies showed a decrease in frequency of both mild and severe hypoglycaemic episodes.

• The annual cost for MDI, with lispro and glargine was 4900 Euro compared to 9373 Euro for pumps.

• Compared to multiple daily injections with insulin glargine, pump therapy was found to be similar or even better in youth, in terms of glycemic control, frequency of hypoglycaemia or adverse events.

• Total daily insulin dose was unchanged in the glargine group, but significantly reduced (p < 0.01) in pump group (1.4 units/kg at baseline vs. 0.9 units/kg).

The woman with type 1 diabetes considering pregnancy requires an intensive, flexible insulin program to normalize glucose levels before conception.

Good glycemic control during pregnancy is associated with less fetal macrosomia and fewer neonatal complications.

Intensive antihyperglycaemic therapy in gestational diabetes is associated with a lower risk of adverse events and maternal and fetal complications, as recently demonstrated by ACHOIS (Australian Carbohydrate Intolerance Study in Pregnancy).

• Insulin pump therapy is ideally suited for these situations due to less variability in blood glucose levels and the possibility to adjust insulin doses in order to rapidly improve glycemic control.

Metabolic benefits: reduced frequency of Metabolic benefits: reduced frequency of hypoglycaemia hypoglycaemia

• Tight glycemic control is associated with an increased risk for hypoglycaemia, as demonstrated by DCCT. Use of insulin pump has been proved to reduce the variability of glucose levels and severe hypoglycaemia in comparison with MDI, with no discernible reduction in glycemic control. This decrease in hypoglycaemic events has been accompanied by an increase in self-reported warning symptoms of hypoglycaemia, as well as by an increase in counter regulatory hormonal responses to hypoglycaemia

Severe hypoglycaemia has now become an accepted indication for initiation of CSII therapy, and may be the greatest advantage offered by CSII.

• Many studies demonstrated a reduced frequency of hypoglycaemia, a decreased risk of nocturnal hypoglycaemia and a decreased risk of activity-induced hypoglycaemia.

• An analysis conducted in the United Kingdom compared the cost-effectiveness of CSII with that of MDI and found that CSII was most cost-effective in patients who had more than 2 severe hypoglycaemic events per year and who required admission to hospital at least once every year.

Metabolic benefits: weight controlMetabolic benefits: weight control

• Intensive insulin therapy followed by significant improvement of glycemic control can be associated with weight gain. Reduced insulin requirements, greater flexibility in food intake and less hypoglycaemia might result in minimal weight gain among patients who use insulin pump therapy.

Indications for insulin pump therapy (CSII) I• Insulin pump therapy should be considered for the

management of:

Type 1 diabetes poorly controlled under conventional multiple insulin injections;

"Dawn” phenomenon or "reverse dawn" phenomenon (basal rate is higher from 9 PM to 3 AM and lower from 3 AM to 6 PM in young children);

– Marked daily variations in glucose levels;Brittle diabetes;Hypoglycaemia unawareness or of

hypoglycaemic events requiring assistance;

– Need for flexibility in lifestyle;

Indications for insulin pump therapy (CSII) IIPregnancy, pre-pregnancy, gestational diabetes;

– Low insulin requirements (< 20 U/day), extreme insulin sensitivity;

Diabetic complications including neuropathy, retinopathy, who require intense diabetes management;

– Type 2 DM inadequately glycemic controlled by multiple daily injections;

– Glycemic control during regular vigorous exercise in people with type 1 diabetes.

– Diabetics with severe peripheral angiopathy – gangrene

Patients who develop DM after pacreatectomy or after pancreatic or islet transplantation

CSII – in pregnancyCSII – in pregnancy

B- breakfast L - lunchD – dinner

Female Bolus: 6 IU + 6 IU + 6 IU Basal rate: 00-08h - 0.6 IU/h 08-00h - 0.9 IU/h

Bolus Bolus Bolus

Basal rate

B L D sleeping

morning afternoon nightevening

• Immediately before the transplantation, they were submitted to intensified insulin treatment comprising 4 daily doses using pen (5 patients) or insulin pump treatment (4 patients) in order to obtain strict metabolic control, and the treatment was continued after transplantation at least for a year.

PATIENTS SELECTION

• Strongly motivated: having necessary cognitive and physical capabilities to operate the pump safety and anticipate and evaluate adjustments made in insulin dosage; patients has demonstrated willingness to perform glycemic self control; Patient has financial resources or reimbursement by healthcare insurance (state, private), sponsors; patients can quantify food intake: carbohydrate counting and carbohydrates equivalents.

PROVIDER ASPECTS

• Ideally, CSII therapy should be Ideally, CSII therapy should be prescribed, implemented, and followed by prescribed, implemented, and followed by a skilled professional team familiar with a skilled professional team familiar with CSII therapy and capable of supporting CSII therapy and capable of supporting the patients.the patients.

““Whole package” of insulin pump therapy Whole package” of insulin pump therapy

Therapeutic patient education generally addressed to diabetes control and specifically to insulin pump is mandatory.

• It is important patient to understand the real benefits of insulin pump therapy and to have realistic expectations.

Rigorous self-monitoring of blood glucose is also required.

• Common misconceptions are related to the belief Common misconceptions are related to the belief that: that: – the insulin pump will cure the patient’s diabetesthe insulin pump will cure the patient’s diabetes the patient will have a totally unrestricted free dietthe patient will have a totally unrestricted free diet

– pump therapy is easy with little or no adjustment pump therapy is easy with little or no adjustment neededneeded

– they will have perfect blood glucose control with the they will have perfect blood glucose control with the pumppump

the patient will not have to check their blood glucose the patient will not have to check their blood glucose levels regularlylevels regularly..

• All these beliefs should be specifically addressed in the education programme, to create the real picture of insulin pump therapy.

Case ReportCase Report

• Patient J.M; female; 17 y. old, pupil.Patient J.M; female; 17 y. old, pupil.

• Came in our diabetic department withCame in our diabetic department with

• MAIN DISCONFORT: fatigue, thirst, MAIN DISCONFORT: fatigue, thirst, drinking increased volume of liquid, drinking increased volume of liquid, increased volume of urine, symptoms and increased volume of urine, symptoms and signs of hypogycaemia signs of hypogycaemia

AnamnesisAnamnesis

• Diabetes mellitus type 1 appeared in 9th year, immediate start of insulin therapy. Due to bad glycoregulation (HbA1c 11.3%) intensive insulin therapy was introduced before 6 moths (Actrapid HM and NPH).

• Insulin daily dose: 3 times premeal rapid acting insulin analogue NovoRapid (25+25+25=75IU) and once long acting NPH as basal insulin (46IU in the evening, before sleep).

• TOTAL DAILY DOSE OF INSULIN = 121 IU !!!

• Frequent hypoglycaemia, medium degree

• Keep the diet insufficient

• BMI =26 kg/m2

• Hyperprolactinemia. Amenorrhoea

• Due to this reasons external insulin pump Due to this reasons external insulin pump (MiniMed 508) was introduced (CSII)(MiniMed 508) was introduced (CSII)

• Basal rate 1 IU / h = 24 IUBasal rate 1 IU / h = 24 IU

• Boluses 14+14+14 = 42 IUBoluses 14+14+14 = 42 IU

• TOTAL DAILY DOSE OF INSULIN = 66 IUTOTAL DAILY DOSE OF INSULIN = 66 IU

• After 2 month: HbA1c 12%, predominat After 2 month: HbA1c 12%, predominat hyperglycaemia, rare hypoglycaemiahyperglycaemia, rare hypoglycaemia

• Daily profile of glycaemia: 07h 15.0mmol/L Daily profile of glycaemia: 07h 15.0mmol/L (before breakfast), 2h after 5.0, before lunch (before breakfast), 2h after 5.0, before lunch 24.9, 2h after 25.6, before dinner 19.4, 2h after 24.9, 2h after 25.6, before dinner 19.4, 2h after 15.6, 24h 14.7, 03h 19.9 mmol/L15.6, 24h 14.7, 03h 19.9 mmol/L

• No ketoses No ketoses

• Multiple insulin injection was introduced again:Multiple insulin injection was introduced again:

• NovoRapid boluses before meal: 18+18+18 IU, NovoRapid boluses before meal: 18+18+18 IU, Insulatard 30 IU in the evening.Insulatard 30 IU in the evening.

• TOTAL DAILY DOSE OF INSULIN = 84 IUTOTAL DAILY DOSE OF INSULIN = 84 IU

Other investigations Other investigations

• Insulin antibody 13.9% Insulin antibody 13.9% INCEREASEDINCEREASED (serum, RIA, (serum, RIA, upper normal limit 5.2%)upper normal limit 5.2%)

• IgE antibodies specific for human insulin <0.35 kUA IgE antibodies specific for human insulin <0.35 kUA (normal range 2-100)(normal range 2-100)

• IgA 2.148 gr/L (normal); IgG 10.34 gr/L (normal); IgM IgA 2.148 gr/L (normal); IgG 10.34 gr/L (normal); IgM 1.24 gr/L (normal) ; Total amount IgE <9.0 kU/L1.24 gr/L (normal) ; Total amount IgE <9.0 kU/L

• Immune complexes: 2.253, Immune complexes: 2.253, INCREASEDINCREASED (normal <0.5) (normal <0.5)

• The new regime of insulin therapy was The new regime of insulin therapy was introduced:introduced:

• Lantus insulin in the morning 44 IU Lantus insulin in the morning 44 IU

• NovoRapid insulin in the morning 14IU and in NovoRapid insulin in the morning 14IU and in the evening 28 IU the evening 28 IU

• TOTAL DAILY INSULIN DOSE = 72 IUTOTAL DAILY INSULIN DOSE = 72 IU

• Keep the diet further insufficientKeep the diet further insufficient

• After one month: After one month:

• Lantus insulin in the morning 40 IU Lantus insulin in the morning 40 IU

• NovoRapid insulin in the morning 14 IU and in the evening NovoRapid insulin in the morning 14 IU and in the evening 14 IU = 28 IU14 IU = 28 IU

• TOTAL DAILY INSULIN DOSE = 68 IUTOTAL DAILY INSULIN DOSE = 68 IU

• Daily profile of glycaemia: mean 9.0 mmol/LDaily profile of glycaemia: mean 9.0 mmol/L

• Rare, mild hypoglycaemia, Rare, mild hypoglycaemia, NOT DURING THE NIGHTNOT DURING THE NIGHT

• Better adherence to diet, motivation, education for IIT, Better adherence to diet, motivation, education for IIT, support from familysupport from family

• Every day 24h contact with our departmentEvery day 24h contact with our department

Summary ISummary I

• Bad glycoregulation in log period of time despite:

• Enormous total daily dose of insulin

• Application of MDII (121 IU) after that CSII (66 IU)

• Immunological insulin resistance: insulin antibodies, >1 IU/kg of insulin

• Bad adherence to diet, no motivation, education, support from family

• Insufficient contact with state diabetic care services

Summary IISummary II

• Good effects of insulin analogues:

Lantus insulin (long acting)

NovoRapid (rapid, short-acting)

Total daily dose ≈ 1 IU/kg

One may expect further decrease of total insulin daily dose

If insulin pump intent to be used again in this patients rapid, short-acting insulin analogues need to be

introduced (NovoRapid ? Lispro ?)

Conclusion Conclusion

• Pup therapy (CSII) has many biological, Pup therapy (CSII) has many biological, medical, social limitations especially if medical, social limitations especially if contraindications are not respectedcontraindications are not respected

• Insulin analogues may be useful in some Insulin analogues may be useful in some cases of MDII and CSII failure cases of MDII and CSII failure

Aspart vs Lispro vs Regular Aspart vs Lispro vs Regular CSII in Type 1 DiabetesCSII in Type 1 Diabetes

N = 146, mean age 38, BMI 25

Aspart Lispro RegularBase 4 mo Base 4 mo Base 4mo

HbA1c % 7.34 7.36 7.29 7.47 7.47 7.63

PG 90 min after dinnermmol/l 7.6 (p<0.02) 9.1 9.5

Pump or line blockage No differences

Hypoglycemia No differencesBode BW et al. Diabetes;50(Suppl 2):A106

Epi

sode

s/m

onth

/pat

ient

Epi

sode

s/m

onth

/pat

ient

0

2

4

6

8

10

12

NovoRapid® human insulin insulin lispro

p<0.05p<0.05

p<0.05p<0.05

NovoRapid® vs human insulin NovoRapid® vs human insulin vsvs insulin lispro insulin lispro in CSII study: Self-in CSII study: Self-Reported HypoglycaemiaReported Hypoglycaemia

ANA 2024, Data on File

• A retrospective study on 82 adults with type 1 diabetes, duration 19.7 ± 9.9 years, who started CSII after a MDI regimen with either NPH or glargine, regular or short acting analogues showed that after 3 months of CSII, HbA1c significantly decreased, 8.35 ± 1.06 % vs. 9.39 ± 1.35%, (p < 0.001) and the reduction was maintained over the whole CSII treatment.

• Significant decrease of severe hypoglycaemic episodes (0.35 ± 0.07 per patient/year during MDI vs. 0.10 ± 0.02 during CSII, p < 0.001) and insulin requirement (52.1 ± 17.5 units/day vs. 38.8 ± 12.3, p < 0.001) have been found.

• According to this study, older age and higher baseline HbA1c predict the better glycemic improvement.

STARTING INSULIN DOSE STARTING INSULIN DOSE • Firstly, reduce TIDD on MDII by 25-30%. Staring dose must Firstly, reduce TIDD on MDII by 25-30%. Staring dose must

be individualized for each patient. TDBD should be 40-60% of be individualized for each patient. TDBD should be 40-60% of TIDD (divide by 24 to obtain hourly BR, usual range 0.5-2.0 TIDD (divide by 24 to obtain hourly BR, usual range 0.5-2.0 U/hour for type 2 diabetics). TDBD can be calculated by U/hour for type 2 diabetics). TDBD can be calculated by multiplying the patients weight in kg by 0.3 (divide by 24 to multiplying the patients weight in kg by 0.3 (divide by 24 to obtain hourly BR). Higher BR from 3-9am, intermediate obtain hourly BR). Higher BR from 3-9am, intermediate during the day, lower at bedtime. For pre-meal BS (from during the day, lower at bedtime. For pre-meal BS (from TDBD): breakfast 20%, lunch 10%, supper 15%, bedtime TDBD): breakfast 20%, lunch 10%, supper 15%, bedtime 5%. Calculation based according to patient’s sensitivity (i.e. 5%. Calculation based according to patient’s sensitivity (i.e. 0.5-2.0 U/15g carbohydrate). Adjusted BR and BS by 10-20% 0.5-2.0 U/15g carbohydrate). Adjusted BR and BS by 10-20% based on BG readings before and after meals, at bedtime and based on BG readings before and after meals, at bedtime and at 3am. All patients on IIT should be provided with correction at 3am. All patients on IIT should be provided with correction BS or supplemental BS guidelines to correct out-of-range BG BS or supplemental BS guidelines to correct out-of-range BG values, using the 1700 rule.values, using the 1700 rule.

PUMP MALFUNCTION PUMP MALFUNCTION If it occurs, use usual dose of short or rapid-acting insulin If it occurs, use usual dose of short or rapid-acting insulin

before meals and long-acting insulin at bedtime. before meals and long-acting insulin at bedtime.

If the patients wish to disconnect pump it is possible up to 2 If the patients wish to disconnect pump it is possible up to 2 to 4 hours without any adverse consequences.to 4 hours without any adverse consequences.

For the period longer than 4 hours the usual basal-bolus For the period longer than 4 hours the usual basal-bolus therapy should be given. therapy should be given.

The dose of the long-acting Glargine will be equal to TDBD.The dose of the long-acting Glargine will be equal to TDBD.

• It is important to teach patients to adjust short or rapid-It is important to teach patients to adjust short or rapid-acting insulin for variations in food intake and to adjust acting insulin for variations in food intake and to adjust insulin for exercise insulin for exercise

• PREVENTION OF HYPERGLYCEMIA AND PREVENTION OF HYPERGLYCEMIA AND HYPOGLYCEMIAHYPOGLYCEMIA as well must be performed as well must be performed continuously. HYPERGLYCEMIA>13.9mmol/l must continuously. HYPERGLYCEMIA>13.9mmol/l must be treated to prevent DKA especially during be treated to prevent DKA especially during pregnancy. pregnancy.

• TO PREVENT HYPOGLYCEMIATO PREVENT HYPOGLYCEMIA educate patient educate patient and family; teach patient a systemic approach to and family; teach patient a systemic approach to matching insulin to food intake and change in routine; matching insulin to food intake and change in routine; patients should check BG levels at least 4 times daily patients should check BG levels at least 4 times daily (before meals and bedtime), weekly at 3am, before (before meals and bedtime), weekly at 3am, before and after exercise, every 2 hours during illness, before and after exercise, every 2 hours during illness, before driving reach BG values>80mg/dl; bedtime snacks driving reach BG values>80mg/dl; bedtime snacks consisting protein and carbohydrate to avoid consisting protein and carbohydrate to avoid nocturnal hypoglycemia.nocturnal hypoglycemia.

SAFETYSAFETY• CSII with pump is as safe as MDII when CSII with pump is as safe as MDII when

recommended indications and procedure are recommended indications and procedure are followed. Undetected interruptions in insulin followed. Undetected interruptions in insulin delivery may result in ketotic episodes more delivery may result in ketotic episodes more often and more quickly with CSII which is of often and more quickly with CSII which is of particular concern in pregnancy. Infections particular concern in pregnancy. Infections or inflammation at the needle cite may occur or inflammation at the needle cite may occur also.also.

CSII EVOLUTIONCSII EVOLUTION• Pump therapy in type 1 diabetics starts in Pump therapy in type 1 diabetics starts in

1970’s. Since than, pumps have become much 1970’s. Since than, pumps have become much smaller more durable and easier to use. smaller more durable and easier to use. Modern pump have electronic memory, Modern pump have electronic memory, multiple BR, different BS options, safety multiple BR, different BS options, safety alarms and remote controls. New software alarms and remote controls. New software permitted the correction BS for an out-of-permitted the correction BS for an out-of-range BG level and how much insulin to give range BG level and how much insulin to give for a certain amount of carbohydrate.for a certain amount of carbohydrate.

FUTURE OF PUMP THERAPYFUTURE OF PUMP THERAPY

• Once continuous glucose monitoring is Once continuous glucose monitoring is available, the effectiveness of pump therapy in available, the effectiveness of pump therapy in achieving near-normal glycemia will be achieving near-normal glycemia will be enhanced and patients than may avoid enhanced and patients than may avoid hypoglycemic or hypoglicemyc episodes. hypoglycemic or hypoglicemyc episodes. Almost the final steps will be closed-loop Almost the final steps will be closed-loop systems as an external or implantible feeding systems as an external or implantible feeding back to an external or implantable pump.back to an external or implantable pump.

• SonorSonor

• MonitorMonitor

• Com-stationCom-station

• SoftwereSoftwere

NEW THERAPEUTIC AREA FOR NEW THERAPEUTIC AREA FOR EXTERNAL PUMPSEXTERNAL PUMPS

• For type 2 DM the CSII is used also. But, For type 2 DM the CSII is used also. But, whether it is ever necessary or advantageous whether it is ever necessary or advantageous compared with a less complex treatment is compared with a less complex treatment is unknown. Nevertheless, in these patients much unknown. Nevertheless, in these patients much lower risk of hypoglycemia exists. Some studies lower risk of hypoglycemia exists. Some studies showed that the glycemic control may be as good showed that the glycemic control may be as good as or better than with MDII regime. Recent as or better than with MDII regime. Recent results shoved the benefit of short term CSII in results shoved the benefit of short term CSII in the case of secondary failure of per oral therapy the case of secondary failure of per oral therapy and in newly diagnosed type 2 DMand in newly diagnosed type 2 DM

Conclusions IConclusions I

In most patients, mean blood glucose levels and glycated haemoglobin In most patients, mean blood glucose levels and glycated haemoglobin A1c are either slightly lower or similar on CSII versus MDI;A1c are either slightly lower or similar on CSII versus MDI;

Hypoglycaemia is markedly less frequent than during intensive Hypoglycaemia is markedly less frequent than during intensive injection therapy;injection therapy;

Diabetes ketoacidosis occurs at the same rate; Diabetes ketoacidosis occurs at the same rate;

Nocturnal glycemic control is improved with insulin pumps;Nocturnal glycemic control is improved with insulin pumps;

Basal rate changes help to minimize the "dawn phenomenon“;Basal rate changes help to minimize the "dawn phenomenon“;

Insulin pump therapy is safe and effective in children and Insulin pump therapy is safe and effective in children and adolescents, where fewer episodes of severe hypoglycaemia have been adolescents, where fewer episodes of severe hypoglycaemia have been found, with no increase in ketoacidosis while maintaining the found, with no increase in ketoacidosis while maintaining the glycemic control.glycemic control. One of the particular benefits of CSII in infants and One of the particular benefits of CSII in infants and toddlers is its ability to reduce the risk of severe hypoglycaemia. Even toddlers is its ability to reduce the risk of severe hypoglycaemia. Even limited use of CSII for overnight basal insulin replacement in limited use of CSII for overnight basal insulin replacement in children 7 to 10 years of age has been shown to be effective. children 7 to 10 years of age has been shown to be effective.

Conclusions IIConclusions II

The small age of the patient should not, itself, be a barrier to The small age of the patient should not, itself, be a barrier to initiation of this therapy.initiation of this therapy.

Use of lispro, aspart or glulisine in CSII is particularly suitable for Use of lispro, aspart or glulisine in CSII is particularly suitable for infants and toddlers, who have unpredictable appetites and eating infants and toddlers, who have unpredictable appetites and eating patterns, because it can be administered either before or after meal, patterns, because it can be administered either before or after meal, depending on the amount of carbohydrate that is eaten; depending on the amount of carbohydrate that is eaten;

• A successful therapy with CSII involves the appropriate selection, A successful therapy with CSII involves the appropriate selection, evaluation and training of individuals, a skilled and motivated health evaluation and training of individuals, a skilled and motivated health care team and close contact between the pump user and the health care team and close contact between the pump user and the health care team.care team.

CGMS usage serves to optimize therapy and metabolic control in CGMS usage serves to optimize therapy and metabolic control in patients children and adults, with type 1 Diabetes mellitus, and CSII. patients children and adults, with type 1 Diabetes mellitus, and CSII. CGMS provides a new level of protection against dangerous CGMS provides a new level of protection against dangerous hyperglicaemia and especially hypoglicaemia. CGMS is an very hyperglicaemia and especially hypoglicaemia. CGMS is an very important part of CSII now in even more in the future.important part of CSII now in even more in the future.