Insulin pump therapy

As early as 1963, the physician Arnold Kadish in Los Angeles developed the "Mill Hill Infusor", an insulin and glucagon pump that had an i.v. supply. It still had the dimensions of a backpack and was not suitable for everyday use because of the risk of infection (Thomas 2010).

In the mid-1970s, researchers from Great Britain developed small syringe pumps that could deliver insulin or other medications s.c. in constant quantities.

At the beginning of the 1980s, special insulin pumps came onto the market in Germany, such as the CPI 9100 in 1980, which for the first time had a programmable basal rate. The Betatron II finally made it possible to set alternative basal rates.

The breakthrough came with the Hoechst infusor MRSI with a 24-step basal rate. Initially, the basal rates were programmed in the practice using an external programming device (Thomas 2010).

At the end of the 1990s, a pump was developed that offered various bolus options, had a direct connection to a blood glucose meter or could optionally be connected to continuous glucose monitoring: the CSII, which is still used today (Thomas 2010).

Insulin pump therapy is a form of insulin treatment in which insulin is continuously infused into the patient using an external pump (Herold 2021).

Insulin pump therapy (CSII = continuous subcutaneous insulin infusion [Kasper 2015]) - like ICT - counts as intensified insulin therapy (Herold 2021).

Prerequisites for a CSII

• Patients must be cooperative
• the possibility and willingness of multiple daily metabolic checks must be given (at least 4 / d, but usually more frequently)
• intensive diabetes training
• ICT training in case of pump failure (Herold 2021)
• SMBG (self-monitoring blood glucose) training (Kasper 2015).
• Management of hypoglycemia should be manageable
• Possibility of self-determination of ketones at a BG of > 250 mg / dl must be mastered
• Care of patients by physicians experienced in diabetes must be ensured (Herold 2021)

Pharmacodynamics

An external pump causes a continuous infusion with insulin. On modern devices, the basal rate can be programmed separately for each hour and controlled with different daily programs for e.g. weekends, menstruation, rotating shifts, etc. This makes it possible to counteract changing loads and the dawn phenomenon.

For the patient, it is possible to have the device administer bolus insulin in addition to meals - depending on the amount of food to be ingested and the preprandial blood glucose.

In the meantime, there are computer-controlled devices (closed-loop system) that have an autonomous sensor, the so-called CGM, which continuously measures the blood glucose value and displays it every 5 minutes. An alarm is given for high and low values. When the BG is low, the pump switches off automatically.

Pumps with an "open loop system", on the other hand, are operated manually by the patient (Herold 2021).

Indications

• Type 1 diabetes mellitus (now the standard therapy [Kolassa 2014])
• Pregnancy (especially in type 1 DM [Herold 2021]).
• Infants (standard therapy for children < 5 years [Kapellen 2013])
• Threat of late complications of DM
• desire for progression inhibition
• pronounced dawn phenomenon with recurrent hypoglycemia (Herold 2021)
• frequent nocturnal hypoglycemias(Lehnert 2010)
• disturbances in the perception of hypoglycemias
• Patient's desire for flexible therapy e.g. due to rotating shifts, frequent travel across different time zones, competitive sports, etc. (Herold 2021)
• Type 2 diabetes mellitus requiring insulin (Rotbard 2017).

However, according to the guideline, insulin pump therapy is rarely indicated in type 2 DM (Bundesärztekammer 2021).

• with ICT only insufficient BG adjustment possible - despite high motivation of the patient.
• desire to have children
• diabetic nephropathy (Lehnert 2010)

Dosage and method of application

Only normal ins ulin or fast-acting analog insulin is used in CSII (Herold 2021).

Under therapy with aspart, the rate of hypoglycemia is lower than with human insulin or insulin lispro (Haak 2018).

Adverse effects

• Infection at the infusion site
• Unexplained hyperglycemia due to blockage of the infusion set
• diabetic ketoacidosis when pump is not connected (Kasper 2015).
• risk of hypoglycemia during BG self-monitoring (Herold 2021)

Advantages of insulin pump therapy

• Optimal metabolic control possible
• Timing of food intake can be planned individually
• Timing of physical stress can be planned individually
• with closed-loop systems:
  • Timely alerting by the pump in the event of hypo- and hyperglycemia with initiation of appropriate countermeasures
  • stable settings of an HbA1c around 5.5 % with low hypoglycemia risk possible (Herold 2021)

Treatment goals

• Avoidance of hypoglycemic reactions
• Aiming for an almost normoglycemic metabolic situation with:
  • BG self-monitoring
  • BG fasting or preprandial 80 - 110 mg / dl (4.4 - 6.1 mmol / l)
  • BG postprandial ≤ 140 mg / dl (≤ 7.8 mmol / l
  • Acetone negative
  • Urine free of glucose
  • Albuminuria < 20 mg / l (Herold 2021).
• Elimination of possible risk factors for premature arteriosclerosis such as:
  • Normalization of blood pressure with target values of:
    • ≤ 140 / 90 mmHg in patients without albuminuria.
    • ≤ 130 / 80 mmHg in patients with albuminuria.
  • Abstinence from smoking (Herold 2021).
• Normalization of HbA1c
• Control every 3 months
  • Type 1 DM:
    • Aim for HbA1c of ≤ 6.5 if this can be achieved with minimal hypoglycemia
  • Type 2 DM:
    • Aim for HbA1c target range < 7 or < 6.5 if possible without hypoglycemia; values < 6.5 show no benefit, but there is an increased risk of:
      • Hypoglycemias
      • cardiovascular complications
      • Probably also an increase in the risk of dementia (Herold 2021).
• normalization of body weight and blood lipids
  • In diabetes mellitus: target value for LDL- cholesterol is < 100 mg / dl (< 2.6 mmol / l). Achievable by statins or PCSK9- inhibitors.
  • In diabetes mellitus and CHD: target value is < 70 mg / dl (1.8 mmol / l). Achievable by statins or PCSK9- inhibitors (Herold 2021).
• early prevention or therapy of complications such as:
  • diabetic retinopathy
  • diabetic foot syndrome
  • diabetic polyneuropathy (dPNP)
  • diabetic macular edema
  • diabetic nephropathy
  • erectile dysfunction
  • autonomic diabetic neuropathy (ADN)

(Herold 2021)

• regular examinations to detect possible late complications
  • Laboratory:
    • Urea
    • creatinine i. S.
    • (micro-) albuminuria
    • Creatinine clearance
  • clinical examination with bare feet every 3 months
  • pulse status (at least 1 x / year)
  • neurological status (at least 1 x / year)
  • ophthalmologist examinations (at least every 2 years)
  • dental check-ups and possible treatment of periodontitis (Herold 2021)

Preparations

• Normal insulin, formerly known as "old insulin". Nowadays, synthetically produced human insulin is mostly used such as:
  • Actrapid
  • Berlinsulin H Normal
  • Huminsulin Normal
  • Insuman Rapid (Alawi 2019)

• Insulin analogues:
  • Insulin Aspart (e.g. NovoRapid)
  • Insulin Glulisin (e.g. Apidra)
  • Insulin Lispro (e.g., Humalog, Liprolog)

(Alawi 2019)

The use of insulin pump therapy

• insulin requirements are reduced by 30 - 50 % (Herold 2021).
• there is a significant reduction in hypoglycaemia (evidence of > 0.4 % [Haak 2018]).
• According to meta-analysis, a reduction in the HbA1c value of 0.51 % can be achieved (Lehnert 2010).
• According to studies, there is a (low) risk of relevant ketoacidosis (Pala 2019), which according to current studies is 0.04 events per patient year (Lehnert 2010).
• weight gain as a result of therapy is not found (Haak 2018)
• cardiovascular mortality decreases (Haak 2018)

1. Alawi H et al (2019) Insulin types and insulin action. Ascensia DiabetesCollege Advisory Board 2019.
2. German Medical Association (2021) National health care guideline type 2 diabetes. AWMF- Registry No.: nvl-001
3. Haak T et al. (2018) S3 guideline therapy of type 1 diabetes. AWMF register no: 057-013
4. Herold G et al (2020) Internal medicine. Herold Publishers 739 - 741
5. Holder, M., Deiss, D., Lilienthal, E. et al. (2012) Insulin pump therapy and continuous glucose monitoring. Monatsschr Kinderheilkd 160, 593-604 https://doi.org/10.1007/s00112-012-2697-2.
6. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2412
7. Kolassa R (2014) Insulin pump therapy. The Diabetologist (10) 472 - 476
8. Lehnert H et al (2010) Rational diagnostics and therapy in endocrinology, diabetology and metabolism. Georg Thieme Verlag Stuttgart / New York 363 - 364
9. Pala L et al. (2019) Continuous subcutaneous insulin infusion vs modern multiple injection regimens in type 1 diabetes: an updated meta-analysis of randomized clinical trials. Meta-analysis: Acta Diabetol. 56 (9) 973 - 980. doi: 10.1007/s00592-019-01326-5
10. Rotbard D (2017) Continuous glucose monitoring: a review of recent studies demonstrating improved glycemic outcomes. Diabetes Technology and Therapeutics Vol. 19 No. S3. doi.org/10.1089/dia.2017.0035.
11. Thomas A (2010) From "backpack" to insulin pump therapy: history of insulin pump therapy. Diabetes and Technology 8 - 9