Base/bolus concept

Synonyms

Basic bolus therapy; NIS (near normoglycaemic insulin substitution); FIT (functional insulin therapy); intensified conventional insulin therapy; flexible insulin therapy; functional insulin therapy; continuous subcutaneous insulin infusion; CSII;

First author

The Austrian diabetologist Kinga Howorka described NIS (near-normoglycemic insulin substitution) in 1983. As this term was not 100% accurate, the term "functional insulin treatment" was used from around 1989 (Howorka 1996).

As early as 1963, the physician Arnold Kadish in Los Angeles developed the "Mill Hill Infusor", an insulin and glucagon pump with i.v. delivery. 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 in the United Kingdom developed small syringe pumps that could deliver insulin or other medications s.c. at a constant rate.

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 breakthrough came with the Hoechst Infusor MRSI with a 24-step basal rate. Initially, the programming of the basal rates still took place via an external programming device in the practice (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).

A basic bolus concept is a particular form of insulin therapy that is based on the breakdown of a healthy person's insulin levels into basal rates and additional boluses at meals (Herold 2021).

The basic bolus concept is part of the intensified insulin therapy. It can be implemented in practice in 2 different forms:

- intensified conventional insulin therapy (ICT)

- Insulin pump therapy (Herold 2021)

Pharmacokinetics

see intensified conventional insulin therapy (ICT) and

insulin pump therapy.

Indications

ICT

• Type 1 diabetes
• Type 2 diabetes
  • in the context of triple therapy
  • in the - in the Anglo-Saxon language area - described as 5-S situations, ICT is recommended in type 2:
    • severe hyperglycemia
    • symptomatic diabetes
    • acute or chronic comorbidity
    • Special situations such as
      • pregnancy
      • childhood
      • adolescence
    • secondary diabetes mellitus, for example:
      • drug-induced
      • in endocrine disorders

(Priya 2020)

For more detailed information, see intensified conventional insulin therapy (ICT).

Indications

Insulin pump therapy:

• Type 1 diabetes mellitus
• Pregnancy (Herold 2021)
• Infants (Kapellen 2013)
• Impending late complications of DM
• Desire for progression inhibition
• Dawn phenomenon (Herold 2021)
• frequent nocturnal hypoglycemia (Lehnert 2010)
• Disturbances in the perception of hypoglycemia
• 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)
• with ICT only insufficient BG adjustment possible
• desire to have children
• diabetic nephropathy (Lehnert 2010)

For further detailed information see. Insulin pump therapy.

Dosage and method of use

see intensified conventional insulin therapy (ICT) or insulin pump therapy.

Preparations

ICT:

As basal insulins: Semilente MC insulin (Hürter 2001), Lantus, Levemir (Schmeisl 2019), biosimilar Abasaglar, Toujeo, Tresiba (Herold 2021).

As bolus insulins: Actraphane 30, human insulin profile III, Humalog Mix 25, Insuman Comb 25, Novomix 30 (Herold 2021), Humalog Lilly, NovoRapid (Hürter 2001).

Insulin pump therapy:

• Normal insulin
• synthetically produced human insulin 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)

For more detailed information, see. Insulin pump therapy.

ICT:

ICT can reduce up to 80% of subsequent damage in type 1 diabetics (Schmeisl 2019).

Advantages of ICT are:

• there is a high degree of flexibility with regard to eating habits (Bundesärztekammer 2021).

Disadvantages are often perceived as:

• the insulin injections several times a day
• the need to check blood glucose several times a day (Priya 2020)
• weight gain
• highest tendency to hypoglycemia compared to all other insulin therapies in type 2 diabetics
• high training effort
• difficult handling (Bundesärztekammer 2021)

Insulin pump therapy

The use of an insulin pump therapy

• the insulin requirementis 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 studies is 0.04 events per patient year (Lehnert 2010)
• weight gain as a result of the therapy is not found (Haak 2018)
• the cardiovascular mortality decreases (Haak 2018)

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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 - 742
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6. Hürter P et al (2006) Compendium of pediatric diabetology. Springer Verlag 214 - 219, 241 - 243, 403
7. Kapellen T M et al. (2013) Children and adolescents with type 1 diabetes in Germany are more overweight than healthy controls: results comparing DPV database and CrescNet database. Journal of Pediatric Endocrinology and Metabolism.https://doi.org/10.1515/jpem-2013-0381
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