Insulin therapy, intensified

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).

The first insulin pump was developed by the physician Arnold Kadish in 1963 in Los Angeles, the so-called "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 from Great Britain developed small syringe pumps that could deliver insulin or other medications s.c. in constant quantities.

After many intermediate developments, a pump came onto the market at the end of the 1990s 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).

Intensified insulin therapy is a form of insulin treatment according to the basic bolus concept, which is adapted to the insulin level of a healthy person and consists of a basal rate and several meal-dependent insulin doses (Herold 2021).

Intensified insulin therapy can mimic the insulin level of a healthy person in 2 ways:

• 1. by ICT (intensified conventional insulin therapy) [Herold 2021]).

This is a form of insulin treatment in which a short-acting insulin is injected in addition to a long-acting insulin at mealtimes and depending on the current BG level (Dellas 2018).

• 2. Insulin pump therapy (CSII = continuous subcutaneous insulin infusion [Kasper 2015]). Insulin pump therapy is a form of insulin treatment in which insulin is continuously infused into the patient by means of an external pump (Herold 2021).

Pharmacodynamics

s. ICT and insulin pump therapy

Requirements

s. ICT and insulin pump therapy

Indication

For ICT:

• Type 1 diabetes (now the standard therapy for type 1diabetes [Schmeisel 2019])
• Type 2 diabetes
  • in the context of triple therapy
  • in the - in the Anglo-Saxon language area as - 5-S situations described constellation, ICT is recommended in type 2:
    • severe hyperglycemia
    • symptomatic diabetes
    • acute or chronic comorbidity
    • special situations such as
      • Pregnancy
      • childhood
      • adolescence
  • secondary diabetes mellitus e.g:
    • drug-induced
    • in endocrine disorders (Priya 2020)

For more details, see. ICT

For insulin pump therapy:

• Type 1 diabetes mellitus (now represents the standard therapy here [Kolassa 2014]).
• Pregnancy (especially in type 1 DM [Herold 2021]).
• young children (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)

For more details see Insulin pump therapy

Dosage and type of application

• Insulin requirement

The daily insulin requirement is 0.67 I. E. / kg / d = approximately 40 I. E. (Dellas 2018).

• Substitution of basal insulin

On the basal insulin supply falls about 40 - 50% of the total insulin daily dose.

In most cases, basal insulin requirements are met by injecting an NPH- delayed-release insulin (Herold 2021) at least twice, such as detemir early in the morning and late in the evening. Alternatively, intermediate insulin can be used: 3x / d, morning, noon, evening or glargine: 1x / d late evening (Greten 2010).

Verification of adequate insulin dose is checked by fasting blood glucose or by skipping a meal (Bundesärztekammer 2021).

• Prandial substitution of insulin

The remaining 50-60% of the daily insulin dose is administered as a meal-related bolus. Normal ins ulin or short-acting insulin analogues are used for this purpose.

The amount of the dose depends on

• The size of the meal (measured in carbohydrate unit = KE = 10 g of carbohydrate [Dellas 2018]).
• the preprandial blood glucose
• the time of day
• The planned physical exertion (Herold 2021).

For more details, see. ICT

Insulin pump therapy:

Only normal insulin or rapid-acting analog insulin is used with CSII (Herold 2021).

For more details see Insulin pump therapy

Adverse effects

s. Insulin pump therapy

Advantages

s. Insulin pump therapy

Preparations

For ICT:

• Basal insulins such as:

Semilente MC insulin (Hürter 2001), Lantus, Levemir (Schmeisl 2019), biosimilar Abasaglar, Toujeo, Tresiba (Herold 2021)

• Bolus insulins such as:

Actraphane 30, Human Insulin Profile III, Humalog Mix 25, Insuman Comb 25, Novomix 30 (Herold 2021), Humalog Lilly, NovoRapid (Hürter 2001).

For insulin pump therapy:

• Normal insulin, formerly known as "altinsulin". Nowadays, synthetically produced human insulin is mostly used such as:
  • Actrapid
  • Berlinsulin H Normal
  • Huminsulin Normal
  • Insuman Rapid (Alawi 2019)
• Insulin analogues such as:
  • Insulin Aspart (e.g. NovoRapid)
  • Insulin Glulisin (e.g. Apidra)
  • Insulin Lispro (e.g., Humalog, Liprolog) (Alawi 2019)

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

By using an insulin pump therapy

• the insulin requirement is 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)

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