Insulin therapy, intensified

Last updated on: 22.03.2022

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History
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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).

Definition
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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).

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

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).

General information
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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)

Note(s)
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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)

Literature
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  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. Dellas C (2018) Short textbook pharmacology. Elsevier Urban and Fischer Publishers Munich 155, 506 - 510, 512.
  4. Greten H et al (2010) Internal medicine. Georg Thieme Verlag Stuttgart 621 - 623
  5. Haak T et al. (2018) S3 guideline therapy of type 1 diabetes. AWMF register number: 057-013
  6. Herold G et al (2020) Internal medicine. Herold Publishers 737, 739 - 741
  7. Howorka K Functional insulin therapy: teaching content, practice and didactics. Springer Verlag Berlin / Heidelberg New York 7
  8. Hürter P et al (2001) Children and adolescents with diabetes. Springer Verlag Berlin / Heidelberg / New York 157 - 158
  9. 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
  10. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2411 - 2412, 2415
  11. Kolassa R (2014) Insulin pump therapy. The Diabetologist (10) 472 - 476.
  12. Lehnert H et al (2010) Rational diagnostics and therapy in endocrinology, diabetology and metabolism. Georg Thieme Verlag Stuttgart / New York 363 - 364
  13. 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
  14. Priya G et al (2020) Initiation of basal bolus insulin therapy. J Pak Med Assoc. 70 (8) 1462 - 1467.
  15. 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.
  16. Schmeisl G W (2019) Diabetes training manual. Elsevier Urban and Fischer Publishing 53, 81 - 83, 204, 271T.
  17. Thomas A (2010) From "backpack" to insulin pump therapy: history of insulin pump therapy. Diabetes and Technology 8 - 9

Last updated on: 22.03.2022