Ict

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).

ICT (intensified conventional insulin therapy) 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).

Together with insulin pump therapy, ICT is part of the so-called "intensified insulin therapy" (Herold 2021).

Pharmacodynamics

The normal physiological pattern of insulin secretion is characterized by:

• a continuous basal secretion (which suppresses hepatic glucose production between meals and at night)
• a bolus secretion after food intake (Priya 2020).

Basal secretion of insulin accounts for approximately 40-50% of total insulin secretion and postprandial insulin at each meal accounts for approximately 10-20% (Priya 2020).

ICT involves mimicking physiological insulin therapy (Dellas 2018). The differentiated prandial and basal rate secretion of beta cells served as a model (Hürter 2006).

One difference, however, is that injected insulin enters the circulation directly, whereas endogenously produced insulin is secreted into the portal system (Kasper 2015).

Indication

• Type 1 diabetes (now represents the standard therapy for type 1 [Schmeisel 2019]).
• Type 2 diabetes
  • In the context of triple therapy
  • in the constellation described in the Anglo-Saxon language as - 5-S situations, ICT is recommended for 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)

Dosage and method of use

• 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).

Short-acting insulin analogues should be injected after or just before the meal (< 10 min), whereas normal insulin is administered approximately 30-45 min before the meal (Kasper 2015). However, an injection-meal interval is not essential (Herold 2021).

Since there is a circadian insulin sensitivity, the insulin requirement per KE varies. There is a ratio of approximately 3: 1: 2. The insulin requirement per KE is approximately 2 I. E., at noon approx. 1.0 I. E. and in the evening at approx.1,5 I. E. (Herold 2021).

When adjusting or correcting insulin administration, consider:

- Lowering blood glucose 30 - 40 mg / dl (1.6 - 2.2 mmol / l) by 1.0 E normal ins ulin or in the case of rapid-acting analog insulin.

- Raise blood glucose 30 - 40 mg / dl (1.6 - 2.2 mmol / l) by 10 g carbohydrate = 1 KE.

A higher dose of insulin may be required for blood glucose > 270 mg / dl, dehydration, infection, fever, detection of ketone bodies.

A lower dose of insulin may be needed in case of insufficiency of the adrenal cortex, severe renal insufficiency, hepatic insufficiency, physical stress (German Medical Association 2021).

Any necessary adjustment of the dose is made at the end of the duration of action. Otherwise, there is a risk of (severe) hypoglycemia (Bundesärztekammer 2021).

Onset and duration of action with s. c. Injection

- NPH insulin: onset after 1 - 2 h, duration 14 h

- Normal insulin: onset after 30 - 60 min, duration 8 h

- Mixed insulin e.g. 70 NPH and 30 normal insulin: onset after 30 - 60 min, duration 14 h

- Degludec (Tresiba): onset after 1 h, duration 19 - 26 h

- Detemir (Levemir): onset after 1 - 2 h, duration > 42 h

- Glargin U 100 (Toujeo): entry after 1 h, duration > 20 - 27 h

- Aspart: onset after 20 - 25 min, duration 4 - 5 h

- Lispro: admission after 20 - 25 min, duration 4 - 5 h (Bundesärztekammer 2021)

Preparations

• Basal insulins: Semilente MC insulin (Hürter 2001), Lantus, Levemir (Schmeisl 2019), biosimilar Abasaglar, Toujeo, Tresiba (Herold 2021)
• Bolus insulins: Actraphane 30, human insulin profile III, Humalog Mix 25, Insuman Comb 25, Novomix 30 (Herold 2021), Humalog Lilly, NovoRapid (Hürter 2001).

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 hypoglycaemia compared to all other insulin therapies (in type 2 diabetics)

- high training effort

- difficult handling (Bundesärztekammer 2021)

1. German Medical Association (2021) National health care guideline type 2 diabetes. AWMF- Register No.: nvl-001
2. Dellas C (2018) Kurzlehrbuch Pharmakologie. Elsevier Urban and Fischer Publishers Munich 155, 506 - 510, 512.
3. Greten H et al (2010) Internal medicine. Georg Thieme Verlag Stuttgart 621 - 623
4. Herold G et al (2021) Internal medicine. Herold Publishers 737, 739
5. Howorka K Functional insulin therapy: teaching content, practice and didactics. Springer Verlag Berlin / Heidelberg New York 7,
6. Hürter P et al (2001) Children and adolescents with diabetes. Springer Verlag Berlin / Heidelberg / New York 157 - 158
7. Hürter P et al (2006) Compendium of pediatric diabetology. Springer Verlag 214 - 219, 241 - 243, 403
8. Kasper D L et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 2411 - 2412, 2415 - 24

9. Priya G et al (2020) Initiation of basal bolus insulin therapy. J Pak Med Assoc. 70 (8) 1462 - 1467

10. Schmeisl G W (2019) Diabetes training manual. Elsevier Urban and Fischer Publishers 53, 81 - 83, 204, 271T.