Normal insulin

In 1869, Paul Langerhans discovered a distinct accumulation of cells in the pancreas. In 1889, Mering and Minkowski demonstrated that total pancreatectomy induced diabetes mellitus in dogs (Kalra 2020).

In the fall of 1920, Frederick Banting, a London surgeon, had the idea of obtaining pancreatic secretions by ligating the pancreatic ducts. He began initial experiments with dogs at the University of Toronto under Prof. J. J. R. Macleod together with Charles Best, which were successful.

On Jan. 11, 1922 (Oyen 1985), the first human, Leonard Thompson, a young diabetic, received animal insulin and survived (Bliss 1982).

In 1923, two years after the discovery of insulin, factory production of insulin began in Europe (Egidi 2019). Normal insulin represents the oldest pharmaceutical preparation of insulin (Danne 2015).

At that time, insulin was administered according to a rigid regimen known as "conventional insulin therapy" (Herold 2022).

Normal insulin is a short-acting insulin. The duration of action and action characteristics of normal insulin were subsequently modified by the addition of protamine and/or zinc (Mehnert 2003).

• Mixing:

Normal insulin can be mixed with other insulins such as NPH insulins (the only exception is zinc-forming insulins [Herold 2022]).

Pharmacodynamics

Short-acting normal insulin mimics physiological insulin secretion during meals (Kasper 2015).

It represents a clear, pH-neutral solution (with the exception of Hoechst's porcine and bovine normal insulins, which have an acidic pH)

(Mehnert 2003)

Insulin in an insulin bottle is present in hexamers. After injection into the subcutaneous adipose tissue, dissociation into di- and monomers takes place. Dilution allows it to diffuse into the capillaries of the subcutaneous adipose tissue (Mehnert 2003).

Indication

• In the context of insulin therapy for diabetes mellitus type 1 and type 2 as:
  • Basic bolus concepts. d. (Alawi 2019) in the context of:
    • intensified conventional insulin therapy (ICT)
    • Insulin pump therapy (CSII = continuous subcutaneous insulin infusion [Kasper 2015])
• Conventional insulin therapy (CT)
• Hyperglycemic coma:

In shock, patients should be treated with normal insulin i. v. only; the duration of action at the insulin receptor is 20-40 min, and the half-life is < 10 min (Herold 2022).

Blood glucose concentration should be reduced by 50 mg / dl / h (2.8 mmol / l), but not lower than 250 mg / dl during the first 24 h to avoid cerebral edema and retinal damage (Herold 2022).

From a blood glucose concentration of 300 mg / dl (16.7 mmol / l), an infusion with 10% glucose should run in parallel to avoid too rapid a drop in blood glucose (Haak 2018) and to avoid lipolysis with an increase in free fatty acids (Herold 2022).

"Low-dose" insulin therapy is recommended in most patients, i.e.:

- initial bolus of 0.10 - 0.15 IU / kg bw i. v. and subsequently about 5 IU normal insulin / h i. v. via the dosing pump (Herold 2022).

If blood glucose does not drop within 2 h, the patient requires higher doses of insulin due to insulin resistance. To break the resistance, the insulin dose should be doubled. In rare cases, an even higher amount of insulin may be needed beyond this (Herold 2022).

For more details, see. Hyperglycemic coma

• Operative measures in diabetics type 1 and type 2:

The basic rule here is:

- 1 IU of normal insulin lowers blood glucose by 0.5 to a maximum of 2.0 mmol / l (depending, for example, on the existing stress metabolism and the type of diabetes [Müller 2021]).

- Normal insulin via perfusor at blood glucose levels between 120 - 180 mg / dl:

- with a daily requirement of < 40 I. E. Administration of 1.0 I. E. / h

- at a daily requirement of 40 - 80 I. E. Administration of 1.5 I. E. / h

- at a daily requirement of > 80 I. E. Administration of 2.0 I. E. / h

- as soon as the blood glucose rises > 200 mg / dl, the administration of an additional 0.5 I. E. normal insulin is required

- at BG values of < 120 mg / dl, 0.5 I. E. normal insulin less should be given

- at BG- values of ≤ 100 mg / dl, the insulin supply should be reduced or stopped and the glucose supply increased. Blood glucose should then be measured every 15-30 min (Herold 2022) For more details, see Diabetes and surgical interventions.

• diabetic ketoacidosis
• In hyperkalemia (Kasper 2015):

Dosage and mode of administration

Normal insulin is approved for

- subcutaneous

- intramuscular

- intravenous (as the only insulin)

- intraperitoneal administration (Mehnert 2003)

The onset of action of normal insulin is approx. 30 - 60 min with s. c. injection. The duration of action is 8 h (Herold 2022).

Both onset and duration of action are dose-dependent (Rietbrock 2013).

Due to its rapid onset of action and short duration of action, it is used in particular as a meal-related, preprandial insulin or as a corrective insulin in the case of elevated BG values. It is also the fast-acting component of mixed insulins (Mehnert 2003).

• Lowering blood glucose:

To achieve a reduction in blood glucose of 30 - 40 mg / dl (1.6 - 2.2 mmol / l), 1.0 I.U. normal insulin is required (Haak 2018).

The injection-eating interval should be between 15 - 30 min for s. c. administration (Herold 2022).

• Basicbolus concept s. d. (Alawi 2019) in the context of:
  • Intensified conventional insulin therapy (ICT): The basal insulin supply accounts for approximately 40-50% of the total insulin daily dose. In most cases, the basal insulin requirement is covered by an injection of an NPH- delay insulin at least twice a day (Herold 2022).

  • The remaining 50-60% of the daily insulin dose is administered as a meal-related bolus. Normal insulin 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 2022) For more details on dosing, see intensified conventional insulin therapy .

  • - Insulin pump therapy (CSII = continuous subcutaneous insulin infusion [Kasper 2015]) Only normal insulin or rapid-acting analog insulin is used in CSII (Herold 2022). For more information on dosing, see insulin pump therapy.

• Conventional insulin therapy (CT):

CT usually uses a mixed insulin, often consisting of 70-75% intermediate insulin (NPH) and 25-30% normal insulin.

- Mixed insulin e.g. 70 NPH and 30 normal insulin: onset of action after 30 - 60 min, duration of action 14 h (Haak 2018).

With two injections / d, 2/3 to ¾ of the required amount of insulin is injected before breakfast and the remaining 1/3 or 1/4 before dinner (Herold 2022).

Sometimes three injections / d have been shown to be more beneficial, using mixed insulin in the morning, normal insulin at noon, and mixed insulin in the evening (Herold 2022). For more details, see Conventional insulin therapy.

• Hyperglycemic coma:

In shock, patients should be treated with normal insulin i. v. only, duration of action is 20-40 min, half-life is < 10 min (Herold 2022).

For more information on dosing, see Hyperglycemic coma.

• Operative measures in diabetics type 1 and type 2:

The basic rule here is:

- 1 IU of normal insulin lowers blood glucose by 0.5 to a maximum of 2.0 mmol / l (depending, for example, on the existing stress metabolism and the type of diabetes [Müller 2021]).

- Normal insulin via perfusor at blood glucose levels between 120 - 180 mg / dl:

- with a daily requirement of < 40 I. E. Administration of 1.0 I. E. / h

- at a daily requirement of 40 - 80 I. E. Administration of 1.5 I. E. / h

- at a daily requirement of > 80 I. E. Administration of 2.0 I. E. / h

- as soon as the blood glucose rises > 200 mg / dl, the administration of an additional 0.5 I. E. normal insulin is required

- at BG values of < 120 mg / dl, 0.5 I. E. normal insulin less should be given

- at BG- values of ≤ 100 mg / dl, the insulin supply should be reduced or stopped and the glucose supply increased. Blood glucose should then be measured every 15-30 min (Herold 2022).

• Diabetic ketoacidosis:

Insulin delivery should be via a perfusor.

In exsiccosis, insulin can act poorly, so primary volume administration is required to achieve a good effect of insulin (Reitgruber 2021).

In shock, patients should be treated with normal insulin i. v. only (Herold 2022).

Blood glucose concentration should be reduced by 50 mg / dl / h (2.8 mmol / l), but during the first 24 hours should not reach lower than 250 mg / dl to avoid cerebral edema and damage to the retina (Herold 2022).

From a blood glucose concentration of 300 mg / dl (16.7 mmol / l), an infusion with 10% glucose should run in parallel to avoid

- a too rapid drop in blood glucose (Haak 2018)

- of lipolysis with an increase in free fatty acids (Herold 2022).

"Low-dose" insulin therapy is recommended in most patients, i.e.:

- initial bolus of 0.10 - 0.15 IU / kg bw i. v. and subsequently about 5 IU normal insulin / h i. v. via the dosing pump (Herold 2022).

If blood glucose does not drop within 2 h, the patient requires higher doses of insulin due to insulin resistance. To break this resistance, the insulin dose should be doubled. In rare cases, an even higher amount of insulin may be needed beyond this (Herold 2022).

• Hyperkalemia:

In hyperkalemia, the recommended dose is 10 I. E. normal insulin i. v. together with 50 ml of 50 % dextrose.

The effect occurs after about 10 - 20 min, reaches its peak after 30 - 60 min and the duration of action is about 4 - 6 h.

Since hypoglycemia is not uncommon with insulin plus glucose administration, 10% dextrose should be administered in parallel via a perfusor at 50 - 75 ml / h with close monitoring of plasma glucose concentration.

In hyperkalemic patients with an initial glucose concentration of ≥ 200 - 250 mg / dl, insulin should be administered without glucose, again with close monitoring of BG values (Kasper 2015).

Adverse effects

- Hypoglycemia:

Hypoglycemia occurs under normal insulin purely statistically 46.1 times per 100 person-years (Hartman 2008)

Preparations

• Actrapid
• Human insulin Normal
• Insuman rapid
• Berlinsulin H standard (Herold 2022)

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