Insulin therapy

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The insulin therapy is a treatment method in the Diabetology , wherein for the treatment of high blood sugar in diabetes mellitus , a preparation of insulin to the lack of the body's metabolic hormone is administered insulin to compensate.

In the first decades of the 20th century, insulin was recognized as the blood sugar lowering substance from the pancreatic tissue and was chemically isolated. In 1922, Frederick Banting introduced the first insulin therapy to a person with type 1 diabetes mellitus.

Insulin delivery options

The previously approved options for delivering insulin are injections using a pen , disposable insulin syringes , or continuous subcutaneous insulin infusion (CSII) with an insulin pump . The injection is usually made in the subcutaneous fat tissue (= subcutaneous), more rarely intramuscularly or intravenously. In the case of subcutaneous injection into the subcutaneous tissue, the location must be changed frequently, otherwise lipohypertrophy can occur.

Insulin preparations for inhalation are still being researched, but the only product previously approved in the EU ( Exubera ) was withdrawn by the manufacturer in 2007.

syringe

Syringes were the norm until the era of insulin pens. Older type 1 diabetics are still familiar with the reusable syringes and the thick reusable needles, which for a long time were responsible for the horror of insulin therapy. These were replaced by disposable syringes with very thin disposable needles. Nowadays, insulin pens are predominantly used in Germany. Disposable syringes and needles are still on the market as emergency equipment. There are insulin syringes for insulin U40 (= 40 units of insulin per milliliter) and insulin U100 (= 100 units of insulin per milliliter).

Length of the injection needles : There are different needle lengths, e.g. B. 4-6 mm in children and very slim adults, still 8 mm; 10 mm and 12 mm.

Insulin pen

So-called insulin pens look similar to thicker ballpoint pens and can be equipped with an insulin cartridge. The insulin dose is set on a rotary knob which, at the push of a button, limits the stroke of a plunger that pushes the piston in the cartridge. There are different sizes of the cartridges, the usual filling volume is 3 ml (with insulin U100, i.e. 100 IU per ml). The matching injection cannulas are sharpened on both sides and have a plastic thread in the middle. They are usually only used once, i.e. screwed on before each injection and pierce through the rubber membrane of the cartridge. They are available in different lengths.

Pre-filled pen

Ready-to-use or disposable pens are permanently equipped with an insulin cartridge and are disposed of after the insulin has been used up.

Insulin pump

Insulin pumps are used to continuously deliver insulin into the subcutaneous fatty tissue. The pre-programmed amount of basal insulin (long-acting insulin) that is administered by the pump provides the body with basic insulin and is also known as the basal rate . Mealtime insulin (short-acting insulin) is also administered as a bolus as required ( bolus administration ).

Forms of therapy

In the past few decades, various diabetologists and diabetes clinics have developed different therapy variants around insulin therapy, each of which often had a specific group of patients or specific problems in mind. To make things easier, the forms of therapy were given memorable acronyms (CT, ICT, FIT, BOT, SIT, CSII), which are briefly explained below.

Conventional insulin therapy (CT)

With conventional insulin therapy, a certain amount of insulin is injected at set times. The CT is typically used in insulin-dependent type 2 diabetes mellitus, mainly in older patients, as these above all have a fixed daily rhythm. A mixed insulin is usually injected two to three times a day. This form of therapy requires the punctual consumption of meals with precisely defined amounts of carbohydrates that affect blood sugar. Due to the action of insulin, you must also have between meals in the morning and in the afternoon, as well as a late meal. Because this therapy requires a non-practical, schematic eating behavior, it is not possible to organize daily meals flexibly. In addition, there is a considerable risk of low blood sugar ( hypoglycaemia ) if you skip meals .

Intensified conventional insulin therapy (ICT)

(see also basic bolus therapy )

The intensified conventional insulin therapy (ICT) is mainly used in type 1 diabetics, but also in type 2 diabetics in the case of insufficient insulin secretion or advanced disease. It consists of a so-called two-syringe therapy, i. H. On the one hand, fast-acting insulin is injected with meals and for correction purposes (bolus); on the other hand, the body needs a basic supply of insulin, regardless of the carbohydrates supplied, which is guaranteed with delayed insulin (basic). This basic bolus principle mimics the insulin secretion of the healthy pancreas . The basic insulin is injected one to three times a day depending on the type of insulin and blood sugar level; the bolus insulin with meals or when blood sugar levels are too high.

The basal rate must be adapted to different physical loads.

ICT enables a more variable way of life than conventional therapy, as it allows better adjustments to the current life situation (movement, rest, work, sport, etc.). In connection with metabolic controls (blood sugar measurement) and the logging of all factors influencing the glucose metabolism, changes in results and adjustments can be made quickly.

The Austrian diabetologist Kinga Howorka coined the term functional insulin therapy . It essentially corresponds to the ICT used today.

Supplementary insulin therapy (SIT)

Supplementary insulin therapy is primarily aimed at diabetics who still have their own insulin secretion. The main problem with type 2 diabetics is that the insulin is impaired and that there is actually far too much insulin. At the same time, the rapid rise in insulin levels after meals is muted. For this purpose, in addition to an insulin-independent therapy with metformin, fast-acting insulin is given with meals. In this way, blood sugar peaks are reliably and effectively cut after meals. The optimized adjustment of insulin with meals improves the metabolism and reduces the risk of hypoglycaemia. Since snacks can be skipped, weight loss is easier.

Basal Assisted Oral Therapy (BOT)

The type 2 diabetic receives z. B. oral antidiabetic drugs at the start of therapy. If the fasting blood sugar levels are elevated, especially in the morning hours, a basal insulin is administered in the evening hours, which suppresses the endogenous gluconeogenesis of the liver in the early morning hours.

Continuous Subcutaneous Insulin Infusion: Pump Therapy (CSII)

Insulin pump therapy ( insulin pump ) is mainly suitable for type 1 diabetics and can be seen as the most progressive form of therapy. Its main problem is that it is significantly more expensive overall than ICT. The health insurance companies therefore need a comprehensible justification why the treating doctor recommends this form of therapy for his patient. In the long term, however, it also saves money for the health insurers by reducing the long-term effects.

The advantages over other forms of therapy are:

Example of a basal rate profile
  • low insulin depots in the subcutaneous fat tissue (lower risk of hypoglycaemia);
  • better adjustability to differences in movement by lowering or increasing the basal rate;
  • more precise dosing of the basal rate as well as the meal-related insulin;
  • better control of a dawn phenomenon (dawn phenomenon = morning hormonal increase in insulin resistance);
  • better options for intervention (especially less conspicuous) with metabolic fluctuations;
  • ideal insulin reduction options before sporting events with much less weight gain through meal-related compulsory carbohydrates to compensate for an increased degree of effectiveness of the basal insulins / improved effectiveness of the receptors (basal rate can be switched off or reduced);
    Example of a profile with subsidence
  • Fewer hypoglycemia episodes by lowering the currently supplied insulin while at the same time having low insulin deposits in the body that no longer have to be absorbed by the intake of additional carbohydrates.
  • Sometimes support in determining the amount of insulin for a meal with documentation support; not with all pumps.

Further indications can be:

  • strongly fluctuating blood sugar values ​​as in the case of a pronounced dawn phenomenon (sharp rise in blood sugar in the early morning hours),
  • low insulin requirement (toddlers, people with high levels of physical activity during the day),
  • shift work
  • Insufficiently adjustable blood sugar with too high HbA1c
  • Pregnancy with otherwise unadjustable blood sugar metabolism

Important aspects

With all forms of therapy, certain common aspects must be observed in order to apply the therapy successfully.

Blood sugar self-checks

Main items: blood sugar , blood glucose meter , continuously measuring glucose sensor

With a blood glucose meter , the diabetic can check his blood sugar himself. For type 1 diabetics, but often also for type 2 diabetics, measuring their own blood sugar during insulin treatment is essential for therapy. In the case of insulin-dependent patients, the costs for self-monitoring of blood sugar are reimbursed by the statutory health insurance companies. The blood sugar measurement with a continuously measuring glucose sensor (CGM system) delivers more closely meshed blood sugar values ​​every minute. The values ​​are displayed graphically on a CGM system or alternatively on the insulin pump . The risk of hypoglycemia or hypoglycemia can be countered by individually adjustable limit values ​​on the CGM system.

Record keeping

The protocol should contain within a feasible framework all data that are necessary for a correct assessment of the metabolic development and thus for the appropriate administration of insulin. This is usually only possible if all factors influencing blood sugar are noted. In addition to the actual blood sugar value, this includes the exact time of the measurement, whether before or after a meal, as well as information on the carbohydrate content of the food consumed. In addition, all those data are important that lead to a lowering of blood sugar levels, such as periods of intense exercise (sport), sweating, but also factors such as workload or stress. The more reliable these entries are, the more certain are the conclusions that can be drawn from such a protocol (BE factors, basal rate changes, assessments of food, etc.).

The log can be kept on paper or electronically using special so-called diabetes management software ; Numerous blood glucose meters can now save and manage the measured values ​​including additional information and transfer them to a computer and / or to a patient file on the Internet via an interface cable or via bluetooth or email, which offers the advantage of remote monitoring: the patient can give the doctor access to the data allow what z. B. is useful for telephone advice and emergency situations.

Alternating shifts and unequal daily rhythm

A changing daily rhythm makes insulin therapy more difficult, especially if it causes sleep disorders . These can lead to the body becoming less sensitive to insulin (up to approx. 40%). Changing shifts , in particular, can - if they result in sleep disorders - cause increased problems with metabolic management.

In particular, a shift in dawn and dusk phenomena (increased hormonal blood sugar peaks in the morning and in the evening caused by the rhythm of the daytime) should be taken into account.

Metabolic fluctuations

Insulin therapy without metabolic fluctuations is not feasible. Blood sugar can - depending on the influencing factor and intensity - be subject to serious changes within an hour. As a rule, however, these fluctuations can be explained by the diabetic himself and can be foreseen over a certain period of time, so that they can also be calculated or estimated within certain bandwidths (expectations). Causes of strong blood sugar fluctuations can be based on processes such as the dawn phenomenon or the Somogyi effect . As Brittle Diabetes (Engl. Fluctuating) is called a hard adjustable diabetes due unsystematic, unexplained blood sugar fluctuations. After the start of insulin therapy for a type 1 diabetic, a so-called "honeymoon phase" (honeymoon) can occur. For reasons that have not yet been fully clarified (including immunological ), the patient's pancreas temporarily produces more of its own insulin than before the start of therapy, so that the need for exogenous insulin initially decreases or more hypoglycaemia is observed.

Insulin therapy for type 2 diabetes

In type 2 diabetes, there is no absolute insulin deficiency at the beginning, but rather an impairment of the action of the insulin ( insulin resistance ) or a relative insulin deficiency due to obesity, so that insulin therapy is only indicated in the third line. The initial therapy consists of training and nutritional advice in order to achieve an improvement in blood sugar levels and possibly a reduction in body weight through a change in lifestyle with regular exercise and an adapted diet. If this is unsuccessful, oral antidiabetic drugs are used as a second priority; insulin is only added if this therapy fails.

Insulin therapy for type 2 diabetes often leads to an increase in body weight as an undesirable side effect, which in turn can lead to higher insulin resistance. In this respect, the overweight type 2 diabetic must try to normalize their body weight and keep the necessary insulin dose as low as possible through adequate nutrition, regular exercise and, if necessary, oral antidiabetic drugs.

In type 2 diabetics, a relative insulin deficiency can soon be detected, which mainly affects the first phase of insulin secretion after ingestion. The first blood sugar spike after the meal is partly responsible for the development of secondary damage such as coronary artery disease (CHD), vascular damage such as micro and macro angiopathies , kidney failure , eye damage ( diabetic retinopathy , blindness) and nerve damage ( neuropathy ).

Insulin sensitivity criteria

The need for insulin fluctuates throughout the day. In the morning, the insulin requirement is due to the body's own hormones such as B. Cortisol highest. The average insulin requirement is lowest at lunchtime and then increases again in the evening. In the late evening, the insulin requirement falls again and reaches its absolute minimum, only to increase again from 3:00 a.m.

With normal physical activity, a ratio of approximately 50% basal insulin and 50% meal-related insulin is calculated. The average insulin requirement is calculated with a total of approx. 40 U per day or, based on body weight, with approx. 0.5-1.0 units / kg body weight.

Insulin sensitivity depends on many individual factors:

  • Type of insulin (in ascending order: very fast-acting analog insulins, normal insulins, NPH insulins, long-acting analog insulins)
  • Place of insulin injection (e.g. faster effect if injected in the abdomen, slower and delayed if injected in the thigh)
  • Type of insulin administration (intravenous, intramuscular, subcutaneous)
  • Length of the injection needle (the lengths are between 4 and 12 mm, a needle that is too short does not bring the insulin deep enough to the supplying blood vessels, a needle that is too long can hit the muscle, the insulin acts faster)
  • Blood flow to the injection site (can be accelerated by exposure to the sun, hot bath, the effect is slowed down in the cold)
  • Starting blood sugar (at high values ​​there is a relative insulin resistance, at low values ​​the blood sugar reacts very sensitively)
  • Food intake (meals rich in fat and protein cause blood sugar to rise slowly, rapidly absorbable carbohydrates quickly)
  • Exercise (endurance sports before or afterwards causes blood sugar to drop faster)
  • Alcohol (consumed the evening before, can lead to hypoglycaemia in the early morning, as the liver - instead of releasing glucose - is busy breaking down alcohol)
  • Disease (an infection increases insulin resistance)
  • Stress (can lead to pronounced increases in blood sugar as well as hypoglycaemia - depending on the type of reaction of the person)
  • Insulin dose (a high dose of insulin injected into one area takes longer to have the maximum effect than if the dose is divided into several individual doses.)

The correction factor indicates how much the blood sugar falls per given unit of insulin. It allows an approximation of how many units of insulin the body needs to go from a higher blood sugar to a target value. The target range for most diabetics is between 80 and 120 mg / dl.

In adults of normal weight and lack of insulin resistance , the correction factor is usually between 30 and 50 mg / dl per IU of insulin. In petite people and children, however, the correction factor is significantly higher (lower volume of distribution) and noticeably lower in taller and thicker people (higher volume of distribution). The insulin dose required in each case must therefore always be determined individually by carefully probing.

If the blood is acidic due to a hyperglycemic metabolic situation with an absolute insulin deficiency in type 1 diabetics ( ketoacidosis ), special regulations apply, which are taught in the training courses.

History of insulin therapy

see history of diabetology

At the beginning of the insulin therapy there were only animal insulins with the duration of action of normal insulin of approx. 4 to 7 hours. Furthermore, blood sugar self- tests were not feasible for many years, so that in outpatient medicine one had to make do with urine sugar controls for many years . Naturally, these only show the blood sugar concentration with a very delay and indirectly. Because of the short duration of the action of the insulin, efforts were made to achieve a simplification for the diabetic. Hans Christian Hagedorn , a Danish researcher, developed the first long-acting insulin preparation from protamine and pig insulin in 1936 , which is still used today under the name Neutral Protamine Hagedorn or NPH insulin (only no longer in conjunction with insulin from animal products).

The increasing improvement in blood sugar self-tests has allowed diabetics to take over their therapy more and more independently. In the 1970s, changes in the color of the test strips wetted with blood made it possible to determine the blood sugar level relatively precisely. Then came the first handy electrical devices that showed the value after a few minutes. Today the times for the measurement process are less than 5 seconds.

Along with the improved techniques, the therapy regimen also loosened up, which in the first decades combined hardly any freedom in diet with little freedom of choice for the patient. Today, the patient is called upon to ideally manage his therapy independently with almost complete freedom in nutrition. And the administration of insulin, which is necessary 6-8 times a day, has often turned into therapy with an insulin pump, the needle of which only needs to be changed every 2-3 days.

An important milestone for independent therapy was the DCCT study , which, along with other studies, provided evidence that independent, intensified insulin therapy offered advantages in terms of avoiding long-term damage.

literature

  • Helmut Hasche (Ed.): Diabetes mellitus in old age. A handbook for the nursing professions . Schlueter, Hannover 1996, ISBN 3-87706-403-5 .
  • Michael Nauck, Georg Brabant, Hans Hauner (Hrsg.): Kursbuch Diabetologie. Course and examination content of the advanced training to become a diabetologist (DDG) . Kirchheim, Mainz 2005, ISBN 3-87409-403-0 .
  • Andreas Thomas: The Diabetes Research Book. New drugs, devices, visions . 2nd revised and expanded edition. Kirchheim + Co, Mainz 2006, ISBN 978-3-87409-411-5 .
  • Hellmut Mehnert, Eberhard Standl, Klaus-Henning Usadel, Hans-Ulrich Häring (eds.): Diabetology in clinic and practice . Georg Thieme Publishing House. 2003, ISBN 3-13-512805-9 ; books.google.de .
  • Renate Jäckle, Axel Hirsch, Manfred Dreyer : Living well with type 1 diabetes . 7th edition. Urban and Fischer-Verlag, 2010, ISBN 978-3-437-45756-2 .

Web links

Individual evidence

  1. ↑ Peter Hien, Bernhard Böhm: Diabetes manual: a guide for practice and clinic . 5th edition 2007, ISBN 978-3-540-48551-3 , p. 178.
  2. ↑ Entry on Exubera, inhalation preparation on ema.europa.eu, the website of the European Medicines Agency ; last accessed on November 5, 2010
  3. ^ Howorka, Kinga: Functional insulin therapy . Springer publishing house. 4th edition 1996. ISBN 3-540-60254-2
  4. ↑ For the basic pension entitlement cf. SGB ​​V. Accessed on January 28, 2011 . The prescription practice differs depending on the KV, cf. beta Institut non-profit GmbH: Regulation of blood sugar test strips . (PDF; 41 kB) 2014, accessed on September 10, 2014 .
  5. ↑ Aly H, Gottlieb P: The honeymoon phase: intersection of metabolism and immunology. . In: Current opinion in endocrinology, diabetes, and obesity . 16, No. 4, Aug 2009, pp. 286-92. doi : 10.1097 / med.0b013e32832e0693 . PMID 19506474 .
  6. ↑ diabetes-deutschland.de UKPDS and DCCT - is a good diabetes control worthwhile? From notabene medici 34 (2004), pp. 19-20