Insulin sensitizers (Thiazolidinedione – after chemical scaffold, a Thiazole-2, 4-dione; Glitazone – after the common suffix) are a group of agents in the form of tablets for the treatment of diabetes mellitus are applied. The name of the group is already on the way, an Empfindlichmachung of the tissue to insulin, out.

The body’s own insulin is therefore in a position again, elevated blood glucose levels. Since both the market drugs Rosiglitazone (Avandia ®) and Pioglitazone (Actos ®) only relative short time available. There are professionals in lively discussion about the benefits and advantages over other anti diabetic agents, especially as the first drug of this group (Troglitazon). Due to hepatic effects in some countries from the market in Some parts of the world and never has been admitted.

Effect

Insulin sensitizer differ in their principle of operation of the other representatives of the so-called oral anti diabetic agents, their joint application area of type 2 diabetes. In general, it is diabetes, a disorder of sugar metabolism in the human organism to understand where the body’s own hormone insulin a supporting role. In contrast to Type 1, where the body no longer able to meet his need for insulin to cover themselves and this is in the form of injections must be artificially produced by type 2 diabetes; the body concerned certain amounts of insulin. This may; however, its functions in the body no longer perceive the extent required. Often we see in connection with this form of diabetes, obesity and poor dietary habits, which become a cause of this disease is viewed. Apparently, however, also plays a role in the genome, especially regarding the so-called insulin resistance, the condition that the tissue is not properly respond to insulin. Insulin resistance is often even before the symptoms of diabetes to determine a preventive therapy would be conceivable. See also: Metabolic Syndrome. Apart from the everyday complaints that diabetes brings with it, you write her a whole series of secondary diseases, the quality of life and significantly affect life expectancy, to (damage to large and small blood vessels). Studies indicate a positive development of these diseases among insulin sensitizers out. Clearly indicated are insulin sensitizers in patients whose blood sugar levels (or the HbA1c value) by treatment with metformin or Sulfonylurea, as well as through weight reduction and diet control is not adequate can be reduced. Due to the different point of attack of the insulin sensitizers are added to the effect in combination with other oral anti diabetic agents. Meanwhile, the drugs in this group also admitted to monotherapy.

Strategy

What idea is behind the use of insulin sensitizers for the treatment of diabetes? Oral anti diabetics of the Sulfonylurea type improve the distribution of insulin, metformin in turn causes the organism to better utilization of glucose. With the help of insulin sensitizers, a fundamentally different way of diabetes therapy trod. This practice varied effects in the body, which ultimately lead to a decrease in insulin resistance. Your body is insulin in order to re-enable those metabolic processes set in motion, which resulted in a decrease in blood glucose levels rise. Logically, the organism must they still be able to produce insulin in the body.

Which way are insulin sensitizers through the organism? The two approved drugs as active ingredients are in the form of tablets on the market. From the gastrointestinal tract, they are almost completely into the blood and then to 99% bound to plasma proteins. The active ingredients are distributed in the body and bring it to their destination within the body cells. Looking into the interior of such a cell, then push it to a whole set of transactions associated with insulin sensitizers is related. Key to its effectiveness is that they are likely to interact with a protein that is often in the nucleus of fat cells is encountered. It is a nuclear receptor of the type of peroxisomes Proliferator Activated Receptors, in short: PPARγ. If the receptor of a ligand and is then filled with a second from its natural ligand occupied receptor protein a complex, then this triggers the transcription of certain genes. Several of these effects can be derived. Thus, even the differentiation of immature fat cells produce adipocytes promoted. This increases the capacity to absorb free fatty acids and triglycerides in the adipose tissue. In addition, the effect of proteins, which are emitted from the adipose tissue, as Adipsin, Leptin, Resistin alfa and tumor associated with insulin resistance are related to it, antagonisiert. Through gene expression is also the formation of glucose transport molecules significantly increased, leading to a direct glucose-lowering effect results. Together with enhanced glucose utilization in muscle cells leads to an overall reduction of insulin resistance. As a result of these effects, there is a lower glucose and insulin level in the blood determined. Even a slight reduction in triglycerides, with increasing HDL and LDL levels and a slight decrease of blood pressure is observed. Certain effects can only individual representatives of this group are ascribed. These will be for the respective drugs mentioned. It is also not yet completely clear whether certain observations, such as effects on blood vessels and decrease the aggregation tendency of blood platelets, the drug itself or the improved glucose and fatty acid metabolism are attributable from the body

Rosiglitazone and Pioglitazone are both highly lipophilic compounds. The human body must be only slightly converted in order to be able to leave again. Enzymes of the type of cytochrome P450, which in high concentrations in the liver can be found, do this. The metabolism sets in, when one of these substances in the body is located within several hours. It is more than half of the injected amount of drug in the blood evidence; however, looking after the converted compound (Rosiglitazone metabolites such as p-hydroxysulfat, which is also a certain effect of exercise), so you can find this much longer time. The excretion of drugs and metabolites is finally done both on the kidney as well as on the chair. Unlike other drugs, for diabetes therapy is available, the effect of Insulin sensitizer not directly but only after two weeks or later.

Costs and Benefits

The expenditure for the treatment of diabetes and its effects amount to about 30 billion euros per year in Some parts of the world. Until 2010, the number of diabetics in Some parts of the world at 10 million, experts estimate. The blood glucose levels can be reduced with metformin. But came up with this medication only about half as many to prevent diseases like diabetes by a shift in lifestyle. Pill swallowing is certainly less cumbersome than the daily half-hour movement, the doctors deem necessary to prevent diabetes. A study of Rosiglitazone showed that this drug amongst the most vulnerable people the risk of diabetes significantly reduces. In a period of three years with Rosiglitazone-treated group infected not even half as many participants as in a comparison group who only received a sham treatment. One must also ask that whether such a “medicalisation” of a health problem would be that you just as well with a change of lifestyle in the grips could.