Pioglitazon patří mezi antidiabetika, která primárně snižují inzulínovou rezistenci. Kromě hypoglykemického působení má proto řadu dalších metabolicky příznivých účinků, které jsou zřejmě zodpovědné za pozitivní ovlivnění výskytu hlavních kardiovaskulárních příhod. Jeho možné nežádoucí účinky lze minimalizovat správným výběrem pacienta a respektováním kontraindikací.
Pioglitazone belongs to the antidiabetic drugs primarily reducing insulin resistance. In addition to hypoglycemic action, it has a number of other metabolically beneficial effects that may be responsible for its reduction of the incidence of major cardiovascular events. Possible side effects can be reduced by choosing the right patient and by respecting contraindications.
Pioglitazon patří do skupiny thiazolidindionů (glitazonů). Tato skupina je určena k léčbě diabetu 2. typu, který je charakterizován inzulinovou rezistencí a sníženou sekrecí inzulinu. Zvýšení inzulinové rezistence je základním patofyziologickým mechanismem vzniku metabolického syndromu. Diabetes mellitus 2. typu je nejdůležitější součástí metabolického syndromu. Thiazolidindiony zvyšují citlivost jaterních i periferních tkání k účinku inzulinu, a zlepšují tedy utilizaci glukózy. Rovněž byly prokázány další účinky příznivé ve vztahu ke kardiovaskulárním onemocněním. Pioglitazon je agonista PPAR-receptorů (peroxisome proliferator-activated receptor) se silnou vazbou ke γ -receptorům, který se váže současně i na α -receptory. To patrně významně přispívá k jeho příznivému vlivu na hladinu lipidů v séru a na výši krevního tlaku.
Pioglitazone is a member of the class of thiazolidinediones (glitazones). This class is intended for use in the treatment of type 2 diabetes mellitus, characterized by insulin resistance and decreased insulin secretion. Increased insulin resistance is the major pathophysiological mechanism for the development of the metabolic syndrome. Type 2 diabetes mellitus is the most important component of metabolic syndrome. Thiazolidinediones enhance susceptibility of the liver and peripheral tissues to the effect of insulin, thus improving glucose utilization. They also proved effective against other disorders associated with cardiovascular diseases. Pioglitazone is a PPAR agonist with a high binding affinity to the PPAR- α and PPAR- γ receptors. This seems to play a major role in the effects of pioglitazone on lipids and blood pressure.
- MeSH
- Liver diagnostic imaging pathology MeSH
- Humans MeSH
- Non-alcoholic Fatty Liver Disease * diagnosis epidemiology therapy MeSH
- Pioglitazone agonists therapeutic use MeSH
- Mass Screening MeSH
- Ultrasonography methods MeSH
- Vitamin E therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline MeSH
Insulin-sensitizing medications were originally used in psychiatric practice to treat weight gain and other metabolic side effects that accompany the use of mood stabilizers, antipsychotics, and some antidepressants. However, in recent studies these medications have been shown to cause improvement in depressive symptoms, creating a potential new indication outside of metabolic regulation. However, it is still unclear whether the antidepressant properties of these medications are associated with improvements in metabolic markers. We performed a systematic search of the literature following PRISMA guidelines of studies investigating antidepressant effects of insulin-sensitizing medications. We specifically focused on whether any improvements in depressive symptoms were connected to the improvement of metabolic dysfunction. Majority of the studies included in this review reported significant improvement in depressive symptoms following treatment with insulin-sensitizing medications. Nine out of the fifteen included studies assessed for a correlation between improvement in symptoms and changes in metabolic markers and only two of the nine studies found such association, with effect sizes ranging from R2 = 0.26-0.38. The metabolic variables, which correlated with improvements in depressive symptoms included oral glucose tolerance test, fasting plasma glucose and glycosylated hemoglobin following treatment with pioglitazone or metformin. The use of insulin-sensitizing medications has a clear positive impact on depressive symptoms. However, it seems that the symptom improvement may be unrelated to improvement in metabolic markers or weight. It is unclear which additional mechanisms play a role in the observed clinical improvement. Some alternative options include inflammatory, neuroinflammatory changes, improvements in cognitive functioning or brain structure. Future studies of insulin-sensitizing medications should measure metabolic markers and study the links between changes in metabolic markers and changes in depression. Additionally, it is important to use novel outcomes in these studies, such as changes in cognitive functioning and to investigate not only acute, but also prophylactic treatment effects.
Pacienti s diabetem 2. typu (DM2T) mají vysoké riziko makrovaskulárních komplikací, které představují hlavní příčinu jejich úmrtí. I při účinné léčbě tradičních kardiovaskulárních (KV) rizikových faktorů zůstává část KVrizika nevysvětlena. Syndrom inzulinové rezistence (IRS) představuje soubor kardiometabolických faktorů souvisejících s inzulinovou rezistencí (IR), který pravděpodobně přispívá k vysvětlení zbývajícího KV-rizika. Pioglitazon snižující inzulinovou rezistenci redukuje KVriziko u komplikovaných pacientů s DM2T. Tato práce ukazuje úlohu IR a IRS v rozvoji aterosklerotických KVkomplikací a zdůrazňuje vliv různých antidiabetik na tyto komplikace.
Patients with type 2 diabetes mellitus (T2DM) are at high risk for macrovascular complications, which represent the major cause of mortality. Despite effective treatment of established cardiovascular (CV) risk factors, there remains a significant amount of unexplained CV risk. Insulin resistance is associated with a cluster of cardiometabolic risk factors known collectively as the insulin resistance syndrome (IRS). Considerable evidence suggests that insulin resistance and the IRS contribute to this unexplained CV risk. CV outcome trials with pioglitazone have demonstrated that this insulin-sensitizing thiazolidinedione reduces CV events in high-risk patients with T2DM. In this review the roles of insulin resistance and the IRS in the development of atherosclerotic CV disease and the impact of antihyperglycemic medications on CV outcomes are discussed.
- Keywords
- kardiovaskulární riziko, makrovaskulární komplikace,
- MeSH
- Diabetes Mellitus, Type 2 * drug therapy complications MeSH
- Insulin Resistance MeSH
- Humans MeSH
- Pioglitazone therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Obesity, Abdominal MeSH
- Liver metabolism pathology MeSH
- Humans MeSH
- Non-alcoholic Fatty Liver Disease * diagnostic imaging drug therapy MeSH
- Obesity epidemiology complications therapy MeSH
- Pioglitazone * therapeutic use MeSH
- Randomized Controlled Trials as Topic MeSH
- Thiazolidinediones MeSH
- Triglycerides MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
