Sažetak | Metabolički sindrom, poznat i kao sindrom X, skupina je biokemijskih i fizioloških poremećaja koji zajedno nose povećan rizik za obolijevanje od kardiovaskularnih bolesti, dijabetesa tipa II, ali i nekih zloćudnih bolesti. Dijagnozu metaboličkog sindroma čine pretilost centralnog tipa, inzulinska rezistencija, dislipidemija i hipertenzija.
Metabolički sindrom vrlo je raširen u svijetu, o čemu govore podaci da je u razvijenim zemljama metabolički sindrom prisutan u 20-30% ljudi srednje i starije dobi. S druge strane, zloćudne bolesti su jedan od najznačajnijih i vodećih zdravstvenih problema te drugi uzrok smrti nakon kardiovaskularnih bolesti. Ovo su brojke koje govore u prilog tome: godišnje u svijetu od raka oboli 11 milijuna, a umre 7 milijuna ljudi.
Kako bismo shvatili na koji je način metabolički sindrom, odnosno pojedine njegove komponente, povezan sa zloćudnim bolestima, bitno je poznavati patogenetske mehanizme i unutarstanične promjene do kojih dovode, čiji je prikaz i cilj ovoga rada. Molekularne mehanizme koji se nalaze u pozadini ove povezanosti možemo podijeliti u dvije velike skupine: pretilost – s kojom je povezano stanje kronične upale niskog intenziteta koje rezultira stvaranjem citokina i poremećajem adipokina i hormona, te inzulinska rezistencija – zbog koje su povišene razina inzulina i IGF-a, a posljedično i prekomjerno stimulirani njihovi receptori. Djelovanjem na unutarstanične signalne puteve, ishod ovih poremećaja rezultirat će procesima koji sudjeluju u karcinogenezi: stimulacijom staničnog ciklusa, pojačanom proliferacijom i rastom stanica, većim preživljenem stanica i inhibicijom apoptoze te stimulacijom angiogeneze.
Značajno je da se metabolički sindrom povezuje s najčešćim karcinomima u populaciji. Na prvome mjestu je postmenopauzalni karcinom dojke, zatim kolorektalni karcinom, karcinom endometrija, prostate, te karcinomi ostalih sijela (gušterača, jajnik, mjehur, hepatocelularni karcinom).
Poznavanje mehanizama povezanosti metaboličkog sindroma i malignih bolesti omogućit će u budućnosti djelovanje na metabolički sindrom kao rizičan čimbenik zloćudnih bolesti, prvenstveno prevencijom, a onda i terapijski. |
Sažetak (engleski) | Metabolic syndrome, also known as syndrome X, is a group of biochemical and physiological disorders, which together carry an increased risk for cardiovascular diseases, type II diabetes, but is also associated with the development of certain malignancies. Diagnosis of metabolic syndrome consists of central obesity, insulin resistance, dyslipidaemia and hypertension.
Metabolic syndrome is quite widespread in the world, which is confirmed by information that it is present in 20-30% of middle-aged and elderly in developed countries. On the other hand, malignant diseases are one of the most important and leading health problems, and the second cause of death. These are figures that speak in favour of it: 11 million people are diagnosed, while 7 million people die of cancer annually in the world. In order to understand the association of metabolic syndrome and its components with malignant diseases, it is important to know the pathogenic mechanisms and intracellular changes they result in, which is the main scope of this review. The molecular mechanisms, in the background of this association, can be divided in two groups: obesity – related with the condition of low intensity chronic inflammation that results in the synthesis of cytokines, hormones and adipocytes disorder, and insulin resistance – that leads to elevated levels of insulin and IGF, and results in hyperstimulation of their receptors. Acting on intracellular signalling pathways, the outcome of these disorders will result in processes involved in carcinogenesis: stimulation of cell cycle, increased proliferation and cell growth, increased cell survival by inhibition of apoptosis and stimulation of angiogenesis.
Significantly, the metabolic syndrome is associated with the most common cancer types in the population; the post-menopausal breast cancer, colorectal cancer, endometrial cancer, prostate cancer and other cancer sites (pancreas, ovary, bladder, hepatocellular carcinoma).
Knowing about the mechanisms of association of metabolic syndrome and malignant disease, will enable to act henceforward on the metabolic syndrome as a risk factor for malignant diseases, primarily with prevention and therapy afterwards. |