Adipokini u bolesnica sa sindromom policističnih jajnika [Adipokines in patients with polycystic ovary syndrome]

Zlopaša, Gordan (2011) Adipokini u bolesnica sa sindromom policističnih jajnika [Adipokines in patients with polycystic ovary syndrome]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Polycystic ovary syndrome (PCOS) is a multisystem endocrinological reproductive-metabolic disorder, characterised with oligo/anovulation, hyperandrogenism and polycystic ovaries. PCOS is often connected with obesity and insulin resistance. Patients with PCOS have increased risk for infertility, diabetes mellitus type 2, hypetension and cardiovascular diseases. ----- STUDY SUBJECTS AND METHODS: The study included 151 women diagnosed with PCOS set by the Rotterdam criteria and 95 healthy women matched by age and weight. We compared the levels of leptin, resistin, ghrelin, and adiponectin, and biochemical parameters of insulin resistance (insulin and HOMA index) and cardiovascular risk factors (cholesterol, LDL, hsCRP) between the two groups to determine differences in their values. Furthermore, we compared the values of these adipokines among different PCOS phenotypes and tried to determine which of the examined factors have the greatest impact on their serum levels. ----- RESULTS: We found statistically significant differences in all adipokines serum levels between PCOS patients and healthy controls (p <0.001). The values of insulin and HOMA index, and cholesterol, LDL, and hsCRP were significantly higher in PCOS group (p <0.001). There were a significant differences in adipokines serum levels between normal weight (BMI ≤25) and overweight (BMI ≥25) PCOS patients (p <0.001). A significant positive correlation for the leptin and resistin concentrations, and significant negative correlation for the adiponectin and ghrelin concentrations with increasing severity of PCOS phenotype was observed (the more risk factors, such as higher BMI, hyperandrogenemia, and greater insulin resistance patient had, the lower concentration of adiponectin and ghrelin, and the higher concentration of leptin and resistin were found). By the method of standard linear regression, we found the greatest impact of the diagnosis of PCOS on adiponectin levels (β = -0.743, p <0.001) and ghrelin levels (β = -0.660, p <0.001) in the serum of patients, whereas on the leptin levels BMI had the greatest impact (β = 0.540, P <0.001). The impact of PCOS diagnosis (β = 491, p <0.001) and BMI (β = 491, p <0.001) on serum resistin levels was nearly identical. Among the PCOS patients, the greatest impact of ITM on the circulating adipokine levels was found. ----- CONCLUSIONS: Women with PCOS have significantly elevated leptin and resistin serum levels, and significantly lower adiponectin and ghrelin serum levels than healthy women, and their concentrations change with the severity of the phenotype. Identification of women with altrued adipokine expression as putative markers of possible metabolic and cardiovascular complications, would be usefull for settingup preventive strategies by life-style changes and/or use of insulin-sensitising agens.

Abstract in Croatian

Sindrom policističnih jajnika (PCOS) je multisistemski, endokrinološki, reprodukcijski i metabolički poremećaj, karakteriziran oligo/anovulacijama, hiperandrogenizmom i policističnim izgledom jajnika. Često je udružen s debljinom i inzulinskom rezistencijom. Žene s PCOS imaju povišen rizik za šećernu bolest tipa 2, dislipidemiju i kardiovaskularne bolesti. Sve je više studija koje govore u prilog da je lučenje hormona masnog tkiva – adipokina (leptina, adiponektina, grelina i rezistina) promijenjeno u bolesnica s PCOS te da bi promjene u lučenju adipokina kod žena s PCOS mogle biti važan pretskazatelj kliničkog tijeka bolesti uključujući nastanak dijabetesa i kardiovaskularnih bolesti. ----- ISPITANICE I METODE: U istraživanje smo uključili 151 ženu s dijagnozom PCOS postavljenu prema Rotterdamskim kriterijima i 95 zdravih žena usklađenih prema dobi i tjelesnoj težini. Usporedili smo razine leptina, rezistina, grelina i adiponektina te biokemijskih pokazatelja inzulinske rezistencije (inzulin i HOMA indeks) i kardiovaskularnog rizika (kolesterol, LDL, hsCRP) između ispitivanih skupina s ciljem utvrđivanja razlika u njihovim vrijednostima. Potom smo usporedili vrijednosti ovih adipokina između različitih fenotipa PCOS i pokušali utvrditi koji od ispitivanih čimbenika ima najveći utjecaj na njihove serumske razine. ----- REZULTATI: Utvrdili smo statistički značajne razlike u serumskim razinama svih adipokina između ispitivanih skupina ( p<0,001). Vrijednosti inzulina i HOMA indeks te kolesterol, LDL i hsCRP bili su značajno viši u PCOS skupini (p<0,001). Značajna razlika nađena je u razinama svih adipokina unutar PCOS skupine kada smo usporedili bolesnice normalne težine s onima prekomjerne težine (p<0,001). Utvrdili smo značajnu pozitivnu povezanost koncentracija leptina i rezistina i značajnu negativnu povezanost koncentracija adiponektina i grelina s porastom težine PCOS fenotipa koji se razlikovao obzirom na nazočnost ili izočnost hiperandrogenemije, inzulinske rezistencije i debljine. Metodom standardne linearne regresije ustanovili smo najveći utjecaj same dijagnoze PCOS na razine adiponektina (β= -0,743, p<0,001) i grelina (β= -0,660, p<0,001), u serumu ispitanica, dok je na razinu leptina najveći utjecaj imao ITM (β= 0,540, P<0,001). Na razinu rezistina utjecaj dijagnoze (β= 491, p<0,001) i ITM (β= 491, p<0,001) bio je gotovo identičan. Unutar skupine PCOS ispitanica na razine svih adipokina u cirkulaciji najviše je utjecala debljina, odnosno ITM. ----- ZAKLJUČAK: Bolesnice s PCOS imaju značajno povišene razine leptina i rezistina i značajno snižene razine adiponektina i grelina u serumu u odnosu na zdrave žene, a njihove koncentracije mijenjaju se s težinom fenotipa. Identifikacijom bolesnica s promjenama u lučenju adipokina, kao putativnih markera kasnijih metaboličkih komplikacija, na vrijeme bi se moglo započeti s preventivnim strategijama u smislu promjena životnih navika i/ili korištenja lijekova koji smanjuju osjetljivost na inzulin.

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