Marko Šimunović

Ime i prezime: dr. sc. MARKO ŠIMUNOVIĆ, dr. med.
 
Naslov disertacije: „KATESTATIN I VITAMIN D U PRETILOSTI I METABOLIČKOM SINDROMU DJECE I ADOLESCENATA“
 
Mentor: prof. dr. sc. VESELIN ŠKRABIĆ
 
Datum obrane: 11. listopada 2019.
 
Poveznica: https://library.foi.hr/dbook/index.php?B=1&item=X02150
 
Kvalifikacijski znanstveni rad za doktorsku disertaciju:
 
Simunović M, Supe-Domic D, Karin Z, Degoricija M, Paradzik M, Bozic J, Unic I, Skrabic V. Serum catestatin concentrations are decreased in obese children and adolescents. Pediatr. Diabetes. 2019;20(5):549-55.
 
Simunović M, Bozic J, Milic L, Unic I, Skrabic V. The Prevalence of Metabolic Syndrome and Cardiovascular Risk Factors in Obese Children and Adolescents in Dalmatia: A Hospital Based Study. Int J Endocrinol. 2016;1823561.
 
SAŽETAK:
 
Pretilost u ranoj životnoj dobi je jedan od vodećih javno zdravstvenih problema u svijetu. Poznato je da pretilost u ranoj životnoj dobi većinom perzistira u odrasloj dobi, a što je važan čimbenik razvoja kardiovaskularnih komplikacija i metaboličkog sindroma (MS). Zbog svega navedenoga postoji stalna potreba za pronalaskom novih molekularnih biljega koji bi dodatno pomogli u praćenju napredovanja metaboličkog poremećaja. Katestatin je peptid koji proteolitičikim cijepanjem nastaje iz kromogranina A te ima široki spektar biološke aktivnosti, poput inhibicije otpuštanja katekolamina, smanjenja krvnog tlaka, poticanja oslobađanja histamina, smanjenja beta-adrenergičke stimulacije i regulacije oksidativnog stresa. Do sada je objavljeno nekoliko studija na odrasloj populaciji, a koje su pokazale da je katestatin značajan rizični faktor za hipertenziju, a koliko nam je poznato, ovo je prvo izvješće o serumskim koncentracijama katestatina u pretile djece i adolescenata. Također, manjkavost vitamina D povezana je s nizom različitih kronični bolesti uključujući pretilost. Uloga vitamina D u pretilosti nije u potpunosti razjašnjena, a potencijalni učinci uključuju regulaciju upalnog odgovora, ekspresiju gena koji reguliraju adipogenezu i adipocitnu apoptozu te utjecaj na lučenje leptina i adiponektina i regulaciju intenziteta metabolizma.
Cilj ovoga istraživanja je bio usporediti serumske koncentracije katestatina i 25- hidroksi vitamin D (25(OH)D) s odrednicama MS-a i ostalim kardiovaskularnim rizičnim čimbenicima između pretilih ispitanika i odgovarajuće kontrolne skupine ispitanika.
U studiju je uključeno 91 pretilo dijete i adolescent s ITM z vrijednosti >2 i kao kontrolna skupina 39 zdrave djece (ITM z vrijednosti <1) koji su usklađeni prema dobi i spolu ispitanika. Svim ispitanicima napravljena su antropometrijska mjerenja, klinički pregled i laboratorijske analiza (katestatin, 25(OH)D i druge laboratorijske vrijednosti) te su pretili ispitanici podvrgnuti oralnom testu opterećenja glukozom (OGTT).
Statistički značajno niže koncentracije katestatina u serumu zabilježene su u skupini pretilih ispitanika u usporedbi s kontrolnom skupinom (10,03 ± 5,05 vs. 13,13 ± 6,25 ng/mL, P=0,004). Daljnjim analizama utvrđena je statistički značajno niža koncentracije katestatina u podskupini pretilih ispitanika s MS-om (9,02 ± 4,3 vs. 10,54 ± 5,36 vs. 13,13 ± 6,25, P = 0,008). Serumske koncentracije katestatina su značajno negativno korelirale s dijastoličkim krvnim tlakom (r =-0,255, P =0,014), homeostatskim modelom procjene inzulinske rezistencije (HOMA-IR) (r=-0,215, P = 0,037) i visoko osjetljivim C reaktivnim proteinom (hsCRP) (r=-0,208) , P=0,044). Dodatno, skupina pretilih ispitanika s MS-om imala je značajno niže serumske koncentracije 25(OH)D u usporedbi sa skupinom pretilih ispitanika bez MS-a i kontrolnom skupinom (46,99 ± 17,11 vs. 54,58 ± 17,93 vs. 64,09 ± 25,82 nmol/L , P=0,003). HOMA-IR je značajno i negativno korelirala sa serumskim koncentracijama 25(OH)D (r =-0,196, P=0,026).
Zaključno, naša studija je demonstrirala da su serumske koncentracije katestatina i 25(OH)D bile značajno niže u pretilih ispitanika s MS-om, u usporedbi s pretilim ispitanicima bez MS-a i kontrolnom skupinom. Serumske koncentracije katestatina su pokazale značajnu korelaciju s HOMA-IR i hsCRP, a dok su serumske koncentracije 25(OH)D pokazale značajnu korelaciju s HOMA-IR.
 
SUMMARY:
 
Childhood obesity is one of the leading public health problems in the world and it is well known that early childhood obesity persists most into adulthood, an important factor in the development of cardiovascular complications and metabolic syndrome (MS). There is a constant need for new molecular biomarkers that will help clinicians decipher the progression of the metabolic disorder. Catestatin is a peptide by proteolytic cleavage derived from chromogranin A and has a wide range of biological activities, such as inhibition of catecholamine release, reduction of blood pressure, stimulation of histamine release, reduction of beta-adrenergic stimulation and regulation of oxidative stress. So far, several studies have been published in the adult population that have shown that catestatin is a significant risk factor for hypertension, and to our knowledge, this is the first report of serum catestatin levels in obese children and adolescents. Also, vitamin D deficiency is associated with a number of different chronic diseases including obesity. The role of vitamin D in obese individuals has not been fully elucidated, but it is considered possible to regulate the inflammatory response, the expression of genes that regulate adipogenesis and adipocyte apoptosis and also affect leptin and adiponectin secretion and regulate energy metabolism.
The aim of this study was to compare serum levels of catestatin and 25-hydroxy vitamin D (25 (OH) D) with components of MS and other cardiovascular risk factors among obese subjects, with control group.
The study included 91 obese children and adolescents with BMI z score >2 and control group of 39 healthy children and adolescents (BMI z score <1), matched by age and gender of the subjects. Anthropometric measurements, clinical examination and laboratory analysis (catestatin, 25(OH)D and other laboratory parameters) were made and all obese subjects were subjected to an oral glucose tolerance test (OGTT).
Significantly lower serum catestatin concentrations were recorded in the group of obese subjects compared with a control group (10.03 ± 5.05 vs. 13.13 ± 6.25 ng/mL, P = 0.004). Further analyses revealed significantly lower catestatin concentrations in the sub- group of obese patients with MS (9.02 ± 4.3 vs. 10.54 ± 5.36 vs. 13.13 ± 6.25, P = 0.008). Serum catestatin concentrations were significantly negatively correlated with homeostatic model assessment of insulin resistance (HOMA-IR) (r=-0.215, P=0.037) and high sensitivity C-reactive protein (hsCRP) (r=-0.208, P=0.044). Additionally, group of obese patients with MS had significantly lower levels of serum 25(OH)D when compared to the group of obese patients without MS and the control group (46.99 ± 17.11 vs. 54.58 ± 17.93 vs. 64.09 ± 25.82 nmol/L, P=0.003). HOMA-IR was in negative correlation with serum concentrations of 25(OH)D (r=-0,196, P=0,026).
In conclusion, our study demonstrated that serum concentrations of catestatin and 25(OH)D were significantly lower in obese subjects with MS, compared with obese subjects without MS and health controls. Serum concentrations of catestatin showed a significant correlation with HOMA-IR and hsCRP, while serum concentrations of 25(OH)D showed a significant correlation with HOMA-IR. Ispiši stranicu