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VPLIV HUJŠANJA NA ENDOTELNO FUNKCIJO
Avtor: David Šuran, Peter Poredoš
Mentor: prof. dr. Pavel Poredoš
Somentor: doc. dr. Alenka Mavri
IZHODIŠCE: Debelost v povezavi s spremljajocimi presnovnimi motnjami sodi med najpomembnejše dejavnike tveganja za srcno-žilne bolezni. Zato pri debelih osebah, tudi tistih, ki še nimajo klinicnih znakov ateroskleroticne bolezni, pricakujemo dolocene spremembe v sestavi in delovanju srcno-žilnega sistema. Med najzgodnejše funkcijske motnje pri aterogenezi sodi endotelijska disfunkcija. Znano je, da hujšanje zmanjša tveganje za srcno-žilne zaplete, ni pa znano, ali hujšanje povsem odpravi presnovne spremembe in motnje v delovanju srcno-žilnega sistema ter kako hitro pride do pricakovanega izboljšanja. NAMEN IN HIPOTEZA: V naši prospektivni študiji smo želeli prouciti, ali že po enem tednu hujšanja pride do zaznavnih sprememb endotelijske funkcije in ali je izboljšanje endotelijske funkcije povezano z zmanjšanjem telesne mase, z izboljšanjem presnovnih motenj ali pri tem sodelujejo še drugi dejavniki. METODE: V raziskavo smo vkljucili 41 debelih žensk (povprecna starost 43 (23-65) let, indeks telesne mase 35,03 4,89 kg/m2), ki so se odlocile za hujšanje z nizkokaloricno dieto in zmerno telesno aktivnostjo, ter 20 normalno prehranjenih žensk (povprecna starost 39 (23-51) let, indeks telesne mase 22,11 1,38 kg/m2). Shujševalni program je trajal 6 mesecev. Debelim ženskam smo pred zacetkom hujšanja, po prvem tednu in ob koncu hujšanja opravili antropometricne meritve in krvne preiskave. Endotelijsko funkcijo smo proucevali z ultrazvocno metodo. Merili smo od endotelija odvisno dilatacijo (ED) brahialne arterije med reaktivno hiperemijo. REZULTATI: Debele ženske so imele pred hujšanjem v primerjavi s suhimi razlicne presnovne motnje: dislipidemijo, zvecane vrednosti inzulina in inzulinsko rezistenco. Nadalje smo pri debelih ženskah v primerjavi s suhimi ugotovili zvecane vrednosti leptina, zmanjšano vrednost adiponektina ter zvecane vrednosti PAI-1 antigena in aktivnosti, CRP in TNF R1. Pri debelih ženskah je bila v primerjavi s suhimi zmanjšana od endotelija odvisna dilatacija brahialne arterije (7,4 (6,3-9,1)% vs. 11,3 (8,5-13,7)%, p<0,001). Endotelijska disfunkcija je bila povezana s telesno maso, PAI-1 antigenom in aktivnostjo, z oznacevalci vnetja in koncentracijo leptina. Program hujšanja je zakljucilo 23 preiskovank, njihova telesna masa se je zmanjšala v povprecju za 17,2%. Že po enem tednu hujšanja so se pomembno izboljšale motnje presnove lipidov (celotni holesterol (4,6 1,1 vs. 5,0 0,9 mmol/l, p<0,01) in trigliceridi (1,0 (0,7-1,2) vs. 1,2 (0,9-2,1) mmol/l, p<0,01)), zmanjšala se je koncentracija inzulina (9,8 (4,5-12,2) vs. 11,4 (8,9-16,9) mIE/L, p<0,01), rezistenca na inzulin (1,95 (0,98-2,62) vs. 2,76 (1,63-3,80), p<0,01), koncentracija TNF R1 (0,76 (0,67-0,85) vs. 0,80 (0,70-0,92) ng/ml, p<0,01) ter koncentracija leptina (19,65 8,72 vs. 35,04 16,45 ng/ml, p<0,01). Vrednost adiponektina se je zvecala šele po 6 mesecih hujšanja (16,86 7,85 vs. 14,21 5,75 mcg/ml, p<0,05). Sposobnost razširitve brahialne arterije se je pomembno povecala že po enem tednu (8,5 (7,1-10,2)% vs. 7,4 (6,3-9,1)%, p<0,01) in dodatno še ob koncu hujšanja (11,1 (7,7-14,7)%, p<0,01) in se je izenacila z vrednostjo preiskovank v kontrolni skupini (11,3 (8,5-13,7)%). Multivariatna analiza je pokazala, da je bilo izboljšanje endotelijske funkcije pomembno povezano le s spremembo vrednosti razmerja pas/boki ob koncu hujšanja, ne pa tudi z drugimi spremenljivkami. ZAKLJUCKI: Rezultati naše raziskave kažejo, da hujšanje pri debelih ženskah izboljša endotelijsko funkcijo in presnovne motnje. Ugodni ucinki hujšanja se pojavijo že po enem tednu, še preden se pojavijo pomembne spremembe v telesni masi in neodvisno od drugih spremljajocih dejavnikov debelosti.
[Abstract / English version]
VPLIV HUJŠANJA NA ENDOTELNO FUNKCIJO
Author: David Šuran, Peter Poredoš
Mentor: prof. dr. Pavel Poredoš
Co-mentor: doc. dr. Alenka Mavri
BACKGROUND: Obesity and accompanying metabolic disorders represent one of the most significant risk factors for vascular diseases. For this reason, certain subclinical vascular changes are expected even in obese subjects without obvious clinical manifestations. Endothelial dysfunction is one of the earliest functional abnormalities in the process of atherogenesis. It is known that weight loss reduces the risk of cardiovascular events in obese subjects. However, it is not known, whether the weight loss is accompanied by a complete recovery of metabolic changes and functional vascular disorders and what lag time after the start of weight reduction is needed for the expected improvement. AIM AND HYPOTHESIS: The aim of our prospective study was to find out if noticeable changes in endothelial function can be observed already one week after the start of weight reduction program. Furthermore, we tried to determine whether the improvement of endothelial function is associated with weight reduction, improvement of metabolic disorders or other factors. METHODS: The studied group comprised of 41 obese women who followed a low-calorie diet program, including moderate physical activity, and the control group consisted of 21 normal-weight women. The weight reduction program lasted for 6 months. Before its beginning, after one week and at the end of the weight reduction program, anthropometric measures and laboratory biochemical investigations were performed. Beside this the flow-mediated dilation of brachial artery was determined using ultrasound. RESULTS: Before starting the weight reduction program, the following metabolic disorders were observed in the obese compared to the lean women: dyslipidemia, elevated insulin level and insulin resistance. Obese women had elevated leptin level, decreased adiponectin level and elevated level of PAI-1 antigen and activity, CRP and TNF R1. The obese women in comparison to the lean had reduced endothelium-dependent dilation of brachial artery (7.4 (6.3-9.1)% vs. 11.3 (8.5-13.7)%, p<0.001). Endothelial dysfunction was associated with body mass, triglyceride concentration, PAI-1 antigen and activity, inflammatory markers and leptin concentration. 23 women ended the weight reduction program, their body mass was reduced on average for 17.2%. Already after 1 week of the weight reduction we observed significant improvement of lipid metabolism disorders (total cholesterol (4.6 1.1 vs. 5.0 0.9 mmol/l, p<0.01) and triglycerides (1.0 (0.7-1.2) vs. 1.2 (0.9-2.1) mmol/l, p<0.01)), decreased insulin level (9.8 (4.5-12.2) vs. 11.4 (8.9-16.9) mIE/L, p<0.01), decreased insulin resistance (1.95 (0.98-2.62) vs. 2.76 (1.63-3.80), p<0.01), decreased TNF R1 level (0.76 (0.67-0.85) vs. 0.80 (0.70-0.92) ng/ml, p<0.01) and leptin level (19.65 8.72 vs. 35.04 16.45 ng/ml, p<0.01). Adiponectin levels increased at the end of the weight reduction (16.86 7.85 vs. 14.21 5.75 mcg/ml, p<0.05). Flow-mediated dilation of brachial artery improved significantly already after 1 week of the weight reduction program (8.5 (7.1-10.2)% vs. 7.4 (6.3-9.1), p<0.01), reached 11.1 ((7.7-14.7)%, p<0.01) at the end and was comparable to the values of lean individuals (11.3%). Multivariate analysis revealed a significant correlation of improvement of endothelial dysfunction to waist-to-hip ratio at the end of the weight reduction program, but no correlation to other parameters. CONCLUSIONS: The results of our study indicate that in obese women the low-calorie-diet weight reduction has favourable effects on endothelial function and metabolic disorders. Favourable effects of the weight reduction appear independently of other accompanied risk factors of obesity already after 1 week of the start of weight reduction program, before significant changes in body mass can be detected.