Uticaj holekalciferola na proteinuriju kod bolesnika sa tipom 2 dijabetesa mellitus

Abstract

Zastupljenost deficita vitamina D3 je mnogo veći kod bolesnika sa dijabetesnom bolesti tipa 2 nego u populaciji zdravih osoba. Bolesnici sa DM tipa 2 i deficitom vitamina D3 imaju veći rizik za razvoj dijabetesne nefropatije. Eksperimenti na životinjama i neka klinička istraživanja ukazuju da bi primena nižih doza vitamina D3 mogla imati renoproktektivno delovanje. Cilj istraživanja je bio da se utvrdi zastupljenost deficita vitamina D3 u populaciji bolesnika sa dijabetesnom nefropatijom koja je definisana proteinurijom ˃0,150 g/du. Drugi cilj je bio da se utvrdi da li primena holekaciferola u dozi koja predstavlja razliku između utvrđenog i optimalnog nivoa vitamina D3 dovodi do statistički značajnog smanjenja proteinurije. Bolesnici sa dijabetesom tipa 2 i proteinurijom ˃0,150 g/du su uključivani u skrining na nivo vitamina D3 (25(OH)D) nakon čega su svrstavani u grupe sa deficitom i normalnim nivoom vitamina D3. Granična vrednost za utvrđivanje deficita vitamina D3 je odreĎivana na osnovu tabele koja definiše ove vrednosti za svaki mesec tokom godine, posebno za muškarce i žene. Bolesnici sa deficitom vitamina D3 su podeljeni u 2 grupe od po 45 ispitanika. Studijska grupa je primala holekaciferol u dozi koja je izračunata na osnovu razlike između izmerene vrednosti i određenog optimalnog nivoa vitamina D3 od 90-100 nmol/L. Kontrolna grupa bolesnika je uzimala svoju uobičajenu terapiju. Istraživanje je trajalo 24 nedelje tokom koje su na drugi mesec praćeni parametri bubrežne funkcije, parametri inflamacije i koštanog metabolizma. Na početku i kraju istraživanja su odreĎeni nivo vitamina D3 u studijskoj grupi, dok su u obe grupe određivani vrednost HbA1c i lipidni profil. Analizom dobijenih podataka je utvrđeno da je zastupljenost deficita vitamina D3 kod bolesnika sa dijabetesnom nefropatijom, uzimajući u obzir sezonske varijacije u nivou ovog vitamina, bila veća od vrednosti od 30-50% koje su postavljene u radnoj hipotezi. Učestalost bolesnika sa nedostakom vitamina D3 je u ispitivanom uzorku je bila 82,56% , dok je normalne vrednosti vitamina D3 imalo 17,43% ispitanika, od toga je bilo 10 (52,63%) muškaraca i 9 (47,36%) žena. Sniženje vrednosti vitamina D3 u odnosu na donje granične vrednosti je bilo izraženije u letnjem periodu i bilo je statistički značajno kod svih ispitanika zajedno, potom u studijskoj grupi, dok je utvrđeno i u kontrolnoj grupi ali je u njoj bilo bez statisičke značajnosti. Utvrđen je porast HbA1c koji je bio veći u kontrolnoj grupi ispitanika. Suplementacija vitaminom D3 je imala povoljan efekat na lipidni profil. Registrovan je porast vrednosti ukupnog holesterola koji je bio izraženiji u kontrolnoj grupi, pad vrednosti triglicerida u grupi bolesnika koji su uzimali vitamin D3 i njihov porast u kontrolnoj grupi ispitanika. U studijskoj grupi je registrovan porast vrednosti HDL-holesterola koji je bio na granici statističke značajnosti dok je istovremeno nađeno njegovo smanjenje u kontrolnoj grupi. Vrednost LDL-holesterola je ostala bez promene pod delovanjem vitamina D3, dok je u kontrolnoj grupi došlo do njegovog porasta. Utvrđeno je snižavanje vrednosti sedimentije, CRP-a i fibrinogena koje je bilo bez statističke značajnosti. Bezbednosni profil vrednosti kalcijuma u serumu i urinu tokom dugotrajnije primene je dobar. Primenom vitamina D3 je došlo do signifikatnog smanjenja proteinurije u grupi bolesnika koji su primali holekaciferol čime je ujedno i potvrđena radna hipoteza.

Alternate abstract:

The prevalence of vitamin D3 deficiency is much higher in patients with type 2 diabetes than in the healthy population. Patients with type 2 DM and vitamin D3 deficiency are at increased risk for developing diabetic nephropathy. Animal experiments and some clinical studies suggest that administration of lower doses of vitamin D3 could have renoprotective effect. The aim of the study was to determine the prevalence of vitamin D3 deficiency in the population of patients with diabetic nephropathy defined by proteinuria ˃0.150 g / du. The second goal was to determine whether the use of cholecaciferol in a dose that represents the difference between the established and optimal levels of vitamin D3 leads to a statistically significant reduction in proteinuria. Patients with type 2 diabetes and proteinuria ˃0.150 g / du were screened for vitamin D3 (25 (OH) D) levels and then classified as deficient and normal vitamin D3. The limit value for determining vitamin D3 deficiency was set on the basis of a table defining these values for each month during the year, separately for men and women. Patients with vitamin D3 deficiency were divided into 2 groups of 45 subjects each. The study group received cholecaciferol at a dose calculated on the basis of the difference between the measured value and the set optimal vitamin D 3 level of 90-100 nmol/L. The control group of patients was taking their usual therapy. The study lasted 24 weeks during which the parameters of renal function, parameters of inflammation and bone metabolism were monitored every second month. At the beginning and end of the study, the levels of vitamin D3 in the study group were determined, while in both groups HbA1c and lipid profile were determined. The analysis of the obtained data showed that the prevalence of vitamin D3 deficiency in patients with diabetic nephropathy, taking into account seasonal variations in the level of this vitamin, was higher than the values of 30-50%, which were set in the working hypothesis. The frequency of patients with vitamin D3 deficiency in the study sample was 82.56%, while the normal values of vitamin D3 were in 17.43% of the subjects, of which 10 (52.63%) were men and 9 (47.36%) woman. The decrease in vitamin D3 compared to the lower limit values was more pronounced in the summer and was statistically significant in all subjects together, as well in the study group, while it was also found in the control group but was not statistically significant. An increase in HbA1c was found to be higher in the control group. Vitamin D3 supplementation had a beneficial effect on the lipid profile. An increase in the total cholesterol level that was more pronounced in the control group, a decrease in triglyceride values in the group of patients taking vitamin D3 and its increase in the control group of subjects were registered. An increase in HDL-cholesterol was reported in the study group, which was at the limit of statistical significance, while at the same time a decrease was found in the control group. LDL-cholesterol levels remained unchanged under the influence of vitamin D3, while in the control group it increased. The decrease in sedimentation, CRP and fibrinogen values was found to be of no statistical significance. The safety profile of serum and urine calcium during long-term administration is good. The use of vitamin D3 resulted in a significant decrease in proteinuria in the group of patients receiving cholecaciferol, which also confirmed the working hypothesis.