Povezanost nivoa leptina i adiponektina sa somatskim i metaboličkim parametrima diskordantnih blizanaca

Abstract

Intrauterusni zastoj rasta (IUZR) je jedan od vodećih uzroka perinatalnog morbiditeta i mortaliteta. Hipertenzija, insulinska rezistencija (IR), dijabetes mellitus tip 2 (T2DM), metabolički sindrom (MS), nizak rast i osteoporoza se dovode u vezu sa IUZR. Skorašnje kliničke i eksperimentalne studije su rasvetlile ulogu koju masno tkivo igra u razvoju insulinske rezistencije i MS kao posledica fetalnog programiranja in utero Cilj ove studije je bio da ispita da li je koncentracija adipokina u krvi pupčanika (P) i u trećem danu (d3) povezana sa usporenim fetalnim rastom i nivoom lipida kod blizanaca sa IUZR. Testirana je povezanost nivoa leptina i adiponektina sa somatskim parametrima i IR na roĎenju i u d3 kod diskordantnih i konkordantnih blizanaca. U studiju je uključeno 36 diskordantnuh (razlika u poroĎajnoj telesnoj masi-TM≥20% računato u odnosu na većeg blizanca) i 42 konkordantna para blizanaca (razlika u TM≤10%), roĎenih≥32 gestacionih nedelja (GN). TM manjeg blizanca je bila ispod 10. percentila (IUZR blizanac) udruženo sa abnormalnim protocima u umbilikalnoj arteriji. Iz venske krvi iz pupčanika kao i iz venske krvi uzete u trećem danu pre jela (d3) su odreĎivani nivoi hormona (leptin, adiponektin, insulin) i bihemijski parametri (glukoza, ukupni holesterol-TC, high density lipoprotein holesterol –HDL C, low density lipoprotein holesterol-LDL C i trigliceridi-TG). Indeksi body mass index-BMI, ponderalni indeks-PI, homeostasis model assesment insulin resistance index-HOMA IR, TG/HDL C i glukoza/insulin (G/I) su izračunati a poslednja tri predstavljaju markere insulinske rezistencije/senzitivnosti. Rezultati: U diskordantnoj grupi nivoi leptina i leptina/TM u krvi iz pupčanika i d3 bili su uporedivi izmeĎu IUZR i blizanaca sa odgovarajućim rastom (appropriate for gestational age-AGA). Kada smo poredili blizance roĎene posle 35 GN koncentracije leptina su bile značajno niže kod IUZR blizanaca u d3 (p=0,011). Nivoi leptina i L/TM u d3 su bili značajno viši kod diskordantnih u odnosu na konkordantne blizance (razlike izmeĎu grupa) (AGA vs. veći, p=0,001 i IUGR vs. manji p=0,004; p=0,001 i p=0,001 respektivno). Koncentracije adiponektina i insulina izmerene na roĎenju i u d3 kao i u podgrupi≥35 GN nisu se statistički značajno razlikovale izmeĎu IUZR i AGA blizanaca. MeĎutim adiponektin/TM je bio viši kod IUZR blizanaca kako u odnosu na AGA blizance tako i u odnosu na manje konkordantne blizance u oba merenja (p=0,002 i p=0,035 respektivno unutar parova i p=0.022 i p=0.002 izmeĎu parova)...

Intrauterine growth restriction (IUGR) is one of the leading causes of perinatal morbidity and mortality. Hypertension, insulin resistance (IR), type 2 diabetes mellitus (T2DM), metabolic syndrome (MS), short stature and osteoporosis were found to be associated with IUGR. The recent clinical and experimental studies have highlighted the role of adipose tissue (AT) in the development of insulin resistance and MS as consequences of fetal programming in utero. The aim of this study was to explore whether adipokines concentrations in cord blood (CB) and on day3 (d3) were related to impaired fetal growth and lipids in IUGR twins. The relationship between leptin and adiponectin levels with somatic parameters and IR at birth and on d3 in discordant and concordant twins were tested. Patients and methods: 36 discordant (birth weight BW discordance ≥20% calculated in relation to the heavier cotwins) and 42 concordant (birth weight discordance ≤10%) twin pairs≥32 gestational weeks (GW) were included. BW of the smaller twins was less than 10th percentile (IUGR twins) with abnormal umbilical artery Doppler velocimetry. Umbilical venous CB and venous blood samples on d3 were obtained from each pair of twins in the fasting state both for hormone determination (leptin, adiponectin and insulin) and biochemical analysis (glucose, total cholesterol-TC, high density lipoprotein cholesterol –HDL C, low density lipoprotein cholesterol-LDL C and triglyceride-TG). Indices body mass index-BMI and ponderal index- PI,. homeostasis model assessment insulin resistance index HOMA IR, TG/HDL C and glucose/insulin (G/I) ratio were calculated as a markers of insulin resistance/sensitivity. Results: Within the discordant group leptin and leptin/PTM levels in cord blood and on d3 were comparable between AGA (appropriate for gestational age) twins and IUGR twins. When we compared late preterm and term twins (≥35 GW) on d3 leptin concentration was significantly lower in IUGR twins (p=0,011). Leptin levels and L/BW were higher in discordant as compared to concordant twins (interpair difference) on day 3 (AGA vs. larger, p=0.001 and IUGR vs. smaller, p=0.004; p=0,001 and p=0,001 respectively). Adiponectin and insulin concentration measured in AGA and IUGR twins as well as in≥35 GW discordant twins at birth and on d3 showed no statistically significant differences. However, adiponectin/BW was higher in IUGR twins as compared to AGA cotwins and to smaller concordant twins in CB and on d3 (p=0,002 and p=0,035 respectively for intrapair and p=0.022 and p=0.002 for interpair difference)...