Psychiatrie - Sekce poruchy příjmu potravy

20
Abstrakta
Závěr: Výsledky ukazují možnost zhodnocení
stavu inzulinové senzitivity z glykémie a inzulinémie
pomocí homeostatických indexů, což je
využitelné v pediatriii. V praxi se jeví jako lépe použitelný
index QUICKI, který vykazuje užší interval
spolehlivosti a tím menší variabilitu hodnot.
Vzhledem k tomu, že klasické metody diagnostiky
inzulinové rezistence jsou velmi náročné
na provedení a naprosto nevhodné pro
vyšetřování většího počtu osob, byly hledány
jiné možnosti, jak jednoduše posoudit homeostatické
vztahy mezi inzulinem a glykémií. Růst
koncentrace inzulinu by měl být za fyziologických
okolností provázen poklesem glykémie
a naopak. Porucha tohoto vztahu je projevem
nedostatečné účinnosti inzulinu a je podkladem
homeostatických modelů posuzování inzulinové
rezistence. Mezi indexy a výsledky clampových
technik byla opakovaně ověřena vysoce signifikantní
korelace.
Plazmatická koncentrace
fibroblastových růstových faktorů
19 a 21 u pacientek s anorexia nervosa
Plasma concetrations of fibroblast growth
factors 19 and 21 in patiens with anorexia
nervosa
Dostálová I., Kaválková P., Haluzíková D., Lacinová
Z., Mráz M., Papežová H., Haluzík M.
3. interní klinika, Klinika sportovního lékařství
a Psychiatrická klinika 1. LF UK a VFN,
Praha
Summary: Fibroblast growth factors 19 and 21
(FGF19 and FGF21) are novel endocrine regulators
with the role in the metabolic response to fasting
in mice. We measured plasma levels of FGF19 and
FGF21 in patients with a restrictive type of anorexia
nervosa (AN) and explored its relationship with
anthropometric and endocrine parameters. Plasma
FGF21 levels were significantly reduced in patients
with AN relative to control group. Partial realimentation
significantly decreased plasma FGF21 levels
in AN. Pre-treatment plasma FGF21 levels in AN were
positively related to weight gain during nutritional
treatment. Plasma FGF21 positively correlated with
serum leptin and insulin and was inversely related
to serum adiponectin in both groups. In contrast,
plasma FGF19 was not related to any of parameters
studied. We concluded that circulating levels of
FGF21 but not FGF19 are strongly related to body
weight and serum levels of leptin, adiponectin and
insulin in both anorectic and normal-weight women.
We suggest that reduced plasma FGF21 levels
could be involved in the pathophysiology of AN or
in a complex adaptive response to this disease.
Souhrn: Fibroblastové růstové faktory 19 a 21
(FGF19 a FGF21) hrají důležitou roli v metabolické
odpovědi na hladovění u myší. Cílem naší studie
bylo stanovit plazmatické koncentrace FGF19
a FGF21 u pacientek s restriktivním typem mentální
anorexie (AN) a zjistit vztah těchto faktorů
k antropometrickým a vybraným endokrinním
parametrům u AN a u zdravých žen s normální tělesnou
hmotností (kontrolní skupina). Plazmatické
koncentrace FGF21 byly významně nižší u pacientek
s AN v porovnání s kontrolami. Nutriční
léčba vedla k dalšímu významnému snížení plazmatických
hladin FGF21 u AN. Hladiny FGF21
před léčbou pozitivně korelovaly s přírůstkem
hmotnosti v průběhu dvouměsíční nutriční léčby
u AN. Plazmatický FGF21 pozitivně koreloval se sérovým
leptinem a sérovým inzulinem a negativně
koreloval se sérovým adiponektinem u obou
sledovaných skupin. Cirkulující hladiny FGF21,
ne však FGF19, mají významný vztah k tělesné
hmotnosti a sérovým hladinám leptinu, adiponektinu
a inzulinu jak u malnutričních pacientek
s AN, tak u žen s normální tělesnou hmotností.
Nízké plazmatické koncentrace FGF21 mohou
být součástí adaptivní metabolické odpovědi na
chronickou podvýživu nebo patofyziologických
metabolických změn u pacientek s AN.
Introduction: Fibroblast growth factors 19
and 21 (FGF19 and FGF21) are novel metabolic regulators
that improve insulin sensitivity and increase
lipolytic rate in mice. Gene expression of FGF21 in the
mouse liver is under tight nutritional control being
stimulated by short-term fasting and ketogenesis
and inhibited by feeding. Despite an important role
of FGF19 and FGF21 in the metabolic response to
starvation in animals, little is still known about the
nutritional regulation and bioactivity of FGF19 and
FGF21 in human. Aim: The aim of this study was
to measure plasma FGF19 and FGF21 levels in patients
with anorexia nervosa (AN) and to explore
its relationship with anthropometric and selected
endocrine parameters. Patients and Methods: 17
untreated women with a restrictive type of AN (age:
25.0 ± 1.34, body mass index (BMI): 15.9 ± 0.33 kg/m2)
and 17 healthy women (control group; age: 24.7 ±
0.59, BMI: 22.9 ± 0.41 kg/m2) were included. 10 from
the patients with AN were examined also after two
months of partial realimentation. Blood samples
for FGF19, FGF21, leptin, leptin receptor, adiponectin,
resistin, insulin, ketone bodies, free fatty acids (FFA),
thyroid hormones, C-reactive protein (CRP), insulinlike
growth factor-1 (IGF-1) and biochemical parameters
evaluation were withdrawn after overnight fast
at 8.00 a.m. Fasting plasma FGF19 and FGF21 were
measured by commercial ELISA kit (Biovendor, Brno,
VII. Mezioborová konference o poruchách příjmu potravy a obezitě s mezinárodní účastí | 19. – 21. 3. 2009
Czech Republic). Results: Fasting serum resistin, glucose,
insulin, glycated hemoglobin, total cholesterol
and triglycerides did not significantly differ between
the groups studied. Fasting serum leptin, IGF-1, FFA,
free T3, free T4, total ketone bodies, and CRP levels
were significantly reduced in the AN group, whereas
fasting serum adiponectin and soluble leptin receptor
were significantly increased in AN relative to controls.
Fasting plasma FGF19 levels did not significantly
differ between the groups studied (246.8 ± 34.1 pg/
ml in AN vs. 205.3 ± 25.9 pg/ml in C), whereas fasting
plasma FGF21 levels were significantly reduced in AN
relative to control group (112.4 ± 23.4 pg/ml u AN
vs. 272.3 ± 40.0 pg/ml u C; p < 0.05). Plasma FGF19
was not related to any of the parameters studied. In
contrast, plasma FGF21 significantly positively correlated
with BMI (r = 0.54; p < 0.001), serum leptin
(r = 0.62; p < 0.001) and serum insulin (r = 0.42; p <
0.05) and was significantly inversely related to serum
adiponectin (r = - 0.48; p < 0.005) levels in both
groups. FGF21 was significantly inversely related to
fT3 in the control group only (r = - 0.54; p < 0.05). All
studied patients with AN gained weight and body
fat during realimentation. Plasma levels of FGF21
in all patients with AN were significantly reduced
after 2 months of realimentation. Plasma levels of
FGF19 tended to decrease after realimentation, but
the difference did not reach statistical significance.
Pre-treatment plasma FGF21 significantly positively
correlated with change in BMI during treatment (r
= 0.62; p < 0.05). Discussion: In mice, the hepatic
expression of FGF21 was up-regulated both by the
starvation and by the ketogenic state, and it decreased
upon feeding (1). The fasting-induced FGF21
in turn contributed to initiation of the response to
fasting in mouse liver and adipose tissue, including
ketosis and lipolysis (2). Here we show, contradictory
to acute fasting animal studies, that the chronic
malnutrition in humans is associated with markedly
reduced circulating FGF21 levels. Decreased FGF21
levels could contribute to the increased rate of lipolysis
in adipose tissue of patients with AN (3,4) and may
also help to maintain euglycemia in these chronically
malnourished patients (5). Circulating FGF21 levels
in AN are under tight nutritional control and may
represent an important part of the complex neuroendocrine
response to chronic malnutrition in AN
patients and possibly also a valuable predictor of the
effectiveness of realimentation therapy. Conclusions:
Circulating levels of FGF21 were significantly reduced
in patients with a restrictive type of AN relative to
normal-weight women. FGF21 levels were closely
related to BMI and leptin, adiponectin, and insulin in
both AN and normal-weight women. Plasma FGF21
levels in patients with AN were tightly regulated by
nutritional treatment. In contrast, we did not find