Does FMF have a property to protect children from obesity?

doi:10.4236/health.2010.23038

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Vol.2, No.3, 268-271 (2010)

doi:10.4236/health.2010.23038

Health

Does FMF have a property to protect children from

obesity?

Faysal Gök1, İsmail Dursun2, İbrahim Gökçe2

1Department of Pediatric Nephrology and Rheumatology, Gülhane Military Medical Academy, School of Medicine, Ankara, Turkey;

faysalgok@yahoo.com

2Department of Pediatric Nephrology and Rheumatology, Gülhane Military Medical Academy, School of Medicine, Ankara, Turkey;

drdursun@hotmail.com, gokcemd@yahoo.com

Received 20 November 2009; revised 11 January 2010; accepted 15 January 2010.

ABSTRACT

Objectives: This study investigates the preva-

lence of obesity in children with familial Medi-

terranean fever (FMF). Material and Methods: We

retrospectively reviewed the medical records of

70 patients with FMF whose cases had been fol-

lowed in our Pediatric Nephrology and Rheuma-

tology Unit. The height and weight measure-

ments of children with FMF were obtained and

body mass index was calculated. Results: The

mean body mass index was 16.7± 2.4 in the boys,

and 17.4±2.9 in the girls. Nine of the children

(five boys, four girls) were found to be over-

weight, a rate of 12.8% in FMF patients. Obesity

was not detected in FMF patients. Conclusions:

We think that there are some unligteening mo-

lecular mechanisms that prevent obesity in FMF

patients. Due to the limited number of patients in

this study, further research involving more pa-

tients are needed.

Keywords: Familial Mediterranean Fever; Obesity;

Children; Adipocytokines

1. INTRODUCTION

Familial Mediterranean fever (FMF), an autosomal re-

cessive disorder common in Mediterranean and Middle

Eastern populations, especially in Sephardic Jewish,

Armenian and Turkish populations, is characterized by

recurrent episodes of fever, abdominal pain, joint pain,

and less frequently, pleuritis, pericarditis and rash, de-

scribed as erysipelas-like erythema [1]. The prognosis of

this disease depends on the development of the amyloi-

dosis of AA type with prominent renal involvement [2].

The molecular mechanism of FMF is still not clear. The

gene causing FMF, known as MEFV (MEditerranean

FeVer), has been mapped on the short arm of chromo-

some 16 [3]. It has been shown that substantial subclinical

inflammation occurs widely and over prolonged periods

in patients with FMF, indicating that the relatively in-

frequent clinically overt attacks represent the tip of the

iceberg in this disorder [4].

Obesity is characterized by a state of chronic low-grade

inflammation [5]. The basis for this view is that increased

circulating levels of several markers of inflammation,

both pro-inflammatory cytokines and acute-phase pro-

teins, are elevated in the obese; these markers include

IL-6, the TNFa system, C-reactive protein (CRP) and

haptoglobin [6]. Nevertheless, it is increasingly evident

that the inflammatory state may be causal in the devel-

opment of insulin resistance and the other disorders as-

sociated with obesity, such as hyperlipidaemia and

metabolic syndrome [5]. While the general assumption is

that inflammation is consequent to obesity, it has been

suggested that obesity is in fact a result of inflammatory

disease [6].

Although studies regarding the etiologic factors of

FMF and obesity have been reported, the eligible etiology

of neither FMF nor obesity is clear yet. The influence of

FMF on the growth parameter has been reported [7-9].

According to literature, the prevalence of both diseases is

high in the Turkish population [10,11]. Thus we aimed to

show the relationship between the diseases and the

prevalence of overweight and obesity in FMF patients.

2. PATIENTS AND METHODS

We retrospectively reviewed the medical records of 70

patients with FMF whose cases had been followed up in

our Pediatric Nephrology and Rheumatology Unit. The

diagnosis of FMF had been made according to the diag-

nostic criteria and mutational analysis [12,13]. Only pa-

tients who had homozygosity and/or compound het-

erozygosity for MEFV mutations were included in this

study. Body height and weight were measured by trained

paediatric specialists. For the measurements, the patients

F. Gök et al. / HEALTH 2 (2010) 268-271

269

were dressed in light indoor clothing and bare feet or

stockings. The subjects were weighed to the nearest 0.1

kg with an electronic scale (SECA 762; Vogel & Hakle,

Hamburg, Germany) calibrated daily at the beginning of

each working day. Height was measured with a stadi-

ometer in the vertical position, erect, with parallel feet

and ankles, and with the shoulders and bottom touching

the wall. The height and weight data were used to calcu-

late the body mass index (BMI) (kg/m2) using the for-

mula: weight (kg) divided by height (m) squared. The

BMI normalized centile curves for Turkish children were

applied to define obesity and the values of 95 percent or

more were accepted as obesity [11].

3. STATISTICAL ANALYSES

All tests were performed using SPSS for Windows 15.0.

The parameters with normal distribution were expressed

as mean ± SD. Comparisons of means were performed

with an unpaired t-test. Comparisons of proportions were

performed with a Pearson-chi-squared test. A P value

<0.05 was accepted as statistically significant.

4. RESULTS

The study population consisted of 70 children with FMF

(34 boys, 36 girls). Table 1 shows the age distribution

and anthropometric parameters of the FMF patients. The

mean age of boys and girls was 8.9±3.5 (range 5-18

years) and 9.4±3.1 (range 5-16 years), respectively. The

mean of BMI was 16.7±2.4 in boys, 17.4±2.9 in girls.

Overweight was diagnosed in 9 (5 boys, 4 girls) and the

prevalence of overweight is 12.8% in FMF patients.

Obesity was not detected in FMF patients. The results of

genotype of the patients with FMF are shown in Table 2.

5. DISCUSSIONS

In this study we investigated the prevalence of obesity in

FMF patients. Obesity is a problem of public health and

its prevalence is increasing rapidly worldwide [14]. The

prevalence of obesity and overweight has been reported

9.7-12.8% and 11.6-25%, respectively, in Turkish chil-

dren [11,15-17]. Regarding the study group, the number

of obese children at least was expected to be seven, but

none were found; and the P value <0.05 was statistically

significant. The rate of overweight in the study group

was the same as in Turkish healthy children.

Shortened growth is a frequent complication in the

chronic inflammatory diseases of childhood [18]. Growth

in children with FMF has been evaluated in three previ-

ous studies [7-9]. Savgan et al. reported that children

with FMF have growth patterns no different from those

of their healthy peers. Zung et al. showed that colchi-

cine therapy has a positive effect on anthropometric

Table 1. Age distrubution and antropometric parameters of the

patients with FMF.

Variables FMF (boys)

(n=34)

FMF (girls)

(n=36)

Age (years) 8,9±3,5 9,4±3,1

BMI (kg/m2) 16,7±2,4 17,4±2,9

Overweight 5 4

Table 2. Major genotypes in FMF patients.

Mutations n (%)

M694V–M694V 28 (40)

M694V–V726A 13 (18.5)

M694V–M680I 11(15.7)

M694V–E148Q 7 (10)

M680I–M680I 3 (4.2)

V726A–E148Q 2 (2.8)

V726A–V726A 1 (1.4)

E148Q– E148Q 1 (1.4)

M694V/R761H 1 (1.4)

M680I/V726A 1 (1.4)

V726A/R761H 1 (1.4)

E148Q/R761H 1 (1.4)

Total 70 (100)

parameters in children with FMF. Turkmen et al. indi-

cated that colchicine therapy caused a slight but signifi-

cant increase in BMI. There was no obese child among

the FMF subjects in this study. In the light of sugges-

tions that obesity is in fact a result of inflammatory dis-

ease, we think that the chronic inflammatory situation

alone is not enough to state the mechanism of the

non-development of obesity in the FMF study group.

The low-grade systemic inflammation in FMF patients

may underlie the clustering of metabolic risk factors,

but their role in children remains to be specified. The

adipocytokines and cytokines appear to be important in

this respect.

Leptin is secreted from adipocytes in response to

changes in body fat and was initially suggested as a

promising “anti-obesity” hormone. The interaction of

leptin with its receptors controls body weight and daily

energy consumption [19,20]. In the hypothalamus, leptin

binds to receptors that stimulate anorexigenic peptides

and inhibit orexigenic peptides [21]. Leptin declines

rapidly during fasting. Therefore, leptin deficiency was

perceived as a state of unmitigated starvation, leading to

compensatory responses, such as hyperphagia, decreased

metabolic rate and changes in hormone levels, designed

to restore energy balance [22]. Leptin reduces intracellu-

lar lipid levels in skeletal muscle, liver and pancreatic beta

cells, and thereby improving insulin sensitivity.

Unlike most adipokines, adiponectin expression and

serum concentrations are reduced in obese and insu-

lin-resistant states. Like leptin, adiponectin enhances

insulin sensitivity. High adiponectin levels were found in

F. Gök et al. / HEALTH 2 (2010) 268-271

270

association with high levels of HDL cholesterol and a

low triglyceride-to-HDL ratio [23]. Adiponectin, impli-

cated as having anti-inflammatory activity, is induced by

PPARg (Peroxisome proliferator-activated receptors) ago-

nism. Weight loss and caloric restriction have been found

to increase adiponectin plasma levels and gene expres-

sion in white adipose tissue. Two case control studies in

obesity-prone Pima Indians and in Caucasians suggested

that individuals with high adiponectin concentrations are

less likely to develop type-2 diabetes than those with

low concentrations [22]. Also, Saltevo et al. showed the

significant negative relationship between adiponectin

measured at adulthood and the relative change of BMI

from childhood to adulthood [24].

It was shown that insulin resistance in lipoatrophic

mice was fully reversed by a combination of physio-

logical doses of adiponectin and leptin, but only partially

by either adiponectin or leptin alone, suggesting that

adiponectin and leptin work together to sensitize periph-

eral tissues to insulin. However, because globular adi-

ponectin improves insulin resistance but not obesity in

ob/ob leptin-deficient mice, adiponectin and leptin ap-

pear to have distinct, albeit overlapping, functions [22].

Another adipokine studied in obese patients is omentin.

Lean subjects have higher plasma omentin levels than do

obese and overweight patients. Plasma omentin levels are

inversely correlated with BMI, waist circumference, leptin

levels and insulin resistance as measured by HOMA-R,

and positively correlated with adiponectin and HDL-

cholesterol levels. Accordingly, omentin gene expression

is decreased with obesity [25].

In addition, adipokines and many cytokines (espe-

cially IL-17A, IL-6, TNF-alfa) also were studied and

found to be associated with lipid metabolism. It was

shown that IL-17A inhibits adipocyte differentiation in

human bone marrow mesenchymal stem cells, while

promoting lipolysis of differentiated adipocytes [26].

In conclusion, the chronic inflammatory situation

alone is not sufficient to state the mechanism of the non-

development of obesity in FMF patients. It is thought

that some unligteening molecular mechanisms are in-

volved in the interaction between cytokines and adipo-

cytokines preventing obesity in FMF patients. Due to the

limited number of patients in this study, further research

with a greater number of patients looking at the wide

range of adipocytokines and cytokines known to be as-

sociated with lipid metabolism and obesity are needed to

confirm this speculation and establish the fundamentals

of the non-development of obesity in FMF patients.

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