INSULIN LIKE GROWTH FACTOR REGULATION OF BODY MASS IN BREASTFED AND MILK FORMULA FED INFANTS

REGULATION OF BODY MASS IN

BREASTFED AND MILK FORMULA FED INFANTS

Data from the EU Childhood Obesity Programme

P. Socha

, R. Janas

, A. Dobrzañska

, B. Koletzko

, I. Broekaert

, D.

Brasseur

, A. Sengier

, M. Giovannini

, C. Agostoni

, R. Closa Monasterolo

, G. Méndez

, EU Childhood Obesity Study Team

1Children's Memorial, Health Institute, Warszawa, Poland, ²Children's University Hospital, Ludwig Maximilians University, Munich, Germany, ³Unité de Nutrition, Hôpital Universitaire des Enfants Reine Fabiola, Bruxelles, Belgium, ⁴⁴Pediatric Department, Ospedale San Paolo, Milano, Italy, ⁵⁵Pediatric Unit, University Rovira i Virgili, Tarragona, Spain

Introduction: The data used for analysis was obtained from the European Union research project “Childhood obesity: programming by infant nutrition?”.

The trial takes place in five countries-it is a randomized double blind placebo controlled trial which remains still blinded. However some laboratory data are available for comparisons between all pooled formula fed infants and breast fed infants. Breast fed infants have a lower risk of obesity and receive less protein which lead to hypothesis of obesity programming by early protein intake- in this particular trial infants fed either low or high protein formula receive more protein than breast fed babies. Insulin-like growth factor axis seems to be stimulated in obese people and these hormonal effects could be also responsible for increasing risk of obesity with formula feeding. However, data on insulin- like growth factor axis in breast fed and formula fed infants are lacking.

The aim of our study was to investigate and compare the insulin-like growth factor 1 axis in formula and breast fed infants.

Methods: We used the preliminary laboratory results obtained from:

• 208 formula fed infants receiving either high protein (21 g/L or 15 % of r energy) & low protein (12,7 g/l or 9,6 % of energy) formula pooled together (1:1)

• 113 breast fed infants (at least 3 m of breast-feeding).

Blood samples were taken at the age of 6 months for analysis of serum free IGF- I, total active IGF-I, IGF-BP-2 and IGF-BP3 (RIA tests- Diagnostic Systems Laboratories, INC., Webster, USA). The results were presented as mean ±SD.

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160 P. Socha et al.

The two groups of infants studied were compared with the Mann-Whitney-U test. Differences were regarded to be statistically significant at p<0.05.

Results: Weight was increased in formula fed infants (7.81 ±0.89 kg vs.

7.60 ±0.89 kg, p<0.05) whereas length did not differ between the groups (67.5 ±2.4 vs. 67.7±2.4 cm). Body mass index was significantly higher in formula fed babies (11.6 ±1.2 vs. 11.1±1.1). In concordance with increased weight concentrations serum total active IGF-I and free IGF-I were significantly higher in formula fed infants (fig. 1,2). The inhibitory protein IGF-BP-2 decreased in formula fed infants, and the stimulatory protein IGF-BP-3 increased in formula fed infants (Fig. 3,4).

Discussion: The anthropometric results from our study confirm previous epidemiological observations of increasing weight and BMI in children fed formula in infancy (1,2). Already at age of 6 months formula fed infants have significantly higher weight and BMI in our trial. We can only speculate about possible protective role of lower protein intake in breast fed babies as we did not evaluate the effects of two different formulas.

Figure

. Total active IGF-1 serum concentration in breast fed and formula fed infants

±SD

±SE Mean

feeding

active IGF I (ng/ml)

-10 10 30 50 70 90 110

breast formula p<0.001

±SD

±SE Mean

feeding

free IGF conc.(ng/ml)

-0,2 0,2 0,6 1,0 1,4 1,8

breast formula

P<0.001

Figure

. Free IGF-1 serum concentration in breast fed and formula fed infants

±SD

±SE Mean

feeding

IGF BP 2 conc. (ng/ml)

8 14 20 26 32 38 44

breast formula P<0.001

Figure

. IGF-BP 2 serum concentration in breast fed and formula fed infants

feeding

IGF BP 3 conc. (ng/ml)

1600 2000 2400 2800 3200 3600 4000 4400

breast formula p<0.001

Figure

. IGF-BP 3 serum concentration in breast fed and formula fed infants

162 P. Socha et al.

Consistent results of insulin like growth factor axis stimulation point to the important role of this hormonal regulation of body weight. In fact, free IGF-1 increases in obesity that was documented in many studies (3,4,5). There were some conflicting results concerning total active IGF-1 serum levels: normal (3,4), low (5,6,7) or high (8,9,10) serum concentrations were described that may be explained by different populations studied with different types of adiposity.

Recently studied pre- and post-menopausal women presented with various concentrations of total IGF-1 that was not clearly related to BMI (11). It may be expected that in pubertal, pre- and postmenopausal populations there are many different hormonal influences interfering with IGF-1 regulations. Our population of infants seems to be more homogenous and sex hormones do not interfere with body mass regulation at this age.

High concentration of free-IGF-1 may be also partially explained by lower levels of IGF-BP-2 , whose production is inhibited by insulin, usually increased with increasing weight. In other populations studied IGF-BP-2 decreased in obesity and the results are very consistent (3,4,5). Furthermore, IGFBP-3 has a complementary stimulatory activity as IGF-1 and this protein is increased in the infants studied. This finding can not be confirmed in all publications as obesity was shown to be associated with normal (4) or high (5) IGFBP-3 concentrations.

Also IGFBP-3 serum levels did not show any clear association with BMI in pre- and postmenopausal women (11). On the other hand, a positive correlation between IGFBP-3 and free-IGF-I levels has been shown in obese children (5).

The results of our study seem to be very consistent to point out stimulatory effect of formula feeding on insulin-like growth factor axis. It can be speculated that increasing weight in formula fed infants is attributed to the stimulation of IGF axis. The role of high protein intake will be studied as soon as two groups of children fed high- and low-protein formulas are available for analysis.

Conclusions: The study presents preliminary results from the European Union research project “Childhood obesity programming by infant nutrition”. Breast fed and formula fed infants at age of 6 months were compared in concern of insulin-like growth factor (IGF) axis: total and free IGF were significantly increased in formula fed infants, IGF-binding protein 2 was decreased and IGF- binding protein 3 was increased. The results point to stimulation of IGF axis by formula feeding that corresponds to higher body weight in these infants.

Key words: obesity, IGF-I, nutritional programming, insulin resistance

Acknowledgement: This project is carried out with financial support of the

European Community, under the 5th Framework Programme for Research,

Technology & Demonstration „Quality of Life and Manage f ment of Living

Resources“, Key Action 1 (Food, Nutrition & Health), contract number QLK1- CT2002-389.

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