Brief Reports

Indian Pediatrics 2000;37: 990-997

Insulin Like Growth Factor-I, Insulin Like Growth Factor Binding Protein-3 and Acid Labile Subunit Levels in Healthy Children and Adolescents Residing in Mumbai Suburbs

Rajbinder Kaur Dehiya
Deepa Bhartiya
Chhaya Kapadia
Meena P. Desai

The actions of growth hormone (GH), a major regulator of growth, are mediated via Insulin like Growth Factor-1 (IGF-1), produced by the liver(1). Almost 95% of IGF-1 in circulation is present in a 150 kDa complex, with its binding protein-3 (IGFBP-3) and another protein, Acid Labile Subunit (ALS,2). This complex stabilizes IGF-1, prolongs its half-life and also regulates its bio-availability to growing tissues(2). These peptides viz., IGF-1, IGFBP-3 and ALS appear to be more stable than GH (which is pulsatile in nature), show minimum diurnal variation and are being used to screen for GH deficiency(3) in an easier manner than the conventional GH measurement. They are also being studied in cases of GH insensitivity(4), intrauterine growth retardation(5), polycystic ovarian syndrome(6) and central precocious puberty(7).

It is a well established fact that children of developing countries do not attain same level of growth as their Western counterparts. Compari-sons with the European countries show that even affluent Indians are shorter and lighter(8,9). It has been shown in the past, that using Western percentiles, there would be unnecessary investigation for short stature in a third of our normal population(10). Recently, Khadagwat et al.(11) found that Agarwal charts(8,9) were better representative of growth of normal Indian children than the NCHS or ICMR charts (the latter were based on Indian children of low socio-economic status families and the study was conducted four decades ago).

Since IGF-1, IGFBP-3 and ALS are essentially involved in postnatal growth, we have analyzed their levels in healthy children and adolescents (from birth to 20 years of age) residing in Mumbai suburbs and have also made comparisons between present study data and that available for Western population.

The study population included 434 children/adolescents (new-born to 20 years of age; atleast 10 males and 10 females per year of age). Samples from healthy full-term new borns, delivered normally after uncomplicated preg-nancies and weighing more than 2.5 kg at birth, were collected from a maternity hospital. To collect samples from older children/adolescents, camps were organized in large residential complexes in Mumbai suburbs. The children included, belonged to well-to-do higher to middle class families with monthly income over Rs. 5000. We worked on the premise that our study population had maximum growth potential, since they did not belong to low socio-economic status families. Nutrition was not a limiting factor in our population was further confirmed by plotting the heights and weights of our study group on Agarwal's growth charts(8,9) generated on children belonging to affluent class of our community. Almost 90% of our children had their heights and weights falling within the 3rd and 97th percentile of Agarwal charts. As weight for height is the best anthropometric index of nutrition, using EPIINFO software, we found 96% of our children above 10 years of age to be more than 90% of mean weight for height by NCHS standards. However, in age group below 10 years, 50% of present study children were more than 50% of mean weight for height by NCHS standards. The children had no history of systemic illness and also no obvious problem in growth/height. None of the girls included in the study had delayed onset of menses. Two ml of blood was collected and the serum was stored in aliquots at –70°C till further analysis.

Measurement of IGF-1, IGFBP-3 and ALS: Commercial kits from Diagnostic Systems Laboratories, USA were used to measure all the three peptides.

Statistical Analysis: Body Mass Index (BMI) was calculated using the formula Weight (kg)/Height2 (meters). Data was analyzed using the Statistical Analysis Software (SAS, North Carolina, USA). Correlation between the peptides and various clinical parameters such as age, weight, height and BMI were studied by multivariate analysis. Graphs were made using the Microsoft Excel Software. Statistical significance of difference between the present study and the Western population(12) was determined by the Students "t" test (two-tailed). A ‘p’ value of less than 0.05 was considered statistically significant.

Levels of all the three peptides, from birth to 20 years of age, are shown in Tables I-III. A steady increase in the circulatory levels of all the three peptides with age was observed. IGF-1 levels in circulation, showed more dramatic alterations in both the sexes, compared to IGFBP-3 and ALS. Almost a thirty fold increase in IGF-1 and a five fold increase in IGFBP-3 levels was noticed at 12-14 years in girls and 15 years in boys followed by a decline. Circulatory levels of ALS showed a seven and a nine fold rise at 14 years in girls and 17 years in boys, respectively, followed by a decline thereafter.

Multivariate analysis with age and BMI as the independent variables revealed that all the three peptides correlated significantly with BMI in females and with age in males.

On comparison of IGF-1 and IGFBP-3 levels (mean ±SE) obtained in present study with the Western population , IGF-1 levels were observed to be lower in the present study population (Fig. 1) than their Western counterparts, at all ages in both the sexes, IGFBP-3 levels showed considerable overlap between the two popula-tions except at birth, where IGFBP-3 levels were significantly lower in the present study group.

In the present study, circulatory levels of IGF-1, IGFBP-3 and ALS were studied in Indian children residing in Mumbai suburbs. Unlike IGFBP-3 and ALS, IGF-1 showed more dramatic changes with age. Though levels increased gradually till 10 years of age, a thirty-fold rise was observed during adolescent years. Early peaks were observed in girls (12-14 years) as compared to boys (15 years) in accordance with the earlier sexual maturation in girsl(13). Interestingly ALS levels peaked later in both girls (14 years) and boys (17 years).

In agreement with earlier studies conducted in healthy Japanese(1). Caucasians(13), and Spanish(14) children, the present data revealed distinct age related alterations in the circulatory levels of all the three peptides. However, peak values of IGF-1 were attained at different ages in all the three groups.

Environment and genetics are the major factors that regulate the physical growth of an individual. Vijayaraghavan et al.(15) had earlier reported that well-to-do Indian girls, without any apparent dietary and environmental constraints were as tall and heavy as American girls up to 12 years of age and considerable deviations were noted in adolescent period. The differences in the growth curves of Indian and American girls emerged and widened to result in a difference of 5 cm at the 18th year, a difference which occurred almost entirely between the 12th and 18th year of age. Although, the number of observations per year are less in the present study, it is of interest to note that IGF-1 levels were lower at all ages, as compared to the Western norms, and achieved statistical signi-ficance in the post-pubertal period (Fig. 1).

Extensive studies need to be carried out to evaluate the clinical usefulness of these peptides in Indian children having various endocrine defects.

Table I__Levels of IGF-1, IGFBP-3 and ALS in Children (New-born to Five Years)

Table II__Levels of IGF-1, IGFBP-3 and ALS in Girls (Six to Twenty Years).

Table III__Levels of IGF-1, IGFBP-3 and ALS in Boys (Six to Twenty Years)

Fig. 1. Comparison of IGF-1 levels (mean ± SE).

We wish to acknowledge the guidance and support of Dr. Sudha Gangal, Director, Research Society and Dr. N.C. Joshi, Dean, Bai Jerbai Wadia Hospital for Children; Deepak, Shamim and Lata helped us in the field work.

Contributors: MPD helped in designing the study. DB co-ordinated the study (designing, interpretation of data, drafting of manuscript); she will act as the guarantor for the paper. RKD helped in sample collection, performing the tests, data compilation and in drafting the paper. CK assisted in field work.

Funding: Department of Science and Technology, New Delhi. ALS kits were provided as gift by Diagnostic Systems Laboratory, USA.
Competing interests: None stated.

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