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Asia Pacific J Clin Nutr (1992) 1, 207-210

Insulin-like growth factor-I and fast growth-hormone levels in mild and moderately malnourished children

Wan Mohamud Wan Nazaimoona PhD, Ali Osmanb MPH, Mee Lian Nga PhD, Tean Tune TanC MRCP, Loo Ling WUd MRCP, Othman SakinahC MD and Abdul Kadir KhalidC PhD, FRACP.

Department(s) of aBiochemistry, bPublic Health, cMedicine and dPediatrics, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jin. Raja Muda Abd. Aziz, 50300 Kuala Lumpur, Malaysia.

Insulin-like growth factor-I (IGF-I)and fasting growth hormone levels were measured in a group of 255 children (163 males and 92 females. age ranged 6-17 years) of varying pubertal development and body mass index (BMI); well-nourished (BMI> 18). mildly-malnourished (BMI = 15-18) and moderately-malnourished (BMI<15). In well-nourished children IGF-I levels increased significantly (P = 0.02) with pubertal development. where girls at Tanner 5 had significantly higher (p = 0.03) IGF-I levels than the boys. Whilst there was no change in fasting GH levels with nutritional status, IGF-I levels of prepubertal boys and girls decreased significantly with BMI (P<0.001 and P = 0.01 respectively). Hence. measurement of IGF-I levels is a sensitive biochemical index in the assessment of mild and moderate form of malnutrition in prepubertal children.

Introduction

Growth hormone (GH) mediates its growth-promoting effect via a group of peptides known as somatomedin-C or insulin-like growth factor-I (IGF-I)1. Generally, short stature is caused by the lack of GH2, although in Laron-type dwarfism, it is due to IGF-I deficiency3. Growth retardation also occurs in children with protein-energy malnutrition (PEM), where IGF-I levels were found to be low1,4,5 and GH were reported to be elevated4,6-8.

Compared to other biological markers such as albumin and transferrin, IGF-I was reported to be very sensitive to changes in nutritional status and was recommended as a potential biological marker in the assessment of chronic malnutrition such as kwashiorkor and marasmus5,9-12. However, as such severe conditions are rarely seen in Malaysia, we undertook this study to evaluate the sensitivity of IGF-I and GH measurements in less severe forms of malnutrition, and to assess their usefulness as biochemical indicators of nutritional status.

Patients and methods

A total of 255 children (163 males and 92 females, age 6-17 years) from three rural villages were studied. Their pubertal development was determined by the method of Tanner, whereby 143 children were prepubertal (scrotum/breast stage 1) and 112 had already achieved puberty (Tanner stages 2 to 5). These children were also grouped into three groups according to their body mass index (BMI); well-nourished (BMI>18), mildly-malnourished (BMI = 15-18) and moderately-malnourished (BMI<15) (Table 1). Informed consent was obtained from all subjects and their parents.

Table 1. Characteristics of the children in the study.

    Pubertal development
    Prepubertal Pubertal
Children Total BMI<15 BMI 15-18 BMI>18 BMI<15 BMI 14-18 BMI>18
Boy 163 51 24 13 10 43 22
Girl 92 33 16 6 0 4 33
Together 255 84 40 19 10 47 55

After an overnight fast, 5 ml of blood was obtained by venepuncture, 2.5 ml being immediately transferred into an EDTA tube and the remainder allowed to clot in a plain tube. All plasmas and sera were separated immediately and stored frozen at -20°C until assayed.

Plasma IGF-I levels were measured by SM-C RIA kit from Nichols Institute, San Juan, Capistrana. CA. USA. Intra-assay coefficient of variations (CVs) at concentrations of 0.5, 0.82 and 1.24 U/ml were 12.0, 9.0 and 7.4% respectively, whilst the respective inter-assay CVs were 12.2, 10.0 and 8% .

Serum samples were assayed for GH using our own in-house enzyme-linked immunoabsorbent assay13. Intra- and inter-assay CVs at concentrations of 3.4-55.7 mIU/I were all within 10%. GH reference standard used was I.S. 80/505 and minimal detectable concentration of the assay was 0.4 mIU/I. As far as possible. samples within each group were assayed in a single assay.

Statistical Analysis

Differences between groups were analysed by nonparametric Kruskal-Wallis and Wilcoxon Rank Sum tests. A P value of <0.05 was regarded as significant.

Results

Plasma IGF-I levels in 74 normal. well-nourished children (BMI>18) (35 males and 39 females) at different Tanner stages arc shown in Fig 1. IGF-I levels increased significantly (P = 0.02) with pubertal development. Sex-difference in IGF-I levels was observed only at Tanner stage 5. Girls in this group had significantly higher (P = 0.03) IGF-I levels than the boys (Fig 1).

Figure 1. Plasma insulin-like growth factor-I (IGF-I) of normal boys and girls at different Tanner stages. 95% confidence limits and interquartile ranges are represented by vertical columns and bars respectively. Numbers above bars represent number of children studied.

Changes in nutritional status (based on BMI) were found to influence only the IGF-I levels of the prepubertal group (Fig 2). Plasma IGF-I levels decreased significantly in the mildly and moderately-malnourished boys and girls (P<0.001 and P =.0.01 respectively). Median IGF-I levels of the moderately-malnourished boys and girls (0.5 and 0.78 U/ml respectively) were significantly lower (P = 0.004 and P = 0.03 respectively) than the respective sex-matched well-nourished group (1.1 and 1.8 U/ml respectively) (Fig 2). On the other hand, there was no significant difference in fasting GH levels between the well-nourished, mildly- and moderately-malnourished prepubertal children (Fig 3) or pubertal boys (Fig 4). We were however, unable to draw any conclusion on the fasting GH levels of the pubertal girls. as there were insufficient data in the mildly- and moderately-malnourished groups (n = 4 and n = 0 respectively) (Fig 4).

Figure 2. Plasma insulin-like growth factor-l (IGF-I) of prepubertal boys and girls at different nutritional status.

Figure 3. Fasting growth hormone of prepubertal boys and girls of different nutritional status.

Figure 4. Fasting growth hormone of pubertal boys and girls of different nutritional status.

Discussion

The pubertal increase in IGF-I levels of normal children seen in this study is comparable to that reported by others14-16. Similarly to the report by Ruland et al.16, who found that girls age 6-14 years had higher IGF-I levels than boys, we found that sex-difference was most significant at Tanner 5 (P = 0.03). We suggest that this was due to the influence of oestrogens17,18.

The various alterations in hormonal levels seen in severe malnutrition are believed to be part of the endocrine adaptive processes to conserve energy and protein metabolism in adverse conditions. In this study, plasma IGF-I levels in prepubertal children were found to decrease significantly with BMI. This finding is comparable to that observed by others4,8. In contrast to previous reports,4,6,8 we found that there was no significant difference in fasting GH levels between the well-nourished, mildly and moderately malnourished children. This is probably due to the less severe form of malnutrition of our subjects, compared to other studies4,7,8 where the children were suffering from marasmus and kwashiorkor.

Hence, in agreement with several previous studies,5,9,11,12 we have showed that measurement of IGF-I concentrations is indeed sensitive to slight changes in nutritional status and thus is a better biochemical index than GH in the assessment of growth retardation due to malnutrition.

References

  1. Phillips LS. Vassilopoulou-Scllin R. Nutritional regulation of somatomedin. Am J Clin Nutr 1979: 32: 1082.
  2. Daughaday WH. Growth hormone and the somatomedins. In: Daughaday WH. cd. Endocrine control of growth. New York: Elsevier. 1981; 1.
  3. Laron. Z. Petzelan A. Karp M. Kowaldlo-Silbergeld A. Daughaday WH. Administration of growth hormone to patients with familial dwarfism with high plasma immunoreactive growth hormone: measurement of sulfation factor. metabolic and linear growth responses. J Clin Endocrinol Metab 1971; 33:332.
  4. Hintz RL. Suskind R. Amatayakul K. Thananykul O. Olson R. Plasma somatomedin and growth hormone values in children with protein-calorie malnutrition. J Pediatr IY78:92:153.
  5. Unterman TG. Vazquez RM. Slas AJ. Martyn PA. Phillips PA. Nutrition and somatomedin. XIII. Usefulness of somatomedin-C in nutritional assessment. Am J Med 1985; 78:228.
  6. Beas F. Contreras 1. Maccioni A. Arena S. Growth hormone in infant malnutrition: the arginine test in marasmus and kwashiorkor. Br J Nutr 1971; 26: 169.
  7. Lunn PG. Whitehead RG. Hay RW. Baker BA. Progressive changes in serum cortisol. insulin and growth hormone concentrations and their relationship to the distorted amino acid pattern during the development of kwashiorkor. Br J Nutr 1973; 29:399.
  8. Smith IF. Latham MC. Azubuike JA. Butler WR. Phillips LS, Pond WG. Enwonwu SO. Blood plasma levels of cortisol. insulin. growth hormones and somatomedin in children with marasmus. kwashiorkor. and intermediate forms of protein-energy malnutrition. Proc Soc Exp Biol Med 1981: 167:607.
  9. Clemmons DR, Underwood LE. Dickerson RN. Brown RO, Hak LJ, MacPhee RD. Heizer WD. Use of plasma somatomedin-C/insulin-like growth factor I measurements to monitor the response to nutritional repletion in malnourished patients. Am J Clin Nutr 1985; 41:191.
  10. Phillips LS. Nutrition. somatomedins and the brain. Metabolism 1986; 35:78.
  11. Minuto F. Barreca A. Adami GF. Fortini P. Del Monte P. Cella F. Scopinaro N. Giordano G. Insulin-like growth factor-I in human malnutrition: relationship with some body composition and nutritional parameters. J Parenter Enteral Nutr 1989; 13:392-6.
  12. Bouhaddioui L. Brun JF, Jacquemin JC. Bouhaddioui N. Kabbaj K. Orsetti A. Immunoreactive somatomedin C in children from Morocco: a biological marker of nutritional growth retardation? Biomed. Pharmacother 1989; 43:59.
  13. Ng ML. Goh KH, Wan Nazaimoon WM. Thean ETT. Khalid BAK. Non-isotopic in-house ELISA as an alternative to RWI RMA for measurement of pituitary peptide hormones. IAEA/WHO International Symposium on RIA and related procedures. Perspectives in Developing Countries. 26-30 Aug 1991, Vienna. Austria. IAEA-SM324/24: 109.
  14. Bala RM, Lopatka J, Leung A. McCoy E. McArthur RG. Serum immunoreactive somatomedin levels in normal adults. pregnant women at term, children at various ages and children with constitutionally delayed growth. J Clin Endocrinol Metab 1981; 52:508.
  15. Luna AM. Wilson DM. Wibbelsman CJ. Brown RC. Nayashima RJ. Hint RL. and Rosenfeld RG. Somatomedins in adolescence: a cross sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels. J Clin Endocrinol Metab 1983; 57:268.
  16. Ruland A. Heinrich U. Hartmann K. Schonberg D. Scrum IGF-I levels during childhood and adolescence. Acta Paediatr Scand [Suppl] 1988: 343:238.
  17. Cuttler L. Van Vliet G. Conte FA. Kaplan SL. Grumbach MM. Somatomedin-C levels in children and adolescents with gonadal dysgenesis: differences from age matched normal females and effect of chronic estrogen replacement therapy. J Clin Endocrinol Metab 1985: 60: 1087.
  18. Rosenfield RL. Furlanetto R. Physiologic testosterone and estradiol induction of puberty increases plasma somatomedin-C. J Pediatr 1985; 107:415.
  19. Brasel JA. Endocrine adaptation to malnutrition. Pediatr Rcs 1980: 14:415.
  20. Laditen AA. Hormonal changes in severely malnourished children. African J Med Sci 1983: 12: 125.

Insulin-like growth factor-I and fast growth-hormone levels in mild and moderately malnourished children

Wan Mohamud Wan Nazaimoon, Ali Osman, Mee Lian Ng. Tean Tune Tan, Loo Ling Wu, Othman Sakinah and Abdul Kadir Khalid

Asia Pacific Journal of Clinical Nutrition 1992; 1: 207-210

ARAS FAKTOR PERTUMBUHAN MENYERUPAI INSULIN I (IGF-I) DAN HORMON PERTUMBUHAN BERPUASA PADA KANAK-KANAK YANG MENGALAMI KEKURANGAN GIZI YANG RENDAH DAN SEDERHANA

Aras faktor pertumbuhan menyerupai insulin I (IGF-I) dan hormon pertumbuhan berpuasa dihitung pada 273 orang kanak-kanak (186 orang kanak-kanak lelaki dan 87 orang kanak-kanak perempuan. yang berusia sekitar 6-17 tahun) dari pelbagai peringkat pubertas dan indeks massa tubuh (BMI); tanpa kekurangan gizi (BMI>18). kekurangan gizi yang rendah (BMI = 15-18) dan kekurangan gizi yang sederhana (BMI<15). Pada kanak-kanak yang tidak mengalami kekurangan gizi. aras IGF-I meningkat secara signifikans (P=0.02) bersama peringkat pubertas, yang mana kanak-kanak perempuan pada Tanner 5 mempunyai aras IGF-I yang signifikans lebih ketara dari kanak-kanak lelaki (P=0.03). Sungguhpun tiada perubahan aras hormon pertumbuhan berbanding status gizi, paras IGF-I pada kanak-kanak lelaki dan perempuan prepubertas menurun secara signifikans bersama-sama BMI (masing-masing P<0.001 dan P=0.01). Oleh itu, perhitungan aras IGF-I merupakan indeks biokiminia yang sensitif untuk menilai kekurangan gizi yang rendah dan sederhana pada kanak-kanak prapubertas.


Copyright © 1992 [Asia Pacific Journal of Clinical Nutrition]. All rights reserved.
Revised: January 19, 1999 .

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