|Year : 2003 | Volume
| Issue : 12 | Page : 543-548
Age dependency of serum insulin - like growth factor (IGF)-1 in healthy Turkish adolescents and adults.
O Tiryakioaylu, P Kadiolgu, NU Canerolgu, H Hatemi
Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Cerrahpasa, Istanbul, 34300, Turkey
Department of Internal Medicine, Cerrahpasa Medical Faculty, University of Istanbul, Cerrahpasa, Istanbul, 34300, Turkey
BACKGROUND: Serum levels of insulin-like growth factor-1 (IGF-1) reflect endogenous growth hormone (GH) secretion in healthy subjects. Measurements of IGF-1 are useful for diagnosis and follow-up of patients with acromegaly and the diagnosis of GH deficiency in children. AIMS: To assess age dependency and normal ranges of serum IGF-1 levels in healthy Turkish population. SETTING AND DESIGN: We therefore studied 272 healthy adolescents and adults between 15-75 years of age. None had diabetes or other endocrine disease or had received estrogen therapy. MATERIAL AND METHODS: Height, weight, body mass index (BMI) and waist-hip ratio were measured in all subjects. Serum samples were obtained during morning hours and IGF-1 was measured by radioimmunoassay. STATISTICAL ANALYSIS: The age-dependent reference range for serum IGF-1 concentrations was calculated by simple least linear regression analysis: the regression line represents the means with 95 percent confidence intervals. Correlation analysis was also done. RESULTS: Ageing was negatively related to serum levels of IGF-1 (P= 0.0001, r=-0.931) with a mean decrease (youngest vs. oldest). IGF-1 levels increased during adolescence, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of IGF-1 was apparent. There were also a significant difference according to gender; females had significantly higher levels (357.909+/-219.167 mg/L) than males (307.962+/-198.41 mg/L) (P=0.012). IGF-1 levels were correlated with body height (P=0.001, r=0.223), body weight (P=0.002,r=-0.188) and BMI (P=0.039, r=0.128). CONCLUSION: IGF-1 serum levels increase in adolescents with a peak in puberty, whereafter IGF-1 levels return to prepubertal levels.
|How to cite this article:|
Tiryakioaylu O, Kadiolgu P, Canerolgu N U, Hatemi H. Age dependency of serum insulin - like growth factor (IGF)-1 in healthy Turkish adolescents and adults. Indian J Med Sci 2003;57:543-8
|How to cite this URL:|
Tiryakioaylu O, Kadiolgu P, Canerolgu N U, Hatemi H. Age dependency of serum insulin - like growth factor (IGF)-1 in healthy Turkish adolescents and adults. Indian J Med Sci [serial online] 2003 [cited 2013 Dec 11];57:543-8. Available from: http://www.indianjmedsci.org/text.asp?2003/57/12/543/11846
| ¤ Introduction|| |
The insulin-like growth factors (IGFs) are members of the larger family of insulin-related peptides, which include insulin, IGF-1, IGF-2, and are among the anabolic substances under consideration as endocrine, paracrine and autocrine modulators of intrauterine and postnatal growth and development., IGF-1 appears to be more sensitive to metabolic status than IGF-2.
IGF-1 and IGF-2 have structures similiar to the proinsulin molecule but differ from insulin in regulation, receptors and biologic effects. Pulsatile growth hormone (GH) secretion stimulates GH- responsive tissues to produce IGF-1. IGF-1 in plasma is primarily derived from the liver and virtually all IGFs circulate bound the spesific IGF-binding proteins (IGFBPs), six of which have been characterized. Most IGF-1 circulates bound to IGFBP-3 in a 150-kDa complex. Serum IGFBP-3 concentrations are directly proportionate to GH concentrations as well as to nutritional status-thus, in malnutrition, IGFBP-3 and IGF-1 fall while GH rises. IGF-1 directly regulates IGFBP-3 as well. Bindings of IGF-1 to type-1 receptors stimulates tyrosine kinase activity and autophosphorylation of tyrosine molecules, so that a cell which has been exposed to competence factor in stage G0 of the cell cycle and transited G1 can, with IGF-1 exposure in G1, undergo division in the S phase of the cell cycle. Besides the stimulatory effects of IGF-1, on cartilage growth, IGF-1 has stimulatory effects upon hematopoiesis, ovarian steroidogenesis, myoblast proliferation and differentiation of the lens.
The clinical use of measurements of IGF-1 has been focused primarily on diagnosing or excluding GH deficiency, and on monitoring GH therapy. Although measurements of IGF-1 are useful for diagnosis and follow-up of patients with acromegaly, the sensitivity and specificity of IGF-1 or IGFBP3 in the diagnosis of GH deficiency in children is a matter of controversy. Because the liver is the principal source of IGF-1 in the circulation, and because hepatic production of IGF-1 is highly influenced by nutritional factors, it is possible that decrements in IGF-1 expected with GH deficiency are modified by nutritional status and other factors, such that only severe GH deficiency produces a clear segregation of children who are deficient from those who are not.
Serum concentrations of the IGFs vary with, age, sex, pubertal stage and physiological condition and ethnicity., But there is no data about normal limit in Turk1sh population of IGF-1. In this cross-sectional study we have measured serum levels of IGF1 of healthy adolescents and adults to describe normal ranges and age dependency in our country.
| ¤ Material and Methods|| |
The normal IGF-1 levels were determined from 272 healthy subjects (161 female and 111 male), aged 15-75 years. The subjects were recruited among hospital staff and by an advertisement in the village clinics and schools. None of them had diabetes and other endocrine disorders or had received estrogen therapy. The elderly subjects were living independently at home. Height, weight, body-mass index (BMI) (kg/m2) and waist-hip ratio (WHR) were measured in all of them. Ethical approval from the central Cerrahpasa research ethics committee and informed parental consent were obtained.
Serum IGF-1 levels were determined in undiluted serum samples by radioimmunoassay (RIA) (DSL, Webster, Texas, USA) after separation of IGFs from IGF-binding proteins by acid-ethanol extraction. The maximum sensitivity of the assay was 2 ng/mL. Inter- and intraassay coefficients of variation were less than 10 and 8%, respectively, at analyte levels of 600, 240, and 40 ng/mL. Serum samples for the determination of IGF-1 were taken in the morning after an overnight fast in all subjects. A single undiluted sample (0.5 mL) was taken for IGF-1 levels at the time of the profile. Blood samples were collected into glass tubes and centrifuged within 30 min of collection, and the serum was removed and stored at - 20 C until assay.
The age-dependent reference range for serum IGF-1 concentrations was calculated by simple least linear regression analysis: the regression line represents the means with 95 percent confidence intervals. Spearman coefficients were used with partial coefficients for multivariate correlation. The value of acceptance for statistical significance was set at P < 0.05. Calculations were made using SPSS software (SPSS, Inc. Evanston, IC).
| ¤ Results|| |
Characteristics of all subjects were shown in [Table - 1].
Measured values of serum IGF-1 concentrations in relation to age were shown in [Table - 2].
Aging was negatively related to serum levels of IGF-1 (P=0.0001, r=-0.931) [Figure - 1] & [Figure - 2]. In subjects, IGF-1 levels increased during adolescence, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of IGF-1 was apparent.
There were also a significant difference according to gender; females had significantly higher IGF-1 levels (357.909±219.167 mg/L) than males (307.962±198.41 mg/L) (P=0.012). IGF-1 levels were correlated with body height (P=0.001, r=0.223), body weight (P=0.002, r=-0.188) and BMI (P=0.039, r=0.128). There was no correlation between IGF-1 levels and WHR (P=0.611, r=-0.035).
| ¤ Discussion|| |
We found that a negative correlation between the circulating IGF-1 level and age which are consistent with previous reports. IGF-1 levels increase during childhood with a peak in puberty, whereafter IGF-1 levels return to prepubertal levels. It was published that mean plasma IGF-1 concentrations increased slowly in prepubertal children from 80-200 mg/L with a further steep increase during puberty to approximately 500 mg/L. After puberty, a subsequent continuous fall in circulating IGF-1 levels was apparent throughout adulthood to a mean of 100 mg/L at the age of 80 yr. Prior studies concerning circulating IGF-1 and IGFBP-3 levels have emphasized issues related to the pathological extremes provided by acromegaly on GH deficiency. However, it is clear that these levels are complex traits determined by interacting genetic and nongenetic factors.
IGF-1 levels were correlated with BMI in our study (P=0.039, r=0.128). The relation between IGF-1 levels and BMI is not clear in the literature. There was an independent relation of IGF-1 with BMI which was found to be negative in a population - based study in retires but not in the other. On the other hand some investigators found a positive correlation between these two parameters like our results. According to the literature, GH levels were related inversely to BMI and WHR and also there was a positive relationship between peak GH levels and plasma IGF-1 and IGFBP-3 levels., The reason of correlation between IGF-1 and BMI is probably one of the results of this correlation between GH and BMI. These varying data suggest that BMI per se is not a major influence on IGF-1 levels.
It was known that GH secretion in humans is sexually dimorphic and the neuroendocrine mechanisms governing this potential difference are not fully established. GH was secreted in a more disorderly manner in females and at a slower and less well defined pulse periodicity. The differences in trough concentrations influenced a number of measures of body composition, particularly WHR. Peak GH concentrations largely determined plasma IGF-1 levels, with the relationship set at a lower value in females. These GH observations might explain the differences in body composition seen in the elderly. From a practical standpoint, these gender differences suggest that in the context of GH replacement in adults, the same level of GH might be expected to influence body composition and IGF-1 levels in different ways in the sexes. In our study, women had significantly higher mean IGF-1 levels than men probably lower mean age levels [Table - 1].
In conclusion, these data shows complex, but identifiable, associations of the IGF-1 levels with anthropometric factors. In our best knowledge, this study is the first IGF-1 levels determining study in Turkish population.
| ¤ References|| |
|1.||Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid gene structures, serum and tissue concentrations. Endocr Rev 1989;10:68-91. |
|2.||Rajaram S, Baylink DJ, Mohan S. 1nsulin-like growth factor-binding proteins in serum and other biological fluids: regulation and functions. Endocr Rev 1997;18:801-31. |
|3.||Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 1995;16:3-34. |
|4.||Cruickshank JK, Heald AH, Anderson S, Cade JE, Sampayo J, Riste LK, et al. Epidemiology of the Insulin-like Growth Factor System in three ethnic groups. Am J Epidemiol 2001;154:504-13. |
|5.||Bussieres L, Souberbielle JC, Pinto G, Adan L, Noel M, Brauner R. The use of insulin-like growth factor 1 reference values for the diagnosis of growth hormone deficiency in prepubertal children. Clin Endocrinol (Oxf) 2000;52:735-9. |
|6.||Tillmann V, Buckler JM, Kibirige MS, Price DA, Shalet SM, Wales JK, et al. Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 1997;82:531-5. |
|7.||Clemmons DR, Klibanski A, Underwood LE, McArthur JW, Ridgway EC, Beitins IZ, et al. Reduction of plasma immunoreactive somatomedin C during fasting in humans. J Clin Endocrinol Metab 1981;53:1247-50. |
|8.||Hall CM, Gill MS, Foster P, Pennels L, Tillmann V, Jones J, et al. Relationship between serum and urinary insulin-like growth factor-I through childhood and adolescence: their use in the assessment of disordered growth. Clin Endocrinology 1999;50:611-8. |
|9.||Lofqvist C, Andersson E, Gelander L, Rosberg S, Blum WF, Albertsson Wikland K. Reference values for IGF-I throughout childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty. J Clin Endocrinol Metab 2001;86:5870-6. |
|10.||Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents and adults: relation to age, sex, stage of puberty, testicular size and body mass index. J Clin Endocrinol Metab 1994;78:744-52. |
|11.||Goodman-Gruen D, Barrett-Connor E. Epidemiology of insulin-like growth factor-1 in elderly men and women: the Rancho Bernado Study. Am J Epidemiol 1997;145:970-6. |
|12.||Maccario M, Ramunni J, Oleandri SE. Relationships between IGF-I and age, gender, body mass, fat distribution, metabolic and hormonal variables in obese patients. Int J Obes Relat Metab Disord 1999;23:612-8. |
|13.||Hindmarsh PC, Fall CHD, Pringle PJ, Osmond C, Brook CGD. Peak and Trough Growth Hormone Concentrations Have Different Associations with the Insulin-Like Growth Factor Axis, Body Composition, and Metabolic Parameters. J Clin Endocrinol Metab 1997;82:2172-6. |
|14.||Hindmarsh PC, Dennison E, Pincus SM, Cooper C, Fall CHD, Matthews DR, et al. A Sexually Dimorphic Pattern of Growth Hormone Secretion in the Elderly. J Clin Endocrinal Metab 1999;84:2679-85. |
|15.||Jaffe CA, Ocampo-Lim B, Guo W, Krueger K, Sugahara I, DeMott-Friberg R, rt al. Regulatory Mechanisms of Growth Hormone Secretion Are Sexually Dimorphic. J Clin Invest 1998;102:153-64. |