Relationship between Plasma (IGF-l) Levels and Body Mass. Insulin-like Growth Factor Index (BMI) in Adults

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1 Endocrine Journal 1993, 40 (1), Relationship between Plasma (IGF-l) Levels and Body Mass Insulin-like Growth Factor Index (BMI) in Adults HIROYuKI YAMAMOTO AND YUZURU KATO First Division, Department o f Medicine, Shimane Medical University, Izumo 693, Japan Abstract. We investigated the relationship between plasma insulin-like growth factor I (IGF-I) levels and the body mass index (BMI) in 558 healthy adults (238 males and 320 females), aged yrs. The subjects were divided into three groups based on the BMI: 1) underweight group (BMI < 20, n=145), 2) normal group (BMI 20-25, n=179) and 3) overweight group (BMI > 25, n=234). Blood samples were obtained after overnight fasting and plasma IGF-I concentrations were measured by specific radioimmunoassay after acid-ethanol extraction. Plasma IGF-I levels declined with age in each group and the regression lines were parallel. In both sexes of each decade, mean plasma IGF-I values were lower in the underweight and overweight groups than in the normal group. Age- and sex-matched analysis revealed that plasma IGF-I values were positively correlated with BMI under 25, whereas plasma IGF-I was reversely correlated with BMI beyond 27. These findings suggest that the plasma IGF-I levels are influenced by body composition independently of aging in adults, aged yrs. Key words: IGF-I, BMI, Underweight, Overweight, Aging. (Endocrine Journal 40: 41-45,1993) CIRCULATING insulin-like growth factor I (IGF- I) is mainly derived from the liver, in which the synthesis and the secretion of IGF-I depends on growth hormone (GH) secretion from the pituitary [1-3]. Plasma IGF-I levels are decreased in aged subjects [4-6], in which plasma GH levels are also decreased [5, 7]. Decreased IGF-I levels in aged subjects may contribute to decreased lean body mass and increased body fat occurring with advancing age in adults [4, 8]. On the other hand, plasma IGF-I levels are lowered in patients with malnutrition and rather associated with increased plasma GH levels [9]. Low plasma IGF-I levels are also found in obesity [4, 10], which is associated with blunted GH secretion. However, interrelation among plasma IGF-I, aging and nutrition remains to be fully elucidated. The body mass index (B MI), defined as weight divided by the square of the Received: August 13, 1992 Accepted: October 30, 1992 Correspondence to: Dr. Hiroyuki YAMAMOTO, sion, Department of Medicine, Shimane Medical Izumo 693, Japan. First University, Divi- height (W/H2) in kg/m, is generally considered to correlate with body fat [11]. In the present study, we investigated the relationship between BMI and aging in regulating plasma IGF-I levels in adults. Subjects Materials and Methods Five hundred and fifty-eight healthy subjects (238 males and 320 females) aged yr were included in the present study. They were randomly selected from a population as a part of a continuing epidemiological study [6] which included detailed history taking, physical examination, urinalysis, complete blood count, blood chemistry, EGG and ophthalmic examination. These subjects were divided into three groups according to their BMI: 1) underweight group (BMI < 20, n=179), 2) normal group (BMI 20-25, n=145) and 3) overweight group (BMI > 25, n=234). After overnight fasting, blood samples were with-

2 42 YAMAMOTO and KATO drawn from the antecubital vein into a tube containing heparin and NaF. Plasma was promptly separated and stored at -20 C until assayed. Measurement o f IGF-I Plasma IGF-I levels were measured by specific radioimmunoassay after extraction with acidethanol as reported previously [6]. Recombinant human IGF-I (lot B 1516YS) and anti-igf-i serum (lot B0166S) were obtained from Fujisawa Pharmaceutical Co. (Osaka, Japan). The purified IGF-I was iodinated with 125I (Amersham, England) by the lactoperoxidase method. The minimum detectable quantity was 0.5 ng/ml in the assay. The mean intra- and interassay coefficients of variation were 3.8 and 5.6%, respectively. There was no considerable cross-reactivity of IGF-II and insulin with the anti-igf-i serum. Statistics Statistical differences were appropriately evaluated by analysis of variance followed by Student's t- test and Duncan's new multiple range test. Correlation was evaluated by linear regression analysis. A P value less than 0.05 was considered significant. Results In each of the three groups, plasma IGF-I levels were declined with advancing age and the regression lines were parallel as shown in Fig. 1. Mean plasma IGF-I was lower in underweight and overweight groups than in normal group in all decades except for yr (Table 1). Mean plasma IGF-I in the second decade of female subjects was higher than in the males in both the underweight and normal groups, whereas there was no statistical sex difference in those in the overweight group (Fig. 2, Table 1). Age-matched cross-sectional analysis revealed that plasma IGF-I levels increased with advancing BMI under 25 and decreased with advancing BMI beyond 27 in the fifth decade of 54 female subjects (Fig. 3). Mean plasma IGF-I in the subjects with BMI ranged from 25 to 27 which was significantly greater in subjects with a BMI under 18 and beyond 27.

3 PLASMA IGF-I AND BODY MASS INDEX 43 Table 1. Mean(±SD) values for the BMI and plasma IGF-I in each decade of underweight, of healthy adults normal weight and overweight groups Fig. 2. Three dimensional analysis of plasma IGF-I, age and (right panel) healthy adults. Mean plasma I.GF-I levels the height of the vertical column. BMI in 238 male (left panel) and 320 female in each decade of the subjects are indicated by

4 44 YAMAMOTO and KATO Discussion It was previously reported that plasma IGF-I declined with age in adults [4-6] and decreased in nutritional disorders [9, 10]. Rudman et al. [4] reported that plasma IGF-I levels decreased with advancing BMI beyond 19. Copeland et al. [12] reported that plasma IGF-I correlated negatively with BMI in males, but not in females of 107 subjects between 17 and 83 yrs. Unterman et al. [13] reported that IGF-I was correlated with serum albumin, transferrin and the lymphocyte count in patients with malnutrition such as kwashiorkor and marasmus. In the present study, we investigated the relationship between plasma IGF-I levels and BMI in a larger number of 558 healthy adults. The statistical analysis showed that plasma IGF-I levels declined with age in each BMI group of adults, aged yrs and that plasma IGF-I levels were lower in both underweight and overweight groups than in the normal group in each decade except for the second decade. These findings indicate that the BMI and aging independently influence plasma IGF-I levels in healthy subjects. Low plasma IGF-I in the underweight group is probably explained by limited substrate available for the synthesis of IGF-I. However, other mechanisms may be involved in reduced plasma IGF-I in the overweight group. It is known that obesity is associated with impaired GH secretion which is normalized after weight reduction [14-16]. An increased deposition of truncal subcutaneous fat in GH-deficient adults is depleted by GH treatment which is associated with an increase in plasma IGF-I and free fatty acids [8, 17]. It is possible, therefore, that relative GH deficiency plays a role, at least in part, in reduced plasma IGF-I levels in the overweight group. The decline in blood GH and IGF-I concentrations with age in adults has been suggested to contribute to the decrease in the lean body mass and the increase in body fat with advancing age [4, 8]. However, it was reported that GH-induced IGF-I synthesis in the liver was not impaired with aging [8], whereas low plasma IGF-I associated with malnutrition was not improved by the administration of human GH [20]. Therefore, decreased IGF-I in aged subjects differs from that in simple nutritional disorders. It is noted that there was no considerable difference in plasma IGF-I levels among three BMI groups of female subjects in the second decade. Increased plasma IGF-I in the female subjects may be explained by increased secretion of estrogen which stimulates the synthesis of GH, IGF-I and IGF-I binding proteins [18, 19]. BMIrelated changes in plasma IGF-I were clearly demonstrated in female subjects in the fifth decade, which were in the postmenopausal state, and these changes were possibly associated with decreased secretion of estrogen. Therefore, BMIand age-related changes in plasma IGF-I are influenced by endogenous estrogen in female subjects. Acknowledgments This work was supported in part by grants from the Ministry of Education Science and Culture, Japan, the Ministry of Health and Welfare, Japan, and the Uehara Memorial Foundation, Japan. We are also indebted to Mrs. Akiko Kawakami for her secretarial assistance.

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