Insulin-Like Growth Factors and Metabolic Syndrome in Obese Children

2017 ◽  
Vol 87 (6) ◽  
pp. 400-404 ◽  
Author(s):  
Elena Inzaghi ◽  
Barbara Baldini Ferroli ◽  
Danilo Fintini ◽  
Armando Grossi ◽  
Valerio Nobili ◽  
...  

Background/Aims: Insulin-like growth factor (IGF)-I is related to cardiometabolic risk in adults, whereas the metabolic role of IGF-II is unclear. The aim of this study was to assess IGFs in obese children and correlate them with metabolic syndrome (MetS) components. Methods: This is a retrospective study including 574 obese children (11.34 ± 3.16 years). All subjects underwent complete anthropometry and biochemical assessment. In a subgroup of 136 subjects, body composition was evaluated. IGF-I was measured in 300 obese subjects and IGF-II in 77 obese and 15 lean children. 177 subjects were divided according to the presence of 1 or more MetS criteria: group 1, subjects with 1 MetS criterion; group 2, subjects with 2 components; and group 3, subjects with MetS diagnosis. Results: IGF-I, IGF-II, and IGF-I/insulin-like growth factor-binding protein-3 ratio were not different among subjects with an increasing number of MetS criteria and were not associated with single components of MetS as well as with body composition parameters. In children younger than 10 years, IGF-I directly correlated with high-density lipoprotein cholesterol (p < 0.005) even after controlling for confounders. IGF-II was significantly higher in obese children and correlated with parameters of insulin sensitivity (p < 0.05). Conclusion: IGFs were neither related to MetS nor to body composition parameters in obese children. Further studies are needed to clarify the mechanisms underlying the relationship between IGF-II and insulin sensitivity.

2001 ◽  
Vol 86 (4) ◽  
pp. 1496-1503 ◽  
Author(s):  
Anne L. Friedlander ◽  
Gail E. Butterfield ◽  
Sharon Moynihan ◽  
Jeanine Grillo ◽  
Margaret Pollack ◽  
...  

The activity of the hypothalamic-GH-insulin-like growth factor I (hypothalamic-GH-IGF-I) axis declines with age, and some of the catabolic changes of aging have been attributed to the somatopause. The purpose of this investigation was to determine the impact of 1 yr of IGF-I hormone replacement therapy on body composition, bone density, and psychological parameters in healthy, nonobese, postmenopausal women over 60 yr of age. Subjects (n = 16, 70.6 ± 2.0 yr, 71.8 ± 2.8 kg) were randomly assigned to either the self-injection IGF-I (15 μg/kg twice daily) or placebo group and were studied at baseline, at 6 months, and at 1 yr of treatment. There were no significant differences between the IGF-I and placebo groups in any of the measured variables at baseline. Fasting blood IGF-I levels were significantly elevated above baseline values (65.6 ± 11.9 ng/mL) at 6 months (330.0 ± 52.8) and 12 months (297.7 ± 40.8) in the IGF-I treated group but did not change in the placebo subjects. Circulating levels of IGF-binding protein-1 and -3 were unaffected by the IGF-I treatment. Bone mineral density of the forearm, lumbar spine, hip, and whole body [as measured by dual-energy x-ray absorptiometry (DXA)] did not change in either group. Similarly, there was no difference in DXA-measured lean mass, fat mass, or percent body fat throughout the treatment intervention. Muscle strength values (grip, bench press, leg press), blood lipid parameters (cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides), and measures of postmeal glucose disposal were not altered by IGF-I treatment, although postmeal insulin levels were lower in the IGF-I subjects at 12 months. IGF-I did not affect bone turnover markers (osteocalcin and type I collagen N-teleopeptide), but subjects who were taking estrogen had significantly lower turnover markers than subjects who were not on estrogen at baseline, 6 months, and 12 months. Finally, the psychological measures of mood and memory were also not altered by the intervention. Despite the initial intent to recruit additional subjects, the study was discontinued after 16 subjects completed the protocol, because the preliminary analyses above indicated that no changes were occurring in any outcome variables, regardless of treatment regimen. Therefore, we conclude that 1 yr of IGF-I treatment, at a dose sufficient to elevate circulating IGF-I to young normal values, is not an effective means to alter body composition or blood parameters nor improve bone density, strength, mood, or memory in older women.


1993 ◽  
Vol 136 (1) ◽  
pp. 91-104 ◽  
Author(s):  
L. R. Donahue ◽  
W. G. Beamer

ABSTRACT Although GH is known to regulate somatic growth during development, its role in regulating adult body composition is less well defined. The effects of GH on individual body compartments – water, fat, protein and mineral – are achieved both by the action of GH and by a GH-induced hormone, insulin-like growth factor-I (IGF-I). We used a genetic model of GH deficiency, the 'little' (gene symbol lit) mouse, to determine the GH regulation of IGF-I and its insulin-like growth factor-binding proteins (IGFBPs) and to define the interaction between these hormones and each body compartment in adults. Our results showed that GH-deficient lit/lit mice had reduced levels of serum IGF-I (range 38–130 μg/l) compared with normal lit/+ littermates (range 432–567 μg/l) between 2 and 52 weeks of age. The lit/lit mice did not experience the fivefold increase in IGF-I between 2 and 4 weeks of age that was seen in lit/+ mice. In lit/lit serum, overall binding of 125I-labelled IGF-I to the four IGFBPs was reduced, solely in response to a reduced amount of IGFBP-3. No overall differences were found between lit/lit and lit/+ mice in the binding of 125I-labelled IGF-I to IGFBP-2, -1 or -4. Age-related declines in IGF-I and IGFBPs were seen in lit/lit mice. However, adult levels of IGF-I were maintained in lit/+ mice to at least 52 weeks of age, as were levels of IGFBP-1 and -4, while IGFBP-3 and -2 declined with age. With respect to body composition, comparison of lit/lit with lit/+ mice showed that the lit/lit mice were characterized by abnormally large adipose tissue stores and reduced body water, protein and mineral from 2 weeks onward. These changes occurred despite normal energy intake in lit/lit mice up to 52 weeks of age, indicating that neither undernutrition nor hyperphagia is characteristic of this GH-induced model of obesity. Furthermore, lit/lit males accrued more body fat beginning at an earlier age than lit/lit females. With advancing age, the per cent body fat increased in both lit/lit and lit/+ mice, while the per cent body water and mineral declined. In lit/lit but not lit/+ mice, per cent protein also declined with age. The changes in body water and fat are attributable to lack of adequate GH in the genetically GH-deficient lit/lit mouse. On the other hand, the changes in body protein are more likely to be effects of IGF-I. Changes in mineral observed in lit/lit mice could be the result of action by GH, IGF-I or both hormones. Therefore, when GH is chronically manipulated by GH deficiency as in lit/lit mice, by GH excess as in acromegaly, or by GH therapy, all four body compartments are affected, suggesting that GH therapy is most valuable when the treatment goal is to alter overall body composition. Journal of Endocrinology (1993) 136, 91–104


2002 ◽  
Vol 92 (4) ◽  
pp. 1611-1618 ◽  
Author(s):  
Bradley C. Nindl ◽  
Charles R. Scoville ◽  
Kathleen M. Sheehan ◽  
Cara D. Leone ◽  
Robert P. Mello

This study evaluated the arm, trunk, and leg for fat mass, lean soft tissue mass, and bone mineral content (BMC) assessed via dual-energy X-ray absorptiometry in a group of age-matched (∼29 yr) men ( n = 57) and women ( n = 63) and determined their relationship to insulin-like growth factor I (IGF-I) and leptin. After analysis of covariance adjustment to control for differences in body mass between genders, the differences that persisted ( P ≤ 0.05) were for lean soft tissue mass of the arm (men: 7.1 kg vs. women: 6.4 kg) and fat mass of the leg (men: 5.3 kg vs. women: 6.8 kg). Men and women had similar ( P ≥ 0.05) values for fat mass of the arms and trunk and lean soft tissue mass of the legs and trunk. Serum IGF-I and insulin-like growth factor binding protein-3 correlated ( P≤ 0.05) with all measures of BMC ( r values ranged from 0.31 to 0.39) and some measures of lean soft tissue mass for women ( r = 0.30) but not men. Leptin correlated ( P≤ 0.05) similarly for measures of fat mass for both genders ( r values ranging from 0.74 to 0.85) and for lean soft tissue mass of the trunk ( r = 0.40) and total body ( r = 0.32) for men and for the arms in women ( r = 0.56). These data demonstrate that 1) the main phenotypic gender differences in body composition are that men have more of their muscle mass in their arms and women have more of their fat mass in their legs and 2) gender differences exist in the relationship between somatotrophic hormones and lean soft tissue mass.


1990 ◽  
Vol 124 (1) ◽  
pp. 151-158 ◽  
Author(s):  
R. A. Siddiqui ◽  
H. T. Blair ◽  
S. N. McCutcheon ◽  
D. D. S. Mackenzie ◽  
P. D. Gluckman ◽  
...  

ABSTRACT A study was conducted to investigate developmental patterns of plasma concentrations of insulin-like growth factor-I (IGF-I), body growth and body composition in mice from lines selected for seven generations on the basis of low (L) or high (H) plasma IGF-I, and in a random-bred control (C) line. Litter size was standardized to eight individuals with equal sex ratios (as far as possible) within 48 h of birth. Pups were weaned at an average of 21 days and separated on the basis of sex. Blood samples were collected from one male and one female of each litter on days, 21, 42, 63 and 105 for analysis of plasma concentrations of IGF-I. The animals were then killed and analysed for water, fat and crude protein content. The plasma concentration of IGF-I was influenced by line (P<0·05) but not by sex. Significant (P< 0·001) differences in liveweight between mice from L and H lines were first evident at 21 days of age. From 28 until 105 days of age the H line was significantly (P< 0·001) heavier than both L and C lines, but differences between C and L lines were inconsistent and mostly non-significant. The growth velocity of the H line was significantly greater than that of C or L lines between 14 and 42 days of age, but differences in growth velocities of C compared with L lines were generally non-significant. Nose–anus length was significantly (P<0·01) affected by sex and line from 42 to 105 days of age, but anus–tail length was not affected by sex or line at any age. Effects of sex and line on empty (digesta-free) body weight and wet weights of carcass and skin plus viscera fractions followed a pattern similar to those of liveweights. The effects of sex and line on protein, water and fat content also paralleled their effects on body size. Differences between males and females, and between the lines, in amount of protein, water and fat could be entirely accounted for by the corresponding differences in body weight. It is concluded from these results that divergent selection on the basis of plasma IGF-I at 42 days of age resulted in lines of animals differing in plasma IGF-I from 21 days of age until maturity. These divergent concentrations of IGF-I are associated with differences between the lines in body growth, particularly during the period of accelerated growth at puberty, but not with changes in body composition. Journal of Endocrinology (1990) 124, 151–158


1998 ◽  
Vol 83 (5) ◽  
pp. 1477-1484 ◽  
Author(s):  
J. L. Thompson ◽  
G. E. Butterfield ◽  
U. K. Gylfadottir ◽  
J. Yesavage ◽  
R. Marcus ◽  
...  

To determine the effects of GH and insulin-like growth factor I (IGF-I) administration, diet, and exercise on weight loss, body composition, basal metabolic rate (BMR), muscle strength, and psychological status, 33 moderately obese postmenopausal women (67.1 ± 5.2 yr) participated in a 12-week randomized, double blind study. Participants were placed on a diet that provided 500 Cal/day less than that needed for weight maintenance, and they walked 3 days and strength trained 2 days each week. Subjects also self-injected GH (0.025 mg/kg BW·day), IGF-I (0.015 mg/kg BW·day), a combination of these doses of GH and IGF-I, or placebo (P). Twenty-eight women completed the study, as five subjects dropped out due to intolerable side-effects (e.g. edema). Weight loss occurred in all groups, with the largest decrease occurring in the GH plus IGF-I group (5.6 ± 1.4 kg). Fat mass significantly decreased in all groups, with the largest losses observed in GH and GH plus IGF-I groups (6.3 ± 1.8 and 8.4 ± 2.8 kg, respectively). Despite weight loss, BMR was maintained in all groups. Muscle strength increased with training for all groups, and depression and anxiety scores decreased in groups receiving IGF-I. These data show that obese postmenopausal women can lose weight and fat without compromising fat free mass, BMR, or gains in muscle strength, and that GH and IGF-I given together may enhance fat loss over either given alone.


2012 ◽  
Vol 97 (8) ◽  
pp. 2637-2643 ◽  
Author(s):  
Gerthe F. Kerkhof ◽  
Ralph W. J. Leunissen ◽  
Anita C. S. Hokken-Koelega

Abstract Background: The relationship between low birth weight and increased risk for metabolic syndrome (MetS) in later life has been frequently described, but mechanisms underlying this association remain unknown. Methods: In 280 young adults of the PROGRAM study, aged 18–24 yr, we investigated associations of birth weight, gain in weight for length during early life, and adult IGF-I sd score (SDS), with number of MetS components (ordinal regression analyses), prevalence of MetS components and MetS (logistic regression analyses), and other metabolic parameters (linear regression analyses). Revised criteria of the National Cholesterol Educational Program (Adult Treatment Panel III) were used to determine components of MetS. The other metabolic parameters were C-reactive protein, insulin sensitivity, trunk fat mass, total cholesterol, and low-density lipoprotein cholesterol. Results: More gain in weight for length SDS in the first 3 months of life was significantly associated with an increased number of MetS components [odds ratio (OR) = 1.34], prevalence of low high-density lipoprotein cholesterol (OR = 1.49), prevalence of MetS (OR = 2.51), increased C-reactive protein levels, and lower insulin sensitivity (P = 0.007) at the age of 21 yr. Low birth weight SDS was associated with lower insulin sensitivity (P = 0.036), but low birth weight SDS and adult IGF-I SDS were not significantly associated with any of the MetS components or MetS prevalence at 21 yr. Conclusion: Our study demonstrates that higher gain in weight for length in the first 3 months of life is associated with a higher prevalence of MetS at 21 yr, whereas low birth weight and low adult IGF-I are not.


1992 ◽  
Vol 133 (1) ◽  
pp. 101-110 ◽  
Author(s):  
M. Tixier-Boichard ◽  
L. M. Huybrechts ◽  
E. Decuypere ◽  
E. R. Kühn ◽  
J.-L. Monvoisin ◽  
...  

ABSTRACT This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth-promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triiodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0·1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0·1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF-I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth. Journal of Endocrinology (1992) 133, 101–110


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