Reduction of Plasma Immunoreactive Somatomedin C during Fasting in Humans*

Clemmons, David R.; Klibanski, Anne; Underwood, Louis E.; McArthur, Janet W.; Ridgway, E. Chester; Beitins, Inese Z.; Wyk, Judson J. Van

doi:10.1210/jcem-53-6-1247

Cited by 362 publications

(142 citation statements)

References 16 publications

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“…12,13 Prolonged (more than 3 days) fasting and caloric restriction lead to peripheral GH resistance and reduced IGF-I synthesis and release. 24 This implies reduction in the negative IGF-I feedback action which plays a major role in the control of somatotroph function, as shown also by recent knock-out studies in mice and rhIGF-I studies in humans. 25 -27 Enhanced GH secretion has been recorded even after short-term fasting before significant reduction in total IGF-I levels; 13 however, we found slight decrease in total IGF-I levels in obese as well as in normal subjects, though statistical significance was reached in the latter group only.…”

Section: Discussionmentioning

confidence: 92%

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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OBJECTIVE: Reduction of growth hormone (GH) secretion in obesity probably reflects neuroendocrine and metabolic abnormalities. Even short-term fasting stimulates GH secretion and distinguishes normal from hypopituitary subjects with growth hormone deficiency (GHD). Marked weight loss improves GH secretion in obesity but the effect of fasting is controversial. We studied the effects of a 36 h fasting on the GH=IGF-I axis and metabolic parameters in obesity. SUBJECTS: We studied nine obese patients (OB; three male and six female; age, 29.2 AE 4.8; range, 18 -59 y; body mass index (BMI), 43.4 AE 2.7 kg=m 2 ; WHR, 0.9 AE 0.1). Fifteen normal subjects (NS; eight male and seven female 28.9 AE 0.6, 25 -35 y; 21.6 AE 0.4 kg=m 2 ) and 10 adult hypopituitary patients with severe GH deficiency (GHD; seven male and three female; 37.6 AE 2.3, 29 -50 y; 24.5 AE 1.0 kg=m 2 ; GH peak < 3mg=l after ITT and=or < 9mg=l after GHRH þ arginine) served as control groups. STUDY DESIGN: We studied the effects of 36 h fasting on 8 h diurnal mean GH, insulin and glucose concentrations (mGHc, mINSc and mGLUc; assay every 30 min from 8.00 am to 4.00 pm) as well as on IGF-I, IGFBP-3, ALS, IGFBP-1, GHBP and free fatty acid (FFA) levels. RESULTS: Before fasting, basal IGF-I and ALS levels in OB were similar to those in NS and both were higher (P < 0.001) than those in GHD. IGFBP-3 levels in OB were lower (P < 0.01) than in NS but higher (P < 0.02) than in GHD. GHBP levels in OB and GHD were similar and both were higher (P < 0.01) than in NS. Glucose levels were similar in all groups. FFA levels in OB were higher (P < 0.01) than in NS but similar to those in GHD. IGFBP-1 in OB were lower (P < 0.05) than in NS and GHD which, in turn, were similar. On the other hand, mINSc in OB was higher (P < 0.01) than that in NS and GHD which, in turn, were similar. The mGHc in OB was similar to that in NS but only the latter was higher (P < 0.05) than in GHD. The individual mGHc in the three groups overlapped. After fasting, IGF-I levels in GHD were unchanged while they decreased in OB (P ¼ NS) as well as in NS (P < 0.01). IGFBP-3 and ALS levels did not change. GHBP levels in OB and GHD were unchanged while they increased in NS (P < 0.01). Glucose and FFA levels were reduced and increased, respectively, in all groups (P < 0.02 and P < 0.01). IGFBP-1 increased while mINSc decreased in all groups (P < 0.02 and P < 0.01); in OB they persisted lower and higher (P < 0.01) respectively, than in NS and GHD. Fasting significantly increased mGHc in NS (P < 0.001) but not in OB as well as in GHD. Individual mGHc in OB showed persistent overlap with GHD. CONCLUSIONS: Short-term fasting does not increase GH secretion in obesity and does not distinguish somatotroph function in obese from that in severe GHD adults. Short-term fasting in obesity has attenuated effects on insulin and IGFBP-1 secretion while it normally increases free fatty acids in spite of any change in GH secretion.

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Section: Discussionmentioning

confidence: 92%

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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“…IGF-I plasma concentrations are low in malnourished patients 8 while, in normal subjects, fasting lowers plasma IGF-I levels under basal conditions 24 and in response to GH administration. 25 In obese subjects, the IGF-I production induced by exogenous GH is gradually impaired by the progressive limitation of energy intake.…”

Section: Discussionmentioning

confidence: 95%

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women

et al. 1998

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OBJECTIVE: Severe energy restriction in the treatment of obesity is limited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and energy metabolism in obese patients undergoing severe dietary restriction. DESIGN: Single-blind placebo-controlled study. Twenty obese women were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and BMI, received vehicle only. SUBJECTS: Twenty women with simple obesity (age: 25.4 AE 1.07 y, BMI: 35.9 AE 0.35 kg/m 2 ). MEASUREMENTS: Plasma IGF-I and leptin, serum markers of bone turnover (serum bone isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expenditure (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks. RESULTS: Mean IGF-I plasma levels, not in¯uenced by energy restriction in patients receiving placebo, displayed a signi®cant increase in the group treated with rhGH. The mean weight reduction and fat mass loss were not signi®cantly different in the two groups (6.0 AE 0.51 vs 7.2 AE 0.30 kg, NS, and 5.36 AE 0.460 vs 4.28 AE 0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma leptin levels decreased signi®cantly in weight-reduced subjects receiving either rhGH (from 16.2 AE 2.37 to 6.4 AE 0.39 ng/ml, P`0.05) or placebo (from 14.3 AE 2.55 to 7.7 AE 3.77 ng/ml, P`0.05). On the contrary, the mean decrease of lean body mass (LBM) was signi®cantly lower in the GH-treated patients than in those receiving vehicle (1.52 AE 0.60 vs 3.79 AE 0.45 kg, P`0.05). In keeping with these ®ndings, the mean daily nitrogen balance was signi®cantly less negative in the GH-treated subjects than in the vehicle-injected patients (mean of the 4 week daily urine collections 7185.7 AE 40.33 vs 7363.9 AE 55.47 mmol/d, P`0.05, respectively). Further, a signi®cant reduction of mean REE was recorded in the energy-restricted placebo-treated patients (from 8807 AE 498 to 7580 AE 321 kJ/24 h, P`0.05), but not in the patients receiving rhGH (from 8367 AE 580 to 8903 AE 478 kJ/ 24 h, NS). Actually, when corrected for LBM, REE was even increased by GH administration (from 197.9 AE 11.76 to 219.3 AE 9.87 kJ/kg LBM/24 h, P`0.05), whereas it was unchanged in the placebo group (from 201.7 AE 13.85 to 190.0 AE 9.87 kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and density. CONCLUSION: rhGH treatment, though unable to enhance diet-induced weight and fat mass reduction...

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“…Similar results have been reported previously, 21±23 but the contradictory ®ndings of increased or decreased IGF-1 levels found by others, although due in part to important clinical differences in age, sex and degree of obesity in the different studies, could be profoundly in¯uenced by nutritional factors. 24,25 In addition, the discordant relationship between GH and IGF-1 in obesity may be also explained by the hyperinsulinaemia present in obesity: 26 insulin may increase hepatic IGF-1 production. 27 We found a positive correlation between the serum total IGF-1 and insulin concentrations.…”

Section: Discussionmentioning

confidence: 99%

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone

et al. 1997

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OBJECTIVES:We investigated the effect of obesity on the serum levels of total and free IGF-1 and their relationship to the circulating levels of insulin and IGF binding proteins (IGFBPs) in age and sex-matched groups. SUBJECTS: The study included 43 obese subjects (ideal body weight; IBW b 120%) and 45 controls (IBW`100%). All of the subjects were male. MEASUREMENT: Total IGF-1, free IGF-1, IGFBP-1, IGFBP-2, IGFBP-3, and insulin were measured in obese subjects and normal control subjects. RESULTS: No signi®cant differences in the circulating levels of total and IGFBP-3 were observed between the obese and control groups. In contrast to total IGF-1, free IGF-1 in obese subjects was signi®cantly increased compared to normal controls (P`0.05). Serum total and free IGF-1 were inversely correlated with age (r À0.42, P 0.001, and À0.44, P 0.001). Fasting serum insulin concentrations were elevated in all the obese subjects (P`0.05) and positively correlated with IBW (r 0.57, P 0.001). The levels of serum GH and IGFBP-1 were suppressed in all the obese subjects (P`0.05). IGFBP-1 was inversely correlated with IBW (r À0.51, P 0.001) and serum insulin concentrations (r À0.48, P 0.001). The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r À0.48, P 0.001). Using multiple linear regression analysis, total IGF-1 and insulin concentrations were positively correlated (r 0.58, P 0.001) and free IGF-1 and IGFBP-1 concentrations were negatively correlated (r À0.57, P 0.001). CONCLUSION: We con®rmed that total IGF-1 and IGFBP-3 concentrations were not signi®cantly different between the obese and control groups, despite GH hyposecretion in obesity. We also found that free IGF-1 concentrations were higher in obese subjects than in normal controls. It seems likely that overnutrition and chronic hyperinsulinaemia in obesity may alter this regulated growth response by insulin stimulation of IGF-1 production and suppression of hepatic IGFBP-1 and IGFBP-2 production, which may inhibit IGF-1 bioactivity.

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Reduction of Plasma Immunoreactive Somatomedin C during Fasting in Humans*

Cited by 362 publications

References 16 publications

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Metabolic effects of biosynthetic growth hormone treatment in severely energy-restricted obese women

Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone

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