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

Abstract

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.

Effects of gastric bypass on the GH/IGF-I axis in severe obesity – and a comparison with GH deficiency

“…Metabolic markers such as lipids and glucose/insulin levels have been extensively studied, while there are only two reports (24,25) examining the GH/IGF-I axis after massive weight loss (in nine and 15 subjects before and after massive weight loss respectively). The present findings based on 63 subjects seem to be in line with other studies regarding GH secretion in obese, fasting and anorectic states (26,27). A positive effect of gastric bypass on glucose homeostasis was clearly demonstrated by a marked improvement in glucose metabolism postoperatively, with normalization of fasting glucose levels in all but one of the patients with diabetes and in 11 of 14 patients with impaired FPG.…”

Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients

“…As described earlier, the GH/IGF-I axis is also a major regulator of metabolism and activates evolutionarily conserved pathways that promote stress sensitivity and aging . In humans, IGF-I levels decrease dramatically in response to a short-term starvation (36-120 h) despite increased GH secretion, which is highly lipolytic (Merimee et al, 1982;Isley et al, 1983;Thissen et al, 1999;Maccario et al, 2001;Norrelund, 2005;Moller and Jorgensen, 2009). This effect may be the result of a major increase in the IGF-I inhibitory protein IGFPB-1 (Zapf, 1995), which decreases further IGF-I bioavailability and prevents the feedback inhibition of GH secretion by IGF-I (Muller et al, 1999).…”

The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3

“…By contrast, IGFBP-1 is acutely responsive to levels of insulin (Sandhu et al, 2002), and since insulin levels are typically elevated in obesity, IGFBP-1 is generally lower as well (Argiles and Lopez-Soriano, 2001;Maccario et al, 2001;Sandhu et al, 2002;Allen et al, 2003). This suggests that while absolute levels of IGF-I may not differ between lean and obese individuals, unbound or bio-available IGF-1 is higher among the obese.…”