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

Abstract

Objective: Overfeeding suppresses GH secretion and makes evaluation of a suspected GH deficiency (GHD) difficult. In normal weight subjects, gender is known to influence GH concentrations, which is most apparent in the ambulatory, morning-fasted state. In this study, we examined the GH/IGF-I axis in obese men and women and the effect of surgically induced weight loss. Design: Sixty-three subjects (body mass index (BMI) 45^6 kg/m 2 ; 54 women, 9 men) were studied prior to, and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. Fifty-four patients with classic GHD (BMI 27^6 kg/m 2 ; 35 men, 19 women) were included for comparison. Methods: Hormones were analysed in fasting morning serum samples. Results: RYGBP resulted in a decreased BMI to 35^kg/m 2 at 6 months and 32^6 kg/m 2 at 12 months. GH and IGF-I increased at 6 months in the women and at 12 months in both sexes by $ 300 and 11% respectively. Prior to RYGBP, GH concentrations were low in the obese men and similar to those of GHD men (mean 0.09 mU/l). Obese women had tenfold higher values than obese men and sevenfold higher than GHD women. IGF-I levels were in the low reference range in the obese and below 22 S.D. for age in 13%. Conclusions: Surgically induced weight loss partially restores GH secretion. Despite a marked suppression of GH values, a gender influence is maintained in severe obesity. In obese women, single morning GH and IGF-I values seem sufficient to exclude a suspicion of classic GHD.European Journal of Endocrinology 154 53-59

Obesity, growth hormone and weight loss

“…However, both ultrafiltrated free IGF-I as well as dissociated free IGF-I levels M a n u s c r i p t 7 have been measured and both found to be significantly decreased in obese women (73). This is in accordance with the previous reported decreased IGF-I/IGFBP-3 molar ratio, a rough estimate of free, biologically active IGF-I, in obesity (26,70) and the normalisation after diet-induced or surgical-induced weight loss consistent with the transient GH-deficient state (26,70). The previous observed differences in measured values of fasting free IGF-I could be due to diurnal induced variations in free IGF-I, IGFBP-1 levels, fasting induced or other hour-to-hour factors influencing the amount of free IGF-I.…”

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia

“…This may nonetheless be attenuated, in light of the participants' loss of weight after surgery. GH levels are suppressed in obesity (21), and Corneli et al (22) found a mean GH response of ;30 mg/L in subjects with a BMI of ;30 kg/m 2 who were subjected to a GH-releasing hormone-arginine test compared with the rise to 15 mg/L during postsurgery hypoglycemia in the current study (BMI 30.1 kg/m 2 ). Insulin levels during clamps were ;25% lower postsurgery versus presurgery, and the absolute insulin amount infused was ;12% lower after surgery (data not shown), indicating increased insulin clearance, and more so if adjustments to body surface are performed.…”

“…Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m 2 [SD 3.1]) were examined before and 23 weeks (range [19][20][21][22][23][24][25] after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery.…”

Hyperinsulinemic hypoglycemia with nesidioblastosis: histologic features and growth factor expression

“…1 In the past few years an increasing number of patients with severe hypoglycemia including neuroglycopenia as a result of endogenous hyperinsulinemia in the postgastric bypass setting have been reported. [3][4][5][6] These patients present with severe hypoglycemic symptoms including visual disturbances, altered mental status, seizures, and loss of consciousness, often postprandially. Nesidioblastosis has been most widely recognized in infants.…”