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  • Author: E T Vestergaard x
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Visceral fat mass is a strong predictor of circulating ghrelin levels in premenopausal women

E Sondergaard, L C Gormsen, B Nellemann, E T Vestergaard, J S Christiansen, and S Nielsen

Objective

A well known inverse relationship exists between obesity and circulating ghrelin concentrations. However, obesity is a heterogeneous disease entity and upper-body obesity (UBO) is associated with more profound metabolic disturbances than lower-body obesity (LBO). We therefore aimed to investigate the impact of body composition on circulating ghrelin levels in women spanning a wide range of body composition phenotypes.

Subjects and methods

Ten (UBO; waist-to-hip ratio (WHR) >0.85, body mass index (BMI) >28 kg/m2), ten LBO (WHR <0.80, BMI >28 kg/m2) and ten lean women (BMI<25 kg/m2) were studied. Total ghrelin levels were measured under basal and hyperinsulinemic (0.6 mU/kg per min) conditions. Body fat distribution was determined by dual X-ray absorptiometry in combination with computed tomography at the L2-L3 level.

Results

As expected, an inverse correlation existed between basal ghrelin concentration and BMI (r=−0.40, P=0.03) and total fat mass (r=−0.39, P=0.04). Visceral fat mass was a strong predictor (r=−0.56, P=0.003) of circulating ghrelin levels, even when adjusted for BMI (P=0.02) or body composition group (P=0.04). The suppressive effect of insulin on ghrelin concentration was significantly diminished in the UBO compared with the lean controls (P=0.012) and a highly significant inverse correlation existed with visceral fat mass (r=−0.52, P=0.004).

Conclusions

Visceral fat mass is a strong predictor of basal ghrelin concentrations and also attenuates the suppressive effect of insulin on ghrelin concentrations. These data provide further evidence that the UBO phenotype is associated with more profound metabolic abnormalities than obesity per se.

Free access

Effects of GH replacement therapy in adults on serum levels of leptin and ghrelin: the role of lipolysis

E T Vestergaard, T K Hansen, S Nielsen, N Moller, J S Christiansen, and J O L Jorgensen

Objective: The regulation and function of systemic ghrelin levels appear to be associated with food intake and energy balance rather than GH. Since GH, in turn, acutely induces lipolysis and insulin resistance in skeletal muscle, we aimed to study the isolated and combined effects of GH, free fatty acids (FFAs) and insulin sensitivity on circulating ghrelin levels in human subjects.

Design: Seven GH-deficient patients (aged 37 ± 4 years (mean ± s.e.)) were studied on four occasions in a 2 × 2 factorial design with and without GH substitution and with and without administration of acipimox, which lowers FFA levels by inhibition of the hormone-sensitive lipase, in the basal state and during a hyperinsulinemic euglycemic clamp.

Results: Serum FFA levels decreased with acipimox administration irrespective of GH status. The GH-induced reduction in insulin sensitivity was countered by acipimox. Fasting ghrelin levels decreased insignificantly during GH administration alone, but were reduced by 33% during co-administration of GH and acipimox (Aci) (in ng/l): 860 ± 120 (−GH − Aci), 711 ± 130 (−GH + Aci), 806 ± 130 (+GH − Aci), 574 ± 129 (+GH + Aci), P < 0.01. The clamp was associated with a further, moderate lowering of ghrelin. GH and acipimox induced a reciprocal 25% increase in serum leptin levels (μg/l): 11.2 ± 4.4 (−GH − Aci), 11.7 ± 4.4 (−GH + Aci), 11.5 ± 4.4 (+GH − Aci), 13.9 ± 4.2 (+GH + Aci), P = 0.005.

Conclusion: Our data suggest that antilipolysis via suppression of the hormone-sensitive lipase in combination with GH administration is associated with significant and reciprocal changes in ghrelin and leptin.

Free access

The follicle-stimulating hormone (FSH) and luteinizing hormone (LH) response to a gonadotropin-releasing hormone analogue test in healthy prepubertal girls aged 10 months to 6 years

Esben T Vestergaard, Mia E Schjørring, Konstantinos Kamperis, Karin Kastberg Petersen, Søren Rittig, Anders Juul, Kurt Kristensen, and Niels H Birkebæk

Objective

Premature thelarche and precocious puberty are frequently diagnosed in girls even below 6 years of age and may be difficult to differentiate in the early stages. A GnRH test is often included in the diagnostic work-up, although interpretation of the GnRH test in girls below 6 years of age is challenging, as no reference interval exists for this age group. The objective is to determine the normal FSH and LH response to a GnRH test in healthy prepubertal girls below 6 years of age.

Design and methods

A standardized GnRH test, baseline reproductive hormones, clinical evaluation and bone age were determined in all participants. Forty-eight healthy normal-weight girls aged 3.5 ± 0.2 years (range: 0.8–5.9 years) were included. Serum concentrations of LH and FSH were measured before and 30 min after the gonadorelin injection.

Results

The 30-min LH responses (mean ± 2 s.d.) were 5.2 ± 4.0 and 2.9 ± 2.5 IU/L and the FSH responses were 23.3 ± 16.2 and 14.5 ± 10.3 IU/L in girls aged 0.8–3.0 years and 3.0–5.9 years respectively. This corresponds to upper cut-off limits for LH of 9.2 IU/L (<3 years) and 5.3 IU/L (3–6 years). The stimulated LH/FSH ratio was 0.23 ± 0.19 (range 0.06–0.43) and did not correlate with age.

Conclusions

We found that LH increases up to 9.2 IU/L during GnRH test in healthy normal-weight girls below 3 years of age and that the stimulated LH/FSH ratio did not exceed 0.43. Our findings have important implications for appropriate diagnosis of central precocious puberty in girls below 6 years of age.