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OBJECTIVE: To compare insulin-like growth factor-I (IGF-I) concentrations in obese and normal subjects, and evaluate the possible relationships between IGF-I concentrations and demographic, anthropometric, metabolic and hormonal variables in obese patients. SUBJECTS AND METHODS: 286 obese outpatients (OB, 234 female and 52 male; age 18-71 y, body mass index (BMI) >27 kg/m²) were recruited. MEASUREMENTS: BMI, waist-to-hip ratio (WHR), serum basal and oral glucose tolerance test (OGTT)-stimulated glucose and insulin concentrations, IGF-I, basal growth hormone (GH), prolactin (PRL), androgens, thyrotropin (TSH), free triiodothyronine (fT[sub 3]), free thyroxine (fT[sub 4]), free fatty acids (FFA), triglycerides, total and high density lipoprotein (HDL)-cholesterol, 24h-urinary cortisol levels and blood pressure (BP) values were measured. IGF-I concentrations were also evaluated in a large population of 326 age-matched controls (controls, 228 women, 98 men; age 20-86 y, BMI <25 kg/m²). RESULTS: IGF-I concentrations were lower in OB than in controls (age-adjusted mean: 21.6 vs 23.6 nmol/L, P<0.03). However, individual IGF-I concentrations in OB were within the age-adjusted normal range. In both groups, IGF-I concentrations were gender-independent, and showed a simple negative correlation with age (r=-0.47). In OB, univariate analysis also shows that IGF-I concentrations were negatively correlated with BMI (r=-0.33), but not WHR, with both basal (r=-0.16) and OGTT-stimulated glucose levels (r=-0.17), as well as FFA levels (r=-0.19), and with both diastolic and systolic BP (both r=-0.17). In OB women, IGF-I concentrations positively correlated with PRL (r=0.31), testosterone (r=0.30), androstenedione (r=0.30), and dehydroepiandrosterone-sulfate (DHEAS) concentrations (r=0.41). No correlation was found with other variables. The multiple regression analysis showed that IGF-I concentrations were inversely and independently related to age and BMI only.... [ABSTRACT FROM AUTHOR]

OBJECTIVES: To further investigate the role, if any, of acetylcholine and the parasympathetic nervous system in modulating β-cell secretion in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min ) alone and preceded by pyridostigmine (PD, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasions, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index(BMI): 34.3±2.1 kg/m2, waist to hip ratio (WHR): 0.83±0.01, aged 39.0±5.3 y) and six normal women (NS, BMI: 22.7±1.9 kg/m2, WHR: 0.74±0.01, aged 37.1±4.8 y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measured in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina using high performance liquid chromatography with electrochemical detection. Pulse rate (PR), systolic (SBP) and diastolic blood pressure (DBP) were also measured every 15 min during the tests by an automated cuff device. RESULTS: OGTT raised glucose concentrations in OB and NS (incremental area: 420±44 vs 288±70 mmol/l. 2 h, respectively) without significant differences between groups(F=0.6, P=ns). On the other hand, OB showed an insulin response to OGTT higher than NS (10 120±1074 vs 6692±1962 μU ml-1 2 h, respectively P<0.01). After OGTT alone NA concentrations increased to the same extent in NS (peak vs basal: 1.40±0.16 vs 1.07±0.10 nmol/l, P<0.05) and in OB (peak vs basal: 1.50±0.14 vs 1.04±0.18 nmol/l P<0.05). Both in NS and in OB, PD administration failed to modify basal glucose and insulin (P=ns for both) as well as basal NA concentrations. In NS, the combined administration of PD and OGTT did not modify... [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH deficiency. DESIGN: Stimulation with GHRH. (1 μg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH + ARG was evaluated in a second session. SUBJECTS: Forty-five patients with simple obesity (OB 11 male and 34 female, age 40.5 ± 1.8 y, BMI 38.8 ± 1.1 kg/m²), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6± 2.4y, 24.7 ± 0.7 kg/m²) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 ± 1.0 y, 21.6 ± 0.3 kg/m²) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at - 60 and 0 min, and than every 15 min up to + 120 min. Basal IGF-I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF-I levels in OB were lower (P < 0.005) than those in NS but higher (P < 0.005) than those in GHD. Mean peak GH response to GHRH + ARG in OB was clearly lower than that in NS (P < 0.005) and higher (P < 0.005) than that in GHD. Sixty-percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 μg/I) while 4% OB and only 53% GHD with GH responses lower than 3 μg/I, the limit under which GH replacement therapy of severe deficiency is allowed. Good intraindividual reproducibility of the GH response to GHRH + arginine test was present in all groups (OB: r=0.78, P < 0.0001; GHD: r= 0.57, P< 0.003; NS: r=0.74, P< 0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH deficiency. Thus, even... [ABSTRACT FROM AUTHOR]

In this review we propose an integrated neuro-endocrine-metabolic point of view on the alterations (adaptations?) of GH/IGF-1 axis in obesity, summarizing the evidence from the literature, particularly focusing the data on humans and adding where possible results from our studies in this field. It is well-known that GH secretion is deeply impaired in overweight patients: we reviewed the multiple mechanisms underlying this issue, considering either central (CNS-related, such as impairment of GHRH tone or increased somatostatin release) or peripheral (ie metabolic: insulin, free fatty acids, glucose) factors. A central point of the debate about GH insufficiency in obesity is if it represents a simple adaptive phenomenon or reflects a true impairment of the axis activity. Evaluation of IGF-I levels and generation in obesity was the mean used to address this question: a bulk of evidence on IGF-I balance in human obesity has been provided, but the matter is still uncertain and unsolved. International Journal of Obesity (2000) 24, Suppl 2, S96–S99. [ABSTRACT FROM AUTHOR]