Predictors of attrition from a weight loss program. A study of adult patients with obesity in a community setting.

PURPOSE: Obesity unit attrition is frequent and contributes to treatment failure. Many studies evaluating attrition predictors were part of randomized trials, and different terminology and criteria were used in the engagement field. We aimed to investigate the factors potentially implicated in early (< 12 weeks) and late (> 12 weeks) attrition from an obesity unit in a community setting METHODS: This was a retrospective cohort study of 250 patients with obesity who were followed-up at our obesity unit. Our program included at least 6 meetings in 12 months. Sociodemographic and anthropometric data, and psychometric questionnaires were collected from all participants. RESULTS: One-hundred thirty-four (53.6%) participants dropped out. Those individuals showed lower BMI, lower overall health status, and increased depression scores. In a multiple regression model, BMI (inversely; OR = 0.90; 95%CI 0.84-0.96) and depression score (directly, OR = 1.05; 1.00-1.10) were associated with attrition risk. Early dropouts (n = 47) had lower weights, smaller waist circumferences and worse mental health scores than late dropouts (n = 87) and more frequently lived alone. When compared to completers, early dropouts had lower weights, BMIs, waist circumferences, overall health and mental status scores, increased depression scores and percentage of individuals living alone. In a multiple regression, lower BMI (OR = 0.83; 0.75-0.92), lower mental status score (OR = 3.17; 1.17-8.59) and living alone (OR = 2.25; 1.02-4.97) were associated with early attrition risk. CONCLUSION: Lower BMI and increased depression score were associated with attrition. Early attrition was associated with lower weight, decreased mental well-being, and living alone. Individuals with these characteristics might need tailored approaches to enhance their engagement. LEVEL OF EVIDENCE: Level V, retrospective descriptive study.

Advanced glycation end products and chronic inflammation in adult survivors of childhood leukemia treated with hematopoietic stem cell transplantation.

BACKGROUND: Among survivors of pediatric acute lymphoblastic leukemia (ALL), those who received hematopoietic stem cell transplantation (HSCT) conditioned with total-body irradiation (TBI) show the highest risk of late complications, including cardiovascular (CV) disease. Advanced glycation end products (AGEs) have been associated with CV disease in diabetes mellitus and other clinical conditions. This study explores AGEs plasma levels, inflammatory status, and lipid profile in survivors of pediatric ALL who received HSCT conditioned with TBI. PROCEDURE: Inclusion criteria were (a) previous diagnosis of ALL at age < 18 years, treated with HSCT conditioned with TBI; (b) age > 18 at the time of the study enrollment; (c) off-therapy for at least five years. Radiotherapy other than TBI, preexisting heart disease, glucose metabolism impairment, body mass index > 25, active graft versus host disease (GvHD), smoking, or treatment with cholesterol lowering medications were exclusion criteria. Eighteen survivors and 30 age-matched healthy controls were enrolled. RESULTS: AGEs plasma levels were markedly higher in ALL survivors than in healthy subjects (2.15 ± 2.21 vs 0.29 ± 0.15 pg/mL, P < 0.01). Survivors also showed higher levels of high-sensitivity C-reactive protein (2.32 ± 1.70 vs 0.88 ± 1.09 mg/dL, P < 0.05), IL-1ß (7.04 ± 1.52 vs 4.64 ± 2.02 pg/mL, P < 0.001), IL17 (37.44 ± 3.51 vs 25.19 ± 6.34 pg/mL, P < 0.001), an increased glutathione/reduced glutathione ratio (0.085 ± 0.07 vs 0.041 ± 0.036, P < 0.05) and slight alterations in their lipid profile. CONCLUSIONS: Our data show AGEs accumulation and chronic inflammation in ALL survivors who received HSCT conditioned with TBI. These alterations may contribute to the increased risk of CV disease reported in these subjects.

University courses, eating problems and muscle dysmorphia: are there any associations?

BACKGROUND: Orthorexia and muscle dysmorphia are disorders affecting above all young adults whose prevalence and social impact are still unclear. We aimed to evaluate the prevalence of the traits of orthorexia and muscle dysmorphia among freshmen attending university courses focused on nutrition (Dietetics) and body care (Exercise and Sport Sciences). Students of Biology were considered as a control group. The prevalence of eating disorder (ED) traits were also evaluated. METHODS: All participants (n = 440; n = 53 Dietetics school, n = 200 Exercise and Sport Sciences school, n = 187 the Biology school) completed the following questionnaires: ORTO-15, Muscle-Dysmorphic-Disorder-Inventory, and Eating Attitudes Test-26. RESULTS: The prevalence of the traits of EDs, orthorexia, and muscle dysmorphia was 9.1%, 25.9%, and 5.9%, respectively. When compared to other students, those attending the Dietetics school showed a 2-fold higher risk of EDs and those from the Exercise and Sport Sciences school a 10-fold higher risk of muscle dysmorphia. The prevalence of orthorexia traits was high in all schools (35.9%, 22.5%, 26.5% in Dietetics, Biology, and Exercise and Sport Sciences schools, respectively). Overall, individuals with traits of any of these disorders were more frequently on diet or on supplement use. In a logistic regression model, attending the Dietetics school (OR = 2.71; 95% CI 1.14-6.48) was significantly associated with the ED traits, but not with the orthorexia traits (OR = 1.75; 95% CI 0.93-3.29), while attending the Exercise and Sport Sciences school was significantly associated with the muscle dysmorphia traits (OR = 5.15; 95% CI 1.44-18.4). Finally, when evaluating the relationships among the types of study programs as dependent variables and traits of these disturbances, the associations between the traits of ED (OR = 3.35; 95% CI 1.38-8.13) and matriculation at the school of Dietetics, and between the traits of muscle dysmorphia (OR = 4.32; 95% CI 1.16-16.1) and the choice of the Exercise and Sport Sciences school were confirmed. CONCLUSIONS: The choice of the university courses might be influenced by pre-existing disorders in eating behaviors, which were relatively frequent in the considered sample.

Eicosapentaenoic Acid: between Cardiovascular Benefits and the Risk of Atrial Fibrillation.

In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on a high-dose eicosapentaenoic acid (EPA)-only approach, instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation (AF) occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians to prescribe EPA safely and effectively, especially in patients at high risk of incipient AF.

[Severe hyponatremia secondary to the syndrome of inappropriate secretion of antidiuretic hormone]. / Severa iponatriemia secondaria a sindrome da inappropriata secrezione di ormone antidiuretico.

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a common and multifactorial cause of hyponatremia that is often overlooked. The common pathophysiological mechanism is the increased production and/or action of antidiuretic hormone within the kidney, resulting in hypotonic hyponatremia. Inadequate correction of hyponatremia may have fatal neurological consequences leading to central pontine myelinolysis. We report the case of a patient with a history of recent head trauma, who came to our observation for acute-onset mental confusion secondary to severe hyponatremia due to SIADH of combined etiology.

Long-term efficacy of empagliflozin as an add-on treatment for chronic SIAD: a case report and literature review.

BACKGROUND: SLGT-2 inhibitors have recently been investigated as a promising therapy for syndrome of inappropriate antidiuresis (SIAD). However, to our knowledge, no report has been published about their use for this indication in the long term. CASE PRESENTATION: We report the case of a 68-year-old male with type 2 diabetes and chronic SIAD, in whom serum sodium levels were not adequately controlled by urea monotherapy. Other treatment options were not viable due to inefficacy or adverse effects. The initiation of empagliflozin, in addition to urea, led to the full normalization of serum sodium. Reduction and subsequent discontinuation of urea were attempted upon patient request, but this resulted in a relapse of hyponatremia. Nevertheless, stable normonatremia was again achieved and maintained for more than 6 months after re-establishing a combination therapy with empagliflozin and urea. CONCLUSIONS: SGLT2 inhibitors might represent an effective treatment for SIAD, even in the long term. Specific clinical trials are needed to confirm this result.

The Effects of Omega 3 and Omega 6 Fatty Acids on Glucose Metabolism: An Updated Review.

Massive changes have occurred in our diet. A growing consumption of vegetal oils rich in omega-6 (ω-6) and a depletion of omega-3 (ω-3) fatty acids (FAs) in our food has led to an imbalance between ω-3 and ω-6. In particular, eicosapentaenoic (EPA)/arachidonic acid (AA) ratio seems to be an indicator of this derangement, whose reduction is associated to the development of metabolic diseases, such as diabetes mellitus. Our aim was therefore to investigate the literature on the effects of ω-3 and ω-6 FAs on glucose metabolism. We discussed emerging evidence from pre-clinical studies and from clinical trials. Notably, conflicting results emerged. Source of ω-3, sample size, ethnicity, study duration and food cooking method may be responsible for the lack of univocal results. High EPA/AA ratio seems to be a promising indicator of better glycemic control and reduced inflammation. On the other hand, linoleic acid (LA) appears to be also associated to a minor incidence of type 2 diabetes mellitus, although it is still not clear if the outcome is related to a reduced production of AA or to its intrinsic effect. More data derived from multicenter, prospective randomized clinical trials are needed.

Copeptin adaptive response to SGLT2 inhibitors in patients with type 2 diabetes mellitus: The GliRACo study.

Introduction: In type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount. Aim: To investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients. Methods: The GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90. Results: Among endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p < 0.001), while copeptin did not. Conclusion: In patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient's baseline volume conditions. Clinical trial registration: Clinicaltrials.gov, identifier NCT03917758.

In Patients with Obesity, Are Affective Temperaments Associated with Attrition? An Evaluation during and before the SARS-CoV-2 Pandemic.

Timely data on attrition from weight loss programs for patients with obesity during the SARS-CoV-2 pandemic are lacking, so we aimed to contribute to filling this gap in the literature by comparing attrition during or outside of the SARS-CoV-2 pandemic and its possible association with patients' affective temperaments, psychopathology, and clinical variables. Two-hundred and eleven outpatients with obesity were recruited and completed the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire, Binge Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory. Those who dropped out during the pandemic period were mostly men, with younger age of weight gain, and with a larger waist circumference than completers. Patients with obesity who dropped out outside of the SARS-CoV-2 pandemic showed marked levels of depression, anxiety, binge eating episodes, and higher affective temperaments (but the hyperthymic one) when compared to their counterparts. The cyclothymic temperament slightly increased attrition (OR = 1.13, 95% CI 1.00-1.27 p = 0.05) outside the pandemic, while during the pandemic, male gender (OR = 3.50, 1.04-11.7, p = 0.04) was associated with attrition. These findings suggested that male patients with obesity are at particular risk of drop-out from weight-loss treatment during the SARS-CoV-2 pandemic; contrariwise, outside the pandemic, affective temperaments could be a useful baseline assessment for defining the attrition risk in these patients.

Affective temperaments and obesity: Is there an association with binge eating episodes and multiple weight cycling?

BACKGROUND: affective temperaments have been so far understudied in the field of obesity. Therefore, we aimed to assess affective temperaments in outpatients with obesity reporting symptoms of binge eating (BE) and multiple weight cycling (MWC) and to investigate the likelihood of an association between affective temperaments and risk of both conditions. METHODS: A total of 300 individuals with obesity seeking treatment at the Obesity Unit of an academic hospital were asked to complete self-report measures of affective temperaments, BE, depressive and anxiety symptoms, and quality of life. RESULTS: Even in the absence of full-blown mental disorders, symptoms of anxiety and depression emerged in the sample; 197 individuals (65.6%) reported BE and 162 (54%) MWC. The most frequent affective temperament was the depressive one. Depression symptoms and cyclothymic scores (directly), and age and hyperthymic score (inversely) were significantly associated with BE risk, while being an active smoker (directly) and hyperthymic score (inversely) were significantly associated with MWC risk, after controlling for confounders in a multiple logistic regression. LIMITATIONS: sample size was small, the study was limited to a single center, no formal definition of weight cycling exists and MWC was self-reported. CONCLUSIONS: A substantial number of outpatients with obesity reported BE and MWC notwithstanding the absence of a formal psychiatric diagnosis. Cyclothymic scores were positively associated with BE while the hyperthymic temperament showed a protective effect on both BE and MWC. These findings suggest the need for multidisciplinary treatments for people with obesity enhancing research on temperament-based psychological interventions.

Ghrelin and anterior pituitary function.

Ghrelin, a 28-amino-acid octanoylated peptide predominantly produced by the stomach, was discovered to be the natural ligand of the type 1a GH secretagogue receptor. Thus, it was considered as a natural GH secretagogue (GHS) additional to GHRH, although later on ghrelin has mostly been considered a major orexigenic factor. The GH-releasing action of ghrelin takes place both directly on pituitary cells and through modulation of GHRH from the hypothalamus; some functional anti-somatostatin action has also been shown. However, even at the neuroendocrine level, ghrelin is much more than a natural GHS. In fact, it significantly stimulates prolactin secretion in humans, independent of both gender and age and probably involving a direct action on somatomammotroph cells. Above all, ghrelin and synthetic GHS possess an acute stimulatory effect on the activity of the hypothalamus-pituitary-adrenal axis in humans, which is, at least, similar to that of the opioid antagonist naloxone, arginine vasopressin and even corticotropin-releasing hormone. Also, ghrelin plays a relevant role in the modulation of the hypothalamic-pituitary-gonadal function, with a predominantly CNS-mediated inhibitory effect upon the gonadotropin pulsatility both in animals and in humans.

Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension.

OBJECTIVES: To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension. METHODS: One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs. RESULTS: Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82-60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44-9.78; P = 0.007), carotid intima-media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02-7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18-15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53-73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73-69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19-8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima-media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension. CONCLUSION: The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease.

Changes in Weight and Nutritional Habits in Adults with Obesity during the "Lockdown" Period Caused by the COVID-19 Virus Emergency.

Our aim is evaluating the changes in weight and dietary habits in a sample of outpatients with obesity after 1 month of enforced lockdown during the COVID-19 pandemic in Northern Italy. In this observational retrospective study, the patients of our Obesity Unit were invited to answer to a 12-question multiple-choice questionnaire relative to weight changes, working activity, exercise, dietary habits, and conditions potentially impacting on nutritional choices. A multivariate regression analysis was performed to evaluate the associations among weight/BMI changes and the analyzed variables. A total of 150 subjects (91.5%) completed the questionnaire. Mean self-reported weight gain was ≈1.5 kg (p < 0.001). Lower exercise, self-reported boredom/solitude, anxiety/depression, enhanced eating, consumption of snacks, unhealthy foods, cereals, and sweets were correlated with a significantly higher weight gain. Multiple regression analyses showed that increased education (inversely, ß = -1.15; 95%CI -2.13, -0.17, p = 0.022), self-reported anxiety/depression (ß = 1.61; 0.53, 2.69, p = 0.004), and not consuming healthy foods (ß = 1.48; 0.19, 2.77, p = 0.026) were significantly associated with increased weight gain. The estimated direct effect of self-reported anxiety/depression on weight was 2.07 kg (1.07, 3.07, p < 0.001). Individuals with obesity significantly gained weight 1 month after the beginning of the quarantine. The adverse mental burden linked to the COVID-19 pandemic was greatly associated with increased weight gain.

Correction to: Tanner-Whitehouse Skeletal Ages in Male Youth Soccer Players: TW2 or TW3?

An Online First version of this article was made available online at https://link.springer.com/article/10.1007%2Fs40279-017-0799-7 on 29 October 2017. Errors were subsequently identified in the article, and the following corrections should be noted.

Tanner-Whitehouse Skeletal Ages in Male Youth Soccer Players: TW2 or TW3?

BACKGROUND: The Tanner-Whitehouse radius-ulna-short bone protocol (TW2 RUS) for the assessment of skeletal age (SA) is widely used to estimate the biological (skeletal) maturity status of children and adolescents. The scale for converting TW RUS ratings to an SA has been revised (TW3 RUS) and has implications for studies of youth athletes in age-group sports. OBJECTIVES: The aim of this study was to compare TW2 and TW3 RUS SAs in an international sample of male youth soccer players and to compare distributions of players by maturity status defined by each SA protocol. METHODS: SA assessments with the TW RUS method were collated for 1831 male soccer players aged 11-17 years from eight countries. RUS scores were converted to TW2 and TW3 SAs using the appropriate tables. SAs were related to chronological age (CA) in individual athletes and compared by CA groups. The difference of SA minus CA with TW2 SA and with TW3 SA was used to classify players as late, average, or early maturing with each method. Concordance of maturity classifications was evaluated with Cohen's Kappa coefficients. RESULTS: For the same RUS score, TW3 SAs were systematically and substantially reduced compared with TW2 SAs; mean differences by CA group ranged from - 0.97 to - 1.16 years. Kappa coefficients indicated at best fair concordance of TW2 and TW3 maturity classifications. Across the age range, 42% of players classified as average with TW2 SA were classified as late with TW3 SA, and 64% of players classified as early with TW2 SA were classified as average with TW3 SA. CONCLUSION: TW3 SAs were systematically lower than corresponding TW2 SAs in male youth soccer players. The differences between scales have major implications for the classification of players by maturity status, which is central to some talent development programs.

Acetylcholine regulates ghrelin secretion in humans.

Ghrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulation of gastric contractility and acid secretion and its orexigenic activity. To clarify whether ghrelin secretion undergoes cholinergic control in humans, we studied the effects of pirenzepine [PZ, 100 mg per os (by mouth)], a muscarinic antagonist, or pyridostigmine (PD, 120 mg per os), an indirect cholinergic agonist, on ghrelin, GH, insulin, and glucose levels in six normal subjects. PD increased (P < 0.05) GH (change in area under curves, mean +/- SEM, 790.9 +/- 229.3 microg(*)min/liter) but did not modify insulin and glucose levels. PZ did not significantly modify GH, insulin, and glucose levels. Circulating ghrelin levels were increased by PD (11290.5 +/- 6688.7 pg(*)min/ml; P < 0.05) and reduced by PZ (-23205.0 +/- 8959.5 pg(*)min/ml; P < 0.01). The PD-induced ghrelin peak did not precede that of GH. In conclusion, circulating ghrelin levels in humans are increased and reduced by cholinergic agonists and antagonists, respectively. Thus, ghrelin secretion is under cholinergic, namely muscarinic, control in humans. The variations in circulating ghrelin levels induced by PD and PZ are unlikely to mediate the cholinergic influence on GH secretion.

Endocrine activities of cortistatin-14 and its interaction with GHRH and ghrelin in humans.

Cortistatin (CST)-14, a neuropeptide with high homology with somatostatin (SS)-14, binds all sst subtypes but, unlike SS, also ghrelin's receptor. In six normal adults, we studied the effects of CST-14 or SS-14 administration (2.0 micro g/kg/h iv) on: 1) GH and insulin secretion; 2) the GH response to GHRH (1.0 microg/kg i.v.); and 3) the GH, prolactin (PRL), ACTH, cortisol, insulin, and glucose responses to ghrelin (1.0 microg/kg i.v.). CST-14 inhibited GH and insulin secretion (P < 0.01) to the same extent of SS-14. The GH response to GHRH was similarly inhibited (P < 0.01) by either CST-14 or SS-14. Ghrelin released more GH than GHRH (P < 0.01); these responses were similarly inhibited (P < 0.05) by either CST-14 or SS-14, that made ghrelin-induced GH rise similar to that after GHRH alone. Neither CST-14 nor SS-14 modified PRL, ACTH, or cortisol responses to ghrelin. The inhibitory effect of CST-14 and SS-14 on insulin was unaffected by ghrelin that, in turn, reduced insulin secretion per se (P < 0.01). Ghrelin increased glucose levels (P < 0.05); CST-14 and SS-14 did not modify this effect. Thus, CST-14 inhibits both basal and stimulated GH secretion in humans to the same extent of SS-14. The GH-releasing activity of ghrelin seems partially resistant to CST-14 as well as SS-14. CST-14 and SS-14 do not affect PRL and ACTH secretion but, like ghrelin, inhibit insulin secretion; the ghrelin-induced inhibition is not additive with that of CST-14 or SS-14, suggesting a common mechanism of action on beta cell secretion.

The endocrine response to ghrelin as a function of gender in humans in young and elderly subjects.

Ghrelin modulates somatotroph, lactotroph, corticotroph, and insulin secretion and glucose metabolism. To clarify the influence of gender and age on the endocrine actions of ghrelin in humans, we studied the effects of ghrelin (1.0 micro g/kg iv) or placebo on GH, prolactin (PRL), ACTH, cortisol, insulin, glucagon, and glucose levels in 18 young subjects (YS) and 16 elderly subjects (ES) of both genders. The GH response to GHRH (1.0 micro g/kg iv) was also studied. The GH response to ghrelin in YS was higher (P < 0.01) than in ES and both higher (P < 0.01) than to GHRH, without gender-related differences. In YS ghrelin also induced: 1) gender-independent increase (P < 0.01) in PRL, ACTH, and cortisol levels; 2) gender-independent increase in glucose levels (P < 0.01); 3) decrease (P < 0.01) in insulin levels in male YS; and 4) no change in glucagon. In ES, ghrelin induced gender-independent PRL, ACTH, and cortisol responses (P < 0.01). In ES ghrelin elicited gender-independent transient decrease in insulin (P < 0.01) coupled with increase in glucose levels (P < 0.05). In conclusion, the GH-releasing effect of ghrelin is independent of gender but undergoes age-related decrease. The effect of ghrelin on lactotroph and corticotroph secretion is age and gender independent. In both ES and YS, ghrelin influences insulin secretion and glucose metabolism.

Ghrelin secretion is inhibited by either somatostatin or cortistatin in humans.

Ghrelin possesses endocrine and non-endocrine actions mediated by the GH Secretagogue (GHS)-Receptors (GHS-R). The regulation of ghrelin secretion is still largely unknown. Somatostatin (SRIF) modulates central and gastroenteropancreatic hormonal secretions and functions. SRIF actions are partially shared by cortistatin (CST), a natural SRIF analogue, that binds all SRIF receptors and also GHS-R. Herein, we studied the effects of SRIF-14 or CST-14 (2.0 micro g/kg/h i.v. over 120 min) and of placebo on ghrelin, GH, insulin, glucagon and glucose levels in 6 normal young men. Placebo unaffected GH, insulin, glucagon, glucose and ghrelin levels. SRIF and CST similarly inhibited (p < 0.05) spontaneous GH secretion of about 90%. After SRIF or CST withdrawal, GH levels recovered to baseline levels. Both SRIF and CST similarly inhibited (p<0.01) insulin secretion of about 45%. In both sessions, after SRIF or CST withdrawal, insulin overrode baseline levels. Both SRIF and CST similarly inhibited (p < 0.01) glucagon levels of about 40%. After SRIF or CST withdrawal, glucagon persisted lower (p < 0.05) than at baseline. Neither SRIF nor CST modified glucose levels. Both SRIF and CST similarly inhibited (p < 0.01) circulating ghrelin levels of about 55%. Ghrelin levels progressively decreased from time +15 min, reaching the nadir at 120 and 105 min for SRIF and CST, respectively. Even 30 min after SRIF or CST withdrawal, ghrelin levels persisted lower (p < 0.05) than those at baseline. In conclusion, this study first shows that SRIF and CST strongly inhibits ghrelin secretion that, differently from GH and insulin secretion, persists inhibited even after stopping the infusion of SRIF or CST.

Ghrelin and synthetic GH secretagogues.

Ghrelin, a 28-amino-acid acylated peptide, produced mainly by the stomach, displays strong growth hormone-(GH)-releasing activity mediated by the hypothalamus-pituitary growth hormone potential secretagogue (GHS) receptor which had been shown to be specific for a family of synthetic, orally active GHS. GHS are reliable provocative tests for the diagnosis of GH deficiency but, as orally active growth-promoting agents, they are not comparable with human recombinant GH in terms of efficacy. The usefulness of GHS in anabolic, anti-ageing drug intervention in the somatopause is still unclear. GHS also act on central and peripheral receptors and show other actions, including an orexigenic effect, an influence on gastroentero-pancreatic functions, and cardiovascular and anti-proliferative effects. Ghrelin mediates the neuroendocrine and metabolic response to starvation. Taking into account its orexigenic effect, GHS analogues acting as agonists or antagonists on appetite could represent a new drug intervention for eating disorders.