E. Dall’Aglio

Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are associated with insulin resistance and the metabolic syndrome

Fatty liver at ultrasounds, with/without raised plasma levels of hepatic enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic fatty liver disease (NAFLD), a potentially progressive disease associated with insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that insulin resistance per se might be associated with hepatocellular necrosis. Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma-glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment-seeking obese patients recruited in 12 Italian medical centers. Insulin resistance was calculated by the homeostasis model assessment method (HOMA-IR; no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased with the obesity class (p<0.0001), and was higher in subjects with elevated ALT (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with elevated enzyme levels were omitted from analysis. Diabetes and hypertriglyceridemia were the features of the MS most commonly associated with raised liver enzymes. In logistic regression, after correction for age, gender, BMI and features of the MS, HOMA-IR maintained a highly predictive value for raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk factor for raised liver enzyme levels, possibly related to NAFLD.

The hormonal pathway to cognitive impairment in older men

In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The “preclinical phase” of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.

Effect of metoclopramide on maternal and fetal hyperprolactinemia

To investigate the effect of metoclopramide (MET), a dopaminergic antagonist drug, on serum PRL concentration in maternal and cord blood (CB) serum, the drug was injected in 94 at term pregnant women whereas 28 mothers received saline. Maternal serum (MS) samples were obtained before MET injection and at the parturition time. According to the interval of time between MET administration and birth, MS specimens were grouped in 7 groups. CB was obtained from neonates whose mothers were injected with saline, group 0 and from newborns whose mothers were treated with MET, groups 1 to 7. In the 7 groups of women the mean PRL concentration before MET ranged between 307 and 439 ng/ml. After MET injection a significant increase has been observed in all groups with a minimum and maximal mean value of 639 and 931 ng/ml. The highest net increment of PRL has been measured ingroup 1 sampled at 5 to 30 minutes after MET. CB PRL concentration in group 0, saline treated, was not different from the values measured in group 1 to 7, treated groups, with a range between 504 and 703 ng/ml. These findings suggest that maternal lactotropes are still responsive to MET. On the opposite, fetal pituitary does not release PRL after MET injection probably because PRL secretory activity is maximal or because the dopaminergic receptors’ system is still immature.

Does calcitonin modulate anterior pituitary hormone secretion

In a group of 5 healthy subjects salmon CT (sCT) infusion was unable to induce significant variations on basal secretory levels of LH, FSH, PRL and TSH. In a second group of 5 normal subjects, GnRH and TRH tests were performed both during sCT and saline infusion; a clear inhibition of TSH-stimulated levels and of PRL area was documented, while gonadotropin secretion was not significantly affected by sCT infusion. These results suggest that CT effect might be attributed to a change in intracellular calcium of pituitary cells; however the different behavior between TRH-and GnRH-stimulated hormones might be due to a different hormonal release mechanism. Furthermore the widespread recognition of CT-likeimmunoreactivity in adenohypoph-ysis and in portions of the central nervous system suggests that CT may be a neurotransmitter or paracrine regulator.

Relationship between use of proton pump inhibitors and igf system in older subjects

Objectivesto investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly.Designcross-sectional.SettingInCHIANTI study.Participants938 older subjects (536 women, 402 men, mean age 75.7±7.4 years).Measurementscomplete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3).ResultsParticipants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1–113.8] than nonusers 110 [77.8–148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (β±SE=−19.60±9.83, p=0.045).ConclusionUse of PPIs was independently and negatively associated with IGF-1 levels.

Weight loss and clinical characteristics of young adults patients seeking treatment at medical centers: Data from the QUOVADIS Study

OBJECTIVE: To compare clinical characteristics, attrition, weight loss, and psychological changes of obese young adults and obese adults seeking treatment. MATERIALS AND METHODS: 1530 individuals seeking treatment in 18 Italian medical centers were evaluated. 382 cases (25%) were classified as young adults (age≤35 years), 1148 (75%) as adults (>35 years). Psychological distress, binge eating, body uneasiness, and attitude towards eating were evaluated, at baseline and after a 12-month weight-loss program, together with BMI changes. Weight-loss expectations and primary motivation for seeking treatment were also recorded. RESULTS: At baseline, young adults reported significantly higher BMI at age 20, weight loss expectations and body uneasiness scores than adults. A significantly higher percentage of young adults also reported improving appearance as primary reason for seeking treatment. The attrition rate was significantly larger in young adults. Among completers, the mean percent weight loss at 12 months and improvement of psychosocial variables were significantly higher in young adults than in adults. By intention to treat, BMI changes were no longer significant between groups. DISCUSSION: Obese young adults lose more weight and considerably improve psychological distress, but show a higher attrition rate after 12 months of continuous care in a real world medical setting.

Absent prolactin (PRL) response to thyrotropin releasing hormone (TRH) and somatostatin (SRIF) in at term fetus.

To study the effect of thyrotropin-releasing hormone (TRH) and somatostatin (SRIF) on prolactin (PRL) secretion in at term human fetus these peptides have been administered to at term pregnant women during labor. Evidence has been reported that TRH and SRIF cross the placental barrier and affect the secretion of pituitary hormones. 400 μg TRH were administered to 37 pregnant women. As control 11 women received saline. In cord blood (CB) of neonates whose mothers received TRH CB PRL concentration was not different from those treated with saline, with values ranging between 192 ± 18 and 342 ± 48 ng/ml. 500 μg cyclic SRIF diluted in saline was infused over a period of 30 min in 55 women. Control subjects were infused with saline. At birth CB PRL concentration in SRIF treated neonates ranged between 266 ± 32 and 327 ± 48 ng/ml. In neonates whose mothers were treated with saline, CB PRL was 305 ± 31 ng/ml. This value was not significantly different from that in SRI F-treated groups. Our findings suggest that in at term human fetus TRH does not stimulate PRL secretion probably because fetal pituitary secretes PRL at maximal releasing activity. Furthermore SRIF administration does not have any effect on fetal PRL secretion as consistently observed in adults.

PP096-SUN: Inverse Relationship Between Carotenoids and Estradiol Levels in Older Women: Implication for Estrogen-Dependent Cancers?

Rationale: The HSCT patients have a tendency to lower serum vitamin D (VD). There is an important role in the regulation of VD and lymphocyte function T. The VD has an immunomodulatory effect that correlates with an increased incidence of Chronic GVHD and may increase mortality in this group of patients. Additionally, serum vitamin D levels are related to bacterial infection, ICU and relapse after HSCT. Objective: Analyse the relationship between disability and serum levels of vitamin D and risk of developing Acute GVHD. Methods: Retrospective study in Oncology and Hematology Department of the Albert Einstein Hospital (HIAE), with 19 patients (10 women, 9 men), adults (>18 years) who underwent HSCT, 42% of allogeneic related, 37% of unrelated allogeneic and 21% haploidential. The mean age was 46 years (±16) and weight 67 kg (±17). Of these patients, 59% had normal body mass index (BMI) (kg/m2), 21% overweight, 5% obese and 16% malnutrition. The exam for measurement of serum vitamin D (25-hydroxyvitamin D) was requested at the time of admission of the patient before the start of HSCT. The results of serum VD were classified into 50 nmol/ml normal. Results: There was a significant and negative correlation between BMI and serum levels of VD (rp = 0.5). 53% of patients had GVHD, but there was no significant relationship of the same with the other variables. There was a trend GVHD in the presence of low serum vitamin D also present in 53% of cases. Conclusion: GVHD is a disease with a high risk for patients undergoing HSCT, having great impact on the quality of life. Overweight and obese patients who have lower levels of VD should be better monitored, as tending to a higher risk of developing this complication.