Fasting concentrations of nesfatin‐1 are negatively correlated with body mass index in non‐obese males

Background We recently identified a novel anorexigenic protein, nesfatin‐1, which is processed from nesfatin/nucleobindin‐2 (NUCB2). However, the clinical importance of this protein has not been determined. Objective To investigate its clinical significance in humans, we have established a new specific enzyme‐linked immunosorbent assay (ELISA) for human nesfatin‐1 in peripheral blood and measured its circulating concentration in healthy subjects. Design The new sandwich‐type ELISA method was validated and then used to measure nesfatin‐1 levels in plasma samples, under overnight fasting conditions, followed by oral glucose tolerance and meal tests. Patients and measurements A total of 43 nonobese males (age: 24·5 ± 0·6 , body mass index (BMI); 21·1 ± 0·3 kg/m²) were recruited to the study for evaluating fasting concentrations of nesfatin‐1. In those, fifteen subjects underwent a 75‐ g oral glucose tolerance test (OGTT) and another 15 underwent a meal test. In addition, fasting concentrations of nesfatin‐1 were measured in nine males with high BMI (age: 32·4 ± 3·7 , BMI; 37·3 ± 3·8 kg/m²). Results Peripheral concentrations of nesfatin‐1 showed a significant negative correlation with BMI, percentage body fat, body fat weight and blood glucose (P < 0·05). Nesfatin‐1 concentrations were not significantly changed during OGTT and meal tests. Fasting nesfatin‐1 levels were significantly lower in subjects with high BMI compared to nonobese subjects (P < 0·05). Conclusions A new specific and sensitive ELISA for nesfatin‐1 was established. Further accumulation of clinical observations is necessary to clarify the role of circulating nesfatin‐1 in various metabolic disorders.     

Decreased plasma adiponectin levels in young obese males

Plasma adiponectin levels are reduced in middle-aged obesity and in patients with type 2 diabetes and coronary artery disease. The purpose of this study was to investigate the effects of early-aged obesity on plasma adiponectin level. Twenty-six male college students (19.2 +/- 1.1 years, obese group: n = 15, [body mass index > 25, percent body fat > 25%], non-obese group: n = 11) participated in the present study. We measured anthropometric parameters and plasma adiponectin and leptin level. Plasma adiponectin levels in the obese group were significantly lower than those in the non-obese group (obese: 4.7 +/- 2.0 micro g/ml, non-obese: 6.8 +/- 2.2 micro g/ml, p < 0.05). On the other hand, plasma leptin levels in the obese group were significantly higher than those in the non-obese group (obese: 8.4 +/- 3.2 ng/ml, non-obese: 2.6 +/- 2.1 ng/ml, p < 0.001). Plasma adiponectin levels were significantly correlated with body weight (r = -0.415, p < 0.05) and percent body fat (r = -0.412, p < 0.05). Stepwise multiple regression analysis revealed that percent body fat was a significant independent predictor of plasma adiponectin level (r = 0.406, p < 0.05). These results show that obesity is associated with reduced plasma adiponectin even in young subjects.     

Androgens in pubertal males with Addison's disease

The time of onset and progression of pubertal development has been documented in seven male patients with Addison's disease. Two patients developed associated autoimmune problems before puberty and were excluded from further study. The mean age of the onset of puberty among the remaining five patients was 12.3 +/- 0.4 yr, not different than the 11.4 +/- 0.4 yr reported for normal American boys. Integrated plasma levels of testosterone, androstenedione, 17-hydroxyprogesterone, progesterone, and dehydroepiandrosterone were also determined in three Addisonian patients who had no associated autoimmune disease before puberty and their study date. Results were compared with integrated plasma levels from three other groups: four agonadal males, four normal adult males, and three pubertal boys. Integrated plasma levels of these steroids confirm that in a male, testosterone is essentially testicular in origin, dehydroepiandrosterone is mainly adrenal in origin, and androstenedione and 17-hydroxyprogesterone are derived from both sources.     

Testosterone metabolism in normal males and male cirrhotics.

The following physiopathological mechanisms for the abnormalities of testosterone metabolism observed in cirrhotic patients may be postulated: 1. The decreased testosterone secretion has a primary testicular origin; it seems probable that, as a result of direct toxicity the 17-beta-reductase is inhibited, resulting in decrease of testosterone and an increase of androstenedione. 2. The hypothalamic-pituitary function is nearly normal in cirrhotics. Basal level of LH and FSH are often slightly elevated, indicating a normal reactivity of the pituitary. 3. The conversion of androgens to oestrogens (androstenedione to oestrone) which occurs essentially extrahepatically, is increaed in cirrhosis.     

Paradoxical increase in arterial compliance in obese pubertal children

We determined whether arterial compliance measured by pulse wave analysis is impaired in obese pubertal children compared to normal weight controls, and assessed whether arterial compliance is associated with ambulatory activity. Body fat percentage was significantly different between the normal (n = 33) and obese (n = 34) participants (P < .001). Large (P = .012) and small (P < .001) arterial compliance were lower in the normal-weight group. After adjusting for height, systolic and diastolic blood pressure, race, sex, and Tanner stage, large arterial compliance was no longer different between groups (P = .066), whereas small arterial compliance remained higher in the obese group (P < .001). Obese pubertal children have paradoxically increased small arterial compliance compared to that of normal weight children, even after adjusting for height, blood pressure, race, sex, and Tanner stage. Thus, obesity in adolescence is not associated with impairments in small arterial compliance.     

Testosterone infusion reduces nocturnal luteinizing hormone pulse frequency in pubertal boys

Administration of testosterone (T) can inhibit LH secretion in early pubertal boys. However, the GnRH pulse generator is relatively resistant to the effects of T, since T infusion beginning at 2100 h, 3 h before the usual nighttime increase in T, does not suppress the characteristic increase in LH pulse frequency or amplitude associated with the onset of sleep in early pubertal boys. To test the hypothesis that the hypothalamic-pituitary axis must be exposed to T for a longer duration to suppress the nocturnal rise in LH pulse frequency and amplitude, we infused saline or T at one third the adult male production rate (320 nmol/h), beginning at 1200 h on two consecutive weekends in each of eight early to midpubertal boys. Blood was obtained from 2000-0800 h every 10 min for LH and every 30 min for T measurements. T infusion increased the mean plasma T concentration from 6.9 +/- 1.7 to 11.8 +/- 1.4 nmol/L (P less than 0.01) between 2000-0800 h. Despite the T infusion, the nocturnal rise in mean LH concentration and LH pulse frequency persisted, suggesting that the nocturnal amplification of LH, and by inference GnRH, secretion is resistant to the negative feedback effects of T. A higher dose of T, approximating the adult male production rate (960 nmol/h), was given to eight additional boys beginning at 1200 h. The mean T concentration increased from 4.2 +/- 1.7 to 20.8 +/- 3.1 (P less than 0.001) nmol/L between 2000-0800 h. The mean plasma LH concentration was suppressed by T infusion from 5.2 +/- 0.5 to 2.9 +/- 0.4 IU/L, and LH pulse frequency decreased from 0.50 +/- 0.04 to 0.27 +/- 0.11 pulses/boy/h (P less than 0.01). There was no nocturnal amplification of LH secretion, but high amplitude LH pulses did occur during the night in six of the eight boys. The low dose T infusion had no effect on pituitary LH release by exogenous GnRH. With the high dose T infusion, however, the ability of GnRH, at 25 ng/kg but not at 250 ng/kg, to release pituitary LH was amplified. Thus, T supplementation at one third the adult male production rate does not blunt the sleep-associated nighttime rise in LH pulse frequency or LH concentration. T infusion approximating the adult male production rate suppresses the nocturnal increase in LH pulse frequency and mean LH concentration, and high amplitude, slow frequency LH pulses similar to patterns seen in adult men persist.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adrenomedullary response to caffeine in prepubertal and pubertal obese subjects.

OBJECTIVE: To investigate whether blunted adrenomedullary responsiveness to stimuli is a primary feature of human obesity in childhood and adolescence DESIGN: Comparison of plasma catecholamine response to caffeine in obese and lean subjects before and after puberty onset. SUBJECTS: Twelve lean prepubertal subjects (six males and six females), 15 prepubertal obese subjects (seven males and eight females), 12 pubertal lean subjects (six males and six females) and 24 pubertal obese subjects (12 males and 12 females) MEASUREMENTS: Plasma levels of Luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17beta-estradiol and testosterone were used to validate Tanner score. Systolic and diastolic blood pressure, pulse rate and plasma catecholamines before and after caffeine administration (4 mg/kg of ideal body weight). RESULTS: Caffeine administration significantly stimulated adrenaline release in all subjects studied. The incremental area of adrenaline response to caffeine, analysed by multiple comparison test, was lower in pubertal obese subjects with respect to other groups. CONCLUSIONS: At variance with what is observed in adulthood obesity, prepubertal obese subjects show an intact adrenomedullary response to caffeine.     

Prevalence of cam‐type deformity on hip magnetic resonance imaging in young males: A cross‐sectional study

Objective

To determine the prevalence of cam‐type deformities on hip magnetic resonance imaging (MRI) in young males.

Methods

This was a population‐based cross‐sectional study in young asymptomatic male individuals who underwent clinical examination and completed a self‐report questionnaire. A random sample of participants was invited for MRI of the hip. We graded the maximal offset at the femoral head–neck junction on radial sequences using grades from 0 to 3, where 0 = normal, 1 = possible, 2 = definite, and 3 = severe deformity. The prespecified main analyses were based on definite cam‐type deformity grades 2 or 3. We estimated the prevalence of the cam‐type deformity adjusted for the sampling process overall and according to the extent of internal rotation. Then we determined the location of the deformity on radial MRI sequences.

Results

A total of 1,080 subjects were included in the study and 244 asymptomatic males with a mean age of 19.9 years attended MRI. Sixty‐seven definite cam‐type deformities were detected. The adjusted overall prevalence was 24% (95% confidence interval [95% CI] 19–30%). The prevalence increased with decreasing internal rotation (P < 0.001 for trend). Among those with a clinically decreased internal rotation of <30°, the estimated prevalence was 48% (95% CI 37–59%). Sixty‐one of 67 cam‐type deformities were located in an anterosuperior position.

Conclusion

Cam‐type deformities can be found on MRI in every fourth young asymptomatic male individual and in every second male with decreased internal rotation. The majority of deformities are located in an anterosuperior position.     

Obesity and post‐operative complications in patients undergoing non‐bariatric surgery

As the prevalence of obesity continues to rise in society, an increasing number of patients undergoing non‐bariatric surgery will be obese. Obesity is known to increase morbidity and mortality in the general population and thus is perceived as a risk factor for adverse post‐surgical outcomes. This association is not clear‐cut, however, and there is a lack of consensus in the literature on the risk between obesity and specific complications, in particular relating to infection, wound healing, respiratory and venous thromboembolism. The paucity of studies, as well as a lack of consistency of definition of obesity, with an over‐reliance on body mass index rather than body composition analysis, may underlie this confusion. Emerging concepts position central/visceral adipose tissue as potentially key to the pathogenesis of the comorbidities associated with obesity, thus this article reviews emerging research investigating the association between visceral obesity, the metabolic syndrome and resulting post‐operative complications. It is hypothesized that the state of chronic inflammation and dysmetabolism observed in visceral obese patients negatively influences post‐operative outcomes and represents a potential target for pharmaconutrition. The need for further research investigating the influence of visceral adiposity on immune function post surgery and its impact on post‐operative morbidity and mortality is highlighted.