Low-intermediate dose testosterone replacement therapy by different pharmaceutical preparations improves frailty score in elderly hypogonadal hyperglycaemic patients.

An open-label follow-up study of low-to-intermediate dose testosterone replacement therapy (TRT) was conducted in 64 overweight patients (aged 65-75 years) with late onset hypogonadism (LOH) and increased fasting plasma glucose (FPG). Patients were subdivided into four treatment groups: oral testosterone (T) (T undecanoate, 80 mg/d), transmucosal T (60 mg/d), transdermal T (30 mg/d) or no treatment (control), and evaluated at 0 and 6 months. FPG, hemoglobin (Hb), prostate-specific antigen (PSA) and total T were measured and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body mass index (BMI), waist circumference, fitness level (6-min walking test), Aging Males' Symptoms (AMS) scale, handgrip strength and energy expenditure with physical activity (Minnesota questionnaire for Leisure Time Physical Activity (LTPA)) were evaluated and a "frailty score" (based on: grip strength, gait speed and LTPA) was calculated. T levels increased in all treatment groups; the oral T group had values still in the hypogonadal range (5.9 ± 1.1 nmol/L). PSA and Hb concentrations did not change in any group. BMI, waist circumference, FPG and HOMA-IR improved in all T-treated groups after 6 months, with a greater effect seen with transmucosal and transdermal T compared with oral T. This study indicates that low-to-intermediate dose TRT may be safely utilized in LOH patients to ameliorate somatic and psychological frailty symptoms in association with improved anthropometric and glycometabolic parameters in aging, overweight men with LOH and impaired fasting glucose.

Metabolic syndrome, adipokines and hormonal factors in pharmacologically untreated adult elderly subjects from the Brisighella Heart Study historical cohort.

OBJECTIVE: Our aim was to evaluate the relation of the sex hormone pattern and the serum level of the main adipokines with metabolic syndrome (MS) and its components in a cohort of pharmacologically untreated adult elderly subjects. METHODS: From the historical cohort of the Brisighella Heart Study we selected 199 adult healthy subjects aged 62.5 ± 12.4 years. Men and women included in the age class subgroups were matched for BMI, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. In these subjects we measured leptin, adiponectin, ghrelin, testosterone, estrone, and deydroepiandrosterone sulphate. RESULTS: Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had a lower leptin level and leptin/adiponectin ratio than women with MS, but had significantly higher adiponectin, estrone, and deydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated with MS diagnosis (OR 3.36, 95% CI 1.40-8.08), while in women adiponectin alone appears to be a protective factor (OR 0.87, 95% CI 0.79-0.95). CONCLUSION: In a sample of pharmacologically untreated adult elderly subjects, leptin/adiponectin ratio seems to be the factor that is more strongly associated with MS (especially in men) and its components, though this is true to a different degree in men and women.

Adipokines and sexual hormones associated with the components of the metabolic syndrome in pharmacologically untreated subjects: data from the brisighella heart study.

We evaluated the association of the sex hormone pattern and the serum level of the main adipokines to metabolic syndrome (MS) and its components in 199 pharmacologically untreated subjects. Men and women included in the age-class subgroups were matched for body mass index, waist circumference, blood pressure, heart rate, fasting plasma glucose, and plasma lipids. Men without MS had significantly lower leptin/adiponectin ratio than men with MS. Women without MS had lower leptin and leptin/adiponectin ratio than women with MS but had significantly higher adiponectin, estrone, and dehydroepiandrosterone levels. In men, the leptin/adiponectin ratio is the main factor associated to MS diagnosis (OR: 3.36, 95% CI 1.40-8.08), while in women adiponectin alone appears to be a protective factor (OR: 0.87, 95% CI 0.79-0.95). In conclusion, in a sample of pharmacologically untreated subjects, leptin/adiponectin ratio seems to be the factor more strongly associated to MS and its components.

Feeding behavior in mammals including humans.

The complex control of food intake and energy metabolism in mammals relies on the ability of the brain to integrate multiple signals indicating the nutritional state and the energy level of the organism and to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Central regulation of feeding is organized as a long-loop mechanism involving humoral signals and afferent neuronal pathways to the brain, processing in hypothalamic neuronal circuits, and descending commands using vagal and spinal neurons. Sensor mechanisms or receptors sensitive to glucose and fatty acid metabolism, neuropeptide and cannabinoid receptors, as well as neurotransmitters and neuromodulators synthesized and secreted within the brain itself are all signals integrated in the hypothalamus, which therefore functions as an integrator of signals from central and peripheral structures. Homeostatic feedback mechanisms involving afferent neuroendocrine inputs from peripheral organs, like adipose tissue, gut, stomach, endocrine pancreas, adrenal, muscle, and liver, to hypothalamic sites thus contribute to the maintenance of normal feeding behavior and energy balance. In addition to transcriptional events, peripheral hormones may also alter firing and/or connection (synaptology) of hypothalamic neuronal networks in order to modulate food intake. Moreover, intracellular energy sensing and subsequent biochemical adaptations, including an increase in AMP-activated protein kinase activity, occur in hypothalamic neurons. Understanding the regulation of appetite is clearly a major research effort but also seems promising for the development of novel therapeutic strategies for obesity.