Felice Strollo

Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM

OBJECTIVE ACE inhibitors and calcium antagonists may favorably affect serum lipids and glucose metabolism. The primary aim of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) was to compare the effects of fosinopril and amlodipine on serum lipids and diabetes control in NIDDM patients with hypertension. Prospectively defined cardiovascular events were assessed as secondary outcomes. RESEARCH DESIGN AND METHODS Inclusion criteria included a diagnosis of NIDDM and hypertension (systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg). Exclusion criteria included a history of coronary heart disease or stroke, serum creatinine >1.5 mg/dl, albuminuria >40 μg/min, and use of lipid-lowering drugs, aspirin, or antihypertensive agents other than beta-blockers or diuretics. A total of 380 hypertensive diabetics were randomly assigned to open-label fosinopril (20 mg/day) or amlodipine (10 mg/day) and followed for up to 3.5 years. If blood pressure was not controlled, the other study drug was added. RESULTS Both treatments were effective in lowering blood pressure. At the end of followup, between the two groups there was no significant difference in total serum cholesterol, HDL cholesterol, HbA1c, fasting serum glucose, or plasma insulin. The patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infarction, stroke, or hospitalized angina than those receiving amlodipine (14/189 vs. 27/191; hazards ratio = 0.49, 95% CI = 0.26–0.95). CONCLUSIONS Fosinopril and amlodipine had similar effects on biochemical measures, but the patients randomized to fosinopril had a significantly lower risk of major vascular events, compared with the patients randomized to amlodipine.

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.

Leptin levels in diabetic and nondiabetic subjects

The role of leptin in human pathophysiology elicits considerable interest in view of its potential role as a treatment tool for obesity and other insulin resistant states, like type 2 diabetes mellitus (T2DM). Leptin has been extensively studied in obese humans, and much less so in other pathologic conditions. Leptin level has been reported to correlate with percent body fat mass (%FM), fasting serum insulin (FPI), insulin sensitivity and blood pressure. The aim of this study was to compare the leptin concentration, and its relationship with some anthropometric and biochemical parameters related to insulin resistance in 140 moderately obese type 2 diabetics (T2DM) and 160 age and weight matched non-diabetic controls in order to get a better insight into the possible role of leptin in the metabolic abnormalities of diabetes. The leptin levels were lower in the diabetic population only when both sexes were combined (p<0.05) and were higher in the females of both groups. Among the nondiabetics, the leptin levels appeared to be related to BMI, %FM, HDL and FPI, while this was not the case in the diabetics. After correction for BMI, leptin appeared to be correlated with the FPI levels only in the non-diabetic females. When plasma leptin was included in a multiple linear regression model with plasma leptin as a dependent variable, BMI, W:Hr and FPI levels were significantly related to leptin in the non diabetic population, while no relationship reached the level of statistical significance among the diabetics, with the exception of the borderline value for the FPI (p=.052). In conclusion, leptin levels were independent of any of the parameters examined in our diabetic population, possibly due to the progressive loss of the normal mechanisms of leptin regulation with advancing disease. Conclusive data can only be obtained from the longitudinal study of a cohort of newly diagnosed diabetic subjects.

Growth hormone insufficiency in a girl with the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy.

Autoimmune polyendocrinopathy-can-didiasis-ectodermal dystrophy (APECED) is an inherited disease which may comprise many endocrine and non-endocrine components. GH insufficiency has not been recognised as a classical manifestation of this syndrome. We describe the case of a girl with APECED, who presented with four endocrine (hypoparathyroidism, Addison’s disease, hypothyroidism, gonadal failure) and three non-endocrine components (candidiasis, ectoder-mal dystrophy and lichen ruber planus). In addition, growth failure was documented beginning at approximately 8 years; bone age was delayed and stimulated GH peaks after clonidine and arginine were 2.2 and 9.2 μg/l, respectively. A partial empty sella was found on a computed tomography scan of the hypothalamic-pituitary region. At 10.5 years rhGH therapy was started and height gain of 26 cm was observed after 2.7 years of treatment. Puberty started at 11.2 years and menarche occurred at 12.7 years. At 13.25 years rhGH therapy was discontinued owing to frequent hypocal-cemic crises; serum IGF-1 levels were persistently low in the following years (between 160 and 180 μg/l, normal range for age 250–600 μg/l). The patient attained a final height of 160.8 cm, which was appropriate for her target height. The presence of lichen ruber planus and GH insufficiency probably secondary to empty sella are two unusual findings in patients with APECED.

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

Abstract 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.

The impact of long-term exposure to space environment on adult mammalian organisms: a study on mouse thyroid and testis.

Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis. In thyroids, volumetric ratios between thyrocytes and colloid were measured. cAMP production in 10−7M and 10−8M thyrotropin-treated samples was studied. Thyrotropin receptor and caveolin-1 were quantitized by immunoblotting and localized by immunofluorescence. In space-exposed animals, both basal and thyrotropin-stimulated cAMP production were always higher. Also, the structure of thyroid follicles appeared more organized, while thyrotropin receptor and caveolin-1 were overexpressed. Unlike the control samples, in the space samples thyrotropin receptor and caveolin-1 were both observed at the intracellular junctions, suggesting their interaction in specific cell membrane microdomains. In testes, immunofluorescent reaction for 3β- steroid dehydrogenase was performed and the relative expressions of hormone receptors and interleukin-1β were quantified by RT-PCR. Epididymal sperm number was counted. In space-exposed animals, the presence of 3β and 17β steroid dehydrogenase was reduced. Also, the expression of androgen and follicle stimulating hormone receptors increased while lutenizing hormone receptor levels were not affected. The interleukin 1 β expression was upregulated. The tubular architecture was altered and the sperm cell number was significantly reduced in spaceflight mouse epididymis (approx. −90% vs. laboratory and ground controls), indicating that the space environment may lead to degenerative changes in seminiferous tubules. Space-induced changes of structure and function of thyroid and testis/epididymis could be responsible for variations of hormone levels in human during space missions. More research, hopefully a reflight of MDS, would be needed to establish whether the space environment acts directly on the peripheral glands or induces changes in the hypotalamus-pituitary-glandular axis.

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.

Effects of Aerobic Exercise Based upon Heart Rate at Aerobic Threshold in Obese Elderly Subjects with Type 2 Diabetes

In obese diabetic subjects, a correct life style, including diet and physical activity, is part of a correct intervention protocol. Thus, the aim of this study was to evaluate the effects of aerobic training intervention, based on heart rate at aerobic gas exchange threshold (AerTge), on clinical and physiological parameters in obese elderly subjects with type 2 diabetes (OT2DM). Thirty OT2DM subjects were randomly assigned to an intervention (IG) or control group (CG). The IG performed a supervised aerobic exercise training based on heart rate at AerTge whereas CG maintained their usual lifestyle. Anthropometric measures, blood analysis, peak oxygen consumption (V˙O2peak), metabolic equivalent (METpeak), work rate (WRpeak), and WRAerTge were assessed at baseline and after intervention. After training, patients enrolled in the IG had significantly higher (P < 0.001) V˙O2peak, METpeak, WRpeak, and WRAerTge and significantly lower (P < 0.005) weight, BMI, %FM, and waist circumference than before intervention. Both IG and CG subjects had lower glycated haemoglobin levels after intervention period. No significant differences were found for all the other parameters between pre- and posttraining and between groups. Aerobic exercise prescription based upon HR at AerTge could be a valuable physical intervention tool to improve the fitness level and metabolic equilibrium in OT2DM patients.

Unexplained Hypoglycaemia and Large Glycaemic Variability: Skin Lipohypertrophy as a Predictive Sign

1Endocrinology and Metabolism, Elle-di, Rome, Italy 2Department of Internal Medicine, Second University of Naples, Naples, Italy 3Diabetes Unit, ASL Napoli 1, Naples, Italy 4Department of Clinical Medicine and Surgery, University “Federico II” of Naples, Naples, Italy 5Diabetes Unit AID Portici, Naples, Italy 6Diabetes and Metabolism Unit, ASL Salerno 1, Salerno, Italy 7Diabetes and Metabolism AID Via Mariano D’Ayala 1, Naples, Italy 8Department of Cardiovascular and Metabolic Diseases at IRCCS MultiMedica in Milan, Italy Research