Sebastiano Bruno Solerte

Relationship Between Erectile Dysfunction and Silent Myocardial Ischemia in Apparently Uncomplicated Type 2 Diabetic Patients

Background—Erectile dysfunction (ED) is associated with coronary artery disease (CAD). In diabetic patients, CAD is often silent. Among diabetic patients with silent CAD, the prevalence of ED has never been evaluated. We investigated whether ED is associated with asymptomatic CAD in type 2 diabetic patients. Methods and Results—We evaluated the prevalence of ED in 133 uncomplicated diabetic men with angiographically verified silent CAD and in 127 diabetic men without myocardial ischemia at exercise ECG, 48-hour ambulatory ECG, and stress echocardiography. The groups were comparable for age and diabetes duration. Patients were screened for ED using the validated International Index of Erectile Function (IIEF-5) questionnaire. The prevalence of ED was significantly higher in patients with than in those without silent CAD (33.8% versus 4.7%; P =0.000). Multiple logistic regression analysis showed that ED, apolipoprotein(a) polymorphism, smoking, microalbuminuria, HDL, and LDL were significantly associated with silent CAD; among these risk factors, ED appeared to be the most efficient predictor of silent CAD (OR, 14.8; 95% CI, 3.8 to 56.9). Conclusions—Our study first shows a strong and independent association between ED and silent CAD in apparently uncomplicated type 2 diabetic patients. If our findings are confirmed, ED may become a potential marker to identify diabetic patients to screen for silent CAD. Moreover, the high prevalence of ED among diabetics with silent CAD suggests the need to perform an exercise ECG before starting a treatment for ED, especially in patients with additional cardiovascular risk factors.

Erectile dysfunction as a predictor of cardiovascular events and death in diabetic patients with angiographically proven asymptomatic coronary artery disease: a potential protective role for statins and 5-phosphodiesterase inhibitors.

OBJECTIVES We sought to investigate whether erectile dysfunction (ED) is a predictor of future cardiovascular events and death in diabetic patients with silent coronary artery disease (CAD) and whether there are predictors of cardiovascular events and death among CAD diabetic patients with ED. BACKGROUND Case-control studies showed that ED is associated with CAD in diabetic patients, but no prospective study is available. METHODS Type 2 diabetic men (n = 291) with silent CAD angiographically documented were recruited. Erectile dysfunction was assessed by the International Index Erectile Function-5 questionnaire. RESULTS During a follow-up period of 47.2 +/- 21.8 months (range 4 to 82 months), 49 patients experienced major adverse cardiac events (MACE). The difference in ED prevalence between patients with and those without MACE was significant (61.2% vs. 36.4%; p = 0.001). Cox regression analysis showed that ED predicted MACE (hazard ratio [HR] 2.1; 95% confidence interval [CI] 1.6 to 2.6; p < 0.001). Among patients with CAD and ED, the Kaplan-Meier method showed that the statin (Mantel log-rank test: 3.921; p = 0.048) and 5-phosphodiesterase (5-PDE) inhibitor use (Mantel log-rank test: 4.608; p = 0.032) were associated with a lower rate of MACE. Cox regression analysis showed that statin use (HR 0.66; 95% CI 0.46 to 0.97; p = 0.036) reduced MACE. Treatment with 5-PDE inhibitors did not enter the model, but its p value was very near to the significant level (HR 0.68; 95% CI 0.46 to 1.01; p = 0.056). CONCLUSIONS Our data first show that ED is a powerful predictor of cardiovascular morbidity and mortality in diabetic patients with silent CAD and that the treatment with statins and 5-PDE inhibitors might reduce the occurrence of MACE among CAD diabetic patients with ED.

Nutritional Supplements with Oral Amino Acid Mixtures Increases Whole-Body Lean Mass and Insulin Sensitivity in Elderly Subjects with Sarcopenia

Decreases in whole-body lean mass can cause sarcopenia, a disease frequently found in the elderly. This condition is frequently associated with frailty and disability in aging as well as the onset and progression of several geriatric syndromes. Sarcopenia therefore must be managed with multidimensional approaches that include physical training, nutritional support, and metabolic and anabolic treatment. The purpose of our study was to assess the effect of an orally administered special mixture of amino acids (AAs) in elderly subjects with reduced lean body mass and sarcopenia. A randomized, open-label, crossover study was conducted in 41 elderly subjects (age range: 66-84 years) with sarcopenia, assigned to 2 distinct treatments (AAs and placebo). All subjects had normal body weight (body mass index within 19-23). The AA treatment consisted of 70.6 kcal/day (1 kcal = 4.2 kJ) of 8 g of essential AA snacks, given at 10:00 am and 5:00 pm. Lean mass was measured with dual-energy x-ray absorptiometry in leg, arm, and trunk tissues. Significant increases in whole-body lean mass in all areas were seen after 6 months and more consistently after 18 months of oral nutritional supplementation with AAs. Fasting blood glucose, serum insulin, and homeostatic model assessment of insulin resistance (an index of insulin resistance) significantly decreased during AA treatment. Furthermore, a significant reduction in serum tumor necrosis factor-alpha (TNF-alpha) and a significant increase in both insulin-like growth factor-1 (IGF-1) serum concentrations and in the IGF-1/TNF-alpha ratio were also found. No significant adverse effects were observed during AA treatment. These preliminary data indicate that nutritional supplements with the oral AA mixture significantly increased whole-body lean mass in elderly subjects with sarcopenia. The improvement in the amount of whole-body lean mass could be linked to increased insulin sensitivity and anabolic conditions related to IGF-1 availability.

Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia

The simultaneous evaluation of the circadian rhythm of plasma melatonin and ACTH and of serum cortisol and DHEAS represents a clinically reliable tool to appreciate the neuroendocrine changes occurring in physiological and pathological brain aging.A selective impairment of the nocturnal melatonin secretion has been observed in elderly subjects, being significantly related either to the age or to the severity of dementia. A significant increase of serum cortisol levels during evening- and night-times was found in elderly subjects, particularly if demented, when compared to young controls. Besides, both the circadian amplitude of cortisol rhythm and the nocturnal cortisol increase were significantly reduced in relation either to age or to cognitive impairment. By comparison to vascular dementia, patients with Alzheimers disease exhibited the highest cortisol concentrations throughout the 24h. The sensitivity of the hypothalamic-pituitary-adrenal axis to the steroid feedback was significantly impaired in old subjects and particularly in the demented ones. The serum DHEAS levels were significantly lower in elderly subjects and even more in demented patients than in young controls. Consequently, a significant increase of the cortisol/DHEAS molar ratio was evident when going from young controls to healthy elderly subjects and to demented patients. In conclusion, the aging process affects many neuroendocrine functions resulting in subtle but clinically relevant consequences; the occurrence of senile dementia seems to play an additive role.

Neuroendocrine correlates of the aging brain in humans

Physiological brain aging is characterized by important biochemical and structural changes and by the unbalance among the different neurotransmitters and neuromodulators. The study of the circadian organization of neuroendocrine functions may be considered a clinically reliable tool to investigate the changes of the CNS and particularly of the limbic-hypothalamic system occurring in aged people. The circadian rhythms of plasma melatonin, ACTH and cortisol and of oral temperature were studied in 16 clinically healthy women aged 66-90 years and in 14 young controls aged 20-30. In addition, the effect of dexamethasone on the plasma cortisol circadian rhythm and the cortisol response to Synacthen pulse intravenous injection were evaluated. All subjects were studied as inpatients, with the same synchronization to the hospital life schedule. When compared with young controls, elderly subjects exhibited a reduction of the mean level and of the amplitude of the circadian rhythm of oral temperature, an increase of the mean level of ACTH and cortisol rhythms and a selective impairment of melatonin nocturnal secretion. Furthermore, elderly subjects showed a reduced sensitivity to the dexamethasone suppression test, by comparison to young controls. These changes were age-related and they may depend either on CNS modification or on alterations of the hormonal metabolic clearance.

Age-related changes of the adrenal secretory pattern: possible role in pathological brain aging

The biosynthetic dissociation of the adrenocortical secretion occurring with age may have a pathogenetic role in the pathophysiology of brain aging. We studied cortisol and DHEAS secretion in healthy old and young subjects, in senile dementia, in major depression of elderly subjects and in healthy centenarians. A clear age-related decline of DHEAS secretion was well evident in healthy centenarians, and a further decrease in DHEAS concentration was found in old depressed patients and moreover in the demented ones, by comparison with age-matched controls. The circadian profile of serum cortisol was clearly flattened in old subjects, due to the selective increase in the cortisol nocturnal levels, particularly evident in demented subjects; on the other hand, the morning serum cortisol levels were not significantly different among centenarians, young and old controls. The molar ratio between cortisol and DHEAS showed a significant age-related increase; the occurrence of senile dementia and of major depression played an additive role, by comparison to physiological aging. The qualitative and quantitative modifications of the adrenocortical secretion occurring with aging seem mainly dependent on age itself, but the occurrence of pathological conditions may amplify these changes. Since cortisol and DHEAS play opposite effects on the central nervous system, the evaluation of the ratio between cortisol and DHEAS seems to be a good marker of the neuroendocrine features in old subjects.

Safety of Type 2 Diabetes Treatment With Repaglinide Compared With Glibenclamide in Elderly People: A randomized, open-label, two-period, cross-over trial

The incidence of type 2 diabetes increases with age (1), and elderly people with this disease may be particularly susceptible to hypoglycemia due to long-acting oral antidiabetic drugs (OADs). The American Geriatric Society clinical guidelines on type 2 diabetes treatment in elderly people report that short-acting hypoglycemic agents are preferable to longer-acting agents (chlorpropramide), which are associated with increased risk of hypoglycemia (2). Repaglinide is an insulin secretagogue with a rapid onset and relatively short duration of action (3,4). Several studies have shown repaglinide to be a safe and effective treatment for type 2 diabetes (5–9). However, few data are available on its use in elderly patients and, in particular, on the incidence of hypoglycemic events. The present study assessed the safety of repaglinide versus glibenclamide in this population, in terms of hypoglycemia and adverse events. This was a 24-week, randomized, open-label, two-period, cross-over comparison between mealtime repaglinide and twice-daily glibenclamide. Patients ( n = 90) were aged ≥65 years and had been previously treated with diet or OADs (mean age 74.6 years, HbA1c [A1C] 7.9%). A subgroup of 37 patients aged ≥75 years was evaluated separately. After screening, previous OAD treatment was discontinued and patients were randomized to first receive either repaglinide (Novonorm; …

Overproduction of IFN-γ and TNF-α from Natural Killer (NK) Cells Is Associated with Abnormal NK Reactivity and Cognitive Derangement in Alzheimer's Disease

Abstract: Alterations of natural killer (NK) function can be involved in the neuroimmune mechanism of neurodegeneration in dementia of the Alzheimers type (DAT). NK cell cytotoxicity (NKCC) and the generation and release of IFN‐γ and TNF‐α (spontaneous and modulated by IL‐2) from pure NK cells (CD 16+, CD 56+, CD 3−) were studied together with circulating IFN‐γ and TNF‐α levels and cognitive function in 22 old patients with DAT and 15 healthy old subjects. Higher (p < 0.001) IL‐2 modulated NKCC (with IL‐2 50 U/mL and 100 U/mL) was demonstrated in DAT patients (+35% and +99% from baseline) than in healthy subjects (+6% and +76% from baseline). Increased spontaneous and IL‐2‐induced release of IFN‐γ and TNF‐α from NK cells were found in DAT patients compared to healthy subjects (p < 0.001), whereas no difference of serum IFN‐γ and TNF‐α was demonstrated between DAT and control groups. Significant negative correlations among the spontaneous release of IFN‐γ and TNF‐α from NK and the decrease of the score of cognitive function (MMSE) were found in patients with DAT. In conclusion, alterations of NKCC control and NK‐derived cytokine release in DAT could be involved in the neuroinflammatory mechanism related to the progression of neurodegeneration and dementia.

Improvement of Blood Glucose Control and Insulin Sensitivity During a Long-Term (60 Weeks) Randomized Study with Amino Acid Dietary Supplements in Elderly Subjects with Type 2 Diabetes Mellitus

A decrease in lean muscular mass causes sarcopenia, a disease frequently found in the elderly population. The reduction of muscle mass may be responsible for reduced insulin sensitivity and decreased glucose uptake, thus increasing the risk for hyperglycemia and insulin-resistance syndrome in elderly subjects with type 2 diabetes mellitus. We therefore wanted to determine the effect of a special mixture of oral amino acids (AAs) on elderly subjects with type 2 diabetes. A randomized, open-label, crossover study was conducted in 34 subjects with diabetes (age range, 65-85 years) assigned to 2 distinct treatments (AAs and placebo). In spite of treatment with oral hypoglycemic drugs or insulin, all subjects were in poor metabolic control (glycated hemoglobin [HbA(1c)] >7%). The subjects studied had normal body weight (ie, body mass index within 19-23). AAs consisted of 70.6 kcal/day (1 kcal = 4.2 kJ) of 8 g of AA snacks, given at 10.00 am and 5.00 pm. Fasting and postprandial (1 hour and 2 hours) blood glucose, serum insulin, and homeostatic model assessment of insulin resistance (an index of insulin resistance) significantly decreased during AA treatment. Furthermore, a significant reduction of HbA(1c) levels was found throughout the study. No significant adverse effects were observed during the active treatment. We suggest that nutritional supplementation with a special mixture of oral AAs is safe and significantly improves metabolic control and insulin sensitivity in poorly controlled elderly subjects with type 2 diabetes. This effect was consistent during the long-term observation period of 60 weeks and was also present after the crossover from AAs to placebo.

Body composition and pulmonary function in the elderly: a 7-year longitudinal study.

Objective:To evaluate over a 7-year follow-up period the relationships between changes in body composition, fat distribution and pulmonary function in a sample of elderly men and women.Design:Longitudinal clinical study.Subjects:A total of 47 women and 30 men aged 71.6±2.3 and 71.7±2.2 years, respectively, at baseline with body mass index (BMI) values of 24.96±3.28 and 27.04±3.35 kg m−2 were followed for 7 years.Measurements:Body weight, waist circumference, sagittal abdominal diameter (SAD), fat-free mass (FFM) and fat mass as measured by dual energy X-ray absorptiometry (DXA) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) by spirometry were evaluated at baseline and after a 7-year mean follow-up.Results:In women as in men there were no significant changes in weight, SAD and BMI. A significant decrease in height and FFM was observed in both women and men. Height-adjusted FEV1 and FVC decreased significantly in women and men over the 7-year follow-up. Changes in SAD were the most powerful predictors of 7-year follow-up of FEV1 and FVC after taking into account, respectively, baseline FEV1 and FVC. Linear regression analysis, performed by using 7-year follow-up lung function variables as dependent variables and changes in body composition variables as independent variables, showed that 1 cm SAD increase predicted a decrease in FEV1 and FVC of 31 and 46 ml, respectively, and 1 kg FFM decrease predicted a decrease in FVC of 38 ml. After subdividing our study population into four categories of change in FFM and SAD, patients with decreased FFM and increased SAD showed the highest probability of having a worsening in FEV1 and FVC.Conclusion:Increase in abdominal fat and FFM decline are significant predictors of lung function decline in the elderly. Old subjects developing both abdominal fat gain and FFM loss show the highest probability of developing worsening in lung function.