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Purpose: To estimate the contribution of cryopreservation to the cumulative live birth rate (CLBR) after law modification in Italy in the era of vitrification and freeze-all. Methods: The Italian National Registry performed a cycle-based data collection. Nine Italian IVF clinics were involved incorporating a total of 10,260 fresh cycles performed between January 2015 and April 2016 resulting in 9273 oocyte retrievals and 3266 subsequent warming cycles from the same oocyte retrievals performed up to December 2016. Mean female age was 37 ± 4.3 years. Primary outcome measure was CLBR per oocyte retrieval. Confounding factors were tested in multivariate regression analysis, and the relative impact of cryopreservation to the CLBR in different patient categories was calculated. Results: CLBR per oocyte retrieval was 32.6%, 26.5%, 18.7%, 13.0%, and 5.5% for women younger than 36, aged 36–39, 40–41, and older than 41 years, respectively. The total relative contribution of oocyte/embryo cryopreservation was 40.6% (95% CI 38.41–42.75). An association between maternal age, number of oocytes retrieved, fertilization rate, cryopreservation, and cumulative live birth was shown. When adjusted for confounders, a 2.3-fold increase was observed in the chance of live birth when cryopreservation was performed (OR 2.3; 95% CI 1.99–2.56). In high responder patients (> 15 oocytes retrieved) where freeze-all was applied in 67.6% of cycles to avoid the risk of hyper stimulation syndrome, the relative contribution of vitrification to the CLBR was 80.6%. Conclusions: Cryopreservation is essential in IVF and should always be available to patients to optimize success rates. Multicentric, cycle-based data analyses are crucial to provide infertile couples, clinicians, and regulatory bodies with accurate information on IVF effectiveness including fresh and cryopreserved cycles.

Skeletal remodelling is a continuous process during life and is still active also in extreme senescence. In the elderly, bone resorption often prevails over bone formation, causing bone loss and fragility. Elderly subjects are exposed to the risk of fractures, and loss of self-sufficiency, if considering that the proximal femur is the most frequently involved site. Bone remodelling can maintain circulating calcium within physiological ranges, at the expense of a substantial loss of this ion from the skeleton, particularly during senescence. Calcium metabolism is regulated at cellular/molecular level by a network of cytokines, growth factors, systemic hormones that act on bone in paracrine/autocrine/systemic fashion. Among the molecules involved in bone metabolism, parathyroid hormone (PTH) and vitamin D present some peculiar aspects during senescence. The osteometabolic features in a consistent group of centenarians have been evaluated. It results that a severe hypovitaminosis D was present in 99 out of 104 centenarians (25-OH vitamin D below 5 nmol/L), and that it plays an important role as a factor inducing a vicious circle involving hypocalcemia, secondary hyperparathyroidism, together with biochemical features indicating a consistent bone loss. Serum C-terminal cross-linking telopeptide, a specific marker of bone resorption was elevated in 92% of these subjects. Moreover, it has been found that several femoral fractures had occurred after 90 years of age. These data offer a rational for the possible prevention of elevated bone turnover, bone loss and consequently the reduction of osteoporotic fractures and fractures-induced disability, in the oldest olds, through the simple supplementation with calcium and vitamin D.

The Italian multicentric study on centenarians (IMSC) was aimed at assessing the level of preservation of the sense of taste, and at estimating to what extent the recognition of various gustative stimuli can give satisfaction and information regarding the surrounding environment for the centenarians. Taste sensitivity has been qualitatively established in a group of 126 Italian centenarians (mean age 101.9+/-1.4 years) and compared to that of a group of 100 elderly subjects (mean age 70.5+/-5.0 years). All the individuals included in the study groups had a mini mental state examination (MMSE) score larger than 19. The results revealed that taste sensitivity is significantly reduced in the centenarians; as a matter of fact, the elderly control subjects are able to perceive taste stimuli in 84.25+/-3.40% of the testing, while the centenarians were successful only in 74.23+/-6.19% of the experiments (P

The effect of the calcium antagonist nicardipine on insulin secretion and glucose homoeostasis was investigated in elderly hypertensives with and without diabetes mellitus; 15 patients with essential hypertension for at least 10 years and normal glucose tolerance according to standard criteria (Group I) and 15 elderly hypertensive patients affected by Type 2 diabetes mellitus and on treatment with diet or oral drugs (Group 2). In the basal state, all patients were submitted to an oral glucose tolerance test (OGTT, 75 g) and an iv arginine test (30 g), on two different days and in random order. The same tests were repeated after one month of treatment with nicardipine 60 mg/day, in three spaced doses, the last being given 1 h before the post-treatment test. Nicardipine did not change overall glucose homoestasis, as assessed by haemoglobin Alc and fructosamine, nor did it significantly affect the plasma insulin response either to glucose or arginine in Groups 1 and 2. Only the glucagon response to arginine was significantly reduced in diabetic hypertensives. Small, non-significant variations in the metabolic and hormonal parameters were seen in additional two groups of patients (Groups 3 and 4), matched with Groups 1 and 2 for age, sex and diseases, who took capsules containing placebo. Thus, nicardipine did not produce any significant overall alteration in glucose homoestasis when given to elderly diabetic or nondiabetic hypertensive subjects.

The systemic and pulmonary blood flows and the ratio of pulmonary to systemic flow were noninvasively evaluated by pulsed Doppler echocardiography in 25 children with left-to-right shunts. Fourteen patients had atrial septal defect and 11 had ventricular septal defect. In patients with atrial septal defect, right ventricular stroke volume was obtained from the recordings of mean velocity flow and the diameter at the level of pulmonary valve in short-axis view. The left ventricular stroke volume was evaluated from the suprasternal approach by positioning the sample volume within the ascending aorta just above the valvar leaflets. In children with ventricular septal defect, the pulmonary blood flow was determined at the level of the mitral orifice, whereas the systemic blood flow was estimated from the ascending aorta. The systemic and pulmonary blood flows and their ratio determined by pulsed Doppler echocardiography in the 25 patients examined, were compared using simple linear regression analysis with the results obtained by cardiac catheterization. The ratio of pulmonary-to-systemic flow showed an excellent correlation in patients with atrial septal defect (r = 0.82) and in those with ventricular septal defect (r = 0.79). Our study validates the accuracy of cross-sectional Doppler echocardiography, especially for minimizing some possibility of errors in the presence of left-to-right shunts by employing new approaches.

Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.

Starting from young to very old subjects, aging is associated with a progressive remodeling. Such an age-dependent remodeling process mainly affects anthropometrics, endocrine and thus, also metabolic factors. Interestingly, it occurs in some individuals successfully, while in others unsuccessfully. Centenarians in good health conditions are a very selected group of subjects representing an exceptional condition. Why the centenarians reach the extreme human life span is still unknown. Thus, in this article we will review the best known causes of age-related insulin resistance, outline the main metabolic differences between aged subjects and healthy centenarians, underline the clinical relevance of insulin resistance in the elderly and finally, we will try to propose a unifying hypothesis for explaining the development of insulin resistance with aging.

The prevalence of varicose veins (VV) in the elderly population of the Campania Region, in Southern Italy, was estimated. A random sample of the people aged more than 65 years was drawn by means of a stratified multistage sampling design warranting that observed percentages were direct estimates of population percentages. The investigation covered 1319 subjects, 560 (42.5%) men and 759 (57.5%) women, their ages ranging from 66 to 96 years with an average value of 74.2 years, who were interviewed and visited by trained physicians. W were defined as any reticular or truncal visible vari cosities of the lower limbs, and investigated symptoms were heaviness, pain, nightly cramps, edema, eczema, hyperpigmentation, and ulceration. Some variables were studied as risk factors: age, sex, lifetime occupation, smoking, alcohol, hypertension, diabetes, and obesity; previous treatment and use of elastic stockings were also studied. Statistical associations were evaluated by Chi-square test, a two-tailed P value of 0.05 being assumed as significance level. In total, 391 (29.6%) subjects were reported to be affected by W, but the clinical examination was positive in only 362 (27.4%) with a good corre- spondence between answers and clinical findings. Prevalence was greatly affected by sex, the percentage being two times higher in women (35.2%) than in men (17%). W developed after a pregnancy in 40.5% of women, but a high percentage of women (38.2%) also reported menopause as a time starting point. No significant association between reported risk factors and W was found among men, whereas obesity was strongly related to W in women. One or more symptoms were reported in 92.1% of persons affected by W, but no previous therapy was reported by 58.9% of subjects. Only 16.9% of patients used elastic stockings with a significant difference between men (7.4%) and women (20.2%).

OBJECTIVES: To evaluate the possible relationship between angiotensin-converting enzyme (ACE) insertion-deletion (ID) genotype and insulin resistance in a population of healthy older Italian subjects. DESIGN: Prospective recruitment of a convenience sample. SETTING: Outpatient clinic. PARTICIPANTS: One hundred twenty-five subjects age 62 to 105 in good health and not taking any drug known to interfere with glucose metabolism. MEASUREMENTS: Anthropometric measurements; fasting plasma glucose (FPG), and fasting plasma insulin (FPI) concentrations; oral glucose tolerance test; homeostatic method assessment (HOMA) to estimate degree of insulin resistance; and ACE genotype by polymerase chain reaction. RESULTS: In the sample population, the relative frequencies of the ACE genotypes deletion-deletion (DD) (0.424), ID (0.400), and insertion-insertion (II) (0.176) were not significantly different from values predicted by Hardy-Weinberg equilibrium. The genotype distribution was similar in men and women. Subjects carrying the II genotype had a higher FPG (P

Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality. Hemodynamic factors, such as 24-h blood pressure (BP) values, are responsible for left ventricular hypertrophy in hypertensives. On the other hand, some metabolic factors have also been suggested to affect LV mass and geometry. In particular, plasma leptin concentrations have been found associated to LV myocardial growth. Because chronic leptin infusion stimulates sympathetic nervous system activity and increases BP levels, the role of 24-h BP values on leptin-related changes in myocardial wall geometry cannot be ruled out. Thus, the aim of our study was to evaluate whether the relationship between plasma leptin levels and LV wall thickness is mediated by 24-h BP values in hypertensive male patients. Thirty-six newly diagnosed hypertensive patients underwent Doppler echocardiographic examination, 24-h ambulatory BP recording, and metabolic (euglycemic hyperinsulinemic glucose clamp and fasting plasma leptin levels) measurements. Left ventricular mass correlated positively only with ambulatory diastolic BP (DBP) values, whereas the indices of myocardial wall growth such as interventricular septum thickness and sum of wall thickness (ie, septal + posterior wall thickness) correlated either with 24 h, daytime, or nighttime DBP, as well as with fasting plasma glucose, fasting plasma leptin, and insulin action after adjustment for age, body mass index (BMI), and waist/hip ratio (WHR). In contrast, plasma leptin concentration did not correlate with clinical and ambulatory BP values. A multiple linear regression analysis allowed to investigate the independent role of main anthropometric and cardiovascular covariates on the sum of wall thickness variability. A model that includes age, BMI, WHR, fasting plasma leptin concentration, plasma Na+ concentration, insulin action, and nighttime DBP explained 68% of the sum of wall thickness variability. In such a model, plasma leptin concentration (P < .001), insulin action (P < .029), and nighttime DBP (P < .002) were significantly and independently associated with myocardial wall thickness. In conclusion, our study demonstrates that in hypertensive men fasting plasma leptin levels are determinant of myocardial wall thickness independently of 24-h BP values.

One hundred and ninety-five aged (mean age: 67+/-4.8 years), non-insulin dependent diabetic patients underwent a randomised single-blind study for investigating the effect of statin administration on insulin resistance and respiratory quotient. After 4 weeks run-in period, all patients were randomised in three groups: placebo (n=67), simvastatin (10 mg/day) (n=61) and atorvastatin (5 mg/day) (n=67). Each treatment period lasted 8 weeks. At the beginning, after the run-in and at the end of the study, insulin resistance was assessed by homeostasis model assessment (HOMA) index, while respiratory quotient (Rq) was evaluated by indirect calorimetry. Statins versus placebo significantly lowered plasma total, LDL-, HDL-cholesterol and triglyceride concentrations and improved insulin resistance and Rq and metabolic control. Atorvastatin had a greater effect than simvastatin on plasma triglyceride concentration (-26.3+/-3.1 vs. -19.7+/-2.8%, P

Vascular disease accounts for the majority of the clinical complications in diabetes mellitus. As an exaggerated oxidative stress degree has been postulated as the link between diabetes mellitus and endothelial function, a possible positive effect of plasma vitamin E (Vit.E) administration on brachial reactivity could be postulated. Our study aims at investigating the possible effect of chronic Vit.E administration on brachial reactivity, oxidative stress indexes, and intracellular magnesium and calcium content in type II diabetic patients free of diabetic complications. Forty adult, type II diabetic patients were enrolled in the study, which was deigned as a double blind, randomized vs. placebo trial. At baseline all patients underwent the following tests: 1) anthropometric and metabolic examinations, 2) evaluation of oxidative stress indexes, 3) intracellular magnesium and calcium measurements, and 4) determination of arterial compliance and distensibility. Then, all patients were randomly assigned to Vit.E treatment at a dose of 600 mg/day (Evion Forte; n = 20) or placebo (n = 20) over 8 weeks. At the end of this treatment period, a complete reevaluation of the patients was made. Vit.E treatment was associated with a significant improvement in the percent change in brachial artery diameter (P

Previous studies have demonstrated that insulin resistance is a common feature of congestive heart failure (CHF), but the clinical significance of such insulin resistance is still debated. We tested the hypothesis that insulin-mediated glucose uptake (IMGU) is a prognostic factor in CHF in aged patients. For this purpose 174 aged patients with CHF participated in a cross-sectional and a longitudinal study of 24 months' duration. In this latter study survival analysis was calculated comparing subjects at the first and second tertile of IMGU with those at third tertile. All subjects underwent anthropometric (body mass index, waist/hip ratio), cardiovascular (arterial blood pressure, 24-hour Holter monitoring, peak VO2, left ventricular ejection fraction, echocardiography), and metabolic (determination of fasting plasma glucose, insulin, catecholamine, free fatty acids, tumor necrosis factor-alpha concentrations, and assessment of IMGU by euglycemic hyperinsulinemic glucose clamp) investigations. In the cross-sectional study, IMGU correlated with age (r = -0.33, p

Previous studies have shown that an elevated basal metabolic rate (BMR) is present in elderly malnourished cancer patients. A possible dysfunction of the autonomic nervous system needs to be demonstrated. In aged weight-losing cancer patients (n = 40), aged non-weight-losing cancer patients (n = 30), and aged weight-losing noncancer patients (n = 18), the baseline BMR and heart rate variability were studied. Aged weight-losing cancer patients (n = 40) underwent bioimpedance analysis, ambulatory electrocardiographic monitoring with analysis of heart rate variability, and determination of the BMR. Then, the patients received infusion of Intralipid (Pharmacia, Uppsala, Sweden) without and with propranolol (6 days of 40 mg twice daily) administration. At baseline, a simple correlation between the BMR and the low-frequency component (LF) (r = .42, P.006) and LF to high-frequency (HF) ratio (r = .51, P.001) was found. After propranolol administration, the percent decline in the BMR was significantly correlated with the percent decline in the LF (r = .39, P.01) and LF/HF ratio (r = .53, P.001). The percent decline in the BMR was not correlated with the HF (r = .13, P.34) or the plasma noradrenaline concentration (r = .21, P.20) at any time. With regard to the BMR and substrate oxidation, 6-day propranolol administration plus Intralipid infusion produced the strongest decline in the BMR. This study demonstrates that autonomic nervous system dysfunction occurs and is responsible for the elevated BMR in elderly cancer patients, propranolol administration rectifies the autonomic dysfunction, and Intralipid infusion combined with propranolol administration is useful for enhancing the daily caloric intake without a strong increase in energy expenditure.

OBJECTIVE: Recent studies have demonstrated that centenarians have a preserved glucose tolerance and insulin action and a more favorable body composition and fat distribution than aged subjects. The strong relationship among glucose tolerance, insulin action, plasma lipid concentration, and lipoprotein metabolism would lead to the hypothesis that healthy centenarians may also have a less atherogenic profile than aged subjects less than 100 years old. DESIGN: Investigation of the relationship between insulin action and lipid metabolism in healthy centenarians. PARTICIPANTS: Fifty-six subjects were categorized into three groups: Adults (≤ 50 years old; n = 20); Aged (≥ 75 years old; n = 22); Centenarians (≥100 years old; n = 14). The latter represented a select group of individuals free of major age-related diseases. MEASUREMENTS: Anthropometric measurements were made in all subjects, fasting blood samples were drawn for metabolite determinations, and an euglycemic glucose clamp was performed. RESULTS: Compared with aged subjects, healthy centenarians appeared to have a less atherogenic plasma lipid profile. Fasting plasma LDL cholesterol (2.4 ± 0.6 vs 3.7 ± .6 mmol/L P < .010) was significantly higher in aged subjects than in centenarians, whereas fasting plasma HDL cholesterol (1.0 ± 0.4 vs 1.7 ± .4 mmol/L P < .005) had an opposite trend. In centenarians, insulin-mediated glucose uptake was greater (34.6 ± 0.5 vs 23.3 ± .05 μmol/Kg FFM × min P < .010) than in aged subjects and correlated with fasting plasma triglycerides, FFA, LDL, and HDL cholesterol, Apo B, and Apo A1 concentrations. Finally, insulin infusion suppressed plasma FFA concentration in similar ways in adults and centenarians. CONCLUSION: Our study demonstrates that centenarians have a less atherogenic plasma lipid and lipoprotein profile than aged subjects J Am Geriatr Soc 45:1504–1509, 1997.

Background: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines. Patients and methods: All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients) were followed up for a median of 7 years. Results: Compared with untreated patients, a significant 30% reduction in breast cancer risk was observed on lowdose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval (CI) 0.51–0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34–0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54–1.17). Treated patients with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast events than untreated ones (HR = 0.61; 95% CI 0.40–0.94), whereas no protective effect has been observed in patients with ER or PgR

Thirty elderly (mean +/- SEM: 73.8 +/- 2.1 y) nondiabetic, moderately obese (body mass index = 28.3 +/- 0.6 kg/m2) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). The study was of a randomized, placebo-controlled, double-blind, and crossover design. Anthropometric indexes were stable throughout the study. Despite similar fasting and 2-h plasma glucose concentrations, vitamin E administration (compared with placebo) lowered fasting (88 +/- 14 and 68 +/- 9 pmol/L, P < 0.02) and 2-h (348 +/- 43 and 263 +/- 28 pmol/L, P < 0.05) plasma insulin concentrations, plasma triglyceride concentrations (1.34 +/- 0.06 and 1.07 +/- 0.03 mmol/L, P < 0.05), and the ratio of plasma LDL to HDL cholesterol (7.64 +/- 0.31 and 5.52 +/- 0.38, P < 0.02). Vitamin E administration was associated with higher nonoxidative glucose metabolism (18.1 +/- 0.5 and 10.6 +/- 0.7 mumol.kg lean body mass-1.min-1, P < 0.03) than was placebo administration during the euglycemic glucose clamp. We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease.

Ten healthy subjects and 30 non-insulin-dependent (type II) diabetic patients matched for age, gender ratio, body mass index, lean body mass (LBM), waist to hip ratio, and arterial blood pressure volunteered for the study. In all subjects, fasting plasma free radical (O2-) levels and basal membrane lipid fluidity (MLF) and protein mobility (MPM) were determined. The whole group of subjects underwent a euglycemic hyperinsulinemic glucose clamp with simultaneous indirect calorimetry for substrate oxidation determination. Diabetic patients versus controls displayed higher fasting plasma glucose (8.3 +/- 0.4 v 5.1 +/- 0.4 mmol/L, P +/- .001), O2- (0.48 +/- 0.02 v 0.16 +/- 0.02 mumol/L x min), and hemoglobin A1c ([HbA1C] 7.9% +/- 0.4% v 5.7% +/- 0.3%, P < .03) levels and a stronger reduction in basal MLF (0.243 +/- 0.006 v 0.318 +/- 0.009, P < .003) and basal MPM (0.348 +/- 0.003 v 0.518 +/- 0.010, P < .002). Whole-body glucose disposal (WBGD) and oxidative and nonoxidative glucose metabolism were also significantly lower in diabetics than in controls. In diabetic patients (n = 30), plasma O2- levels correlated with basal MLF (r = -.59, P < .005), basal MPM (r = -.84, P < .001), fasting plasma insulin level (r = .51, P < .004), WBGD (r = -.53, P < .002), and nonoxidative (r = -.45, P < .01) glucose metabolism. In conclusion, our results demonstrate that a relationship between plasma O2- levels and insulin action occurs in non-insulin-dependent diabetics.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

BACKGROUND Many studies have shown a significant association between the magnitude of insulin resistance and the plasma insulin levels in non-diabetic patients. It has also been shown that all major cardiovascular risk factors are associated with the presence of hyperinsulinemia or insulin resistance. However, studies have not addressed the possible metabolic differences in insulin action that can occur in patients with and without coronary heart disease (CHD) but with a superimposable cluster of risk factors. METHODS Three groups of patients matched for age, sex, and lean body mass, but different in their absence of risk factors (group A; n = 8), presence of risk factors but no clinical and electrocardiographic signs of CHD (group B; n = 12), and the presence of risk factors, family history of CHD, and clinical and electrocardiographic signs of CHD (group C; n = 14) volunteered for the study. Patients in groups B and C were also matched for main risk factors. All patients were submitted to a euglycemic hyperinsulinemic glucose clamp during which a an infusion of 3H-glucose and indirect calorimetry facilitated the determination of glucose turnover parameters and substrate oxidation. RESULTS Patients with CHD (group C) had the highest fasting plasma insulin levels (98 +/- 13 pmol/l) compared with patients in group B (86 +/- 4 pmol/l; P < 0.05) and in group A (63 +/- 4 pmol/l; P < 0.05) and the lowest insulin-mediated stimulation in non-oxidative glucose metabolism. Fasting lipid oxidation was similar in the three groups, but a stronger insulin-mediated inhibition in the control patients (group A) was found. Multiple regression analysis of the pooled data from the patients in groups B and C (n = 26) demonstrated that all risk factors considered correlated (t = 1.58, P < 0.04) with total body glucose disposal (TBGD) and accounted for 77% of the variability in TBGD. Furthermore, a separate analysis for groups B and C demonstrated a different contribution of all risk factors (89% and 65% for groups B and C, respectively) to the variability in TBGD. In group C patients, a multiple logistic regression analysis encompassing all risk factors studied, but also the family history of CHD, explained 92% of the variability in TBGD. CONCLUSION In patients with and without CHD but with similar risk factors, a significant reduction in non-oxidative glucose metabolism occurs; nevertheless, such impaired glucose handling seems to be worsened in the presence of CHD. Further studies will be needed to determine the cause of such differences.

Background. The relative contribution of malnutrition and cancer to insulin resistance in elderly patients is still poorly understood. Methods. Twenty malnourished and 15 well-nourished patients with cancer matched for age (70 ± 0.3 versus 69 ± 0.3 years; P = not significant), mean arterial blood pressure (104 ± 8 versus 107 ± 7 mm Hg; P = not significant), gender ratio (10 males/10 females versus 7 males/8 females), and sedentary life style underwent an euglycemic glucose clamp. Simultaneous infusion of 3-DH-glucose and indirect calorimetry allowed the authors to determine glucose turnover parameters and analyze substrates oxidation. Results. Malnourished patients displayed a reduced total body glucose metabolism (36 ± 2 versus 31 ± 3 μmol/kg of lean body mass X min P < 0.04), despite higher glucose oxidation. In the same group of patients, the authors demonstrated a significant increase in lipid oxidation and the lack of the inverse relationship between glucose and lipid oxidation (r = 0.07; P = not significant). Insulin infusion enhanced glucose oxidation and suppressed lipid oxidation, but such changes were at lower extent in malnourished patients. Conclusions. Our study confirms the presence of insulin resistance in malnourished patients and demonstrates the relative contribution of substrates oxidation to the insulin resistance itself.

Eight aged (70.1 +/- 2.1 years), nonobese (body mass index [BMI] = 26.3 +/- 0.4), hypertensive (systolic blood pressure [SBP] = 184 +/- 4.1; diastolic blood pressure [DBP] = 105 +/- 2.4 mm Hg) subjects underwent a euglycemic hyperinsulinemic (7.1 pmol/kg x min during 240 min) glucose clamp with four different infusions: a) 0.9% NaCl; b) 1.0 micrograms/kg x min nifedipine; c) 100 mumol/min magnesium; d) 1.0 micrograms/kg x min nifedipine plus 100 mumol/min magnesium. All tests were performed in random order. Simultaneous D-3-H glucose infusion and indirect calorimetry allowed us to determine glucose turnover parameters and substrate oxidation. Insulin infusion per se stimulated erythrocyte magnesium (1.83 +/- 0.04 v 1.98 +/- 0.03 mmol/L, P < .03) and calcium (4.7 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02) accumulation, and enhanced total body glucose disposal oxidative and nonoxidative glucose metabolisms. Infusion of insulin and nifedipine v insulin alone reduced insulin-mediated increase in intracellular calcium (5.4 +/- 0.3 v 6.2 +/- 0.4 mumol/L, P < .02), but potentiated the insulin effect upon nonoxidative glucose (15.4 +/- 0.4 v 11.1 +/- 0.3 mumol/kg lean body mass [LBM] x min, P < .03) metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective To identify the sequence and significance of left ventricular filling abnormalities associated with progressive aging in humans. Design Cross-sectional study comparing three age groups. Setting: Department of Geriatrics at University of Naples. Participants Seventy-five healthy subjects in three age groups: 25 subjects from 25 to 45 years (Group I), 25 subjects from 46 to 65 years (Group II), and 25 subjects from 66 to 85 years (Group III). Intervention None. Main Outcome Measures All underwent pulsed-doppler echocardiography under color guide to measure the following parameters: peak velocity flow for early (E wave) and late (A wave) mitral flow; A/E wave ratio; deceleration time of mitral flow (MDt); isovolumic relaxation time (IRT); ratio of velocity time integrals of the A wave to the velocity time integrals of the entire mitral spectrum (VTIA/VTIM). Results Peak velocity of the E wave was slightly lower in Group II and III compared to Group I; in contrast, peak velocity of the A wave was greater (P < 0.005) in aged individuals. Also A/E wave ratio, MDt, and IRT were significantly greater with advancing age (P < 0.01; P < 0.05 and P < 0.001, respectively). Finally, VTIA/VTIM tended to be greater in the oldest group, but not significantly so. Conclusions Left ventricular relaxation is progressively impaired in late middle age and old age, presumably an early marker of cardiac aging. Increased left atrial pressure is compromised only in the oldest group, presumably representing a compensation for impaired left ventricular relaxation.

Sixteen patients suffering from rheumatoid arthritis (RA) (n = 8), systemic lupus erythematosus (SLE) (n = 5), and systemic sclerosis (SSc) (n = 3), and 10 healthy subjects matched for age, sex, and body mass index, were submitted to an intravenous (IV) glucose tolerance test (GTT) (0.33 g/kg of body weight in 3 minutes) and to a euglycemic hyperinsulinemic glucose clamp to study insulin response and action. In the euglycemic clamp, along with the two insulin infusion rates (0.5 mU/kg.min from 0 to 120 minutes and 1 mU/kg.min from 121 to 240 minutes), a primed (20 microCi) continuous (0.2 microCi/min) infusion of 3H-glucose allowed determination of glucose kinetics. Our data show that patients versus controls have (1) a significant increase in basal plasma insulin levels (87.2 +/- 14.8 v 41.3 +/- 6.0 pmol/L, P less than .05); (2) similar glucose-induced acute insulin response; and (3) a lower glucose disappearance rate (Rd), glucose metabolic clearance rate (gMCR), and glucose infusion rate (GIR) when the lowest insulin infusion rate was delivered. These differences disappeared when the insulin infusion rate was doubled. Furthermore, basal plasma insulin levels and glucose disappearance rate significantly correlated with the main inflammatory indices of each disease studied. We conclude that in our patients impaired glucose handling is mainly due to peripheral insulin resistance.

Glibenclamide, a hypoglycemic sulfonylurea, is a blocker of the adenosine triphosphatase-modulated potassium ion channels. The opening of these channels in the myocardial cells, induced by acute myocardial hypoxia, can be responsible for ischemic ventricular arrhythmias. To evaluate the antiarrhythmic effects of this drug 19 non-insulin-dependent diabetic patients were selected. They had coronary artery disease and evidence on Holter monitoring of ventricular premature complexes or nonsustained ventricular tachycardia, or both, induced by transient myocardial ischemia. In all patients, 24-hour electrocardiographic monitoring was performed to evaluate the number and duration of myocardial ischemic events, the frequency of ventricular premature complexes and nonsustained ventricular tachycardia per minute of ischemia and the percentage of ventricular premature complexes versus total ischemic beats. Selected patients were classified in 2 groups: group A (9 patients) received metformin (placebo) and group B (10 patients) was treated with glibenclamide. On the fourteenth day patients underwent 24-hour control monitoring. Then a crossover between the 2 groups was made and a new Holter monitoring sequence was performed at the end of the second phase. Results indicate that glibenclamide significantly (p less than 0.001) reduced both the frequency of ventricular premature complexes and the episodes of nonsustained ventricular tachycardia during transient myocardial ischemia, but did not change the number and duration of acute myocardial ischemic attacks and did not reduce the spontaneous ventricular arrhythmias. Thus, glibenclamide appears to have an antiarrhythmic effect in preventing ventricular arrhythmias induced by transient myocardial ischemia.

The aim of this study was to see if the greater effect of insulin on hepatic glucose output when insulin is given using 13-min pulses in man remains when the same amount of insulin is delivered using 26-min pulses. The study was performed on nine male healthy volunteers submitted to a 325 min glucose-controlled glucose iv infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin. Three experiments were performed in each subject on different days and in random order. In all cases glucagon was replaced (58 ng min-1). The amounts of insulin infused were identical in all instances and were 0.2 mU kg-1 min-1 (continuous), 1.3 mU kg-1 min-1, 2 min on and 11 min off (13-min pulses) or 2.6 mU kg-1 min-1, 2 min on and 24 min off (26-min pulses). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using D-[3-3H] glucose infusion allowed to study glucose turnover. When compared with continuous insulin, 13-min insulin pulses induced a significantly greater inhibition of endogenous glucose production. This effect disappeared when insulin was delivered in 26-min pulses. We conclude that, in man, an adequate pulse frequency is required to allow the appearance of the greater inhibition of pulsatile insulin on endogenous glucose production.

In normal man oxytocin infusion under basal conditions and at pharmacological doses evoked a rapid surge in plasma glucose and glucagon levels followed by a later increase in plasma insulin levels. Simultaneous [D-3H]glucose infusion indicated that oxytocin also produced a prompt and significant increase in hepatic glucose output with a secondary increase in glucose disappearance rate. Eight healthy volunteers were studied during euglycemic glucose clamp and simultaneous [D-3H]glucose infusion, during suppression of endogenous pancreatic secretion by cyclic somatostatin (250 μg/h) and during exogenous glucagon (67 ng/min) and insulin (0.15 mU · kg−1 · min−1 from 0 to 120 min and 0.40 mU · kg−1 · min−1 from 121 to 240 min) replacement. During the first 60 min oxytocin (0.2 U/min) evoked a transient but significant increase in plasma glucose levels and hepatic glucose output with a simultaneous suppression of the glucose infusion rate. No difference in glucose disappearance and metabolic clearance rates were recorded throughout the clamp irrespective of whether oxytocin was infused or not. So we conclude that oxytocin exerts a hyperglycemic effect through an A-cell stimulation and a glycogenolytic action.

The presence of glucose intolerance in aged people is a well known physio-pathological condition. Nevertheless, the mechanisms by which it takes place are still unclear. In the present report we have reviewed the possible mechanisms (impaired insulin secretion and action, role of the environmental factors) which may contribute to the impaired glucose handling of aging. Moreover, we have also pointed out that not all aged subjects are glucose intolerant; in fact it seems clear that only aged subjects who present more than one of the pathological findings reported above may develop impaired glucose handling.

In a study of ten young and seven elderly healthy men we have performed an oral glucose tolerance test (75 g) and employed a euglycemic hyperinsulinemic (0.25 mU× kg/min) glucose clamp technique in order to determine insulin sensitivity. This latter experimental protocol consisted of 120 min of euglycemic clamp followed by 60 min in which the clamp and a mild muscular exercise (35% VO 2 max ) were combined. d -[ 3 H]glucose infusion allowed a determination of the glucose turnover parameters. Our results show that in elderly subjects glucose disappearance rate and glucose metabolic clearance rate are significantly lower during both clamp, and clamp + muscular exercise studies. On the contrary, hepatic glucose production was similar under both conditions and was independent of age.

Aims: We studied the relationship between the Beck Depression Inventory (BDI) and the 15-item Geriatric Depression Scale (GDS-15) in young–old hemodialysis and hospitalized patients in order to evaluate the possible usefulness of GDS-15 in hemodialysis patients. Methods: Thirty-one hospitalized and 31 young–old hemodialysis patients aged 65–74 (young–old) were enrolled in the study. Comprehensive geriatric assessment (Mini Mental State Examination (MMSE), BDI, GDS-15, Cumulative Illness Rating Scale (CIRS) and Activities of Daily Living (ADL)) was made for all patients. The internal consistency between BDI and GDS-15 was evaluated with Cronbach’s α coefficient. Sensitivity, specificity and receiver operating characteristic (ROC) curves for GDS-15 were determined using BDI as the standard. Results: In the hospitalized group, the prevalence of depressive symptoms, as evaluated by BDI (≧14) and GDS-15 (≧6), were 29 and 32%, respectively. In the hemodialysis group, the prevalence of depressive symptoms, as evaluated by BDI and GDS-15, were 61 and 58%, respectively. A significantly positive correlation between the BDI and GDS-15 was found in hospitalized (r = 0.808; p < 0.001), hemodialysis (r = 0.692; p < 0.001) and both patient groups together (r = 0.777; p < 0.001). The area under the ROC curve was 0.99 in the hospitalized and 0.95 in the hemodialysis groups. The ROC curves indicate a best effectiveness cutoff point (balancing sensitivity and specificity) of ≧6 for GDS-15 compared to BDI. Conclusions: The GDS-15 could be a useful instrument for evaluating depressive symptoms in young–old hemodialysis patients.

This study was aimed to evaluate the effect of different recombinant LH (rLH) doses on the ovarian outcome of normogonadotrophic women with an initial inadequate response to recombinant FSH (rFSH) after pituitary downregulation. METHODS: Only women undergoing a 'long protocol' with a GnRH-agonist followed by rFSH administration were enrolled. On the eighth day of stimulation, 46 patients with serum E2 levels < 180 pg/ml and with no follicle > 10 mm were randomized in two groups to receive a supplementation with a daily rLH dose of 75 (group A) or 150 IU (group B), respectively. Forty-six normal responders continuing their monotherapy with rFSH formed the control group (C). RESULTS: The mean number of oocytes retrieved and the percentage of mature oocytes in the group B (9.65 +/- 2.16, 79.0%) were comparable with those observed in the group C (10.65 +/- 2.8, 82.5%) and significantly higher when compared with the group A (6.39 +/- 1.53, 65.7%). The mean number of ampoules of rLH was significantly higher in the group B (14.4 +/- 2.0 vs. 9.65 +/- 1.1), whereas these patients received a significantly lower mean number of rFSH ampoules (44.6 +/- 7.4 vs. 36.1 +/- 3.8). Seven (30.4%), 9 (39.1%) and 22 (47.8%) pregnancies were achieved in the groups A, B and C, respectively. CONCLUSIONS: These results suggest that patients with initial inadequate responses to rFSH after pituitary downregulation benefit from the addition of a daily dose of 150 IU of rLH, starting from the eighth day of stimulation.

Background. Heart rate variability parameters were evaluated in 10 healthy subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD) patients (11 non-diabetic and nine type II diabetic) undergoing chronic haemodialysis. The study was divided in two phases. Methods. In the first phase all subjects underwent electrocardiograph (ECG) recording under baseline conditions. In the second phase only ESRD patients underwent haemodialysis and ECG recording. On the day of dialysis and ECG recording the ECG recording was started 1 h before the haemodialysis session (pre-dialytic period), and continued throughout the dialysis (dialytic period), until the morning after (post-dialytic period). Results. Compared with ESRD patients, non-ESRD patients showed the lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic period (P

Background: Fatty acids have been shown to stimulate the sympathetic nervous system in rats. Power spectral analysis of heart rate variability (HRV) is a safe and useful tool with which to evaluate cardiac autonomic nervous system (ANS) activity. Whether changes in plasma fatty acid concentrations affect the sympathetic nervous system or HRV in humans is unknown. Objective: We investigated the possible changes in HRV after a significant increase in plasma fatty acid concentration. Design: Subjects were randomly assigned to receive an infusion of lipid emulsion (10% triacylglycerol emulsion for 180 min) + heparin (a bolus of 200 U followed by 0.2 U.min -1 .kg body wt -1 ; n = 20) or 0.9% NaCl (for 180 min; n = 10). Results: Lipid emulsion + heparin infusion was associated with a rise in plasma epinephrine and norepinephrine concentrations. The rise in plasma fatty acid concentration was associated with a significant decline in the RR interval (P < 0.03) and in total power (P < 0.03). Analysis of the different components of HRV showed that lipid emulsion + heparin infusion stimulated low-frequency (LF) components (P < 0.03 at the second hour and P < 0.01 at the third hour) and inhibited high-frequency (HF) components (P < 0.03 at the second and third hours). Consequently, the LF-HF ratio was significantly stimulated (P < 0.03 at the second hour and P < 0.01 at the third hour). Such results persisted, although attenuated, when the study was repeated in association with a propranolol infusion (n = 8). Conclusion: Elevated plasma fatty acid concentrations may stimulate cardiac autonomic nervous system activity.

Previous studies have shown that leptin stimulates sympathetic nervous system; heart rate variability (HRV) is a widely used technique for assessing the sympathovagal balance at the cardiac level. The aim of our study was to investigate a possible relationship between plasma leptin levels and the autonomic regulation using spectral analysis of HRV. In 120 healthy nonobese subjects the plasma leptin concentration was determined, and HRV was recorded at baseline and during tilt. All subjects were categorized in quartiles of plasma leptin concentration. Analysis of data showed a significant increase in body mass index, body fat, fasting plasma insulin, triglyceride concentration, and homeostatic model assessment values throughout the different quartiles of plasma leptin concentration. Concerning cardiovascular parameters, heart rate, arterial blood pressures, and RR intervals were not significantly different among the quartiles. Total power and high frequency (HF) in normalized units were significantly decreased, whereas low frequency (LF) normalized units was progressively increased from the first to the fourth quartile. Thus, the LF/HF ratio rose gradually and significantly from the lowest to the highest quartile. Such results were independent of the body fat estimate (P < 0.03 for the trend). The change in the LF/HF ratio was significantly enhanced during tilt (P < 0.001 vs. rest values for all quartiles); the effect was stronger in subjects in the fourth quartile of plasma leptin concentration (P < 0.005 for the trend). The latter parameter was also independent of body fat content and distribution (P < 0.01). Our study shows that increasing fasting plasma leptin concentrations are associated with a shift of the sympathovagal balance toward a progressive increase in sympathetic activation and an increased response to orthostatic stimulus in nonobese subjects with different body fat contents.

The objective of this study was to evaluate the relationship of whole blood viscosity and its major determinants (plasma fibrinogen level, hematocrit, hemoglobin and blood cell count) to advancing age. A total of 249 subjects (mean age 49.9+/-21.5; range 19-102 years) were included in the study. They were divided into three groups, (A)30 years of age, n, 58; (B) 30-60 years, n, 107; (C)60 years, n, 84. Whole blood viscosity at two different rates of shear (450 and 45 s(-1)) was evaluated using a cone-plate digital viscosimeter. The hematological parameters (hematocrit, hemoglobin and blood cell count) were evaluated using an automatic Coulter Counter. Plasma fibrinogen concentration was measured by a clotting method. When both sexes are considered together, whole blood viscosity shows no significant difference among age groups. Plasma fibrinogen concentration significantly increases with age (P0.001); hemoglobin, red blood cell count and platelet count, on contrary, are significantly lower in aged group. In the male sex, blood viscosity at higher shear rate (450 s(-1)) negatively correlates with advancing age (P0.005). The age-related decrease of hematocrit value in the male sex accounts for this occurrence.

Abstract —Leptin, the product of the ob gene, has been shown to increase heart rate and blood pressure through a stimulation of cardiac sympathetic nervous system activity, a phenomenon also involved in the pathogenesis of left ventricular hypertrophy in hypertensives. Thus, we hypothesize that plasma leptin concentration is associated with left ventricular hypertrophy. Forty hypertensive males and 15 healthy male subjects underwent anthropometric and echocardiographic evaluations, assessment of insulin sensitivity through euglycemic glucose clamp combined with indirect calorimetry, and determination of fasting plasma leptin concentration. Fasting plasma leptin levels were higher in hypertensives than in controls (6.48±2.9 versus 4.62±1.5 ng/mL, P P r =0.46, P r =0.50, P r =−0.27, P r =0.34, P r =0.38, P r =0.68, P + concentration, whole-body glucose disposal, and diastolic blood pressure explained 68% of the variability of the sum of wall thicknesses with fasting plasma leptin concentration ( P P P

The low-frequency to high-frequency ratio (LF/HF ratio) is an index of cardiac sympathovagal balance. We hypothesized that insulin might also stimulate the LF/HF ratio. Thus, 15 lean and 15 obese subjects were studied. Each subject underwent sequential hyperinsulinemic clamps (insulin infusion rate 0.50, 1, and 2 mU/kg x min) while the heart rate was recorded by the Holter technique continuously. Indirect calorimetry allowed determination of the respiratory quotient (Rq) and substrate oxidation. The leg blood flow (LBF), leg vascular resistance (LVR), and plasma norepinephrine concentration were also measured. In seven lean subjects, hyperinsulinemic clamps were repeated along with propranolol infusion (0.1 mg x kg(-1) as an intravenous bolus dose followed by continuous intravenous infusion of 0.5 mg x kg(-1) x min(-1) throughout the study). Lean subjects had better insulin action than obese subjects. Insulin infusion was associated with an increase of the deltaLF/HF ratio in both lean (P < .001 for time-dependent changes) and obese (P < .02 for time-dependent changes) subjects; however, the extent of insulin-mediated stimulation of the LF/HF ratio was greater in lean versus obese subjects. Insulin infusion did not significantly affect HF values in both groups. Independently of gender, body fat, changes in the plasma norepinephrine concentration, LBF, and LVR, the deltaLF/HF ratio at the end of the fastest insulin infusion (0.8 +/- 0.2 v 0.3 +/- 0.2, P < .04) was still greater in lean versus obese subjects. The deltaLF/HF ratio was also more stimulated during insulin versus insulin + propranolol infusion in lean subjects. In conclusion, insulin stimulates the LF/HF ratio in both lean and obese subjects and thus produces a shift in the cardiac autonomic nervous system activity toward sympathetic predominance.

OBJECTIVE: Our study aims at investigating the degree of oxidative stress in centenarians DESIGN: Indices of oxidative stress (reaction products of malondialdehyde with thiobarbituric acid (TBARS) and lipid hydroperoxides (LPO)), and plasma concentrations of antioxidant defenses (plasma vitamin E and C concentrations and reduced/oxidized glutathione ratio (GSH/GSSG)) were determined. SUBJECTS: Eighty-two subjects volunteered for the study. They were divided into three groups: (1) adults (< 50 years of age, n = 30); (2) aged subjects (70–99 years, n = 30); (3) centenarians (age ≥ 100 years, n = 22). MEASUREMENTS: TBARS and LPO, plasma vitamin E and C concentrations, and plasma GSH/GSSG ratio were determined. Insulin action was assessed by euglycemic hyperinsulinemic glucose clamp. MAIN RESULTS: TBARS (0.44±0.07 vs 0.31 ±.05 nmol malondialdehyde/mL plasma, P =.020) and LPO (0.36 ± 0.05 vs 0.31 ±.04 μmol/L, P =.050) were lower in centenarians than in aged subjects. In contrast, plasma GSH/GSSG ratio (0.82 ± 0.09 vs 1.17 ±.06, P =.010), vitamin C (72.3 ± 4.6 vs 59.4 ± 3.8 μmol/L P =.010), and vitamin E (29.1 ± 2.2 vs 24.4 ± 2.3 μmol/L P =.050) concentrations were more elevated in centenarians than in aged subjects. Differences in daily vegetable intake, in fasting plasma glucose and free fatty acid (FFA) concentrations, and in insulin action are significant determinants of degree of oxidative stress. A specific genetic background in centenarians might also provide a possible explanation. CONCLUSIONS: The degree of oxidative stress is lower in healthy centenarians than in aged subjects.

The goal of the study was to investigated the prevalence of disability, cognitive impairment, depressive symptomatology and chronic diseases in a sample of the elderly population. A cross-sectional study was carried out on a random sample from the general population of elderly located in a geographically well defined Mediterranean area of Southern Italy. We examined 1339 subjects. Investigated diseases were: chronic obstructive lung disease, hypertension, arthrosis, diabetes mellitus, neurological disease, myocardial infarction, angina, atrial fibrillation, peripheral artery disease and congestive heart failure. Cognitive status was assessed by means of the Mini-Mental State Examination (MMSE), depression symptomatology was evaluated by Geriatric Depression Scale (GDS) and disability by means of Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). This methodological study showed that 27.9% had a MMSE score24 and the score decreased with age in both sexes. A total of 9.8% of the subjects had severe depression (GDS score20). Comorbidity was evaluated from the past medical history and confirmed by a clinical exam by a physician. Only 8.7% of subjects were found without chronic illness. Median number of diseases was two, with 26.6% declaring four diseases or more. Comorbidity increased with age, an overall slight decrease of the number of diseases being observed in the subjects85 years old. Subjects disabled in ADL were 7%, while disabled in IADL were 46.7%. The disability prevalence increased with age, affecting more female than male.

OBJECTIVE: Congestive heart failure (CHF) is potentially preventable, and the identification of modifiable risk factors for cognitive impairment (CI) for older persons is a very important issue. We examined the cross-sectional relationship between CHF and CI in an older population. DESIGN: A cross-sectional survey. SETTING AND PARTICIPANTS: A total of 1339 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. MEASUREMENTS: Sociodemographic characteristics were recorded, as was the presence of cardiovascular diseases, including CHF classified according to the New York Heart Association (NYHA) guidelines for disease severity; CI evaluated by means of the Mini-Mental State Examination (MMSE), with a score of

It is often difficult to study the alterations of aging heart because there is a very large spectrum of cardiovascular function among elderly population. Aging is associated to an increase in prevalence and incidence of coronary disease. In fact, the 50% of aging subjects have a known or latent coronary artery disease and only few of them underwent invasive studies to exclude coronary heart failure. Furthermore, a decline in cardiac performance can be related also to an age-related reduction in daily physical activity with a secondary deconditioning. For all these reasons it is not so easy to clarify what is “normal heart” in the elderly people. In our opinion interactions among aging, disease, and lifestyle could be considered in interpreting age-associated changes in cardiovascular structure and function (1).

In hypertensive patients the presence of left ventricular (LV) hypertrophy has been associated with a more severe degree of insulin resistance. Whether myocardial wall thickness or LV geometry are associated with a different degree of insulin resistance is still unknown in essential hypertensives. For this reason 26 men with new diagnosed essential hypertension were enrolled. All patients underwent echocardiographic examination and euglycemic hyperinsulinemic glucose clamp combined with indirect calorimetry. According to LV mass and relative wall thickness data, all patients were categorized in four groups: 1) patients with a normal geometric LV pattern (n = 8) (PAT = 0); 2) patients with concentric remodeling LV mass (n = 8) (PAT = 1); 3) patients with eccentric LV hypertrophy (n = 3) (PAT = 2); and 4) patients with concentric LV hypertrophy (n = 7) (PAT = 3). All groups were similar for anthropometric characteristics. Patients with normal echocardiographic LV pattern (PAT = 0) had higher whole body glucose disposal (WBGD), oxidative and nonoxidative glucose metabolism, and lower lipid oxidation than patients with abnormal echocardiographic LV patterns (PAT = 1 to 3). Nevertheless, no significant differences among the groups with abnormal echocardiographic patterns were found. After controlling for age, body mass index (BMI), waist/hip ratio (WHR), and mean arterial blood pressure, only sum of the wall thickness was significantly correlated with fasting plasma insulin (r = -0.38, P < .05), WBGD (r = - 0.50, P < .009), and NOGM (r = - 0.48, P < .02). In multivariate analysis, a model made by age, BMI, WHR, systolic and diastolic blood pressure, and WBGD explained 38% of the echocardiographic pattern variability. In this model, WBGD (P < .02) was significantly and independently associated with echocardiographic patterns explaining 19% of the echocardiographic pattern variability. In conclusion, our data demonstrate that in arterial hypertension hyperinsulinemia/insulin resistance mainly affects myocardial wall thickness, whereas only a trivial association with LV geometry occurs.

The relationship between insulin resistance and aging is still debated. This study aims to investigate the role that age-related differences in plasma dehydroepiandrosterone sulfate (DHEAS) concentration may have on insulin action. For this reason, 75 subjects (42 men and 33 women) with a wide age range (21 to 106 years) were studied. In all subjects, plasma DHEAS and total testosterone concentrations were measured and a euglycemic clamp was used, but substrate oxidation was not determined in centenarians (n = 15). Plasma DHEAS correlated with age (r = -.77, P.001) and whole-body glucose disposal (WBGD) (r = .57, P.001). After controlling for age, sex, body fat, and waist to hip ratio (WHR), the association between plasma DHEAS and WBGD was still observed (r = .31, P.005). Comparing subjects at the third tertile versus those at the first and second tertiles of plasma age-adjusted DHEAS concentration, the former group showed a weaker association between WBGD and age (r = -.38, P.05) than the latter group (r = -.43, P.002). The difference between the two regression lines was also significant (P.03). After controlling for sex, body fat, and WHR, the association between plasma DHEAS and WBGD was dependent on the age of the subjects, being strong in adults (n = 30, age50 years, r = .69, P.001), weak in old subjects (n = 30, age 51 to 99 years, r = .23, P.05), and absent in centenarians (r = -.05, P.88). With the subjects divided by sex throughout the different age groups, the univariate association between plasma DHEAS and WBGD was present in females (r = .43, P.01) but not in males (r = .17, P.32). Plasma total testosterone and insulin-like growth factor-1 (IGF-1) concentrations declined with advancing age and were significantly correlated with DHEAS and WBGD. In a multivariate analysis with WBGD as the dependent variable, a model including age, sex, body fat, WHR, DHEAS, total testosterone, and IGF-1 explained 66% of WBGD variability, with DHEAS significantly and independently associated with WBGD (P.004). In conclusion, the negative relationship between advancing age and insulin action seems related to plasma DHEAS concentration. Differences in plasma total testosterone and IGF-1 concentrations may provide a further contribution to the relationship between DHEAS and WBGD.

We investigated the association between free fatty acid (FFA) concentration and ventricular premature complexes (VPCs) in nonischemic patients with non-insulin-dependent diabetes mellitus using 3 approaches: cross-sectional analysis (n = 142), intervention including induction of elevated FFA levels with Intralipid heparin (n = 15), and reduction in FFA levels with Acipimox (n = 34) and a longitudinal follow-up study (n = 59). Patients at the third tertile of fasting plasma FFA concentration had the strongest increase in VPCs. Independently of age, sex, body mass index (BMI), waist/hip ratio, left ventricular mass index, glycated hemoglobin, fasting plasma insulin and triglyceride concentration, and daily physical activity, FFA concentration and VPCs were significantly correlated (r = 0.21 p

It has been demonstrated that healthy centenarians have more favorable anthropometric characteristics and insulin-mediated glucose uptake than aged subjects. The plasma insulin-like-growth factor I (IGF-I) concentration may account for such differences. Three groups of subjects were studied: 1) adults (50 yr; n = 30), 2) aged subjects (75-99 yr; n = 30), 3) centenarians (100 yr; n = 19). In all subjects, fasting plasma IGF-I, IGF-binding protein-3 (IGFBP-3), leptin, and lipid concentrations were determined; body composition was assessed by bioimpedance analysis; and insulin-mediated glucose up-take was evaluated by euglycemic hyperinsulinemic glucose clamp. IGF-I declined with advancing age, but no differences between aged subjects and centenarians were found. IGFBP-3 showed a trend similar to IGF-I, but lower values were present in centenarians than in aged subjects. Nevertheless, centenarians had a plasma IGF-I/IGFBP-3 molar ratio greater than that in aged subjects. Centenarians had also a whole body glucose disposal (WBGD) greater than that in aged subjects, but similar to that in adults. Mini Mental State Examination (27 +/- 2.1 vs. 18.3 +/- 3.1; P0.02) and Instrumental Activities Daily Living (26 +/- 2.6 vs. 8.4 +/- 4.1; P0.001) scores were significantly different in aged subjects and centenarians, respectively. In centenarians, the plasma IGF-I/IGFBP-3 molar ratio correlated with the body mass index (r = -0.55; P0.009); the amount of body fat (r = -0.62; P0.003); fat-free mass (r = 0.56; P0.008); fasting plasma leptin (r = -0.63; P0.004), triglycerides (r = -0.58; P0.01), free fatty acid (r = -0.64; P0.005), and low density lipoprotein cholesterol (r = -0.59; P0.009) concentrations; Mini Mental State Examination (r = 0.53; P0.0.03); and WBGD (r = 0.64; P0.005). All correlations were independent of daily fat and carbohydrate intake and WBGD (P0.05 for all). No significant correlations between the plasma IGF-I/IGFBP-3 molar ratio and plasma total (r = 0.31; P = NS) and high density lipoprotein cholesterol (r = 0.34; P = NS) concentrations were present. The correlation between the plasma IGF-I/IGFBP-3 molar ratio and WBGD persisted after adjustment for body fat, fasting plasma insulin concentration, daily carbohydrate and fat intake, and daily physical activity (r = 0.55; P0.009), but not after further adjustment for plasma free fatty acid concentration (r = 0.30; P = 0.17). In conclusion, healthy centenarians have plasma IGF-I/IGFBP-3 molar ratio greater than aged subjects. A more elevated plasma IGF-I/IGFBP-3 molar ratio might improve insulin action and plasma lipid concentration in centenarians.