Showing papers by "Giuseppe Paolisso published in 2005"

Effects of soy isoflavones on endothelial function in healthy postmenopausal women

Abstract: Objective: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. Design: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of NG-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. Results: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of NG-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. Conclusions: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.

Insulin Resistance and Muscle Strength in Older Persons

Abstract: Background. The functional consequences of an age-related insulin resistance (IR) state on muscle functioning are unknown. Because insulin is needed for adequate muscle function, an age-related insulin-resistant state may also be a determining factor. We evaluated the relationship between IR and handgrip muscle strength in men and women from a large population-based study (n ¼ 968). Methods. The degree of IR was evaluated by the homeostasis model assessment (HOMA) and muscle strength was assessed using handgrip. Results. Simple sex-stratified correlations demonstrated that, in men, body mass index-adjusted handgrip strength correlated positively with physical activity (r ¼0.321; p , .001), muscle area (r ¼0.420; p , .001), muscle density (r ¼ 0.263; p ¼ .001), plasma albumin (r ¼ 0.156; p ¼ .001), insulin-like growth factor-1 (r ¼ 0.258; p , .001), calcium (r ¼ 0.140; p ¼.006), and testosterone (r ¼0.325; p , .001) concentrations, whereas a negative association was found for age (r ¼� 0.659; p , .001) and myoglobin plasma levels (r ¼� 0.164; p ¼ .001). In women, body mass index-adjusted handgrip strength correlated positively with physical activity (r ¼ 0.280; p , .001), muscle area (r ¼ 0.306; p , .001), muscle density (r ¼ 0.341; p ¼ .001), plasma albumin (r ¼ 0.140; p ¼ .001), and insulin-like growth factor-1 (r ¼ 0.300; p , .001), whereas a negative association was found for age (r ¼� 0.563; p , .001), myoglobin levels (r ¼� 0.164; p ¼ .001), and IR (r ¼� 0.130; p ¼ .04). Conclusions. Sex-stratified analyses adjusted for multiple confounders showed that the relationship between IR and handgrip strength was found significant in women, whereas it was negligible and not significant in men.

Circulating leptin correlates with left ventricular mass in morbid (grade III) obesity before and after weight loss induced by bariatric surgery : A potential role for leptin in mediating human left ventricular hypertrophy

Abstract: Context: Obesity is frequently associated with left ventricular hypertrophy, even when uncomplicated by hypertension or diabetes mellitus. Left ventricular hypertrophy is an important risk factor for congestive heart failure. Objective: The objective of this study was to evaluate the relationship between leptin and left ventricular mass in uncomplicated, morbid (grade 3) obesity and the existence of leptin receptors and intracellular signaling proteins in the human heart.

Insulin resistance in cognitive impairment: the InCHIANTI study.

Abstract: Objective To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population. Design Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI). Participants A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (Mini-Mental State Examination [MMSE] score Results The insulin resistance profile of patients in the CI/SF+ group was similar to that of individuals who had experienced stroke, whereas the profile of individuals with cognitive impairment without subcortical features (CI/SF− group) was similar to that of individuals in the no CI group. Patients in the CI/SF− group showed insulin resistance comparable to individuals in the no CI group (age-adjusted P = .27, .19, and .64, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI in linear regression models) and lower than patients with stroke (age-adjusted P = .01, .02, and .07, respectively). On the contrary, patients in the CI/SF+ group had insulin resistance and sensitivity values similar to those of the stroke group (age-adjusted P = .80, .84, and .75, respectively, for difference in fasting blood insulin level, HOMA-IR, and QUICKI) but significantly different from those in the no CI group (age-adjusted P = .01, .03, and .02, respectively). Conclusions Cognitive impairment with but not without subcortical features is associated with biochemical and clinical features of insulin resistance syndrome. In epidemiologic populations, insulin resistance might contribute to cognitive impairment through a vascular mechanism.

Cardiac autonomic activity and Type II diabetes mellitus

Abstract: CAN (cardiac autonomic neuropathy) is a common complication of diabetes. Meta-analyses of published data demonstrate that reduced cardiovascular autonomic function, as measured by heart rate variability, is strongly associated with an increased risk of silent myocardial ischaemia and mortality. A major problem in ischaemia-induced impairment of vascular performance in the diabetic heart is unrecognized cardiac sympathetic dysfunction. Determining the presence of CAN is based on a battery of autonomic function tests and techniques such as SPECT (single-photon emission computed tomography) and PET (positron emission tomography). Nevertheless, spectral analysis of heart rate variability seems to remain the primary technique in evaluating CAN, due to its low cost, easy use and good intra-individual reproducibility.

Repaglinide administration improves brachial reactivity in type 2 diabetic patients.

Abstract: OBJECTIVE —Several studies have demonstrated that endothelial dysfunction plays a central role in diabetic mortality and that the prooxidative effect of postprandial hyperglycemia may actively contribute to atherogenesis. Thus, we investigated the possible effect of short-acting (repaglinide) and long-acting (glibenclamide) insulin secretagogues on endothelial function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS —Sixteen type 2 diabetic patients undergoing diet treatment and with poor glucose control volunteered for the study. The study was designed as a 4-month, randomized, cross-over, parallel-group trial of repaglinide (1 mg twice a day) versus glibenclamide (5 mg twice a day). All patients underwent the following investigations: 1 ) anthropometrics determinations, 2 ) blood sampling for routine laboratory analyses and for assessment of oxidative stress indexes, and 3 ) a brachial reactivity test to evaluate the endothelial function through the study of arterial diameter and flow changes with and without intraarterial infusion of N G -monomethyl-l-arginine, an inhibitor of nitric oxide synthase and tetraethylammonium chloride (TEA), a Ca 2+ -activated K + (K Ca ) channel blocker. All patients were randomly assigned to receive repaglinide or glibenclamide for a period of 4 weeks. RESULTS —Repaglinide administration was associated with a significant reduction in 2-h plasma glucose levels ( P P P P CONCLUSIONS —Repaglinide administration, through good control of postprandial glucose levels, improves brachial reactivity and declines oxidative stress indexes.

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women

Abstract: Summary Objective Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women. Patients At baseline and 40 days after dermolipectomy, 20 obese women underwent indirect calorimetry and hyperinsulinaemic glucose clamp. Twenty obese nonsmoking females (age range 25–40 years) volunteered for the study. All subjects had a stable body weight for 2 months before the study. No patient was affected by cardiovascular and/or pulmonary disease, type 2 diabetes, thyroid dysfunction, acute or chronic hepatitis, renal insufficiency or cancer. No patients was receiving any drug therapy and all measurements were made during the follicular phase of the menstrual cycle. Results At baseline, fat mass (FM) correlated with plasma triglycerides (r = 0·58, P < 0·009), free fatty acids (FFA) (r = 0·73, P < 0·001), insulin (r = 0·70, P < 0·002), leptin (r = 0·55, P < 0·01), adiponectin (r = –0·32, P < 0·02) and resistin (r = 0·31, P < 0·01), insulin sensitivity (IS) (r = –0·59, P < 0·005) and respiratory quotient (Rq) (r = 0·62, P < 0·002). With regard to inflammatory markers, FM was significantly correlated with plasma interleukin (IL)-6 (r = 0·71, P < 0·001), IL-10 (r = –0·67, P < 0·002), tumour necrosis factor-α (TNF-α) (r = 0·78, P < 0·001) and soluble IL-6 receptor (sIL-6r) (r = –0·65, P < 0·003). Dermolipectomy resulted in a significant decline in total FM of 2·3 ± 0·2 kg. A significant decline in BMI was also observed (30·0 ± 0·08 vs. 31·1 ± 0·7 kg/m2). After 40 days a significant decline in plasma resistin (P < 0·001) and inflammatory markers and an increase in plasma adiponectin (P < 0·03) were observed. Those metabolic changes were accompanied by a significant improvement in insulin-mediated glucose uptake (P < 0·001), substrate oxidation and degree of inflammation. Changes in FM following dermolipectomy correlated with the changes in IS (P < 0·01), substrate oxidation and FFA (P < 0·001). Conclusions In obese patients, dermolipectomy is associated with weight lost, improved glucose handling and lower inflammatory markers.

Changing the metabolic profile by large-volume liposuction : A clinical study conducted with 123 obese women

Abstract: Adipose tissue is a metabolically active tissue. The hypertrophic fat cells of obese patients produce increased quantities of leptin and tumor necrosis factor-α (TNF-α) and are less sensitive to insulin. This study aimed to determine whether aspirating large amounts of these subcutaneous fat cells by large-volume liposuction (LVL), could change the metabolic profile in 123 obese women. All the patients had a main central body fat distribution (waist–hip ratio, 0.91±0.01) and a body mass index of 32.8 ± 0.8 kg/m). They were studied for 90 days after LVL to determine their changes in insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. During 3 months of follow-up evaluation, LVL resulted in a significantly improved insulin sensitivity, resting metabolic rate, serum adipocytokines, and inflammatory marker levels. Such parameters correlate with a decrease in fat mass and waist–hip ratio. Interestingly, no significant changes were seen between the first (21 days) and second (90 days) metabolic determinations after LVL. However, these findings, confirm other preliminary data published previously, and could change the actual role of LVL in the multidisciplinary treatment of obesity.

Resting metabolic rate and respiratory quotient in human longevity

Abstract: Significant changes in body composition, body fat distribution, and resting metabolic rate (RMR) occur with aging. Interestingly, studies on human longevity pointed out that long-lived subjects are less prone to the anthropometrics and metabolic derangement normally observed in the elderly. Indeed, the relationship between energy expenditure and longevity has been poorly investigated. Thus, energy expenditure parameters of 28 long-lived subjects were assessed and compared with those of 26 adults and 27 younger elderly. All subjects enrolled were female. In the whole population, RMR was negatively correlated with age (P < 0.05), waist to hip ratio (WHR) (P < 0.001), fat mass (P < 0.001), and percent body fat (P < 0.03); respiratory quotient (Rq) displayed an age-related decrease (P < 0.001) and was negatively correlated with WHR (P < 0.001) and fat-free mass (FFM) (P < 0.006). In multivariate analysis, both RMR and Rq had FFM, WHR, but not body mass index as significant and independent determinants. Splitting the whole study group into subgroups according to age, long-lived subjects had oxygen volume, carbon dioxide volume, and Rq significantly higher than aged subjects but lower than adult subjects. In addition, long-lived subjects had total volume of expired air and RMR greater than aged subjects but not different from ones found in adults. In long-lived subjects, Rq was negatively correlated with percent body fat (P < 0.02), plasma glucose (P < 0.05), free fatty acid (P < 0.05), and WHR (P < 0.05), whereas RMR was negatively correlated with WHR (P < 0.05). No significant associations of RMR and Rq with FFM were found. In conclusion, our data demonstrate that human longevity seems protected toward an age-related decline. It is likely that the lack of the anthropometrics derangement may preserve long-lived subjects from the age-related decrease in energy metabolism.

Study of the association with -330T/G IL-2 in a population of centenarians from centre and south Italy.

Abstract: Immune response in elderly is characterised by a progressive loss of the ability to cope environmental stressors with a characteristic remodelling of cytokine network. One of the data constantly reported in literature is the decrease of IL-2 production. An IL-2 central role in the reconstitution of T cell function in vitro is largely documented. Studies on a T→G polymorphism at −330 nt of IL-2 gene promoter region have demonstrated that T lymphocytes from 330GG homozygous subjects are able to produce in vitro higher amount of IL-2, than −330TG heterozygous or −330TT homozygous subjects. As a genetic background conditioning the maintaining of an efficient immune response would exert positive effects on healthy ageing, we have typed for 330T/G IL-2 single nucleotide polymorphism (SNP), 168 centenarians and 214 control subjects matched for age and ancestry from Centre and South Italy to check the 330GG genotype association to longevity. The statistical analysis doesn’t show a significant difference of genotypic and allelic frequencies at −330 IL-2 T/G SNP among centenarians and controls. Comparing the two cohorts of subjects by extended Mantel Haenszel procedure a marginally significant trend for an increased -330TT genotype frequency was observed. Our data seem to be paradoxical considering the role attributed to a well-conserved T cell function in the successful ageing. On the other hand, in a recent study on a sample of Irish octogenarians a similar distribution of −330T/G genotype even was observed. These data suggest that a genetic background favouring an increased IL-2 production might be detrimental for longevity. On the other hand, an increase of IL-2 and other pro-inflammatory cytokine production characterise the Alzheimer’s disease serum profile. All in all our data seem to suggest that reduction of −330G allele frequency might be protective for healthy ageing limiting cell mediated inflammation implied in age associated diseases.

Plasma glucose excursions in older persons with Type 2 diabetes mellitus.

Abstract: Type 2 diabetes is a complex and heterogeneous metabolic disorder with a continuously growing prevalence worldwide. Thus, the need to prevent diabetic complications by maintaining better metabolic control has become a common goal for health practitioners. Elevated fasting plasma glucose concentrations, frequently observed in Type 2 diabetic patients, are a marker for disturbances in glucose control which can lead to subsequent complications. However, such levels may be considered an incomplete index of glucose control in light of the fact that mealtime glucose excursions are also responsible for overall glucose control. Recently, studies have underlined the fact that plasma glucose fluctuations, such as those occurring in an absorptive state, may not only be an important determinant of overall glucose control and risk of diabetic complications, but they may also exert an independent negative effect on the long-term outcome of diabetes. Many mechanisms have been described by which mealtime glucose excursion could pose a potential risk factor for cardiovascular disease in diabetic patients. Acute elevations of plasma glucose concentrations trigger an array of tissue response that may contribute to the development of vascular complications. Therefore, we will discuss how post-prandial glucose excursions are a fundamental risk factor for the development of cardiovascular disease, especially in older persons with Type 2 diabetes.

Clinical and biochemical evaluation changes over aging.

Abstract: It is widely recognized that the assessment of diseases status performed according to the traditional dichotomy “no disease vs. disease” is insufficient to understand the complexity of problems that influence health and well being in older persons. This concept was recognized long ago by geriatricians and implemented in the paradigm of “Comprehensive Geriatric Assessment”. Accordingly, many researchers and clinicians have proposed that the direct assessment of physical and cognitive function provides the essential information that is needed to design effective interventions in frail older persons. However, this approach has never been completely translated into clinical practice and many geriatricians claim that the administration of any available medical treatment is still conditioned to a previous diagnosis of specific diseases and hypotheses about specific pathophysiological pathways. Furthermore, significant changes in health status may occur and be amenable to effective treatment long before any clear effect on physical and cognitive function is detected.