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In humans, taurine (TAU) is a conditionally essential nutrient that exhibits pleiotropic activity in several and different biological processes suggesting its use in the prevention and therapy for a long time. However, its actual role in prevention and treatment is still incomplete and unclear. This review focuses on the potential therapeutic effect of TAU in genetic diseases, cardiovascular diseases (heart failure, hypertension), metabolic syndrome, and on the first pandemic of the third millennium, namely, diabetes mellitus and some gestational diseases such as gestational diabetes, intrauterine growth restriction, and pre-eclampsia, discussing the role of TAU in developmental trajectory. Previous preclinical and clinical TAU investigations predominately enrolled male animals, including humans, even though sex and gender differences play a critical role both in numerous physiological and pathological conditions. This review aims to outline some biological actions of TAU and evidences the sex and gender gap must be reduced in order to establish the role of TAU in prevention and therapy for all individuals.

To analyze hospitalization for lower extremity amputations (LEAs) and amputee rates in persons with and without diabetes in Italy. All patients with LEAs in the period 2001-2010 were identified analyzing the National Hospital Discharge Record database. For each year, amputee and hospitalization rates for LEAs were calculated either for persons with diabetes or without. Time trend for major and minor amputations were analysed. From 2001 to 2010 a mean annual number of 11,639 individuals underwent a lower extremity amputation: 58.6% had diabetes accounting for 60.7% of total hospitalizations. In 2010, the crude amputee rate for LEAs was 20.4 per 100,000 inhabitants: 247.2 for 100.000 persons with diabetes, and 8.6 for those without diabetes. Having diabetes was associated to an increased risk of amputation (Poisson estimated RR 10.9, 95%CI 9.4-12.8). Over the whole period, a progressive reduction of amputee rates was observed for major amputations either among persons with diabetes (-30.7%) or without diabetes (-12.5%), while the rates of minor amputations increased progressively (+22.4%) among people without diabetes and were nearly stable in people with diabetes (-4.6%). A greater number of minor amputations were performed among persons with than without diabetes: in 2010, the minor-to-major ratio among persons with diabetes (2.5) was more than twice than in those without diabetes (1.0). The nationwide analyses confirm a progressive reduction of hospitalization and amputee rates for major LEAs, suggesting an earlier and more diffuse approach aimed at limb salvage.

Variability in daily blood pressure (BPV) recorded 24-h ambulatory blood pressure monitoring (ABPM) is known to be related to left ventricular hypertrophy and an increased incidence of cardiovascular events in hypertensive patients. The aim of this study was to evaluate whether left atrium dimension, which increases early in hypertensive subjects, was related to BPV in a group of 167 drug-naive patients (100M/67F, age: 46±11yr). The patients were chosen among those consecutively sent by their general practitioners to confirm the existence of arterial hypertension and afterwards diagnosed as hypertensive (mean 24-h ABPM ⩾130/80 mm Hg). In each patient, the left atrial posteroanterior diameter index for height (LADi) and the left ventricular mass standardized for body surface area (LVMi) were measured using standardized echocardiographic methods. BPV was calculated as the weighted mean of daytime and nighttime systolic and diastolic blood pressure s.d.'s (ws.d.), according to the formula ws.d.=[(daytime s.d. × 10)+nighttime s.d. × 6)]/16. An increase in left atrial dimension (LADi>24 mm m(-1)) was present in 36 patients (21.6% of the total population). In a univariate regression, LVMi was significantly related to systolic BPV (r=0.24; P=0.02) only in men, whereas LADi was significantly related to both systolic and diastolic BPV in both genders. After adjusting for sex, age, BMI, heart rate, diastolic function and estimated glomerular filtration rate, both systolic and diastolic BPV remained significantly related to LADi (P=0.02 for both) but not to LVMi. In conclusion, this study suggests that BVP, as measured as BPws.d., is significantly and independently associated with increased LADi in newly diagnosed, treatment-naive hypertensive patients.

AimsDiabetic foot syndrome (DFS) increases the risk for atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or mortality. The present study aims at ascertaining whether such DFS-related excess risk differs between genders, retrospectively investigating a population with diabetes from Tuscany, Italy, followed-up for 6 years (2011–2016).MethodsPeople with diabetes living in Tuscany on January 1st 2011 identified by administrative databases, were divided by baseline history of prior DFS hospitalizations, stratified by presence/absence of peripheral vascular disease and evaluating, by Cox regression analysis, whether adjusted DFS-related excess risk of incident ASCVD, CKD or mortality differed between genders.ResultsIn an overall population of 165,650 subjects with diabetes (81,829M/83,821F), basal prevalence of DFS was twice higher among males, who were moreover at a significantly greater risk of all considered outcomes along the 6-year period. On the contrary, baseline DFS significantly increased the hospitalization risk for ASCVD, CKD and mortality equally or at a slightly greater extent in females, while the risk for stroke was significantly associated with DFS only among females (HR: 1.622 (1.314–1.980); p = 0.0001 vs. HR: 1.132 (0.955–1.332); p = NS). This finding was even reinforced in non-vascular DFS, which was associated with a significant raised risk for stroke, heart failure or mortality exclusively in females.ConclusionsIn this population, DFS prevalence and overall risk for ASCVD, CKD or mortality were significantly higher among males. Baseline co-presence of DFS, however, conferred a similar adjusted risk for all these outcomes between genders, and in case of non-vascular DFS the risk was significantly increased only among females.

Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients Elza Muscelli 1 , Andrea Mari 2 , Arturo Casolaro 1 , Stefania Camastra 1 , Giuseppe Seghieri 3 , Amalia Gastaldelli 1 , Jens J. Holst 4 and Ele Ferrannini 1 1 Department of Internal Medicine and Consiglio Nazionale delle Ricerche (CNR) Institute of Clinical Physiology, University of Pisa, Italy 2 CNR Institute of Biochemical Engineering, Padova, Italy 3 Division of Internal Medicine, Spedali Riuniti, Pistoia, Italy 4 Department of Medical Physiology, Panum Institute, Copenhagen, Denmark Corresponding author: Ele Ferrannini, MD, Department of Internal Medicine, Via Roma, 67, 56122 Pisa, Italy. E-mail: ferranni{at}ifc.pi.cnr.it Abstract OBJECTIVE— To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS— Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20–61 kg/m 2 ). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration dose-response curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique. RESULTS— The incretin effect on total insulin secretion and β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT ( P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile ( P ≤ 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27–0.59, P ≤ 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response ( r = 0.53, P < 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients. CONCLUSIONS— Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another. AUC, area under the time concentration curve FFM, fat-free mass GIP, glucose-dependent insulinotropic polypeptide GLP, glucagon-like peptide IGT, impaired glucose tolerance NGT, normal glucose tolerance OGTT, oral glucose tolerance test TTR, tracer-to-tracee ratio Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 27 December 2007. DOI: 10.2337/db07-1315. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted December 17, 2007. Received September 14, 2007. DIABETES

Soccer (football) practice can induce a limitation of ankle range of motion (ROM) that is a possible risk factor for injury and other negative consequences over time. The main objective of this research was to investigate the effects of soccer practice on ankle ROM throughout the entire period of a sports career of soccer players (SP). Furthermore, the relationship between ankle ROM and muscle strength in SP of different ages was studied. A total of 204 SP (range 6.7–45.1 years) and 87 controls (range: 7.5–45.2 years) matched for age, body mass index (BMI), and gender, were assessed. Ankle ROM in both plantar flexion (APF) and dorsiflexion (ADF) in addition to handgrip strength (HGS) were evaluated using an inclinometer and the Jamar hydraulic hand dynamometer, respectively. The comparison between SP and control groups showed a significant reduction in ankle ROM of both APF (26.3 ± 7.2° vs. 32.6 ± 7.4°; d = −0.90; p < 0.001) and ADF (95.5 ± 15.6° vs. 105.5 ± 15.8°; d = −0.66; p < 0.001). In SP, the results of the ANOVAs test indicate that age had a significant effect on ADF (F = 4.352, p = 0.038, partial eta-squared (ηp2) = 0.015) but not on APF (F = 0.430, p = 0.746, ηp2 = 0.001). Moreover, considering only the SP, a weak inverse correlation between ADF and HGS group ADF was found (rs = −0.27; p < 0.001). Factors such as the non-linear trend of growth in young SP could hinder the definition of the relationship between ankle ROM, age, and muscle strength. However, the appropriate consideration of age and muscle strength could facilitate the management of ankle ROM in PF of different ages.

Lower extremity ulcers represent the most ominous, feared, and costly complications of diabetes mellitus. The aim of this review is to highlight the role of daily life physical activities (PAs) and continuous movement monitoring (CMM) in the prevention of foot ulcers. Peripheral neuropathy and peripheral vascular disease are the main causes of foot ulceration and contribute, in turn, to the development of additional risk factors such as foot deformities and/or joint and muscular alterations. Moreover, a deficit of balance, posture abnormalities, followed by gait alterations, increases the risk of ulceration. PA can play a key role in the management of patients with diabetes and in the prevention of ulcers; however, even if it has been reported that some of these risk factors significantly improve after a few weeks of exercise therapy (ET), the real preventive role of ET has not yet been demonstrated. These uncertain results can occur due to some limitations in the management of the same relationship between PA and diabetic foot prevention. Technological advances during the last years enable timely management of overall daily PA. The use of these modern technologies and devices allows CMM assessment and description of daily PA even in the long term. The data collected from these devices can be used to properly manage patients' PA and thus contribute to the prevention of foot ulcers.

To investigate whether gender affects therapeutic response by exenatide twice a day (BID) in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. We considered a cohort of 315 (154 male/161 female) patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas), who were given exenatide (10 μg/BID) and who fully completed 4 months, 8 months, and 12 months of follow-ups. Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A1c (HbA1c), it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037), and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018). Target glycemic response (1-year HbA1c ≤ 7%) was achieved in a significantly higher proportion of males than females (38% versus 27%; χ(2) = 4.66; P = 0.03). Target weight loss expressed as 1-year weight percent fall from baseline ≥ 75th percentile (8.5%) was significantly higher in females at 8 and 12 months (P < 0.05; for both). One-year glycemic target response was inversely related to baseline HbA1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy) was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic response only in women (P = 0.009). Target 1-year weight loss was predicted by longer diabetes duration among males and by lower baseline HbA1c among females. Finally, no significant difference between genders was noted as to gastrointestinal side effects after exenatide therapy. According to this \"real world\" experience, predictors of glycemic control and body weight loss after 12 months of exenatide BID therapy are different between genders in type 2 diabetes.

Low birth-weight (BW) is related to rise in blood pressure (BP) later in life. Aim of this study is investigating whether presence of overweight-obesity modifies this relationship, independently from any additional correlate of metabolic syndrome. We studied 535 (216 M/319 F) otherwise healthy overweight-obese people (body mass index≥25 kg/m2), recording systolic, diastolic and pulse BP as well as plasma glucose and lipids, additionally interviewing them about BW and weight-change after age of 18 years. The reciprocal of BW was related only to pulse pressure (PP, r=0.14; P=0.04), uniquely in men and individuals with BW≤2500 g had a higher relative risk of having PP above upper quartile (>60 mmHg), independently of sex. After adjusting for confounders each 1 kg rise in BW was associated with 2.84±0.88 (standard error) mmHg decrease in PP; P=0.0042. Moreover, again only among males, the lower BW the higher was the risk of a PP>60 mmHg [odds ratio (95% confidence interval): 2.43 (1.39-4.24); P=0.0018]. In conclusion BW was inversely related only with PP in overweight-obese subjects, uniquely in men, being such effect independent from other correlates of metabolic syndrome. Since elevated PP can be considered a proxy of vascular damage, these findings further stress the importance of inquiring about BW to better stratify the risk of vascular damage, in adult overweight-obese individuals.