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Aims (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre-existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality.Methods All 3892 patients with Type 2 diabetes attending our Diabetic Clinic during 1995 and alive on 1 January 1996 were identified and followed for 4.5 years. Information on vital status (100% complete) and causes of death (98.5% complete) for 599 deceased subjects was derived from death certificates.Results In comparison with the general population, standardized mortality ratios (x 100) were: 125 (95% confidence interval 104-148) in patients aged < 75 and 85 (75-95) in patients >/=75 years. Cardiovascular diseases and diabetes were responsible for most of the excess deaths. In a Cox-proportional hazard model, renal damage was a powerful predictor of death (hazard ratio = 2.39; 95% confidence intervals = 2.00 2.85). The severity of renal damage was associated with increasing hazard ratios for death from all-cause mortality and from specific causes (especially coronary artery disease, other cardiovascular causes and diabetes) after multiple adjustments. Other significant predictors of death were: greater age, glycated haemoglobin, smoking, lower body mass index, pre-existing coronary and peripheral artery disease and known co-morbidity (cirrhosis and cancer).Conclusions Renal damage of any severity is significantly associated with subsequent mortality from all causes and from cardiovascular diseases. These associations are not confounded by pre-existing co-morbidity or coronary diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Lower levels of selenium and vitamin E have been described in gestational diabetes, a condition similar to type 2 diabetes, but few data are available about zinc (known to be associated with diabetes) and gestational hyperglycemia. This study evaluated the dietary intake of antioxidant vitamins, zinc, selenium, and serum levels of zinc and selenium in women with gestational hyperglycemia and normoglycemia. METHODS: A food-frequency questionnaire was administered to 504 pregnant women (210 with hyperglycemia and 294 with normoglycemia). Serum levels of zinc and selenium were analyzed during pregnancy in a second cohort of 71 hyperglycemic and 123 normoglycemic women, with a mean age and body mass index similar to those in the first cohort. RESULTS: Dietary intakes of zinc and selenium were significantly lower in hyperglycemic patients. In multiple logistic regression analysis, intakes were negatively associated with gestational hyperglycemia (odds ratios of 0.89 for zinc and 0.97 for selenium) after multiple adjustments. There were no significant differences in vitamin intakes. In the second cohort of 194 patients, serum levels of zinc and selenium were significantly lower in patients who had impaired glucose tolerance and negatively associated with gestational hyperglycemia in a multiple logistic regression model (odds ratios of 0.93 for serum zinc and 0.92 for serum selenium). CONCLUSIONS: Our data suggested a significant inverse association of dietary intakes and serum levels of zinc and selenium with gestational hyperglycemia. If future studies confirm these results, it might be a useful interventional approach to appropriate dietary counseling in order to evaluate the possible decrease in gestational metabolic abnormalities and their adverse consequences. [ABSTRACT FROM AUTHOR]

Since the passage of the landmark Americans with Disabilities Act of 1990, the United States federal government, states, and localities have passed laws and created policies intended to ensure that people with disabilities had full and equal access to public spaces. Nevertheless, more than three decades after the ADA, people with disabilities continue to face architectural and other barriers to community inclusion and participation. This article describes laws, policies, and initiatives that are implemented in the United States at the federal, state, and local levels to address these barriers, examines their effectiveness, and describes the views of advocates working in furtherance of the rights of people with disabilities and the inclusiveness of public spaces. We conclude by providing brief recommendations for ways federal, state, and local governments may ensure people with disabilities have full and equal access to public spaces., Competing Interests: Conflicts of Interest: The authors declare no conflicts of interest.

The polyphenol resveratrol is considered to exert many beneficial actions, such as antioxidant, anti-inflammatory, insulin-sensitizer and anticancer effects. Its benefits in patients with type 2 diabetes mellitus (T2DM) are controversial. Our aims were to determine whether resveratrol supplementation at two different dosages (500 and 40mg/day) for 6 months i) reduced the concentrations of C-reactive-protein (CRP) and ii) ameliorated the metabolic pattern of T2DM patients. In the present double-blind, randomized, placebo-controlled trial, 192 T2DM patients were randomized to receive resveratrol 500mg/day (Resv500arm), resveratrol 40mg/day (Resv40arm) or placebo for 6-months. At baseline and at the trial end, CRP values, anthropometric, metabolic and liver parameters were determined. No serious adverse event occurred. A dose-dependent, though not significant, CRP decrease of 5.6% (Resv40arm) and 15.9% (Resv500arm) was observed vs placebo. We failed to detect significant differences in weight, BMI, waist circumference, and values of arterial blood pressure, fasting glucose, glycated hemoglobin, insulin, C-peptide, free fatty acids, liver transaminases, uric acid, adiponectin, interleukin-6, in both the Resv500 and Resv40 arms vs placebo. Total cholesterol and triglycerides slightly increased in the Resv500arm. Subgroup analyses revealed that lower diabetes duration (in both Resv500 and Resv40arms), and, in the Resv500arm, younger age, aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo. The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations, nor improve the metabolic pattern of T2DM patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aims: To evaluate cross-sectional associations between dietary magnesium intake and the metabolic pattern of very-low-birth-weight (VLBW, <1500 g) pre-term children, in pre-school years (>2 and <6 years)., Methods and Results: Fifty-eight Italian children without major congenital malformations/conditions were enrolled; dietary intakes, clinical and (in 34 cases) laboratory characteristics were evaluated. Subjects with lower magnesium intake showed significantly higher fasting glucose, insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels. At simple regression analysis, fasting glucose was significantly associated with magnesium intake (inversely) and catch-up growth (CUG). Fasting insulin and HOMA-IR values were inversely associated with intakes of magnesium and fibres, and directly with Body Mass Index (BMI) and CUG. In a multiple regression model, after adjusting for multiple confounders and fibre intake, magnesium intake was inversely associated with glucose (beta=-0.018; 95%CI -0.026 to -0.010), but not with insulin or HOMA-IR levels. In the same model, dietary fibres remained inversely associated with insulin (beta=-0.075; -0.14 to -0.008) and HOMA-IR levels (beta=-0.06; -0.11 to -0.01)., Conclusion: These results suggest a significant association between reduced magnesium intake and fasting glucose, and between reduced fibre intake and insulin resistance and this is present even in earlier childhood, and independently of BMI and growth characteristics.

Rationale, Aims and Objectives: Type 2 diabetes represents a condition significantly associated with increased cardiovascular mortality. The aims of the study are: (i) to estimate the cumulative incidence function for cause-specific mortality using Cox and Aalen model; (ii) to describe how the prediction of cardiovascular or other causes mortality changes for patients with different pattern of covariates; (iii) to show if different statistical methods may give different results., Methods: Cox and Aalen additive regression model through the Markov chain approach, are used to estimate the cause-specific hazard for cardiovascular or other causes mortality in a cohort of 2865 type 2 diabetic patients without insulin treatment. The models are compared in the estimation of the risk of death for patients of different severity., Results: For younger patients with a better covariates profile, the Cumulative Incidence Function estimated by Cox and Aalen model was almost the same; for patients with the worst covariates profile, models gave different results: at the end of follow-up cardiovascular mortality rate estimated by Cox and Aalen model was 0.26 [95% confidence interval (CI) = 0.21-0.31] and 0.14 (95% CI = 0.09-0.18)., Conclusions: Standard Cox and Aalen model capture the risk process for patients equally well with average profiles of co-morbidities. The Aalen model, in addition, is shown to be better at identifying cause-specific risk of death for patients with more severe clinical profiles. This result is relevant in the development of analytic tools for research and resource management within diabetes care.

Background and Aims: An excess of long-term mortality in type 2 diabetes is mainly due to cardiac diseases, predicted by diabetes-related conditions; less is known about early death from clinical diagnosis. The aim of this study was to evaluate pattern and predictors of mortality after a 4.5 year follow-up in a cohort of type 2 diabetic patients, according to diabetes duration., Methods and Results: A mortality follow-up was carried out in 1200 patients with < or = 5 years diabetes duration and 2692 patients with >5 (median 2 and 15) years diabetes duration in 1995. Four-year survival was 92.0% and 83.7%, respectively; most deaths are due to cardiovascular diseases (36% and 41%, respectively). The duration of diabetes is no longer a significant predictor of death after adjustments for age, HbA1c and chronic complications (which are all significantly higher in patients who have had diabetes for longer time). In a Cox proportional hazard model, best predictors of death are nephropathy, insulin therapy and pre-existent co-morbidity in both groups. Nephropathy is significantly associated with cardiovascular deaths in the younger cohort., Conclusion: Clinical nephropathy is a significant predictor of early and late mortality from clinical diagnosis, above all cardiovascular deaths, indicating that an aggressive approach should be adopted for prevention or treatment of renal impairment right from the clinical onset of diabetes.

Aim: To examine the relationships between gamma-glutamyl-transferase (GGT), alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample., Methods: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1 339 subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy)., Results: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference, hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders. In the same model, median NT levels are significantly associated with the increasing GGT tertile (beta = 1.06; 95%CI 0.67-1.45), but not with the AST and ALT tertiles. In a multiple regression model, after adjusting for age, sex, BMI, waist, smoking, and alcohol consumption, both NT (beta = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (beta = 0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia., Conclusion: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

Objective: Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT))., Subjects: A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values., Results: Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45)., Conclusions: Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.

Objectives and Study Design: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM)., Results: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001)., Conclusions: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.

Aims: Studies on plasma nitrotyrosine (NT) levels, a measure of oxidative injury, in diabetes are limited and discordant; the amount of antioxidants might represent a possible explanation for the discordant results. The aim of this paper is to evaluate the association between plasma NT levels and glucose tolerance status, according to antioxidant vitamin intakes., Methods: In three hundred men randomly selected from a population-based cohort, NT levels were measured and dietary intake assessed by a food-frequency questionnaire. Results NT values were similar in patients with diabetes (n = 34), impaired fasting glucose (n = 77) and normoglycaemic subjects (n = 189). However, in subjects with lower than recommended daily intakes of antioxidant vitamins C and A, NT levels were significantly higher in the diabetic patients. In a multiple regression model, after adjustments for age, body mass index (BMI) and smoking habits, NT levels were significantly associated with fasting glucose in patients with lower intakes of vitamin C (beta = 11.4; 95% CI 1.3-21.5) and vitamin A (beta = 14.9; 95% CI 3.9-25.9), but not in subjects with lower intake of vitamin E., Conclusion: A significant positive correlation between NT levels and fasting glucose is evident only in the presence of a reduced intake of some antioxidant vitamins. These findings might explain, at least in part, the discrepant results of previous studies and, if confirmed by further studies, suggest a simple measure (a balanced diet) to alleviate the increased oxidative stress of diabetes.

Background: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects., Design: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia., Results: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile., Conclusions: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.

Objective: We describe the rate, causes, and predictors of hospitalization for all patients with type 2 diabetes in a diabetes clinic in Turin, Italy and compare their hospitalization rates with those of the general population., Study Design and Setting: All patients were recruited and followed up for hospital admissions from January 1996 to June 2000. The role of risk factors was analyzed with a conditional proportional hazard model for repeated events., Results: More than 50% of the patients had been admitted to hospital at least once for any cause, and 30% had had multiple admissions, accounting for nearly 90% of all days in hospital. For these patients, older age, high glycated hemoglobin level, obesity, insulin treatment, presence of nephropathy, coronary and peripheral artery disease and comorbidity were statistically independent predictors of hospital admission. The standardized hospital admission ratios were 158.8 for men <65 years of age and 113.3 for men > or = 65 years and 245.2 for women <65 years of age and 135.3 for women > or = 65 years of age. The highest ratios were for diabetes, vascular (cardiac and cerebral) diseases, and eye diseases in younger women., Conclusion: Patients with type 2 diabetes, and particularly younger women, had higher rates of hospitalization than the general population, with an excess risk of about 30%.

Objective: To evaluate the prevalence of prolonged QT interval and dispersion in a population-based cohort of type 2 diabetic patients and their relationship with clinical and metabolic variables., Design: Cross-sectional population-based cohort., Setting: Diabetes clinics and general practitioners in Casale Monferrato (Northern Italy)., Subjects: A total of 1357 patients with known type 2 diabetes (70% of the cohort)., Main Outcomes Measures: Albumin excretion rate and coronary heart disease (CHD); a standard supine 12-lead electrocardiogram (ECG) was recorded and coded according to the Minnesota code criteria. QT interval corrected for heart rate (QTc) > 0.44 s and QTc dispersion > 0.080 s were considered abnormally prolonged., Results: Prevalence of increased QTc duration and QTc dispersion were 25.8% (95% CI 23.5-28.3) and 33.1% (95% CI 30.6-35.7), with no sex differences. No metabolic differences were found, apart from fibrinogen and creatinine levels, which were higher in patients with increased QTc dispersion. Patients with CHD had higher mean adjusted values of QTc and QTc dispersion, whereas no association was found with albumin excretion rate (AER) and diabetes treatment. QTc duration and QTc dispersion were significantly correlated (0.17, P < 0.001). In multiple regression analysis, only CHD was independently associated with QTc, after adjustment for age and sex (beta=0.010, P < 0.001, R2=2.5%); as regards QTc dispersion, a similar association with CHD was found (beta=0.20, P < 0.001, R2=4.8%)., Conclusions: This population-based study shows a considerably high prevalence of increased QTc and QTc dispersion in type 2 diabetic patients and their association with CHD. These findings have both epidemiological and clinical relevance, as they might be implicated in the excess mortality risk of type 2 diabetic patients.

Background: A number of reports have investigated the association between various gene polymorphisms and the phenotypic expression of myocardial infarction. No investigations have evaluated the prognostic role of genetic factors in young people with premature coronary disease. The aim of this study was to investigate the influence of genetic factors compared with that of conventional risk factors on follow-up events in a population of Italian young adults with myocardial infarction., Methods and Results: The study population consisted of 106 young patients (mean age 40 +/- 4 years, range 23 to 45 years) with diagnosis of acute myocardial infarction. Clinical and genetic data from the group of patients with events during follow-up were compared with those from patients without events. The following genetic polymorphisms were tested: angiotensin I converting enzyme, angiotensin II type I receptor, apolipoprotein E (ApoE), endothelial constitutive nitric oxide synthase, and platelet glycoprotein IIIa. Coronary angiography was performed in 94 patients. Coronary angiography showed coronary artery disease in 93% of patients. During follow-up (46 +/- 12 months, range 25 to 72) the overall combined end points (cardiac death, myocardial infarction, and revascularization procedures) accounted for 21 events. Family history of coronary artery disease, smoking, stenosis of the left anterior descending artery at coronary angiography, and ApoE polymorphism (presence of epsilon4 allele) were significantly more prevalent (univariate analysis) in the group of patients with events. Logistic multivariate analysis showed that ApoE polymorphism (P =. 004, odds ratio [OR] 6.8, 95% confidence interval [CI] 2 to 22), family history (P =.005, OR 8.3, 95% CI 2 to 35), smoking after acute myocardial infarction (P =.008, OR 10.9, 95% CI 2 to 62), and left anterior descending coronary artery disease (P =.02. OR 6.6, 95% CI 1.3 to 33) were independent predictors of adverse events., Conclusions: Myocardial infarction at a young age is commonly characterized by evidence of multiple cardiovascular risk factors and by a favorable prognosis in short- and medium-term follow-up. Evidence of significant disease at coronary angiography suggests the presence of a premature atherosclerotic process. ApoE polymorphism (presence of epsilon4 allele) appears to be a strong independent predictor of adverse events, suggesting a remarkable influence in the accelerated coronary disease.

The purpose of the study is to evaluate the effect of diet and physical exercise on the dyslipemia of renal transplant (RT) patients 52 pts, transplanted between 12/85 and 4/87, subdivided into 2 groups (A and B), were studied. Characteristics of the diet adopted in patients in group A are: low carbohydrates, moderate animal protein, unsaturated and polyunsaturated fat in high rate. The second group had a lower animal protein and more fiber rich diet than the first one and a program of PE. By comparing A and B1 we noticed and increase in body weight, more slight in the group B, at the 24 months (56 +/- 8 59 +/- 10 vs 59 +/- 10 61 +/- 10). The study of lipid behaviour has showed a trend to normalization of triglycerides at 24 months in A (189 +/- 88 106 +/- 33) and in B1 (173 +/- 81 103 +/- 40), more evident normalization of cholesterol in group B1 (195 +/- 72 185 +/- 42), and increase of CT-HDL in A (42 +/- 12 63 +/- 17) and in B1 (44 +/- 10 61 +/- 14, p less than 0.05). It should be noted that CT-LDL increase in A (100 +/- 34 131 +/- 40) but not in B1 (103 +/- 35 111 +/- 33). With the aim of this program we obtained a positive effect on DL with a slight increase in body weight, a significant increase in CT-HDL without variation of total CT and CT-LDL levels.

The effect of the somatostatin analog (GHRIH-A) D-Trp8, D-Cys14 on plasma levels of growth hormone, pancreatic glucagon, insulin and glucose was studied in four acromegalic patients and in four maturity-onset mild diabetics. Acromegalics received a bolus iv injection of 25 microgram of GHRIH-A, followed by a continuous infusion of 25 microgram in saline over an hour. Mild diabetics were submitted in two different days to two tests: arginine (30 g in 30 min) +/- GHRIH-A (bolus iv injection of 25 microgram followed by an infusion of 25 microgram/h over 120 min) and arginine + saline. GHRIH-A lead to a significant (2 p less than 0.01) fall in GH basal secretion in acromegalics, and significantly reduced the GH response to arginine in maturity-onset diabetics. The inhibitory effect of insulin secretion was less impressive, but significative in both groups. No significant changes in plasma pancreatic glucagon values were noted. In mild diabetics, GHRIH-A infusion induced a small but significant increase in the blood glucose increment due to arginine. Our data suggest that this somatostatin analog may be potentially useful only when GH suppression is the main therapeutic goal to be reached, as in acromegaly and in severe diabetic retinopathy, but not in metabolic control of mild diabetic patients with a good residual insulin secretion.