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ABSTRACT: Objective: Smokers are characterized by a low-grade systemic inflammatory state and an oxidant-antioxidant imbalance. Few human studies were conducted on the effects of resveratrol, a natural compound with anti-inflammatory and antioxidant properties, and no trial on smokers has been performed to date. We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers. Methods and Results: A randomized, double-blind, cross-over trial was performed in 50 healthy adult smokers: 25 were randomly allocated to "resveratrol-first" (30-days: 500mg resveratrol/day, 30-days wash-out, 30-days placebo) and 25 to "placebo-first" (30-days placebo, 30-days wash-out, 30-days 500mg resveratrol/day). Resveratrol significantly reduced C-reactive protein (CRP) and triglyceride concentrations, and increased Total Antioxidant Status (TAS) values. After analyzing data with general linear models to assess period and carry-over effects, the ratios of the values after resveratrol to those after placebo were respectively: 0.47 (95%CI 0.38-0.59) -CRP- and 0.71 (95%CI 0.65-0.78) triglycerides-, while TAS increased by 74.2 µmol/L (95%CI 60.8-87.6). Uric acid, glucose, insulin, cholesterol, liver enzyme concentrations, and weight, waist circumference, and blood pressure values did not significantly change after resveratrol supplementation. Conclusions: Because resveratrol has anti-inflammatory, anti-oxidant, and hypotriglyceridemic effects, its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers.
Current Medicinal Chemistry 12/2012; · 4.86 Impact Factor
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ABSTRACT: We prospectively assessed the impact of a sterol regulatory element-binding factor-2 (SREBF-2) polymorphism on the risk of developing nonalcoholic fatty liver disease (NAFLD) and on liver histology and lipoprotein and glucose metabolism in biopsy-proven NAFLD. We followed 175 nonobese, nondiabetic participants in a population-based study, without NAFLD or metabolic syndrome at baseline, characterized for the SREBF-2 rs133291 C/T polymorphism, dietary habits, physical activity, adipokines, C-reactive protein (CRP), and endothelial adhesion molecules. A comparable cohort of NAFLD patients underwent liver biopsy, an oral glucose tolerance test with minimal model analysis to yield glucose homeostasis parameters, and an oral fat tolerance test with measurement of plasma lipoproteins, adipokines, and cytokeratin-18 fragments. After 7 years, 27% of subjects developed NAFLD and 5% developed diabetes. SREBF-2 predicted incident NAFLD and diabetes and CRP and endothelial adhesion molecule changes. In biopsy-proven NAFLD patients, SREBF-2 predicted nonalcoholic steatohepatitis (odds ratio 2.92 [95% CI 2.08-4.18], P = 002) and the severity of tissue insulin resistance, β-cell dysfunction, and oral fat intolerance (characterized by higher postprandial lipemia, cholesterol enrichment of triglyceride-rich lipoproteins and oxidized LDLs, HDL cholesterol fall, adipokine imbalance, and postprandial apoptosis activation). An SREBF-2 polymorphism predisposes individuals to NAFLD and associated cardiometabolic abnormalities and affects liver histology and glucose and lipid metabolism in biopsy-proven NAFLD.
Diabetes 12/2012; · 8.29 Impact Factor
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ABSTRACT: The headword "overlap syndromes" of liver diseases includes the coexistence of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. These syndromes often represent a diagnostic and therapeutic challenge for hepatologists; it remains unclear whether these overlap syndromes form distinct entities or they are only variants of the major autoimmune liver diseases. The most frequent reported association occurs between autoimmune hepatitis and primary biliary cirrhosis, whereas the overlap between autoimmune hepatitis and primary sclerosing cholangitis is less frequent, typically at young age and often attendant with an inflammatory bowel disease. The choice therapy is based on ursodeoxycholic acid and immunosuppressive drugs, used at the same time or consecutively, according to the course of disease. The diagnostic scores for autoimmune hepatitis can help for diagnosis, even though their definitive soundness is lacking.
Digestive Diseases and Sciences 10/2012; · 2.12 Impact Factor
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ABSTRACT: There are few prospective data on the prognosis of insulin-sensitive and insulin-resistant normal-weight (NW) or obese individuals.
The estimated liver fat content, incidences of hyperglycemia and cardiovascular disease, and all-cause and cardiovascular mortality rates were investigated in a population-based cohort of 1658 individuals who were categorized according to BMI and insulin resistance as defined by HOMA-IR values ≥2.5 and the presence of metabolic syndrome.
This was a prospective cohort study with a 9-y follow-up. Anthropometric values, blood pressure, and blood metabolic variables were measured, and information on vital status was collected from demographic files at follow-up.
A total of 137 of 677 NW individuals (20%) were classified as insulin resistant and normal weight (IR-NW), and 72 of 330 obese individuals (22%) were classified as insulin sensitive and obese (IS-obese). Incidences of diabetes, impaired fasting glucose, and cardiovascular events were 0.4%, 6.3%, and 3.3%, respectively, in insulin-sensitive and normal-weight (IS-NW) individuals (reference category); 5.8%, 10.2%, and 6.6%, respectively, in IR-NW individuals; and 5.6%, 8.3%, and 8.3%, respectively, in IS-obese individuals. In a multiple logistic regression model, risks of incident hyperglycemia and cardiovascular events increased in both groups compared with in the reference category [HR (95% CI): 2.54 (1.42, 4.55) and 1.98 (0.86, 4.54) in IR-NW subjects; 2.16 (1.01, 4.63) and 2.76 (1.05, 7.28) in IS-obese subjects]. The estimated liver fat content significantly increased during follow-up only in the IR-NW group in the same model. Cardiovascular mortality was 2-3-fold higher in IR-NW and IS-obese than in IS-NW individuals in a Cox regression model.
Our data refute the existence of healthy obese phenotypes because IS-obese individuals showed increased cardiometabolic risk. The existence of unhealthy NW phenotypes is supported by their increased risk of incident hyperglycemia, fatty liver, cardiovascular events, and death.
American Journal of Clinical Nutrition 10/2012; 96(5):962-9. · 6.67 Impact Factor
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Chiara Giordanino,
Simone Ceretto, Simona Bo,
Antonina Smedile,
Alessia Ciancio,
Elisabetta Bugianesi,
Rinaldo Pellicano,
Sharmila Fagoonee,
Elisabetta Versino,
Giuseppe Costa,
Daniele Arese,
Marco Sacco,
Mario Rizzetto,
Giorgio Saracco
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ABSTRACT: The long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C.
Retrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02±4.9 years.
50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p=0.006; 18% vs 5.7%, p=0.007, respectively) with a mortality of 14% vs 1.5% (p=0.0003). Baseline cirrhosis (p=0.002) and non-sustained virological response (p=0.01) were independent risk factors for liver events; diabetes mellitus (p=0.01) and hypertension (p=0.0017) were independent factors for diabetes-related events.
In patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.
Digestive and Liver Disease 01/2012; 44(5):406-12. · 3.05 Impact Factor
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world (it affects 30% of the general adult population). The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.
International journal of hepatology. 01/2012; 2012:464706.
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ABSTRACT: Nonalcoholic steatohepatitis (NASH) affects 3-5% of the general adult population and predisposes to cirrhosis, cardiovascular disease (CVD), and diabetes through unclear mechanisms. Lectin-like oxidized LDL receptor-1 (LOX-1) has been connected to CVD risk in the general population and to insulin resistance and hepatic fibrogenesis in experimental models.
The objective was to assess the effect of the common functional LOX-1 IVS4-14 A→G polymorphism on liver disease, adipokines, oxidative stress, lipoprotein metabolism, and glucose homeostasis in NASH.
Forty nonobese, nondiabetic, normolipidemic biopsy-proven NASH patients and 40 age-, sex-, BMI-, and LOX-1 IVS4-14 A→G polymorphism--matched healthy control subjects underwent an oral-fat-load test (OFT), with measurement of plasma triglyceride-rich lipoprotein (TRLP) subfractions, oxidized LDL, total antioxidant status (TAS), adipokines (resistin and adiponectin), and cytokeratin-18 fragments (marker of hepatocyte apoptosis). The subjects also underwent an oral-glucose-tolerance test (OGTT), with minimal model analysis to yield variables of glucose homeostasis.
The LOX-1 polymorphism was independently associated with liver histology (G allele carriers had more severe liver disease); during the OFT, the G allele was associated with small TRLP accumulation, lower TAS, adipokine imbalance (higher resistin and lower adiponectin), and increased cytokeratin-18 fragments. The G allele was also independently associated with insulin resistance, impaired pancreatic β cell function, and incretin effect during the OGTT.
In NASH, the LOX-1 polymorphism is associated with liver disease severity and may predispose to CVD through modulation of postprandial small TRLPs and adipokine balance and to diabetes by affecting both insulin secretion and insulin sensitivity.
American Journal of Clinical Nutrition 08/2011; 94(4):1033-42. · 6.67 Impact Factor
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ABSTRACT: Few studies suggest that metformin decreases cancer mortality in type-2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other-than-cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area.
In 1995, all T2DP (n = 3685) at our diabetes clinic in Turin (∼12% of all T2DP in the city), without cancer at baseline, were identified. Vital status was assessed after a mean 4.5-year follow-up.
Metformin users had greater adiposity, while insulin users had more co-morbidities. All-cause- and cancer-related deaths occurred in: 9.2 and 1.6% of metformin users, 13.1 and 3.0% of sulfonylureas users and 26.8 and 4.8% of insulin users, respectively. In a Cox regression model for competing risks, adjusted for propensity score, metformin users showed a lower cancer mortality risk [hazard ratio (HR) = 0.56; 95% confidence interval (CI) 0.34-0.94], while insulin was positively associated with other-than-cancer mortality (HR = 1.56; 95%CI 1.22-1.99). Each 5-year metformin exposure was associated with a reduction in cancer death by 0.73, whereas every 5-year insulin exposure was associated with 1.25-fold increase in other-than-cancer death. Standardized mortality ratios for cancer and other-than-cancer mortality in metformin users were 43.6 (95%CI 25.8-69.0) and 99.1 (95%CI 79.3-122.5), respectively, in comparison with the general population.
Metformin users showed a lower risk of cancer-related mortality than not users or patients on diet only; this may represent another reason to choose metformin as a first-line therapy in T2DP.
Diabetes Obesity and Metabolism 08/2011; 14(1):23-9. · 3.38 Impact Factor
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ABSTRACT: We hypothesized that LOX-1 polymorphism may impact on inflammation and cardiovascular risk by modulating systemic resistin expression.
276 men were randomly selected from a population-based cohort. Metabolic and inflammatory markers were evaluated at baseline and after 6-years follow-up, OLR1 (loxin) IVS4-14 A>G polymorphism was assessed.
Mean plasma resistin and nitrotyrosine values were significantly higher, and TAS was significantly lowered in homozygous for the G allele. The G allele was significantly and directly associated with resistin and nitrotyrosine values.
Enhanced oxidized-LDL uptake by LOX-1 G-allele carriers is associated with increased pro-oxidant status and resistin levels, suggesting a major uptake of ox-LDL by macrophages, smooth muscle cells, and monocytes.
Clinical biochemistry 06/2011; 44(12):1015-7. · 2.02 Impact Factor
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ABSTRACT: This article aims to describe the various approaches in multivariable modelling of healthcare costs data and to synthesize the respective criticisms as proposed in the literature.
We present regression methods suitable for the analysis of healthcare costs and then apply them to an experimental setting in cardiovascular treatment (COSTAMI study) and an observational setting in diabetes hospital care.
We show how methods can produce different results depending on the degree of matching between the underlying assumptions of each method and the specific characteristics of the healthcare problem.
The matching of healthcare cost models to the analytic objectives and characteristics of the data available to a study requires caution. The study results and interpretation can be heavily dependent on the choice of model with a real risk of spurious results and conclusions.
International Journal for Quality in Health Care 06/2011; 23(3):331-41. · 1.96 Impact Factor
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ABSTRACT: We aim at evaluating how data-mining statistical techniques can be applied on medical records and administrative data of diabetes and how they differ in terms of capabilities of predicting outcomes (e.g. death). Data on 3,892 outpatient patients with a diagnosis of type 2 diabetes from the San Giovanni Battista Hospital in Torino. Six statistical classifiers were applied: Logistic regression (LR), Generalized Additive Model (GAM), Projection pursuit Regression (PPR), Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Artificial Neural Networks (ANN). All models selected the same subset of covariates. ANN is the model performing worse, whereas simpler models, like LR, GAM and LDA seem to perform better. GAM is associated with a very small misclassification rate. The agreement in predicting individual outcomes among models is 0.23 (SE 0.06, Kappa). Monitoring on the basis of patients' characteristics is highly dependent from the statistical properties of the chosen statistical model.
Journal of Medical Systems 04/2011; 35(2):277-81. · 1.13 Impact Factor
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ABSTRACT: Observational studies suggest that some trace elements and magnesium (Mg) improve glucose metabolism, markers of inflammation, and oxidative stress, but supplementation studies have yielded inconsistent results. Our objective was to evaluate whether a lifestyle intervention trial, aimed at reducing total and saturated fat and increasing fiber intake, can affect also the intake of selenium (Se), zinc (Zn), copper (Cu), chromium (Cr), and Mg.
Dietary intake of Se, Cr, Zn, Cu, and Mg was evaluated at baseline and at the end of a lifestyle intervention trial performed in 335 dysmetabolic adults.
At baseline, trace element and Mg intake in the intervention (n = 169) and control (n = 166) groups of the trial were not significantly different. The former significantly increased their intake of Se, Mg, and Cr, while the latter reduced the intake of Mg, Zn, and Cr. Between-group differences were significant for Mg, Cr, and Se.
Healthier lifestyle recommendations might improve the pattern of micronutrient and Mg intake, which might play an independent role in ameliorating some metabolic, inflammatory, and oxidative markers.
Nutrition 01/2011; 27(1):108-10. · 3.03 Impact Factor
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Journal of the American Society of Nephrology 07/2010; 21(7):1067-8. · 9.66 Impact Factor
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ABSTRACT: To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control.
Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort.
At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for beta-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35-3.20] and 3.56 [2.11-5.98] in CT and TT genotypes, respectively).
The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.
Diabetes care 03/2010; 33(6):1233-5. · 8.09 Impact Factor
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Simona Bo,
Roberto Gambino,
Giovannino Ciccone,
Rosalba Rosato,
Nadia Milanesio,
Paola Villois,
Gianfranco Pagano,
Maurizio Cassader,
Luigi Gentile,
Marilena Durazzo,
Paolo Cavallo-Perin
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ABSTRACT: TCF7L2 is the strongest locus linked to type 2 diabetes that has been identified thus far, and rs7903146 is the most significantly associated variant. Few intervention studies have shown that it has negative effects on metabolic improvement after lifestyle programs.
Our objective was to assess the effects of this variant on lifestyle intervention-induced changes in glucose values and metabolic variables at 1- and 4-y follow-ups.
The rs7903146 variant was genotyped in 335 nondiabetic, dysmetabolic participants in a randomized lifestyle intervention trial.
Subjects with the unfavorable TT genotype showed higher values of fasting glucose and lower homeostasis model assessment of beta cell function at baseline. Lifestyle modifications were successful in the amelioration of metabolic traits in all genetic subgroups after 1 y. At 4-y follow-up most of the metabolic benefits had disappeared. In a multiple regression model, values for glucose and homeostasis model assessment of beta cell function at 4 y were significantly associated with the T allele (for glucose and homeostasis model assessments, respectively: beta = 6.6; 95% CI: 2.5, 10.7; P = 0.001; and beta = -0.37; 95% CI: -0.54, -0.20; P < 0.001) but not with intervention. There was no interaction between genotype and intervention. After 1 y, impaired fasting glucose and diabetes incidence were inversely associated with intervention. After 4 y, the presence of a T allele was associated with impaired fasting glucose (odds ratio: 3.04; 95% CI: 1.53, 6.04; P = 0.001) and diabetes (odds ratio: 2.63; 95% CI: 1.00, 6.96; P = 0.05) but not with intervention.
Lifestyle modifications improved the metabolic pattern in all genetic subgroups. At the end of the trial, however, weight gain occurred, and carriers of the T allele developed first hyperglycemia and decreased insulin secretion, which suggests the need for different "after-care" preventive approaches tailored to each genotype's metabolic risk.
American Journal of Clinical Nutrition 10/2009; 90(6):1502-8. · 6.67 Impact Factor
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ABSTRACT: Iron supplementation in pregnancy seems beneficial for neonatal/maternal outcomes, but it was associated with diabetes and hypertension in the general population.
We investigated the association between iron supplementation during midpregnancy and metabolic/hypertensive abnormalities in 500 consecutive gestational diabetes mellitus (GDM) and 500 normoglycemic women.
Iron-supplement users (n = 212/1000) showed significantly higher values of prepregnancy body mass index (BMI), actual BMI, waist circumference, blood pressure, fasting glucose, Homeostasis-Model-Assessment-Insulin-Resistance, and lower high-density lipoprotein-cholesterol than nonusers. The prevalence of GDM (70.8% vs 44.4%), hypertension (25.9% vs 9.8%), metabolic syndrome (25.9% vs 10.4%) was significantly higher in the former with a 2- to 3-fold-increased risk at multiple regression analyses. Most glucose values of the oral glucose tolerance test were significantly higher in iron supplemented women, both in GDM and normoglycemic individuals.
Iron supplementation is associated with glucose impairment and hypertension in midpregnancy; its potential harmful effects might be carefully debated regarding its effectiveness.
American journal of obstetrics and gynecology 07/2009; 201(2):158.e1-6. · 3.28 Impact Factor
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Marilena Durazzo,
Grazia Niro,
Alberto Premoli,
Enrico Morello,
Erik Rosa Rizzotto,
Roberto Gambino, Simona Bo,
Giovanni Musso,
Maurizio Cassader,
Gianfranco Pagano,
Annarosa Floreani
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ABSTRACT: Cytokines may play an important role as inflammatory factors in liver diseases. There is some evidence suggesting a link between adiponectin-biliary function and liver disease. The aim of this study was to clarify the behavior of adipokines in autoimmune hepatitis type 1.
We assessed the circulating levels of adiponectin, tumor necrosis factor-alpha, resistin and leptin in 42 patients with autoimmune hepatitis, comparing them with 42 healthy subjects who were matched for age and sex and with 31 patients with nonalcoholic steatohepatitis (NASH), evaluating the associations with markers of cytolysis, cholestasis, and histological severity.
Adiponectin and TNF-alpha values were higher in patients compared to controls. The patients showed significantly higher Homeostasis Model Assessment values, suggesting an increased insulin resistance and serum levels of adiponectin positively correlated with gamma-glutamyltranspeptidase and alkaline phosphatase values after a simple regression analysis. Serum levels of resistin positively correlated with elevated aminotransferases and bilirubin values, and serum levels of TNF-alpha positively correlated with elevated alanine-aminotransferase and resistin values. The concentration of adiponectin increased significantly with staging of the disease. Patients with NASH showed lower levels of adiponectin and higher levels of resistin than AIH patients and controls.
Patients with AIH showed significantly higher adiponectin concentrations than controls despite their higher HOMA-IR values. The significant correlation between adiponectin levels and serological features of cholestasis suggested an association with biliary function. Our results indicate that adiponectin may be a possible marker for disease progression in AIH.
Journal of Gastroenterology 04/2009; 44(5):476-82. · 4.16 Impact Factor
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ABSTRACT: Healthcare cost distribution generally presents a high level of skewness, with a relatively small number of subjects accounting for a large portion of healthcare expenditures. Information on factors that predict high expenditures is of interest in healthcare planning. The aim of this paper was to inspect the behaviour of extreme regression (ER) models.
We performed a simple simulation study, based on the LogNormal distribution, to assess the performance of ER in the special cases of heterogeneity and strong asymmetry of the cost variable. We then discussed the application of ER models to the analysis of three data sets of diabetes, lung cancer and myocardial infarction patients.
The ER showed to be able to cope fairly well with skewed distribution but under the condition that all observations have strictly positive costs.
The main advantage of the ER model is to unify these approaches in a unique framework, where the estimation of the cut-offs and the production of the prediction rules are performed simultaneously for a continuous response variable. The final model can thus be analysed at any desiderate quantile of the cost distribution, avoiding the need of pre-specifying any cut-off.
Journal of Evaluation in Clinical Practice 03/2009; 15(1):164-71. · 1.23 Impact Factor
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ABSTRACT: A Few population-based studies have shown that high-normal blood pressure clusters with other cardiovascular risk factors. Increased inflammation, endothelial dysfunction, oxidative stress, and reduced adiponectin values have sporadically been reported in these patients.
We cross-sectionally compared blood pressure categories with cardiovascular risk factors in an adult population-based cohort (n = 1658) and evaluated the relationships between C-reactive-protein, nitrotyrosine, total antioxidant status, E-selectin, vascular adhesion molecule-1, intercellular adhesion molecule-1, resistin, adiponectin values and blood pressure categories in a subgroup of healthy lean individuals from this cohort (n = 107) in order to exclude the impact of obesity/insulin resistance on these variables.
Glucose, triglyceride, low-density lipoprotein-cholesterol, alanine aminotranferase, gamma-glutamyl transferase values, and diabetes and metabolic syndrome prevalence were significantly higher in high-normal compared with the optimal blood pressure category. In the healthy subgroup, adiponectin (beta = - 4315.3; 95% confidence interval - 5916.4 -2654.2), total antioxidant status (-0.15; -0.3 -0.04) were significantly lower, and nitrotyrosine (1.2; 0.3 2.1), E-selectin (11.7; 1.8 21.6), vascular adhesion molecule-1 (0.3; 0.1 0.5), and intercellular adhesion molecule-1 (0.3; 0.1 0.5) were higher in high-normal compared with the optimal blood pressure category, at multiple regression analyses.
Individuals with high-normal blood pressure had a higher prevalence of cardiovascular and metabolic risk factors than those with optimal, and, even if healthy, they showed reduced adiponectin values, early signs of endothelial dysfunction, and oxidative stress. Further research is needed to determine whether they will benefit from blood pressure reduction.
Journal of Hypertension 02/2009; 27(1):102-8. · 4.02 Impact Factor
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Chiara Giordanino,
Elisabetta Bugianesi,
Antonina Smedile,
Alessia Ciancio,
Maria Lorena Abate,
Antonella Olivero,
Rinaldo Pellicano,
Maurizio Cassader,
Roberto Gambino, Simona Bo,
Giovannino Ciccone,
Mario Rizzetto,
Giorgio Saracco
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ABSTRACT: Patients with chronic hepatitis C are at risk of developing type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG), and this risk may increase among hepatitis C virus (HCV) patients not responding to an antiviral therapy.
To compare the incidence of glucose abnormalities (IFG or DM) after an antiviral therapy between HCV+ patients with a long-term virological response (LTR) and nonresponders (NR; persistently positive HCV-RNA).
All 202 HCV+ patients without the baseline glucose abnormalities enrolled by our center in investigational trials or routinely treated with interferon (IFN)/peginterferon (Peg-IFN) (+/- ribavirin) from 1988 to 2001, with the available baseline sera stored at -80 degrees C, were considered. The baseline data included age, sex, body mass index (BMI), viral load, genotype, liver histologic staging and steatosis, glucose, and cholesterol. The homeostatic assessment of insulin resistance (HOMA-IR) was calculated in the baseline serum. The incidence of IFG or DM at the end of follow-up was compared between patients with LTR and NR.
After a median follow-up of 8.0 yr (range 5-16), the cumulative risk of DM (N = 7) or IFG (N = 33) among the 202 HCV+ included patients was 16.9% (95% confidence interval [CI] 11.3-22.5). The 8-yr risk was not significantly lower between LTRs (14.5%) compared to NRs (18.8%) (hazard ratio [HR] 0.60, CI 0.30-1.20, P= 0.16). The HR adjusted for the baseline risk factors for DM and the predictors of a poor response (age, sex, HOMA-IR, BMI, family history of diabetes, HCV genotype 1, high viral load, cirrhosis, and steatosis) was 0.88 (CI 0.38-2.02, P= 0.76). Among other factors, those more associated to IFG-DM were an increasing age (P= 0.017), a higher BMI (P= 0.054), and a family history of DM (P= 0.065).
After adjustment for several baseline risk factors, the incidence of glucose abnormalities was not significantly different between LTRs and NRs. Our data suggest that HCV clearance does not significantly reduce the risk of glucose intolerance.
The American Journal of Gastroenterology 09/2008; 103(10):2481-7. · 7.28 Impact Factor
