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Andrews M.,University of Chile | Soto N.,Endocrinology and Diabetes Unit | Arredondo-Olguin M.,University of Chile
Nutrition | Year: 2015

Objective: The aim of this study was to determine the association between iron parameters and inflammation in obese individuals with and without type 2 diabetes mellitus (T2DM). Methods: We studied 132 obese individuals (OB), 60 individuals with T2DM, 106 obese individuals with T2DM (T2DOB), and 146 controls (C). All of were men aged >30 y. Biochemical, iron nutrition, and oxidative stress parameters were determined. Peripheral mononuclear cells were isolated and total RNA was extracted to quantify tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, interleukin (IL)-6, toll-like receptor (TLR)-2/4 and hepcidin by quantitative reverse transcription polymerase chain reaction. Results: OB, T2DM, and T2DOB individuals had higher ferritin, retinol-binding protein 4, and thiobarbituric acid reactive substance (TBAR) levels than controls. T2DOB and T2DM individuals showed high high-sensitivity C-reactive protein (hsCRP) levels and OB with and without T2DM had elevated levels of serum hepcidin. Heme oxygenase activity was high in OB and T2DM and there were no differences observed in superoxide dismutase and glutathione parameters. A correlation between TBARS and ferritin in T2DOB was observed (r = 0.31; P < 0.006). Multiple linear regression analysis showed an association between diabetes and obesity with ferritin, TBARS, and hsCRP levels. The upper quartiles of ferritin, TBARS and hepcidin showed an adjusted odd ratio for T2DM of 1.782, 2.250, and 4.370, respectively. TNF-α, IL-6, hepcidin, NF-κB, TLR-2/4 mRNA abundances were increased in T2DM and T2DOB. Conclusion: Elevated hsCRP and hepcidin levels, and increased gene expression of TNF-α, IL-6, NF-κB, and TLR-2/4 in patients with diabetes, obesity, or both exacerbate and perpetuate the insulin resistance and inflammatory state. © 2015 Elsevier Inc.

Pedicelli S.,University of Rome Tor Vergata | Alessio P.,University of Rome Tor Vergata | Scire G.,University of Rome Tor Vergata | Cappa M.,Endocrinology and Diabetes Unit | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: It is still controversial whether all girls with central precocious puberty (CPP) should undergo brain magnetic resonance imaging (MRI) for unveiling intracranial pathology. Objectives: The objectives of the study were to determine the prevalence and type of intracranial lesions in otherwise normal girls with central precocious puberty (idiopathic CPP) and to identify the clinical and biochemical predictors of brain abnormalities. Design and Setting: This was a retrospective study conducted at the Endocrine Unit of "Bambino Gesù" Children's Hospital (Rome, Italy) from 1990 to 2012. Patients: Onehundred eighty-two girls were consecutively diagnosed with CPP. All girls underwent a thorough endocrine assessment and brain MRI with a detailed examination of the hypothalamicpituitary area. None of them had a history of neurological diseases, endocrine disorders, neurofibromatosis or other genetic syndromes, or previous hormonal therapies. Main Outcome Measure: Prevalence of brain abnormalities at MRI scan was measured. Results: Brain MRI showed no alteration in 157 (86%), incidentalomas of the hypothalamic-pituitary area unrelated to CPP in 19 (11%), and hamartomas in six girls (3%). Girls with hamartomas were younger than 6 years and had significantly higher mean baseline and stimulated LH values (P < .001), LH to FSH ratio (P < .001), serum 17β-estradiol levels (P < .001), and uterine length (P < .05). However, all the parameters overlapped extensively in girls with or without cerebral alterations. Conclusions: Our data cast doubt on the need of routine screening by brain MRI in girls with idiopathic CPP older than 6 years. Evidence-based criteria to drive clinical decision making about the use of MRI are lacking. Copyright © 2014 by the Endocrine Society.

Pugliese G.,University of Rome La Sapienza | Solini A.,University of Pisa | Bonora E.,University of Verona | Fondelli C.,University of Siena | And 3 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study is an ongoing observational survey that examines the role of estimated glomerular filtration rate (eGFR) as an independent predictor of cardiovascular and renal outcomes in 15,773 Italian subjects with type 2 diabetes. The analysis of data collected at the enrollment visit provided a picture of chronic kidney disease (CKD) and its association with other complications, risk factors for cardiovascular disease (CVD) and treatments in a large contemporary cohort. Main results of this analysis were that (a) non-albuminuric renal impairment is the predominant clinical phenotype in patients, particularly women, with reduced eGFR; (b) concordance between CKD and diabetic retinopathy is low, with only a minority of patients with renal dysfunction presenting with any or advanced retinal lesions; (c) the non-albuminuric form is associated with a significant prevalence of CVD, especially at the level of the coronary vascular bed; (d) CKD is associated with hemoglobin (Hb) A1c variability more than with average HbA1c, whereas retinopathy and CVD are not; (e) in elderly individuals with moderate-to-severe eGFR reduction, use of agents which are not recommended, such as sulphonylureas and metformin, is still frequent; and (f) though complications are generally more prevalent in men (except non-albuminuric renal impairment) women show a less favorable CVD risk profile and achieve therapeutic targets to a lesser extent than men, despite the fact that treatment intensity is not lower. These data update existing information on the natural history of CKD in patients with type 2 diabetes. © 2014 Elsevier B.V.

Penno G.,University of Pisa | Solini A.,University of Pisa | Zoppini G.,University of Verona | Orsi E.,Endocrinology and Diabetes Unit | And 8 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular fi ltration rate (eGFR), in the large cohort of the Renal Insuf ficiency And Cardiovascular Events (RIACE) Italian multicenter study. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital -based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was de fined based on albuminuria and eGFR. RESULTS - CKD was present in 58.64%of subjects with advanced DR, whereas advanced DR was detectable only in 15.28%of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A 1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis. CONCLUSIONS - Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR ismore frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype. © 2012 by the American Diabetes Association.

Solini A.,University of Pisa | Penno G.,University of Pisa | Bonora E.,University of Verona | Fondelli C.,University of Siena | And 8 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - Although a reduced estimated glomerular filtration rate (eGFR) was shown to be a powerful independent predictor of cardiovascular disease (CVD), other studies suggested that it confers a much lower risk than albuminuria alone, whereas the combination of the two abnormalities is associated with multiplicative risk. This study aimed at assessing the independent association of previous CVD events, either total or by vascular bed, with eGFR and albuminuria and chronic kidney disease (CKD) phenotypes. RESEARCH DESIGN AND METHODS - This cross-sectional study evaluated 15,773 patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study in 19 outpatient diabetes clinics in years 2007-2008. Albuminuria was assessed by immunonephelometry or immunoturbidimetry. GFR was estimated by the simplified Modification of Diet in Renal Disease Study and the Chronic Kidney Disease-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL/min/1.73 m 2 or micro- or macroalbuminuria. Major acute CVD events were adjudicated based on hospital discharge records or specialist visits. RESULTS - CVD risk increased linearly with eGFR decline and albuminuria and became significant for values <78mL/min/1.73m 2 and ≥10.5mg/24 h, respectively. Beyond traditional CVD risk factors, total CVD showed an independent association with albuminuria alone (odds ratio 1.20 [95% CI 1.08-1.33]), reduced eGFR alone (1.52 [1.34-1.73]), and both abnormalities (1.90 [1.66-2.19]). However, coronary events were associated predominantly with reduced eGFR alone, whereas cerebrovascular and peripheral events showed a stronger correlation with the albuminuric CKD phenotypes. CONCLUSIONS - These data, although cross-sectional, show that reduced eGFR, irrespective of albuminuria, is associated with significant CVD, particularly in the coronary district. © 2012 by the American Diabetes Association.

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