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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.

Objective: In type 2 diabetes, prevalence of nonalbuminuric renal impairment is increasing worldwide, though its clinical significance remains unclear. This large-cohort study aimed at evaluating the association of this phenotype with cardiovascular risk factors and other complications. Methods: Type 2 diabetic patients from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study (n=15773), visiting consecutively 19 hospital-based Diabetes Clinics in years 2007-2008, were examined. Serum creatinine was assessed by the Jaffe method; albuminuria was measured by immunonephelometry or immunoturbidimetry. Results: Of patients with renal impairment, as identified by an estimated glomerular filtration rate (eGFR) less than 60ml/min per 1.73m, 56.6% were normoalbuminuric, 30.8% were microalbuminuric, and 12.6% were macroalbuminuric. Percentages were similar when GFR was estimated using the more accurate Chronic Kidney Disease Epidemiology Collaboration equation instead of the simplified Modification of Diet in Renal Disease formula, and were independent of age, thus indicating that the increasing prevalence of this phenotype does not reflects misclassification of elderly patients. Nonalbuminuric renal impairment was not associated with HbA1c and correlated less strongly with retinopathy and hypertension than albuminuria, either alone or associated with reduced eGFR. It was associated with a higher prevalence of cardiovascular disease (CVD) than albuminuria alone, but lower than albuminuric renal impairment. Female sex correlated with nonalbuminuric renal impairment and male sex with the albuminuric forms. Conclusion:S: These data show that type 2 diabetic patients with nonalbuminuric renal impairment exhibit distinct clinical features, suggesting predominance of macroangiopathy as underlying renal pathology, and that this phenotype is associated with significant CVD burden.

Item does not contain fulltext BACKGROUND: The constitutive endothelial isoform of nitric oxide synthase (ecNOS) and nitric oxide (NO) production are increased in patients with Bartter syndrome (BS) and Gitelman (GS) syndrome and may reduce vascular tone. Moreover, these patients present an abnormal cell signaling [reduced stimulated intracellular calcium ([Ca(2+)](i)) and inositol-1,4,5,triphosphate ([IP(3)](i)) in neutrophils], suggesting the presence of a generalized reduction of protein kinase C (PKC) and cell reactivity. Since PKC regulates ecNOS gene expression, we evaluated the signal transduction system involving Gq protein, PKC, and ecNOS in circulating nucleated cells from patients with BS/GS. METHODS: Nucleated blood cells from 2 BS and 7 GS and from 10 controls (C) were used. PKC activity was evaluated in neutrophils by radioenzymatic assay; PKC alpha concentration was evaluated in monocytes by Western blot analysis. ecNOS and G alpha q mRNA production was evaluated in monocytes by reverse transcription-polymerase chain reaction (RT-PCR) analysis using specific primers and quantitated by PCR-based semiquantitative analysis of ecNOS and G alpha q mRNA expression. RESULTS: Cytosol and membrane basal PKC activity were similar in neutrophils from BS/GS and C (70 +/- 3 vs. 80 +/- 2; 37 +/- 3 vs. 46 +/- 2 pmol/min/mg protein, respectively), while fMLP-stimulated membrane PKC activity increased to a lower extent in BS/GS (from 43 +/- 2 to 53 +/- 3 vs. 38 +/- 2 to 66 +/- 3 pmol/min/mg protein, P < 0.05 for the difference). Membrane PKC alpha expression was similar in basal conditions (8.5 +/- 1.5 vs. 12.4 +/- 4.0 densitometric units), but increased after fMLP was reduced in BS/GS (4.5 +/- 1.4 vs. 9.5 +/- 2.1, P < 0.01). In BS/GS, PKC stimulation with PMA dose dependently reduced ecNOS gene expression (from 0.80 +/- 0.05 to 0.78 +/- 0.03 densitometric units; PMA 50 nmol/L, P = NS; to 0.55 +/- 0.07, PMA 100 nmol/L, P < 0.001) to an undetectable expression (PMA 200 nmol/L). Qualitatively similar effects were seen in monocytes from control subjects. Incubation of monocytes from patients and controls with the PKC inhibitor GF109203X increased ecNOS mRNA, with no difference between patients and controls. G alpha q mRNA was reduced in BS/GS versus controls (0.87 +/- 0.013 vs. 0.98 +/- 0.005 densitometric units, P < 0.0004). CONCLUSION: An abnormal G alpha q expression blunts cell signaling and PKC production in BS/GS. A reduced PKC up-regulated NO system may contribute to the vascular hyporeactivity of BS/GS.

Objectives Poorer control of risk factors for cardiovascular disease (CVD) has been reported in diabetic women, as compared with diabetic men. It has been proposed that this finding is due to gender disparities in treatment intensity. We investigated this hypothesis in a large contemporary cohort of subjects with type 2 diabetes. Design Observational, cross-sectional study. Subjects and setting Consecutive patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study (n = 15 773), attending 19 hospital-based diabetes clinics in 2007–2008. Main outcome measures Traditional CVD risk factors, macro- and microvascular complications and current glucose-, lipid- and blood pressure (BP)-lowering treatments were assessed. Results Although CVD was more prevalent in men, women showed a less favourable CVD risk profile and worse performance in achieving treatment targets for haemoglobin A1c, LDL, HDL and non-HDL cholesterol, systolic blood pressure (BP) and in particular obesity [body mass index (BMI) and waist circumference], but not for triglycerides and diastolic BP. However, women were more frequently receiving pharmacological treatment for hypertension and to a lesser extent hyperglycaemia and dyslipidaemia than men, and female gender remained an independent predictor of unmet therapeutic targets after adjustment for confounders such as treatments, BMI, duration of diabetes and, except for the systolic BP goal, age. Conclusions In women with type 2 diabetes from the RIACE cohort, a more adverse CVD risk profile and a higher likelihood of failing treatment targets, compared with men, were not associated with treatment differences. This suggests that factors other than gender disparities in treatment intensity are responsible.

The metabolic syndrome is becoming increasingly prevalent in the general population and carries significant incremental morbidity and mortality. It is associated with multi-organ involvement and increased all-cause mortality, resembling a precocious aging process. The mechanisms that account for this phenomenon are incompletely known, but it is becoming clear that longevity genes might be involved. Experiments with overactivation or disruption of key lifespan determinant pathways, such as silent information regulator (SIR)T1, p66Shc, and mammalian target of rapamycin (TOR), lead to development of features of the metabolic syndrome in mice. These genes integrate longevity pathways and metabolic signals in a complex interplay in which lifespan appears to be strictly dependent on substrate and energy bioavailability. Herein, we describe the roles and possible interconnections of selected lifespan determinant molecular networks in the development of the metabolic syndrome and its complications, describing initial available data in humans. Additional pathways are involved in linking nutrient availability and longevity, certainly including insulin and Insulin-like Growth Factor-1 (IGF-1) signaling, as well as FOXO transcription factors. The model described in this viewpoint article is therefore likely to be an oversimplification. Nevertheless, it represents one starting platform for understanding cell biology of lifespan in relation to the metabolic syndrome.

La produzione di ghianda e faggiola è stata monitorata nel 2001 e 2002 nell'area del progetto LIFE tramite griglia di plot (maglia= 500 m) distribuiti in maniera sistematica nell'area di studio. In faggeta sono stati campionati 214 plot da settembre a dicembre 2001 e 130 tra ottobre e novembre 2002. Nei querceti sono stati campionati 143 plot da gennaio a marzo 2002 e 143 plot da settembre a dicembre 2002. Nei plot (circolari, Ø= 40 m) i frutti sono stati raccolti in 17 stazioni (superficie= 1 m²) e sono stati successivamente divisi in 5 tipi in base alla grandezza e condizione del seme. Sia il numero totale di faggiole raccolte (148.1369 vs. 9.412) sia il numero medio di faggiole/plot (692,2 vs. 72,4) è stato maggiore nel 2001 rispetto al 2002. Analogamente, la densità media di faggiole (tipo 1+2) nell'autunno 2001 è stata maggiore di quella del 2002 (26,8 vs. 1,8). La produzione della ghianda di cerro è stata maggiore nel 2002 rispetto al 2001. Nell'inverno 2001/2002 sono state raccolte 5.445 ghiande, mentre nell'autunno 2002 il numero di ghiande raccolte è stato pari a 13.814. Il numero medio di ghiande di cerro totali / plot è stato pari a 57,9 nel 2001/2002 e a 121,2 nel 2002. Le evidenti differenze di produzione di faggiola (0,34 1259 g) e ghianda (0,434 - 9,99 g) tra i plot sembrano attribuibili alla gestione selvicolturale. Infatti, analisi preliminari hanno evidenziato che i fattori stazionali (quota, esposizione) non incidono in misura significativa sulla quantità di frutti prodotti. L'uso dello spazio nell'orso bruno è influenzato dalla disponibilità trofica, che nel periodo autunnale è importante in relazione a svernamento e gravidanza. Poiché, in funzione della disponibilità di faggiola risulta una variazione nell'alimentazione, si raccomandano interventi di monitoraggio della produzione e distribuzione della faggiola e delle fonti trofiche che ad essa si alternano. Così, sarà possibile inquadrare in un contesto territoriale coerente gli interventi di gestione come, p. es., il foraggiamento supplementare, la restrizione all'accesso in alcune aree e l'attività venatoria.