Paolo Cavallo Perin

Università degli Studi di Torino, Torino, Piedmont, Italy

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Publications (86)388.73 Total impact

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    ABSTRACT: Background Both metabolic syndrome (MetS) and NT-proBNP confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared to subjects who met none of the defining criteria of the MetS.MethodsA case-cohort study from the non-diabetic population-based Casale Monferrato Study was performed, after exclusion of all subjects with established CVD, CKD (eGFR < 60 ml/min/1.73 m2) and CRP values ≥3 mg/l. Cases (n = 161) with MetS were compared to all subjects within the cohort (n = 124) who were completely free of any component of the MetS. Serum NT-proBNP were centrally measured by immunoenzymatic assay.ResultsNT-proBNP levels were significantly higher in cases than in control subjects [35.4 (15.5-98.2) vs 24.4 (11.7-49.6) pg/ml, p = 0.014]. In logistic regression analysis, compared to NT-proBNP values in the lower quartiles (≤49.64 pg/ml), higher values conferred OR 4.17 (1.30-13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP, eGFR, and central obesity. This association was evident even after the exclusion of hypertensive subjects. Further adjustment for log-HOMA and diastolic blood pressure did not modify the strength of the association, while central obesity was a negative confounder.Conclusions Compared to people without any component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor diabetes, had increased NT-proBNP values, even if they were normotensive and though absolute values were still in the low range. The insulin-resistance state did not mediate this association, while central obesity was a negative confounder. This article is protected by copyright. All rights reserved.
    Diabetes/Metabolism Research and Reviews 11/2014; · 2.97 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) have been shown to abrogate in vitro the proinflammatory response in type 1 diabetes. The mechanism involves paracrine factors, which may include microvesicles (MVs). We evaluated whether MVs derived from heterologous bone-marrow MSCs exert an immunomodulatory effect on T cell responses against GAD (glutamic acid decarboxylase) antigen in type 1 diabetes.
    Diabetologia 05/2014; · 6.49 Impact Factor
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    ABSTRACT: Among people with type 2 diabetes the relationship between central obesity and cardiovascular mortality has not been definitely assessed. Moreover, NT-proBNP is negatively associated with central obesity, but no study has examined their combined effect on survival. We have examined these issues in a well-characterized population-based cohort. Survival data of 2272 diabetic people recruited in 2000 who had no other chronic disease have been updated to 31 December 2006. NT-proBNP was measured in a subgroup of 1690 patients. Cox proportional hazards modeling was employed to estimate the independent associations between cardiovascular and all-cause mortality and waist circumference. Mean age was 67.9 years, 49.3% were men. Both age and NT-proBNP were negatively correlated with waist circumference (r = -0.11, p<0.001 and r = -0.07, p = 0.002). Out of 2272 subjects, 520 deaths (221 for CV mortality) occurred during a median follow-up of 5.4 years. Central obesity was not associated with CV mortality (hazard ratio, HR, adjusted for age, sex, diabetes duration, 1.14, 95% CI 0.86-1.52). NTproBNP was a negative confounder and age a strong modifier of this relationship (p for interaction<0.001): age<70 years, fully adjusted model HR = 3.52 (1.17-10.57) and age ≥70 years, HR = 0.80 (0.46-1.40). Respective HRs for all-cause mortality were 1.86 (1.03-3.32) and 0.73 (0.51-1.04). In diabetic people aged 70 years and lower, central obesity was independently associated with increased cardiovascular mortality, independently of the negative effect of NT-proBNP. In contrast, no effect on 6-years survival was evident in diabetic people who have yet survived up to 70 years.
    PLoS ONE 01/2014; 9(5):e96076. · 3.53 Impact Factor
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    ABSTRACT: AIMS/HYPOTHESIS: The United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model can be used to estimate the lifetime occurrence of major diabetes-related complications in order to calculate health economic outcomes. The aim of the study was to assess the performance of the model by comparing the predicted and observed mortality and the incidence of macrovascular complications in an Italian population-based cohort with type 2 diabetes. METHODS: We used data from the Casale Monferrato Survey, a cohort enrolled in 1988 and surveyed in 1991 (n = 1,967) to assess the prevalence of cardiovascular risk factors. In 2000, a new survey included all the members of the original cohort who were still alive (n = 860), and in addition all individuals identified with a new diagnosis of type 2 diabetes since 1993 (n = 2,389). We compared the mortality predicted by the model for the 1991 survey over the subsequent 17-year period with the observed risk. The following outcomes were analysed in the 2000 survey: myocardial infarction (MI), other ischaemic heart disease, stroke, congestive heart failure (CHF) and amputation. RESULTS: For all-cause mortality, the predictions from the model at 5 and 10 years (23% and 47%, respectively) were identical to the observed risks. At 15 years, the risk of death was slightly overestimated (an estimate of 67% vs 64% observed, 95% CI 61%, 66%). The performance of the model was best for patients with a recent history of disease (duration <6 years). Among the complications, the predicted cumulative incidences of MI and CHF were very close to those observed. CONCLUSIONS/INTERPRETATION: External validation is essential to assess the accuracy of simulation models. The UKPDS Outcomes Model satisfactorily predicted a set of actual incidences of mortality and complications in an Italian diabetes cohort up to a duration of approximately 12 years. The longer term performance of such models should be carefully evaluated.
    Diabetologia 05/2013; · 6.49 Impact Factor
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    ABSTRACT: OBJECTIVE: Available data about mortality of type 2 diabetic patients treated with different sulfonylureas are scarce and contradictory. Design: We evaluated the associations between all-cause and cause-specific mortality and treatments with different sulfonylureas in a retrospective cohort of type 2 diabetic patients from a diabetes clinic. Methods: All 1277 patients treated with sulfonylureas during 1996-1997 were enrolled: 159 patients were treated with tolbutamide, 977 glibenclamide, and 141 gliclazide. The baseline data (centralised laboratory parameters, anthropometric data, presence of chronic complications) were abstracted from the clinical records. Information on vital status were collected from demographic files after 14-year-follow-up. Adjusted hazard ratios were estimated with Cox (all-cause mortality) or Fine and Gray models (cause-specific mortality), including several potential confounders. Results: 556 patients died during the follow-up: 262 from cardiovascular causes, 158 from cancer, and 136 from other causes. When compared to the glibenclamide-users, the gliclazide- and tolbutamide-users showed a significantly lower cancer mortality (HR=0.30;95%CI 0.16-0.55, and HR=0.48;95%CI 0.29-0.79, respectively). These results were strongly confirmed in the 555 patients on sulfonylurea-monotherapy. None of the patients who were treated with gliclazide monotherapy died from cancer during the follow-up, and the patients on tolbutamide exhibited a lower cancer mortality than the glibenclamide-users (HR=0.40;95%CI 0.22-0.71). Data did not change after stratification for the duration of sulfonylurea treatment from diabetes diagnosis to the study enrolment. CONCLUSIONS: Cancer mortality was markedly reduced in the patients on gliclazide and tolbutamide. These results suggest additional benefits for these drugs beyond their blood glucose-lowering effect and strongly advocate for further investigation.
    European Journal of Endocrinology 05/2013; · 3.14 Impact Factor
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    ABSTRACT: OBJECTIVE To study whether NH2-terminal probrain natriuretic peptide (NT-proBNP) is a short-term independent predictor of both all-cause and cardiovascular (CV) mortality in type 2 diabetic patients and to establish whether albuminuria and C-reactive protein (CRP) affect this relationship.RESEARCH DESIGN AND METHODS The prospective study included 1,825 type 2 diabetic patients from the population-based cohort of the Casale Monferrato study. CV risk factors, preexisting CVD, and NT-proBNP levels were evaluated at baseline. All-cause and CV mortality were assessed 5.5 years after baseline examination. Multivariate Cox proportional hazards modeling was used to estimate mortality hazard ratios (HRs).RESULTSDuring the follow-up period, 390 people died (175 for CVD) out of 9,101 person-years of observations. A significantly increased mortality risk by quartiles of NT-proBNP was observed (test for trend, P < 0.001). NT-proBN P values >91 pg/mL conferred HRs of 2.05 (95% CI 1.47-2.86) for all-cause and 4.47 (2.38-8.39) for CV mortality, independently of CV risk factors, including CRP and albumin excretion rate (AER). The association was also significant for modest rises in NT-proBNP levels and in patients without microalbuminuria and CVD at baseline (upper quartiles HRs 3.82 [95% CI 1.24-13.75]) and 3.14 [1.00-9.94]). Albuminuria and NT-proBNP had an additive effect on mortality, though the association was stronger for NT-proBNP.CONCLUSIONSNT-proBNP is a strong independent predictor of short-term CV mortality risk in elderly people with type 2 diabetes, including those without preexisting CVD. This association is evident even in people with slightly increased values, is not modified by CRP, and is additive to that provided by AER.
    Diabetes care 04/2013; · 7.74 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: Type 1 diabetes (T1DM) affects young people during the most active years of their life. Our aim was to assess quality of life (QoL) and associated variables in a large cohort of adults with childhood-onset and adult-onset T1DM. METHODS: A cohort of adult patients (18 years and older) from the T1DM Registry of Turin, Italy, was recruited. Clinical characteristics and Diabetes QoL (DQOL) questionnaire were assessed by standardized procedures. RESULTS: 310 adults completed the questionnaire. Age and diabetes duration at assessment (mean ± SD) were 32.8 ± 7.3 years and 17.3 ± 6.3 years, respectively. DQOL and its subscores were in the lower quartiles of their distributions, indicating a good level of QoL. However, scores were significantly higher in females than in males, particularly for the subscale of diabetes-related worries. In multivariate analysis, lower QoL was independently associated with female sex (β = 1.07, 95% CI 1.03-1.11, p = 0.003), higher age at onset (β = 1.03, 1.00-1.05, p = 0.009), lower schooling (β = 1.05, 1.00-1.09, p = 0.02), higher fasting plasma glucose (β = 1.03, 1.01-1.05, p = 0.008), daily SMBG >4 (β = 1.06, 1.01-1.10, p = 0.01), severe hypoglycemia over the last year (β = 1.06, 1.01-1.11, p = 0.02), lower numbers of diabetologic visits (β = 1.07, 1.01-1.13, p = 0.02) and hypertension (β = 1.06, 1.02-1.10, p = 0.005). Autonomic neuropathy was associated with diabetes impact. Female sex (β = 4.36, 2.43-7.83) and daily SMBG >4 (β = 3.77, 1.72-8.30) were independently associated with worst level and CSII with better level (β = 0.22, 0.07-0.68) of diabetes-related worries. CONCLUSIONS: The impact of T1DM on QoL may depend on demographic, metabolic control-related variables, presence of complications and insulin delivery modality.
    Nutrition, metabolism, and cardiovascular diseases: NMCD 02/2013; · 3.52 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs), a class of small non-protein-encoding RNAs, regulate gene expression via suppression of target mRNAs. MiRNAs are present in body fluids in a remarkable stable form as packaged in microvesicles of endocytic origin, named exosomes. In the present study, we have assessed miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Results showed that miR-130a and miR-145 were enriched, while miR-155 and miR-424 reduced in urinary exosomes from patients with microalbuminuria. Similarly, in an animal model of early experimental diabetic nephropathy, urinary exosomal miR-145 levels were increased and this was paralleled by miR-145 overexpression within the glomeruli. Exposure of cultured mesangial cells to high glucose increased miR-145 content in both mesangial cells and mesangial cells-derived exosomes, providing a potential mechanism for diabetes-induced miR-145 overexpression. In conclusion, urinary exosomal miRNA content is altered in type 1 diabetic patients with incipient diabetic nephropathy and miR-145 may represent a novel candidate biomarker/player in the complication.
    PLoS ONE 01/2013; 8(11):e73798. · 3.53 Impact Factor
  • Diabetes care 12/2012; 35(12):e89. · 7.74 Impact Factor
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    ABSTRACT: Levels of serum heat shock protein 27 (sHsp27) have been studied in numerous cancer types, but their potential relevance in patients with hepatocellular carcinoma (HCC) is undetermined. Our aim was to compare sHsp27 levels in patients with HCC and HCC-free controls. Specifically, we recruited 71 patients with HCC (80 % with early tumour), 80 patients with chronic liver disease (59 with liver cirrhosis and 21 with chronic active hepatitis) and 42 healthy subjects. sHsp27 was measured by immunoenzymatic assay. Results showed that sHsp27 levels were significantly (p < 0.001) higher in patients with HCC than in the other groups, particularly in those with hepatitis C virus (HCV)-related disease. In HCC patients, sHsp27 levels were not associated with prognostic risk factors, such as size/multiplicity of nodules and stage. In logistic regression analysis, performed in patients with liver disease, log-sHsp27 was associated with a significant age-adjusted 2.5-fold increased odds ratio of HCC and with a significant 4.4-fold higher odds ratio of HCC in the subgroup with HCV-related liver disease. In receiver operating characteristic curve analysis, sensitivity and specificity of the best sHsp27 cut-off value (456.5 pg/ml) for differentiating patients with HCC from those with HCC-free chronic liver disease were 70 and 73 %, respectively. In conclusion, sHsp27 levels are enhanced in patients with HCC and may represent a candidate biomarker of HCC.
    Cell Stress and Chaperones 10/2012; · 2.48 Impact Factor
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    ABSTRACT: Hippocampal abnormalities are believed to increase the risk of cognitive decline in diabetic patients. The underlying mechanism is unknown, but both hyperglycemia and oxidative stress have been implicated. Cellular stresses induce the expression of heat shock protein 25 (HSP25) and this results in cytoprotection. Our aim was to assess hippocampal expression of HSP25 in experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset hippocampal HSP25 expression was studied by immunoblotting and immunohistochemistry (IHC). Expression of glial fibrillary acidic protein, nitrotyrosine, iNOS, HSP72, HSP90, and Cu/Zn superoxide dismutase (SOD) was assessed by either IHC or immunoblotting, Cu/Zn-SOD activity by enzymatic assay, and malondialdehyde (MDA) content by colorimetric assay. Hippocampal HSP25 was significantly increased in diabetic as compared to non-diabetic animals and localized predominantly within the pyramidal neurons layer of the CA1 area. This was paralleled by overexpression of nitrotyrosine, iNOS, SOD expression/activity, and enhanced MDA content. In experimental diabetes, HSP25 is overexpressed in the CA1 pyramidal neurons in parallel with markers of oxidative stress.
    Neuroscience 09/2012; · 3.12 Impact Factor
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    ABSTRACT: Circulating levels of NH(2)-terminal probrain natriuretic peptide (NT-proBNP), a marker of acute heart failure, are associated with increased risk of cardiovascular disease (CVD) in the general population. However, there is little information on the potential role of NT-proBNP as a biomarker of vascular complications in type 1 diabetic patients. We investigated whether serum NT-proBNP levels were associated with micro- and macrovascular disease in type 1 diabetic subjects. A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 507 type 1 diabetic patients was performed. Case subjects (n = 345) were defined as those with one or more complications of diabetes; control subjects (n = 162) were those with no evidence of any complication. We measured NT-proBNP levels by a two-site sandwich electrochemiluminescence immunoassay and investigated their associations with complications. Mean NT-proBNP levels were significantly higher in case than in control subjects. In logistic regression analyses, NT-proBNP values >26.46 pg/mL were independently associated with a 2.56-fold increased risk of all complications. Odds ratios of CVD (3.95 [95% CI 1.26-12.35]), nephropathy (4.38 [1.30-14.76]), and distal symmetrical polyneuropathy (4.32 [1.41-13.23]) were significantly increased in patients with NT-proBNP values in the highest quartile (>84.71 pg/mL), independently of renal function and known risk factors. These associations were no longer significant after inclusion of TNF-α into the model. In this large cohort of type 1 diabetic subjects, we found an association between NT-proBNP and diabetic micro- and macrovascular complications. Our results suggest that the inflammatory cytokine TNF-α may be involved in this association.
    Diabetes care 06/2012; 35(9):1931-6. · 7.74 Impact Factor
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    ABSTRACT: Frequent episodes of severe hypoglycemia may increase the risk of cardiovascular disease (CVD) in people with diabetes. Our aim was to study the relationship between severe hypoglycemic episodes and CVD incidence in subjects with type 1 diabetes, and further, to assess if markers of inflammation/endothelial injury were enhanced in individuals who experienced hypoglycemic episodes. The prospective study included 2,181 type 1 diabetic patients from the EURODIAB Prospective Complications Study. At baseline, frequency of self-reported severe hypoglycemia, defined as episodes serious enough to require the help of another person, was assessed based on responses to a patient questionnaire. Both fatal/nonfatal CVD was assessed 7.3 years after baseline examination. At the follow-up visit, data on both severe and nonsevere hypoglycemic episodes in the previous year were collected through a questionnaire and markers of inflammation/stress response/endothelial injury measured by enzyme-linked immunosorbent assays in the 531 subjects of the nested case-control study, including 363 case subjects with one or more complications of diabetes and 168 control subjects with no evidence of any complication. During the follow-up period, 176 patients had incident CVD. Logistic regression analysis showed that severe hypoglycemia at the baseline examination was not associated with incidence of CVD (adjusted odds ratios [95% CI]: one to two episodes, 0.87 [0.55-1.37]; three or more episodes, 1.09 [0.68-1.75]). Furthermore, follow-up serum levels of markers of endothelial damage/inflammation were not cross-sectionally associated with the frequency of hypoglycemic episodes. Taken together our data do not support the hypothesis that in type 1 diabetes, severe hypoglycemia increases the risk of CVD.
    Diabetes care 05/2012; 35(7):1598-604. · 7.74 Impact Factor
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    ABSTRACT: Pancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia. Islet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1β and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured. Islet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1β and VEGF-A. The ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.
    Diabetologia 04/2012; 55(4):1058-70. · 6.49 Impact Factor
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    ABSTRACT: Our aim was to assess whether severe hypoglycemic attacks were cross-sectionally associated with abnormalities of the QTc interval in type 1 diabetic patients. The study included 3,248 type 1 diabetic patients from the EURODIAB IDDM Complications Study. Severe hypoglycemia was defined as an attack serious enough to require the help of another person. A corrected QTc interval (QTc) >0.44 s was considered abnormally prolonged. Nineteen percent of patients declared one to two attacks, and 13.2% of patients had three or more attacks. Prevalence of QTc prolongation was greater in patients who experienced three or more hypoglycemic attacks. Logistic regression analysis showed that the frequency of severe hypoglycemia was independently associated with QTc prolongation, even after adjustment for diabetes complications, including autonomic neuropathy (odds ratio 1.27, 95% CI 1.02-1.58). We have provided evidence that severe hypoglycemic attacks are independently associated with a prolonged QTc interval in type 1 diabetic patients from the EURODIAB IDDM Complications Study.
    Diabetes care 11/2011; 35(1):125-7. · 7.74 Impact Factor
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    ABSTRACT: Diabetic retinopathy is the leading cause of blindness in adults, and oxidative stress has been pathogenically associated with retinal neurodegeneration. Cellular stresses induce expression of heat shock proteins (HSPs) and this results in cytoprotection. Our aim was to assess retinal expression of HSP25 in early experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset retinal HSP25 expression were studied by real-time PCR, immunoblotting and immunohistochemistry (IHC). Expression of nitrotyrosine and Cu/Zn superoxide dismutase (SOD), was assessed by IHC and apoptosis by TUNEL. Retinal HSP25 mRNA and protein expression was significantly increased in diabetic as compared to non-diabetic animals and localised predominantly within the retinal ganglion cells (RGC) layer. This was paralleled overexpression of nitrotyrosine and SOD and enhanced apoptosis. In early experimental diabetes, HSP25 is overexpressed in the RGC layer in parallel with markers of oxidative stress and apoptosis.
    Acta Diabetologica 11/2011; · 4.63 Impact Factor
  • Paolo Cavallo Perin, Paolo Fornengo
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    ABSTRACT: The pathophysiology of hyperglycemia in type 2 diabetes (T2DM) involves 3 main defects: insulin deficiency, excess hepatic glucose output, and insulin resistance. Oral anti-diabetic agents act in a variety of ways. These include agents that stimulate insulin secretion, reduce hepatic glucose production, delay digestion and absorption of intestinal carbohydrate or improve insulin action. Because of improved knowledge of pathophysiology, new drugs with mechanisms of action focussed on specific pathophysiological alterations have appeared, in order to utilize all the possibilities of treating this condition. Here, we focus on the new agents used in the latest years and the overcoming ones in future, in particular incretin-based therapies, drugs inhibiting kidney glucose reabsorption (SGLT2 inhibitors), and glucokinase activators. The strategy for new drug development advocated here is to establish a broad range of anti-diabetic medicines with different mechanisms of action and potential opportunities for effective combination therapies.
    Internal and Emergency Medicine 10/2011; 6 Suppl 1:135-8. · 2.35 Impact Factor
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    ABSTRACT: The cannabinoid receptor type 2 (CB2) has protective effects in chronic degenerative diseases. Our aim was to assess the potential relevance of the CB2 receptor in both human and experimental diabetic nephropathy (DN). CB2 expression was studied in kidney biopsies from patients with advanced DN, in early experimental diabetes, and in cultured podocytes. Levels of endocannabinoids and related enzymes were measured in the renal cortex from diabetic mice. To assess the functional role of CB2, streptozotocin-induced diabetic mice were treated for 14 weeks with AM1241, a selective CB2 agonist. In these animals, we studied albuminuria, renal function, expression of podocyte proteins (nephrin and zonula occludens-1), and markers of both fibrosis (fibronectin and transforming growth factor-β1) and inflammation (monocyte chemoattractant protein-1 [MCP-1], CC chemokine receptor 2 [CCR2], and monocyte markers). CB2 signaling was assessed in cultured podocytes. Podocytes express the CB2 receptor both in vitro and in vivo. CB2 was downregulated in kidney biopsies from patients with advanced DN, and renal levels of the CB2 ligand 2-arachidonoylglycerol were reduced in diabetic mice, suggesting impaired CB2 regulation. In experimental diabetes, AM1241 ameliorated albuminuria, podocyte protein downregulation, and glomerular monocyte infiltration, without affecting early markers of fibrosis. In addition, AM1241 reduced CCR2 expression in both renal cortex and cultured podocytes, suggesting that CB2 activation may interfere with the deleterious effects of MCP-1 signaling. The CB2 receptor is expressed by podocytes, and in experimental diabetes, CB2 activation ameliorates both albuminuria and podocyte protein loss, suggesting a protective effect of signaling through CB2 in DN.
    Diabetes 08/2011; 60(9):2386-96. · 7.90 Impact Factor
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    ABSTRACT: Compressive ultrasonography (CUS) of the lower limbs is the first choice for identifying deep venous thrombosis (DVT) in patients with symptomatic pulmonary embolism (PE). The aim of this study was to uncover clinical characteristics and CUS findings in patients with proven PE and their correlations with PE extent. A total of 524 consecutive cases of proven symptomatic PE diagnosed between January 1996 and December 2006 were reviewed. Mean age was 71.06 ± 14.43 SD years; 244 patients (46.6%) were men. DVT signs or symptoms were present in 30.9% of patients and were associated with the femoral site (P = 0.029). CUS was performed in 383 patients (73.1%) and DVT was found in 75.5%. In 94.1% of patients DVT was proximal (popliteal and/or femoral), which would have been then identified by simplified CUS. CUS was performed significantly more often in presence of signs or symptoms of DVT (P < 0.001), less often in presence of medical illnesses (P = 0.040), age ≥75 years (P = 0.001) and death in hospital (P < 0.001). Signs or symptoms of DVT were predictors of positive CUS (P < 0.001), presence of medical illnesses (P = 0.020), central venous catheter (P = 0.035), death in hospital (P = 0.032) were predictors of negative CUS findings. Neither clinical findings nor CUS were associated with PE extent. In patients with proven symptomatic PE, signs or symptoms of DVT are present only in 1/3 of cases and are significantly more frequent when DVT is extended to the femoral vein. Simplified CUS of the lower limbs has a high sensitivity in finding proximal DVT. CUS is not able to predict PE extent.
    Southern medical journal 06/2011; 104(6):405-11. · 0.92 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) exert an immunosuppressive effect on the immune system. However, studies on the immunomodulatory potential of MSCs in type 1 diabetes are lacking. We aimed to evaluate whether human MSCs may inhibit in vitro pancreatic islet antigen-specific T cell activation in type 1 diabetes. Human MSCs were isolated and characterized. Peripheral blood mononuclear cells (PBMCs) were obtained from nine type 1 diabetic patients at disease onset and 13 healthy control subjects. IFN-gamma, IL-10, and IL-4 enzyme-linked immunospot responses of lymphocytes incubated with glutamic acid decarboxylase 65 (GAD65) were investigated in PBMC cultures and PBMC/MSC cocultures. Levels of prostaglandin E2 (PGE2), IFN-gamma, IL-4, and IL-10 in supernatants were measured by ELISA. PGE2 inhibition experiments with NS-398 and indomethacin were also performed. Five diabetic patients were identified with a positive PBMC IFN-gamma response to GAD65 and negative IL-10 and IL-4 response. PBMC/MSC cocultures resulted in a significant decrease in the number of spots and in detection of IL-4-secreting cells. PGE2 inhibitors abrogated the immune-suppressive effect, indicating an involvement of PGE2 production, and the constitutive production of PGE2 by MSCs was enhanced in PBMC/MSC coculture. Moreover, in GAD-responder patients, GAD-stimulated PBMC/MSC cocultures significantly decreased secretion of IFN-gamma and IL-10 and increased secretion of IL-4. These results provide evidence that human MSCs abrogate in vitro a proinflammatory T helper type 1 response to an islet antigenic stimulus in type 1 diabetes. MSCs induce IL-4-producing cells, suggesting a possible switch to an antiinflammatory T helper type 2 signaling of T cells.
    The Journal of Clinical Endocrinology and Metabolism 05/2010; 95(8):3788-97. · 6.31 Impact Factor

Publication Stats

1k Citations
388.73 Total Impact Points

Institutions

  • 1995–2014
    • Università degli Studi di Torino
      • Department of Medical Science
      Torino, Piedmont, Italy
  • 2013
    • Azienda Ospedaliera Città della Salute e della Scienza
      Torino, Piedmont, Italy
  • 2008
    • Santa Croce e Carle General Hospital
      Coni, Piedmont, Italy
  • 2007
    • University of Insubria
      Varese, Lombardy, Italy
  • 2006
    • Hôpital Universitaire Necker
      Lutetia Parisorum, Île-de-France, France
  • 1999–2001
    • Ospedale Ordine Mauriziano di Torino, Umberto I
      Torino, Piedmont, Italy
    • Ospedale San Giovanni Battista, ACISMOM
      Torino, Piedmont, Italy