S. Pinach - Academia.edu (original) (raw)

Papers by S. Pinach

Research paper thumbnail of The possible role of autoimmunity in the pathogenesis of diabetes in B-thalassemia major

Diabetes & metabolism, 2001

OBJECTIVE To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associate... more OBJECTIVE To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-thalassemia, we studied a cohort of 53 B-thalassemic individuals, under long term blood transfusion, that included twelve patients with diabetes (22.6%). MATERIAL AND METHODS To evaluate the activation of an autoimmune response, individuals were tested for islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) autoantibodies, insulin autoantibodies (IAA) and serum anti-nuclear antibodies (ANA). RESULTS Nine of the total B-thalassemic population (16.98%) were ICA-positive. The frequency of ICA-positive subjects among thalassemic individuals was higher than in the general population. Five (41.6%) of the ICA-positive individuals were diabetic. Of these, three were serum C-peptide-negative (<0.21 nmol/l). HLA class II typing of our thalassemic population did not reveal significantly different allelic frequencies with respect to the control population. CONCLUSIONS Our stud...

Research paper thumbnail of The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells

Kidney International, 2006

Both inflammatory and haemodynamic factors have been implicated in the pathogenesis of diabetic a... more Both inflammatory and haemodynamic factors have been implicated in the pathogenesis of diabetic and other progressive glomerulopathies. Mesangial cell exposure to mechanical stretch induces both intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression. CC Chemokine receptor 2 (CCR2), the cognate MCP-1 receptor, has been recently demonstrated in human mesangial cells (HMCs). We tested whether MCP-1 binding to CCR2 affects ICAM-1 expression in HMCs and, secondly, if stretch-induced ICAM-1 is mediated by MCP-1 via an autocrine mechanism. Serum-deprived HMCs were exposed to either rh-MCP-1 (0.1-1-10-50-100 ng/ml) or mechanical stretch in the presence and in the absence of RS102895, a specific CCR2 inhibitor. ICAM-1 expression was assessed both by immunofluorescence and cytofluorimetry. Monocyte-HMC interaction was tested by adhesion assay. CCR2 expression was studied by reverse transcriptase-polymerase chain reaction, immunoblotting, and flow cytometry. HMCs exposure to rh-MCP-1 induced a significant twofold increase in ICAM-1 expression at 24 h, leading to enhanced monocyte adhesion. This effect occurred via the CCR2 receptor as CCR2 was expressed in HMCs and CCR2 blockade prevented ICAM-1 upregulation. Stretch-induced ICAM-1 expression was not altered by CCR2 blockade and stretch significantly reduced CCR2 mRNA and protein expression via an MCP-1-independent mechanism. In conclusion, stretch and MCP-1 independently induce ICAM-1 expression in HMCs. Stretch-induced CCR2 downregulation may favour MCP-1 paracrine activity.

Research paper thumbnail of Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

Diabetologia, 2007

Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulat... more Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Methods Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-β1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-β1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-β1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. Results In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-β1-and NF-κB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-β1 and fibronectin mRNA and protein levels. Conclusions/interpretation Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy.

Research paper thumbnail of Incidence of Type 1 and Type 2 Diabetes in Adults Aged 30-49 Years: The population-based registry in the province of Turin, Italy

Diabetes Care, 2005

OBJECTIVE -Incidence of type 1 diabetes is considered to be low in adults, but no study has been ... more OBJECTIVE -Incidence of type 1 diabetes is considered to be low in adults, but no study has been performed in Mediterranean countries.

Research paper thumbnail of Residual  -Cell Function and Male/Female Ratio Are Higher in Incident Young Adults Than in Children: The registry of type 1 diabetes of the province of Turin, Italy, 1984-2000

Diabetes Care, 2005

OBJECTIVE -The hypothesis of age-dependent variations in epidemiologic and clinical features at o... more OBJECTIVE -The hypothesis of age-dependent variations in epidemiologic and clinical features at onset of type 1 diabetes has been assessed in the registry of the province of Turin, Italy.

Research paper thumbnail of Effect of the Monocyte Chemoattractant Protein-1/CC Chemokine Receptor 2 System on Nephrin Expression in Streptozotocin-Treated Mice and Human Cultured Podocytes

Diabetes, 2009

OBJECTIVE-Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine rec... more OBJECTIVE-Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes.

Research paper thumbnail of Anti-CD38 autoantibodies: characterisation in new-onset type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies

Diabetologia, 2002

Serum anti-CD38 autoantibodies (aAbs) have been reported in 17 to 19% of patients with long-stand... more Serum anti-CD38 autoantibodies (aAbs) have been reported in 17 to 19% of patients with long-standing Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus. Whether these aAbs are also found in new-onset Type I diabetes and in Latent Autoimmune Diabetes in Adults (LADA) is not known, as is their relationship with conventional islet aAbs. These issues were addressed by studying new-onset Type I and LADA diabetic cohorts with a recently developed anti-CD38 enzymatic immuno-assay. Anti-CD38 aAb prevalence among new-onset Type I patients (3.8%) was lower than previously found in long-standing Type I diabetes (11.7%, as defined with the 97.5 percentile cutoff; p=0.01), suggesting a late appearance of these aAbs. Among LADA patients, 14.9% were anti-CD38(+). Anti-CD38 were only associated with anti-GAD aAbs in new-onset Type I diabetes. Although the CD38 target molecule was expressed in human pancreatic islets, anti-CD38 aAbs did not contribute ...

Research paper thumbnail of The possible role of autoimmunity in the pathogenesis of diabetes in B-thalassemia major

Diabetes & metabolism, 2001

To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-t... more To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-thalassemia, we studied a cohort of 53 B-thalassemic individuals, under long term blood transfusion, that included twelve patients with diabetes (22.6%). To evaluate the activation of an autoimmune response, individuals were tested for islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) autoantibodies, insulin autoantibodies (IAA) and serum anti-nuclear antibodies (ANA). Nine of the total B-thalassemic population (16.98%) were ICA-positive. The frequency of ICA-positive subjects among thalassemic individuals was higher than in the general population. Five (41.6%) of the ICA-positive individuals were diabetic. Of these, three were serum C-peptide-negative (<0.21 nmol/l). HLA class II typing of our thalassemic population did not reveal significantly different allelic frequencies with respect to the control population. Our study demonstrates evidence of immune system activation...

Research paper thumbnail of Immunological profile, choice of immunotherapy and CMV viraemia in pancreas transplant

Research paper thumbnail of Isoleucine-to-methionine substitution at residue 148 variant of PNPLA3 gene and metabolic outcomes in gestational diabetes

American Journal of Clinical Nutrition, 2014

A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin g... more A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin gene (rs738409 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G) is strongly associated with nonalcoholic fatty liver disease; to our knowledge, no data are available on the impact of this PNPLA3 SNP on liver and metabolic outcomes during pregnancy in patients with gestational diabetes (GD). We evaluated the impact of the PNPLA3 rs738409 SNP on liver enzymes, metabolic indexes, and maternal and neonatal outcomes in 200 GD patients enrolled in a lifestyle intervention. In a randomized trial with a 2 × 2 factorial design, exercise significantly improved maternal and neonatal outcomes in GD patients. Effects of the G allele on metabolic and liver indexes and maternal and neonatal outcomes were evaluated in these patients. At the end of the trial, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly lower and liver enzymes significantly higher in PNPLA3 G-allele carriers. In a multiple regression model, the G allele was associated directly with aspartate aminotransferase (β = 2.60; 95% CI: 0.99, 4.20), alanine aminotransferase (β = 3.70; 95% CI: 1.78, 5.62), and γ-glutamyl transferase (β = 3.70; 95% CI: 0.80, 6.60) and inversely with insulin (β = -2.01; 95% CI: -3.24, -0.78) and HOMA-IR (β = -0.39; -0.64, -0.14) values at the end of the trial. In a multiple logistic regression model, the G allele was associated directly with risk of developing liver enzyme elevation during pregnancy (OR: 4.21; 95% CI: 1.78, 9.97) and inversely with the birth of large-for-gestational-age newborns (OR: 0.19; 95% CI: 0.06, 0.62). No diet × genotype or exercise × genotype interaction was shown. The PNPLA3 SNP rs738409 G allele was associated with risk of mildly elevated transaminases in GD independent of a lifestyle intervention and despite a significant reduction in insulin resistance and risk of macrosomic offspring. This trial was registered at clinicaltrials.gov as NCT01506310.

Research paper thumbnail of Hippocampal heat shock protein 25 expression in streptozotocin-induced diabetic mice

Neuroscience, 2012

and sharing with colleagues.

Research paper thumbnail of Phytosterol-Enriched Yogurt Increases LDL Affinity and Reduces CD36 Expression in Polygenic Hypercholesterolemia

Lipids, 2009

Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce pla... more Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols (equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity and the reduction in CD36 expression may reflect an important antiatherogenic effect.

Research paper thumbnail of ANTI-HSP60 and ANTI-HSP70 antibody levels and micro/ macrovascular complications in type 1 diabetes: the EURODIAB Study

Journal of Internal Medicine, 2009

ANTI-HSP60 and ANTI-HSP70 antibody levels and micro ⁄ macrovascular complications in type 1 diabe... more ANTI-HSP60 and ANTI-HSP70 antibody levels and micro ⁄ macrovascular complications in type 1 diabetes: the EURODIAB Study. J Intern Med 2009; 266: 527-536.

Research paper thumbnail of P846 Serum Free Fatty Acid Composition is Associated with Different Degrees of Fibrosis

Journal of Hepatology, 2014

Research paper thumbnail of Prior gestational hyperglycemia: A long-term predictor of the metabolic syndrome

Journal of Endocrinological Investigation, 2004

Little is known about the association between prior gestational hyperglycemia of different severi... more Little is known about the association between prior gestational hyperglycemia of different severity and the subsequent risk for the metabolic syndrome. Eighty-one women with prior gestational diabetes mellitus (GDM), 25 with one abnormal value at the oral glucose tolerance test (OGTT), and 65 with normal OGTT were studied after a mean of 8.5 yr from the index pregnancy. Patients with prior gestational hyperglycemia (both one abnormal value at the OGTT and GDM) showed a worse metabolic pattern than subjects with gestational normoglycemia [respectively higher values of body mass index (BMI), waist, blood pressure, serum glucose, insulin, C-peptide, homeostatic model assessment (HOMA), fibrinogen and lower levels of HDL-cholesterol]. Prevalence of the metabolic syndrome and its components was 2-4-fold higher in women with prior gestational hyperglycemia (and 10-fold higher if pre-pregnancy obesity coexisted) when compared to normoglycemic controls; in a Cox proportional hazard model, after adjustments for age and pre-pregnancy BMI, gestational hyperglycemia and pre-pregnancy BMI predicted subsequent metabolic syndrome [respectively: hazard ratio (HR)=4.26 and HR=1.21] and most of its components. In the same model, the highest quartile of fasting serum glucose at the OGTT of the index pregnancy was significantly associated to the metabolic syndrome and its components. Gestational hyperglycemia and fasting glucose values were also associated to subsequent fibrinogen values, but not to albumin excretion rates. In young adult women, prior gestational hyperglycemia (particularly abnormal fasting glucose values), above all in combination with pre-pregnancy obesity, anticipates a subsequent syndrome at high cardiovascular risk and, possibly, a mild chronic inflammatory response.

Research paper thumbnail of Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus

International Journal of Andrology, 2005

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essen... more The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from L-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). .001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r ¼ )0.34, p < 0.01) and with the duration of DM (r ¼ )0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Research paper thumbnail of A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years

Diabetic Medicine, 2004

To assess if a clinically orientated approach improves screening for latent autoimmune diabetes i... more To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50.

Research paper thumbnail of Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to β-cell antigens

Diabetic Medicine, 2003

To evaluate the prevalence of β -cell autoantibodies in women with gestational diabetes and impai... more To evaluate the prevalence of β -cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies.

Research paper thumbnail of Prevalence of Type 1 Diabetes-Related Autoantibodies in Adults With Celiac Disease

Diabetes Care, 2003

Results from a population-based survey O ur objective was to evaluate the diagnostic proficiency ... more Results from a population-based survey O ur objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey. Details of the sampling procedures have been previously described (3). The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period. For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults). The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574). After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively. The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.

Research paper thumbnail of Anti-Heat Shock Protein 27 Antibody Levels and Diabetes Complications in the EURODIAB Study

Diabetes Care, 2009

OBJECTIVE -To assess whether serum anti-heat shock protein 27 (HSP27) antibody levels are associa... more OBJECTIVE -To assess whether serum anti-heat shock protein 27 (HSP27) antibody levels are associated with micro-and macrovascular complications of type 1 diabetes.

Research paper thumbnail of The possible role of autoimmunity in the pathogenesis of diabetes in B-thalassemia major

Diabetes & metabolism, 2001

OBJECTIVE To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associate... more OBJECTIVE To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-thalassemia, we studied a cohort of 53 B-thalassemic individuals, under long term blood transfusion, that included twelve patients with diabetes (22.6%). MATERIAL AND METHODS To evaluate the activation of an autoimmune response, individuals were tested for islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) autoantibodies, insulin autoantibodies (IAA) and serum anti-nuclear antibodies (ANA). RESULTS Nine of the total B-thalassemic population (16.98%) were ICA-positive. The frequency of ICA-positive subjects among thalassemic individuals was higher than in the general population. Five (41.6%) of the ICA-positive individuals were diabetic. Of these, three were serum C-peptide-negative (<0.21 nmol/l). HLA class II typing of our thalassemic population did not reveal significantly different allelic frequencies with respect to the control population. CONCLUSIONS Our stud...

Research paper thumbnail of The MCP-1/CCR2 system has direct proinflammatory effects in human mesangial cells

Kidney International, 2006

Both inflammatory and haemodynamic factors have been implicated in the pathogenesis of diabetic a... more Both inflammatory and haemodynamic factors have been implicated in the pathogenesis of diabetic and other progressive glomerulopathies. Mesangial cell exposure to mechanical stretch induces both intercellular adhesion molecule 1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) expression. CC Chemokine receptor 2 (CCR2), the cognate MCP-1 receptor, has been recently demonstrated in human mesangial cells (HMCs). We tested whether MCP-1 binding to CCR2 affects ICAM-1 expression in HMCs and, secondly, if stretch-induced ICAM-1 is mediated by MCP-1 via an autocrine mechanism. Serum-deprived HMCs were exposed to either rh-MCP-1 (0.1-1-10-50-100 ng/ml) or mechanical stretch in the presence and in the absence of RS102895, a specific CCR2 inhibitor. ICAM-1 expression was assessed both by immunofluorescence and cytofluorimetry. Monocyte-HMC interaction was tested by adhesion assay. CCR2 expression was studied by reverse transcriptase-polymerase chain reaction, immunoblotting, and flow cytometry. HMCs exposure to rh-MCP-1 induced a significant twofold increase in ICAM-1 expression at 24 h, leading to enhanced monocyte adhesion. This effect occurred via the CCR2 receptor as CCR2 was expressed in HMCs and CCR2 blockade prevented ICAM-1 upregulation. Stretch-induced ICAM-1 expression was not altered by CCR2 blockade and stretch significantly reduced CCR2 mRNA and protein expression via an MCP-1-independent mechanism. In conclusion, stretch and MCP-1 independently induce ICAM-1 expression in HMCs. Stretch-induced CCR2 downregulation may favour MCP-1 paracrine activity.

Research paper thumbnail of Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells

Diabetologia, 2007

Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulat... more Aims/hypothesis Diabetic nephropathy is characterised by mesangial extracellular matrix accumulation. Monocyte chemoattractant protein-1 (MCP-1), a chemokine promoting monocyte infiltration, is upregulated in the diabetic glomerulus. We performed in vitro and in vivo studies to examine whether MCP-1 may have prosclerotic actions in the setting of diabetes, presumably via its receptor, chemokine (C-C motif) receptor 2 (CCR2), which has been described in mesangial cells. Methods Human mesangial cells were exposed to recombinant human (rh)-MCP-1 (100 ng/ml) for 12, 24 and 48 h and to rh-MCP-1 (10, 100 and 200 ng/ml) for 24 h. Fibronectin, collagen IV and transforming growth factor, beta 1 (TGF-β1) protein levels were measured by ELISA and pericellular polymeric fibronectin levels by western blotting. The intracellular mechanisms were investigated using specific inhibitors for CCR2, nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase and protein kinase C, and an anti-TGF-β1 blocking antibody. In both non-diabetic and streptozotocin-induced diabetic mice that were deficient or not in MCP-1, glomerular fibronectin accumulation was examined by immunohistochemistry, while cortical Tgf-β1 (also known as Tgfb1) and fibronectin mRNA and protein levels were examined by real-time PCR and western blotting. Results In mesangial cells, MCP-1 binding to CCR2 induced a 2.5-fold increase in fibronectin protein levels at 24 h followed by a rise in pericellular fibronectin, whereas no changes were seen in collagen IV production. MCP-1-induced fibronectin production was TGF-β1-and NF-κB-dependent. In diabetic mice, loss of MCP-1 diminished glomerular fibronectin protein production and both renal cortical Tgf-β1 and fibronectin mRNA and protein levels. Conclusions/interpretation Our in vitro and in vivo findings indicate a role for the MCP-1/CCR2 system in fibronectin deposition in the diabetic glomerulus, providing a new therapeutic target for diabetic nephropathy.

Research paper thumbnail of Incidence of Type 1 and Type 2 Diabetes in Adults Aged 30-49 Years: The population-based registry in the province of Turin, Italy

Diabetes Care, 2005

OBJECTIVE -Incidence of type 1 diabetes is considered to be low in adults, but no study has been ... more OBJECTIVE -Incidence of type 1 diabetes is considered to be low in adults, but no study has been performed in Mediterranean countries.

Research paper thumbnail of Residual  -Cell Function and Male/Female Ratio Are Higher in Incident Young Adults Than in Children: The registry of type 1 diabetes of the province of Turin, Italy, 1984-2000

Diabetes Care, 2005

OBJECTIVE -The hypothesis of age-dependent variations in epidemiologic and clinical features at o... more OBJECTIVE -The hypothesis of age-dependent variations in epidemiologic and clinical features at onset of type 1 diabetes has been assessed in the registry of the province of Turin, Italy.

Research paper thumbnail of Effect of the Monocyte Chemoattractant Protein-1/CC Chemokine Receptor 2 System on Nephrin Expression in Streptozotocin-Treated Mice and Human Cultured Podocytes

Diabetes, 2009

OBJECTIVE-Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine rec... more OBJECTIVE-Monocyte chemoattractant protein-1 (MCP-1), a chemokine binding to the CC chemokine receptor 2 (CCR2) and promoting monocyte infiltration, has been implicated in the pathogenesis of diabetic nephropathy. To assess the potential relevance of the MCP-1/CCR2 system in the pathogenesis of diabetic proteinuria, we studied in vitro if MCP-1 binding to the CCR2 receptor modulates nephrin expression in cultured podocytes. Moreover, we investigated in vivo if glomerular CCR2 expression is altered in kidney biopsies from patients with diabetic nephropathy and whether lack of MCP-1 affects proteinuria and expression of nephrin in experimental diabetes.

Research paper thumbnail of Anti-CD38 autoantibodies: characterisation in new-onset type I diabetes and latent autoimmune diabetes of the adult (LADA) and comparison with other islet autoantibodies

Diabetologia, 2002

Serum anti-CD38 autoantibodies (aAbs) have been reported in 17 to 19% of patients with long-stand... more Serum anti-CD38 autoantibodies (aAbs) have been reported in 17 to 19% of patients with long-standing Type I (insulin-dependent) diabetes mellitus and Type II (non-insulin-dependent) diabetes mellitus. Whether these aAbs are also found in new-onset Type I diabetes and in Latent Autoimmune Diabetes in Adults (LADA) is not known, as is their relationship with conventional islet aAbs. These issues were addressed by studying new-onset Type I and LADA diabetic cohorts with a recently developed anti-CD38 enzymatic immuno-assay. Anti-CD38 aAb prevalence among new-onset Type I patients (3.8%) was lower than previously found in long-standing Type I diabetes (11.7%, as defined with the 97.5 percentile cutoff; p=0.01), suggesting a late appearance of these aAbs. Among LADA patients, 14.9% were anti-CD38(+). Anti-CD38 were only associated with anti-GAD aAbs in new-onset Type I diabetes. Although the CD38 target molecule was expressed in human pancreatic islets, anti-CD38 aAbs did not contribute ...

Research paper thumbnail of The possible role of autoimmunity in the pathogenesis of diabetes in B-thalassemia major

Diabetes & metabolism, 2001

To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-t... more To evaluate the possible role of autoimmunity in the pathogenesis of diabetes associated with B-thalassemia, we studied a cohort of 53 B-thalassemic individuals, under long term blood transfusion, that included twelve patients with diabetes (22.6%). To evaluate the activation of an autoimmune response, individuals were tested for islet cell antibodies (ICA), glutamic acid decarboxylase (GAD) autoantibodies, insulin autoantibodies (IAA) and serum anti-nuclear antibodies (ANA). Nine of the total B-thalassemic population (16.98%) were ICA-positive. The frequency of ICA-positive subjects among thalassemic individuals was higher than in the general population. Five (41.6%) of the ICA-positive individuals were diabetic. Of these, three were serum C-peptide-negative (<0.21 nmol/l). HLA class II typing of our thalassemic population did not reveal significantly different allelic frequencies with respect to the control population. Our study demonstrates evidence of immune system activation...

Research paper thumbnail of Immunological profile, choice of immunotherapy and CMV viraemia in pancreas transplant

Research paper thumbnail of Isoleucine-to-methionine substitution at residue 148 variant of PNPLA3 gene and metabolic outcomes in gestational diabetes

American Journal of Clinical Nutrition, 2014

A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin g... more A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin gene (rs738409 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;G) is strongly associated with nonalcoholic fatty liver disease; to our knowledge, no data are available on the impact of this PNPLA3 SNP on liver and metabolic outcomes during pregnancy in patients with gestational diabetes (GD). We evaluated the impact of the PNPLA3 rs738409 SNP on liver enzymes, metabolic indexes, and maternal and neonatal outcomes in 200 GD patients enrolled in a lifestyle intervention. In a randomized trial with a 2 × 2 factorial design, exercise significantly improved maternal and neonatal outcomes in GD patients. Effects of the G allele on metabolic and liver indexes and maternal and neonatal outcomes were evaluated in these patients. At the end of the trial, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were significantly lower and liver enzymes significantly higher in PNPLA3 G-allele carriers. In a multiple regression model, the G allele was associated directly with aspartate aminotransferase (β = 2.60; 95% CI: 0.99, 4.20), alanine aminotransferase (β = 3.70; 95% CI: 1.78, 5.62), and γ-glutamyl transferase (β = 3.70; 95% CI: 0.80, 6.60) and inversely with insulin (β = -2.01; 95% CI: -3.24, -0.78) and HOMA-IR (β = -0.39; -0.64, -0.14) values at the end of the trial. In a multiple logistic regression model, the G allele was associated directly with risk of developing liver enzyme elevation during pregnancy (OR: 4.21; 95% CI: 1.78, 9.97) and inversely with the birth of large-for-gestational-age newborns (OR: 0.19; 95% CI: 0.06, 0.62). No diet × genotype or exercise × genotype interaction was shown. The PNPLA3 SNP rs738409 G allele was associated with risk of mildly elevated transaminases in GD independent of a lifestyle intervention and despite a significant reduction in insulin resistance and risk of macrosomic offspring. This trial was registered at clinicaltrials.gov as NCT01506310.

Research paper thumbnail of Hippocampal heat shock protein 25 expression in streptozotocin-induced diabetic mice

Neuroscience, 2012

and sharing with colleagues.

Research paper thumbnail of Phytosterol-Enriched Yogurt Increases LDL Affinity and Reduces CD36 Expression in Polygenic Hypercholesterolemia

Lipids, 2009

Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce pla... more Dietary enrichment with phytosterols (plant sterols similar to cholesterol) is able to reduce plasma cholesterol levels due to reduced intestinal absorption. The aim of this study was to investigate the effect of phytosterol-enriched yogurt consumption on the major serum lipid parameters, low density lipoprotein (LDL) receptor activity, LDL-receptor affinity, and CD36 expression in hypercholesterolemic subjects. Fifteen patients affected by polygenic hypercholesterolemia were evaluated in a single-blind randomized crossover study after a 4 weeks treatment with a phytosterol-enriched yogurt containing 1.6 g esterefied phytosterols (equivalent to 1.0 g free phytosterol). Lipid parameters were compared with a phytosterol-free placebo-controlled diet. The effect of the two treatments on each variable, measured as percentage change, was compared by paired samples t test and covariance analysis. The treatment induced a modest but significant decrease in LDL-cholesterol levels (4.3%, P = 0.03) and a significant increase in high density lipoprotein (HDL) 3-cholesterol (17.1%, P = 0.01). Phytosterol consumption had no effect on LDL-receptor activity whereas patient LDL-receptor affinity significantly increased (9.7%, P = 0.01) and CD36 expression showed a marked significant decrease (18.2%, P = 0.01) in the phytosterol-enriched yoghurt patients. Our data show that the oral administration of a phytosterol-enriched yogurt has modest but significant effects on commonly measured lipid parameters. The improvement of LDL-receptor affinity and the reduction in CD36 expression may reflect an important antiatherogenic effect.

Research paper thumbnail of ANTI-HSP60 and ANTI-HSP70 antibody levels and micro/ macrovascular complications in type 1 diabetes: the EURODIAB Study

Journal of Internal Medicine, 2009

ANTI-HSP60 and ANTI-HSP70 antibody levels and micro ⁄ macrovascular complications in type 1 diabe... more ANTI-HSP60 and ANTI-HSP70 antibody levels and micro ⁄ macrovascular complications in type 1 diabetes: the EURODIAB Study. J Intern Med 2009; 266: 527-536.

Research paper thumbnail of P846 Serum Free Fatty Acid Composition is Associated with Different Degrees of Fibrosis

Journal of Hepatology, 2014

Research paper thumbnail of Prior gestational hyperglycemia: A long-term predictor of the metabolic syndrome

Journal of Endocrinological Investigation, 2004

Little is known about the association between prior gestational hyperglycemia of different severi... more Little is known about the association between prior gestational hyperglycemia of different severity and the subsequent risk for the metabolic syndrome. Eighty-one women with prior gestational diabetes mellitus (GDM), 25 with one abnormal value at the oral glucose tolerance test (OGTT), and 65 with normal OGTT were studied after a mean of 8.5 yr from the index pregnancy. Patients with prior gestational hyperglycemia (both one abnormal value at the OGTT and GDM) showed a worse metabolic pattern than subjects with gestational normoglycemia [respectively higher values of body mass index (BMI), waist, blood pressure, serum glucose, insulin, C-peptide, homeostatic model assessment (HOMA), fibrinogen and lower levels of HDL-cholesterol]. Prevalence of the metabolic syndrome and its components was 2-4-fold higher in women with prior gestational hyperglycemia (and 10-fold higher if pre-pregnancy obesity coexisted) when compared to normoglycemic controls; in a Cox proportional hazard model, after adjustments for age and pre-pregnancy BMI, gestational hyperglycemia and pre-pregnancy BMI predicted subsequent metabolic syndrome [respectively: hazard ratio (HR)=4.26 and HR=1.21] and most of its components. In the same model, the highest quartile of fasting serum glucose at the OGTT of the index pregnancy was significantly associated to the metabolic syndrome and its components. Gestational hyperglycemia and fasting glucose values were also associated to subsequent fibrinogen values, but not to albumin excretion rates. In young adult women, prior gestational hyperglycemia (particularly abnormal fasting glucose values), above all in combination with pre-pregnancy obesity, anticipates a subsequent syndrome at high cardiovascular risk and, possibly, a mild chronic inflammatory response.

Research paper thumbnail of Glutathione levels in patients with erectile dysfunction, with or without diabetes mellitus

International Journal of Andrology, 2005

The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essen... more The reduced form of glutathione (GSH) is the most important cell antioxidant and is also an essential cofactor for nitric oxide (NO) synthase that synthesizes NO from L-arginine. Reduced levels of GSH, due both to a hyperglycaemia-induced increase of free radical production and to a decrease of NADPH levels [like in diabetes mellitus (DM)], can hamper the endothelial cell functions. This condition may play an important role in the aetiology of some clinical signs, like erectile dysfunction (ED). The aim of this study was to test the hypothesis that GSH concentration is reduced in patients with ED and type 2 diabetes mellitus. We studied 111 male patients with ED: 64 with diabetes (ED/DM) and 47 without diabetes (ED/wDM); 20 patients with diabetes but without ED (DM) and 26 male normal subjects as a control group (C). .001 respectively). GSH showed a negative correlation with fasting glucose concentrations (r ¼ )0.34, p < 0.01) and with the duration of DM (r ¼ )0.25, p < 0.05). A GSH depletion can lead to a reduction of NO synthesis, thus impairing vasodilation in the corpora cavernosa.

Research paper thumbnail of A clinically orientated approach increases the efficiency of screening for latent autoimmune diabetes in adults (LADA) in a large clinic-based cohort of patients with diabetes onset over 50 years

Diabetic Medicine, 2004

To assess if a clinically orientated approach improves screening for latent autoimmune diabetes i... more To assess if a clinically orientated approach improves screening for latent autoimmune diabetes in adults (LADA) in patients developing diabetes over age 50.

Research paper thumbnail of Clinical characteristics and outcome of pregnancy in women with gestational hyperglycaemia with and without antibodies to β-cell antigens

Diabetic Medicine, 2003

To evaluate the prevalence of β -cell autoantibodies in women with gestational diabetes and impai... more To evaluate the prevalence of β -cell autoantibodies in women with gestational diabetes and impaired glucose tolerance, and identify clinical characteristics differentiating hyperglycaemic patients with and without autoantibodies.

Research paper thumbnail of Prevalence of Type 1 Diabetes-Related Autoantibodies in Adults With Celiac Disease

Diabetes Care, 2003

Results from a population-based survey O ur objective was to evaluate the diagnostic proficiency ... more Results from a population-based survey O ur objective was to evaluate the diagnostic proficiency of the World Health Organization (WHO) and the National Cholesterol Education Program (NCEP)-III definitions (1,2) for the metabolic syndrome in a Mexican nationwide, population-based survey. Details of the sampling procedures have been previously described (3). The population was composed of 2,158 men and women aged 20 -69 years sampled after a 9-to 12-h fasting period. For the WHO criteria, insulin resistance was diagnosed if a nondiabetic case had fasting insulin concentrations Ն126 pmol/l (21 U/ml) (Ͼ75th percentile in Mexican adults). The ageadjusted prevalence was 13.61% for the WHO criteria (n ϭ 268) and 26.6% for the NCEP-III definition (n ϭ 574). After excluding patients with diabetes, the prevalence was 9.2 and 21.4%, respectively. The agreement between the definitions was assessed in 1,969 subjects; 189 cases were eliminated due to the lack of a urine sample.

Research paper thumbnail of Anti-Heat Shock Protein 27 Antibody Levels and Diabetes Complications in the EURODIAB Study

Diabetes Care, 2009

OBJECTIVE -To assess whether serum anti-heat shock protein 27 (HSP27) antibody levels are associa... more OBJECTIVE -To assess whether serum anti-heat shock protein 27 (HSP27) antibody levels are associated with micro-and macrovascular complications of type 1 diabetes.