Giuseppe Scavone

Effect of carbohydrate counting and medical nutritional therapy on glycaemic control in Type 1 diabetic subjects: a pilot study.

Diabet. Med. 27, 477–479 (2010)

Association Between Osteoprotegerin G1181C and T245G Polymorphisms and Diabetic Charcot Neuroarthropathy: A case-control study

OBJECTIVE Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role. RESEARCH DESIGN AND METHODS We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy. RESULTS Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3–4.1], P = 0.006; Ch vs. H, 2.10 [1.3–3.3], P = 0.002; and ND vs. H, 0.90 [0.7–1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2–19.7], P < 0.001; Ch vs. H, 3.56 [1.9–6.7], P = 0.001; and ND vs. H, 0.54 [0.6–5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06–0.5], P = 0.002) and with ND (0.17 [0.05–0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43–2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy. CONCLUSIONS This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.

Targeting prolyl-isomerase Pin1 prevents mitochondrial oxidative stress and vascular dysfunction: insights in patients with diabetes

AIM Diabetes is a major driver of cardiovascular disease, but the underlying mechanisms remain elusive. Prolyl-isomerase Pin1 recognizes specific peptide bonds and modulates function of proteins altering cellular homoeostasis. The present study investigates Pin1 role in diabetes-induced vascular disease. METHODS AND RESULTS In human aortic endothelial cells (HAECs) exposed to high glucose, up-regulation of Pin1-induced mitochondrial translocation of pro-oxidant adaptor p66(Shc) and subsequent organelle disruption. In this setting, Pin1 recognizes Ser-116 inhibitory phosphorylation of endothelial nitric oxide synthase (eNOS) leading to eNOS-caveolin-1 interaction and reduced NO availability. Pin1 also mediates hyperglycaemia-induced nuclear translocation of NF-κB p65, triggering VCAM-1, ICAM-1, and MCP-1 expression. Indeed, gene silencing of Pin1 in HAECs suppressed p66(Shc)-dependent ROS production, restored NO release and blunted NF-kB p65 nuclear translocation. Consistently, diabetic Pin1(-/-) mice were protected against mitochondrial oxidative stress, endothelial dysfunction, and vascular inflammation. Increased expression and activity of Pin1 were also found in peripheral blood monocytes isolated from diabetic patients when compared with age-matched healthy controls. Interestingly, enough, Pin1 up-regulation was associated with impaired flow-mediated dilation, increased urinary 8-iso-prostaglandin F2α and plasma levels of adhesion molecules. CONCLUSIONS Pin1 drives diabetic vascular disease by causing mitochondrial oxidative stress, eNOS dysregulation as well as NF-kB-induced inflammation. These findings provide molecular insights for novel mechanism-based therapeutic strategies in patients with diabetes.

Adaptive immunity, inflammation, and cardiovascular complications in type 1 and type 2 diabetes mellitus.

Diabetes mellitus (DM) is a pandemics that affects more than 170 million people worldwide, associated with increased mortality and morbidity due to coronary artery disease (CAD). In type 1 (T1) DM, the main pathogenic mechanism seems to be the destruction of pancreatic β-cells mediated by autoreactive T-cells resulting in chronic insulitis, while in type 2 (T2) DM primary insulin resistance, rather than defective insulin production due to β-cell destruction, seems to be the triggering alteration. In our study, we investigated the role of systemic inflammation and T-cell subsets in T1- and T2DM and the possible mechanisms underlying the increased cardiovascular risk associated with these diseases.

Association Between Osteoprotegerin G1181C and T245G Polymorphisms And Charcot Diabetic Neuroarthropathy: a case – control study

OBJECTIVE Charcot neuroarthropathy is a disabling complication of diabetes. Although its pathogenesis remains unknown, we suppose that genetics may play a relevant role. RESEARCH DESIGN AND METHODS We performed a case-control study with 59 subjects with diabetic Charcot neuroarthropathy (Ch group), 41 with diabetic neuropathy without Charcot neuroarthropathy (ND group), and 103 healthy control subjects (H group) to evaluate the impact of two single nucleotide polymorphisms (SNPs) of the osteoprotegerin gene (G1181C and T245G) on the risk of Charcot neuroarthropathy. RESULTS Regarding the SNPs of G1181C, we found a significant linkage between the G allele and Charcot neuroarthropathy (Ch vs. ND, odds ratio [OR] 2.32 [95% CI 1.3–4.1], P = 0.006; Ch vs. H, 2.10 [1.3–3.3], P = 0.002; and ND vs. H, 0.90 [0.7–1.9], P = 0.452); similarly, we found a linkage with the G allele of T245G (Ch vs. ND, 6.25 [2.2–19.7], P < 0.001; Ch vs. H, 3.56 [1.9–6.7], P = 0.001; and ND vs. H, 0.54 [0.6–5.7], P = 0.304), supporting a protective role for the allele C and T, respectively. For this reason we investigated the frequency of the protective double homozygosis CC + TT (7% in Ch) that was significantly lower in Ch compared with H (0.18 [0.06–0.5], P = 0.002) and with ND (0.17 [0.05–0.58], P = 0.006), whereas there was no difference between H and ND (1.05 [0.43–2.0], P = 0.468). In a multivariate logistic backward regression model, only weight and the lack of CC and TT genotypes were independently associated with the presence of Charcot neuroarthropathy. CONCLUSIONS This is the first study that shows an association between genetic regulation of bone remodeling and Charcot neuroarthropathy.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients.

Effect of α-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic Patients

OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity. We investigated whether α-lipoic acid (ALA) has any effect on platelet reactivity in these patients. RESEARCH DESIGN AND METHODS We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured. RESULTS Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups. CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.

Severe leucopenia associated with Sitagliptin use

We report the case of a type 2 diabetes subject who developed severe leucopenia associated with treatment with the dipeptidil-peptidase 4 enzyme inhibitor Sitagliptin and highlights DPP4 inhibitors as a possible cause of unexplained hematolgical abnormalities in patients receiving DPP4-inhibitor treatment.

Autoantibodies to post‐translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus

Charcot neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is as yet unknown. In autoinflammatory diseases, such as rheumatoid arthritis, characterized by inflammation and joint involvement, autoantibodies against oxidative post‐translationally modified (oxPTM) collagen type I (CI) and type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in charcot neuroarthropathy, investigating the presence of autoantibodies oxPTM‐CI and oxPTM‐CII, in participants with charcot neuroarthropathy.

A case of chronic hepatitis C developing insulin-dependent diabetes, thyroid autoimmunity and stiff-person syndrome as complications of interferon therapy.

We describe the case of a 66-year-old man with chronic hepatitis C who developed type 1 diabetes mellitus (T1DM) and thyroid autoimmunity during Interferon alpha (INFalpha) therapy and then stiff-person syndrome (SPS). This is the first reported case in which SPS has appeared as complication of IFNalpha therapy.