Metabolic Diseases and Diabetology Unit

Ancona, Italy

Metabolic Diseases and Diabetology Unit

Ancona, Italy

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Garagnani P.,University of Bologna | Garagnani P.,Applied Biomedical Research Center | Giuliani C.,University of Bologna | Pirazzini C.,University of Bologna | And 23 more authors.
Aging | Year: 2013

Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed allelic/genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10-7). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared. © Paolo Garagnani1et al.


Testa R.,Italian National Research Center on Aging | Vanhooren V.,Inflammation Research Center | Vanhooren V.,Ghent University | Bonfigli A.R.,Italian National Research Center on Aging | And 15 more authors.
PLoS ONE | Year: 2015

Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome. Methods We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.6 ±8.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.5±12.4 years). N-glycome was evaluated in serum glycoproteins. Results We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, α(1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with α(1,6)- and α(1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme "unhealthy" phenotype (T2DM+ with MS). Conclusions Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS. © 2015 Testa et al.


Balistreri C.R.,University of Palermo | Bonfigli A.R.,Metabolic Diseases and Diabetology Unit | Boemi M.,Metabolic Diseases and Diabetology Unit | Olivieri F.,Marche Polytechnic University | And 10 more authors.
Mediators of Inflammation | Year: 2014

T2DM is today considered as world-wide health problem, with complications responsible of an enhanced mortality and morbidity. Thus, new strategies for its prevention and therapy are necessary. For this reason, the research interest has focused its attention on TLR4 and its polymorphisms, particularly the rs4986790. However, no conclusive findings have been reported until now about the role of this polymorphism in development of T2DM and its complications, even if a recent meta-analysis showed its T2DM association in Caucasians. In this study, we sought to evaluate the weight of rs4986790 polymorphism in the risk of the major T2DM complications, including 367 T2DM patients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication's prevalence. In particular, AG carriers had higher risk prevalence for neuropathy (P = 0.026), lower limb arteriopathy (P = 0.013), and the major cardiovascular pathologies (P = 0.017). Their cumulative risk was significant (P = 0.01), with a threefold risk to develop neuropathy, lower limb arteriopathy, and major cardiovascular events in AG cases compared to AA cases. The adjusted OR for the confounding variables was 3.788 (95% CI: 1.642-8.741). Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients. © 2014 Carmela Rita Balistreri et al.


PubMed | Metabolic Diseases and Diabetology Unit, Scientific Direction and IRCCS INRCA U.Sestilli
Type: | Journal: Journal of clinical hypertension (Greenwich, Conn.) | Year: 2016

Patients with type 2 diabetes mellitus are at high risk for atherosclerotic disease, and proper blood pressure measurement is mandatory. The authors examined the prevalence of an interarm difference (IAD) in blood pressure and its association with cardiovascular risk factors and organ damage (nephropathy, retinopathy, left ventricular hypertrophy, and vascular damage) in a large diabetic population. A total of 800 consecutive patients with type 2 diabetes mellitus were evaluated with an automated simultaneous bilateral device (men: 422 [52.8%]; mean age: 68.112.2years). Diabetic patients with systolic IAD 5 and systolic IAD 10mm Hg showed an increased risk of having vascular damage (adjusted odds ratios: 1.73 and 2.49, respectively) and higher pulse pressure. IAD is highly prevalent in patients with diabetes, is associated with vascular damage, even for IAD 5mm Hg, and should be accurately obtained to avoid underdiagnosis and undertreatment of hypertension.


PubMed | Italian National Research Center on Aging, Marche Polytechnic University, IRCCS Gruppo Multimedica Sesto San Giovanni MI, University of Bologna and 3 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Glycosylation, i.e the enzymatic addition of oligosaccharides (or glycans) to proteins and lipids, known as glycosylation, is one of the most common co-/posttranslational modifications of proteins. Many important biological roles of glycoproteins are modulated by N-linked oligosaccharides. As glucose levels can affect the pathways leading to glycosylation of proteins, we investigated whether metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), pathological conditions characterized by altered glucose levels, are associated with specific modifications in serum N-glycome.We enrolled in the study 562 patients with Type 2 Diabetes Mellitus (T2DM) (mean age 65.68.2 years) and 599 healthy control subjects (CTRs) (mean age, 58.512.4 years). N-glycome was evaluated in serum glycoproteins.We found significant changes in N-glycan composition in the sera of T2DM patients. In particular, (1,6)-linked arm monogalactosylated, core-fucosylated diantennary N-glycans (NG1(6)A2F) were significantly reduced in T2DM compared with CTR subjects. Importantly, they were equally reduced in diabetic patients with and without complications (P<0.001) compared with CTRs. Macro vascular-complications were found to be related with decreased levels of NG1(6)A2F. In addition, NG1(6)A2F and NG1(3)A2F, identifying, respectively, monogalactosylated N-glycans with (1,6)- and (1,3)-antennary galactosylation, resulted strongly correlated with most MS parameters. The plasmatic levels of these two glycans were lower in T2DM as compared to healthy controls, and even lower in patients with complications and MS, that is the extreme unhealthy phenotype (T2DM+ with MS).Imbalance of glycosyltransferases, glycosidases and sugar nucleotide donor levels is able to cause the structural changes evidenced by our findings. Serum N-glycan profiles are thus sensitive to the presence of diabetes and MS. Serum N-glycan levels could therefore provide a non-invasive alternative marker for T2DM and MS.


Campanati A.,Marche Polytechnic University | Ganzetti G.,Marche Polytechnic University | Giuliodori K.,Marche Polytechnic University | Marra M.,Metabolic Diseases and Diabetology Unit | And 3 more authors.
International Journal of Dermatology | Year: 2015

Background: Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases. Objectives: This study was conducted to evaluate the effects of tumor necrosis factor-α (TNF-α) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis. Methods: Serum levels of adiponectin, resistin, visfatin, leptin, TNF-α, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF-α inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits. Results: At baseline, mean serum levels of TNF-α, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P > 0.005). Conclusions: Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF-α inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines. © 2015 The International Society of Dermatology.


PubMed | Metabolic Diseases and Diabetology Unit, Marche Polytechnic University and Experimental Models in Clinical Pathology
Type: Journal Article | Journal: International journal of dermatology | Year: 2015

Adipocytokines are bioactive molecules that are deeply involved in the occurrence of atherosclerosis, obesity, and autoimmune inflammatory diseases.This study was conducted to evaluate the effects of tumor necrosis factor- (TNF-) inhibitors on serum levels of adipocytokines in patients with chronic plaque psoriasis.Serum levels of adiponectin, resistin, visfatin, leptin, TNF-, and interleukin-6 (IL-6) were evaluated in sera obtained from 47 patients with psoriasis, both at baseline and after they had received TNF- inhibitors for 24 weeks. Equivalent data were obtained for 39 control subjects matched by age, sex, body mass index, waist : hip ratio, geographical origin, Mediterranean dietary habits, and smoking habits.At baseline, mean serum levels of TNF-, IL-6, leptin, resistin, and visfatin were higher in the psoriasis group than in healthy controls; these differences were statistically significant (P < 0.05). Conversely, mean serum levels of adiponectin were significantly lower in patients with psoriasis than in controls (P < 0.0001). Serum levels of adipocytokines did not linearly correlate with anthropometric indices in psoriasis patients (P > 0.05), except in the case of leptin, for which serum levels were related to waist : hip ratio in both men and women (P < 0.05). After 24 weeks of treatment, although serum levels of proinflammatory adipocytokines were decreased, only that of leptin showed a statistically significant reduction (P = 0.0003). Serum levels of adiponectin, an anti-inflammatory adipocytokine, were only mildly increased and persisted at a significantly lower level than in healthy controls (P > 0.005).Patients with psoriasis show an imbalance between pro- and anti-inflammatory adipocytokines, which is reduced but not normalized after administration of TNF- inhibitors for 24 weeks. This partial rebalancing seems to be mainly related to a reduction in proinflammatory adipocytokines, rather than an increase in anti-inflammatory adipocytokines.

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