Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients

T2DMis 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 T2DMcomplications, including 367 T2DMpatients complicated for the 55.6%. Patients with A/A and A/G TLR4 genotypes showed significant differences in complication\u2019s 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\u20138.741).Thus, the rs4986790 polymorphism may be an indicative of prevalence of complications in T2DM patients

FLNA is implicated in pulmonary neuroendocrine tumors aggressiveness and progression

Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase. FLNA is highly expressed in PNTs with high malignant grade. FLNA silencing reduces cyclin D1 levels (-51\uc2\ub15, p < 0.001) and cell proliferation in PNT cells (-37\uc2\ub14, p < 0.05), colony formation and VEGF expression (-39\uc2\ub19%, p < 0.01) in H727 cells. FLNA and Rap1 co-localize in cellular protrusions and FLNA silencing up-regulates Rap1 expression (+73\uc2\ub118%, p < 0.01). Rap1 silencing prevents cell adhesion increase (+43%\uc2\ub118%, p < 0.01) and cell migration decrease (-56\uc2\ub17%, p < 0.01) induced by FLNA silencing, without affecting cell proliferation reduction. In conclusion, FLNA is implicated in PNT progression, in part through Rap1, thus providing a potential diagnostic and therapeutic target

Mitochondrial DNA Backgrounds Might Modulate Diabetes Complications Rather than T2DM as a Whole

Mitochondrial dysfunction has been implicated in rare and common forms of type 2 diabetes (T2DM). Additionally, rare mitochondrial DNA (mtDNA) mutations have been shown to be causal for T2DM pathogenesis. So far, many studies have investigated the possibility that mtDNA variation might affect the risk of T2DM, however, when found, haplogroup association has been rarely replicated, even in related populations, possibly due to an inadequate level of haplogroup resolution. Effects of mtDNA variation on diabetes complications have also been proposed. However, additional studies evaluating the mitochondrial role on both T2DM and related complications are badly needed. To test the hypothesis of a mitochondrial genome effect on diabetes and its complications, we genotyped the mtDNAs of 466 T2DM patients and 438 controls from a regional population of central Italy (Marche). Based on the most updated mtDNA phylogeny, all 904 samples were classified into 57 different mitochondrial sub-haplogroups, thus reaching an unprecedented level of resolution. We then evaluated whether the susceptibility of developing T2DM or its complications differed among the identified haplogroups, considering also the potential effects of phenotypical and clinical variables. MtDNA backgrounds, even when based on a refined haplogroup classification, do not appear to play a role in developing T2DM despite a possible protective effect for the common European haplogroup H1, which harbors the G3010A transition in the MTRNR2 gene. In contrast, our data indicate that different mitochondrial haplogroups are significantly associated with an increased risk of specific diabetes complications: H (the most frequent European haplogroup) with retinopathy, H3 with neuropathy, U3 with nephropathy, and V with renal failure

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Monitoring energy poverty in Northern Greece: the energy poverty phenomenon

The last two decades’ scientists have become increasingly interested in the aspects of energy poverty. In order to study the dynamics of energy poverty in Northern Greece a field study was carried out. The evidence presented is based on a comprehensive study of 350 questionnaires mainly for Western (47%) and Central Macedonia (45%), in Northern Greece. The questionnaire focused on the household’ and users’ characteristics, allowing for regional specific effects. Additionally, in an effort to study and quantify the relation between households’ net-income and the most common indicators of energy poverty a Chi-square test was estimated. At the same time six temperature and humidity loggers have been distributed to selected participants to record real-time data. Overall, the results of the survey unveiled that various characteristics of the domestic demand for heating are linked with the household’s net-income

HbA1c: miglior controllo con meno tempo di esercizio fisico nei diabetici over 65

Introduzione: La Whole Body Vibration (WBV) è una metodologia di allenamento capace d’incrementare alcune specifiche caratteristiche del muscolo (forza, flessibilità, sensibilità insulina). Lo scopo della ricerca è stato di osservare, su un gruppo di pazienti con diabete di tipo 2, gli effetti di un training di WBV, in alternativa all’esercizio fisico aerobico, per migliorare il parametro Emoglobina Glicata (HbA1c) con un ridotto tempo di esercizio. Metodi: Un totale di 48 soggetti diabetici, di età compresa tra i 45 e i 78 anni, in cura presso l’Ospedale INRCA-IRCCS di Ancona - U.O.C. Diabete e Malattie Metaboliche, è stato randomizzato in due gruppi sottoposti a due differenti tipi di intervento: esercizio fisico aerobico (gruppo AG) e Whole Body Vibration (gruppo VG). I dati del parametro HbA1c sono stati raccolti all’inizio del trattamento (T0) e dopo 12 settimane, al termine del trattamento (T1). Risultati: Nei soggetti over 65 anni di entrambi i gruppi si è evidenziata una riduzione dei valori dell’HbA1c, nel gruppo VG con significatività (p<0.05): - gruppo AG: -1.1% (dopo un tempo di esercizio di 360’); - gruppo VG: -6.4% (dopo un tempo di esercizio di 156’). Conclusione: La WBV è una alternativa concreta all’esercizio aerobico; essa è particolarmente efficace in pazienti over 65 nell’incrementare la sensibilità insulinica con sedute di allenamento di breve durat