Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes.

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66-85), oldest old (>85-98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians

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

Effect of etanercept on insulin sensitivity in nine patients with psoriasis

Metabolic syndrome is associated to chronic low grade inflammation, characterized by increased levels of inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-6 (IL-6). In particular, TNF-alpha causes a decrease in the insulin-stimulated kinases related to the early phases of the insulin cascade, thereby leading to insulin resistance. Etanercept is a human fusion protein used in the treatment of psoriasis and inflammatory arthritis. It blocks inflammatory response by interfering in the binding of TNF-alpha to its receptors. The aim of this case report study is to verify the effect of Etanercept on insulin sensitivity, lipid profile and inflammatory status in psoriatic patients. Nine psoriatic patients with stable, active, plaque type psoriasis were enrolled and treated with Etanercept for 24 weeks. We found an improvement in the metabolic assessment with a significant reduction of insulin plasma levels. In particular, this treatment allows to maintain their euglycemic state with lower insulin plasma levels, as confirmed by the improved Homeostasis Model Assessment (HOMA) index. We conclude that Etanercept, probably acting on inflammation, improves insulin sensitivity in psoriatic subjects

Endovascular repair of thoracic aortic disease with the EndoFit stent-graft: short and midterm results from a single center.

PURPOSE: To analyze the outcomes of endovascular treatment of thoracic aortic pathologies performed at a single center with the EndoFit thoracic stent-graft system. METHODS: From January 2002 to January 2007, 41 patients (33 men; mean age 69.3+/-9.7 years, range 48-84) were treated for thoracic aortic disease with the EndoFit stent-graft system. Patient data were retrieved from a retrospective review of hospital records. Indications for treatment were progression of aneurysm size in atherosclerotic aneurysms (n = 24, mean aneurysm diameter 7.19+/-1.48 cm), acute contained aortic rupture (n = 5), aortic dissection (n = 6), penetrating atherosclerotic ulcers (n = 4), post-traumatic pseudoaneurysm (n = 1), and post coarctation repair aneurysm (n = 1). RESULTS: The EndoFit stent-graft was successfully deployed in all 41 patients. The in-hospital and 30-day mortality rate was 7.3% (3 patients). Three (7.3%) postoperative endoleaks were recorded: a proximal type Ia and a distal Ib both resolved spontaneously at 1 and 3 months, respectively. The third patient had a persistent type Ia endoleak; conversion was necessary after 1 year. There was only 1 case of spinal ischemia, with consequent lower extremity weakness; no paraplegia was observed. During a mean 24.8-month follow-up, 2 secondary type Ia endoleaks were treated with additional stent-grafts. There were 7 (17%) deaths during follow-up. At 2 years, overall patient survival by Kaplan-Meier analysis was 70%; aneurysm-related survival was 89%. CONCLUSION: Endovascular treatment of vascular disease involving the descending thoracic aorta can be safely performed with the EndoFit thoracic stent-graft system

Effect of 4G/5G PAI-1 polymorphism on the response of PAI-1 activity to vitamin E supplementationin Type 2 diabetic patients

Plasminogen activator inhibitor type 1 (PAI-1) is an independent cardiovascular risk factor and increases in patients with Type 2 diabetes mellitus. The 4G/5G polymorphism of PAI-1 has been reported to be involved in the incidence of cardiovascular disease by regulation of PAI-1 levels, but this relation is still under debate. The aim of the study was to test the effect of 4G/5G polymorphism on the lowering of PAI-1 levels in Type 2 diabetic patients during vitamin E supplementation. Ninety-three Type 2 diabetic subjects (age+/-SD, 62.1+/-6.1 yr) were enrolled and treated with vitamin E (500 IU/die) for 10 weeks. We determined the 4G/5G polymorphism and PAI-1 activity at baseline, during (5(th) and 10(th) week) and after (30(th) week) vitamin E supplementation. No significant differences were found in PAI-1 and its determinants among the three genotypic groups at baseline. Decrements were detected in the whole group in PAI-1 at the 5(th) and the 10(th) week from baseline followed by an increase at the 30(th) week (p<0.001). Patients with 4G/4G and 4G/5G genotypes showed a different trend with respect to those with 5G/5G in PAI-1. In particular, there was a decrease in 4G/4G and 4G/5G PAI-1 levels from the loth week, while a decrease in 5G/5G PAI-1 was observed from the 5(th) week (p<0.01). The delayed decrease, found in patients with at least one 4G allele with respect to those with 5G/5G genotype, demonstrates that 4G/5G polymorphism mainly influences the rate of decrease of PAI-1 after supplementation with vitamin E in Type 2 diabetic subjects