Search

Abstract: Aims: The hyperglycemic hyperosmolar syndrome (HHS) is a life-threatening diabetic complication. We aimed to portrait the short and long term outcome after a HHS episode and to describe features associated with increased early mortality. Methods: We collected data from consecutive HHS cases, defined based on rigorous glucose and osmolality criteria. We retrieved anthropometric measures, history of diabetes, other cardiovascular risk factors and chronic co-morbidity. Clinical and biochemical parameters were recorded at admission, after 24h and at discharge. We assessed incidence of complications, as well as short (≤30 days) and long term mortality. Results: Patients were about 80-year old. Fifty-one cases were included, characterized by severe hyperglycemia (55.5mosm/L) and hyperosmolality (385mosm/L). Thirty-three percent developed at least one complication. Short term mortality was 16%; lower Glasgow Coma Scale, higher plasma glucose and mild acidosis were predictive of short term mortality. The long term mortality (median follow-up 1.27 years) was not significantly different from historical mortality data after hypoglycemic coma. Conclusion: In this study, early mortality of HHS was 16% and some clinical features at presentation were predictive of an adverse short term outcome. Long term survival after a HHS episode did not appear to be severely impaired. [Copyright &y& Elsevier]

Abstract: The expanding diabetic epidemic and the high risk of cardiovascular events in diabetic patients suggest that screening heart disease in this population is an important issue. Nonetheless, the advisability of large-scale screening in asymptomatic individuals with diabetes is debated, because available techniques are expensive and have suboptimal diagnostic accuracy. Moreover, all diabetic patients should be treated aggressively as if they all had a positive screening test, because diabetes could be considered a coronary risk equivalent. In this article, we underline the importance of an early diagnosis of coronary artery disease and heart failure in diabetic patients, suggesting that positive screening tests have significant implications in clinical management. [Copyright &y& Elsevier]

Abstract: The current wisdom indicates that insulin''s positive effects, normoglycemia, vasodilation, and anti-inflammation, are mediated by the canonical phosphoinositide 3-kinase (PI3K)/Akt pathway whereas the negative effects are mediated by the mitogen-activated protein kinase (MAPK)/extracellular regulated kinase (ERK) pathway. Much of the intracellular oxidant stress is mediated by the MAPK/ERK pathway which is a downstream signal also for other proatherogenic hormones such as angiotensin II. However, recent evidence links MAPK activation to antioxidant activity and vascular protection. We argue against a dichotomization of insulin signaling also in light of the concept that ERK-MAPK represents a critical node in the intracellular insulin network responsible for several positive effects related not only to vascular function but also to life span. [Copyright &y& Elsevier]

To evaluate the role of elevation of non-esterified fatty acids on forearm nitric oxide (NO) dependent and independent relaxation, four studies were performed in the forearms of 14 normals: (1) endothelium-dependent and -independent vasodilations were assessed during acetylcholine (Ach) and sodium nitroprusside (SNP) infusions; (2) flow-mediated vasodilation (FMD) was assessed; (3) bradykinin (BK) was infused during NO and prostaglandin inhibition (NO clamp); (4) blood flow (FBF) was measured during Ouabain, a Na+/K+ ATPase, and BaCl2, rectifying potassium channel (KIR) blockers, respectively. All studies were performed before and after 120 min. Intralipid+heparin (high-NEFA) infusion. Ach-mediated FBF increase was lower at high-NEFA (332±34 vs. 436±44% at 45 μg l forearm−1 min−1; % of ratio infused: control arm P<0.05), while SNP response was similar. FMD did not differ before and during high-NEFA, which induced a blunted response of FBF during BK with or without NO clamp. Ouabain and BaCl2-mediated FBF inhibition was lower (P<0.01) at high-NEFA. During ouabain alone FBF decreased slightly. In conclusion: High-NEFA exerts a negative role on both NO-dependent and independent vasodilations. The decrease in FBF, mediated by KIR inhibition, is blunted by high-NEFA: these substrates interfere with hemodynamic/metabolism coupling, possibly through the inhibition of these channels. [Copyright &y& Elsevier]

Ischemia–reperfusion (IR) leads to severe organ injury and dysfunction. Sirtuins (SIRTs) are a family of histone deacetylases (HDACs) that require nicotinamide adenine dinucleotide (NAD + ) for the deacetylation reaction. SIRTs play a major role in counteracting cellular stress and apoptosis. This study aimed to investigate the mechanisms of heart protection against apoptosis by SIRTs and the molecular pathways involved in SIRTs regulation and function in a rat model of IR injury. Hearts of male Wistar–Kyoto rats were subjected to 30-min ischemia followed by reperfusion up to 6 h. IR increased cardiomyocyte apoptosis; the cleavage of caspase 3, induced a transient upregulation of SIRT1 and downregulation of SIRT6 expression, but decreased SIRT1 activity and reduced NAD + content. IR also increased forkhead box protein O1 (FoxO1) expression and FoxO1 binding to SIRT1 promoter region. Resveratrol restored SIRT1 activity and NAD + level by an AMPK-dependent mechanism, reduced cardiomyocyte apoptosis, and attenuated caspase 3 cleavage via heat shock factor-1 deacetylation and heat shock protein (HSP) expression upregulation. Our data show new potential molecular mechanisms of up and downstream regulation of SIRT1 in IR. The interplay among FoxO1, SIRT1, NAD + , AMPK, HSP, and SIRT6 depicts a complex molecular network that protects the heart from apoptosis during IR and may be susceptible to therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objectives: We sought to establish whether a reduction in endothelial progenitor cells (EPCs) has a putative role in peripheral vascular disease (PVD) of type 2 diabetic patients. Background: Peripheral vascular disease is a common and severe complication of diabetes mellitus. Impaired collateralization of diabetic vasculopathy has been extensively shown, but causes leading to its pathogenesis are not fully understood. Recently, EPCs have been found to contribute to vascular repair and angiogenesis. Diabetes has been associated with low levels of circulating EPCs, but no data are available in the literature on the relationship between EPCs and PVD in diabetes. Methods: Flow cytometric analysis was used to quantify circulating progenitor cells (CPCs, CD34+) and EPCs (CD34+KDR+) in 51 patients and 17 control subjects. Results: The CPCs and EPCs from diabetic patients were reduced by 33% and 40%, respectively, compared with healthy subjects (p &#60; 0.001). An inverse correlation was found between the number of EPCs and the values of fasting glucose (r = −0.49, p = 0.006). Peripheral vascular disease was associated with a 47% reduction in EPCs (p &#60; 0.0001) and EPC levels directly correlated with the ankle-brachial index (r = 0.70, p = 0.01). The subgroup of diabetic patients with PVD also had reduced CPCs by 32% (p = 0.037), whereas patients with ischemic foot lesions had the lowest levels of both EPCs and CPCs (p = 0.02). Conclusions: Our data demonstrate decreased EPC levels in diabetic patients and, for the first time, show that PVD is associated with an extensively low number of EPCs. Depletion of circulating EPCs in diabetic patients may be involved in the pathogenesis of peripheral vascular complications. [Copyright &y& Elsevier]

Type 2 diabetes (T2D) is characterized by low HDL cholesterol (HDL-C) and HDL dysfunction. We herein tested whether lowering HbA1c affects HDL-C and reverse cholesterol transport (RCT). Forty-two uncontrolled T2D patients initiating basal insulin were included. HbA1c, HDL-C and RCT were assessed at baseline and after 6 months. At baseline, HDL-C and RCT were directly correlated (r = 0.50; p < 0.001). After 6 months of insulin therapy, HbA1c dropped from 8.8 ± 0.16% to 7.1 ± 0.1%, while average HDL-C and RCT did not change. Follow-up HDL-C and RCT were still correlated (r = 0.31; p = 0.033) and ΔHDL-C correlated with ΔRCT (r = 0.32; p = 0.029). ΔHbA1c correlated with ΔHDL-C (r = 0.43, p = 0.001), but not with ΔRCT. In patients with ΔHbA1c above the median value (1.3%), HDL-C (but not RCT) increased significantly. In conclusion, glucose control correlates with increased HDL-C, but not with improved RCT. Thus, persistent HDL dysfunction despite improved HbA1c and HDL-C can contribute to residual cardiovascular risk in T2D. [ABSTRACT FROM AUTHOR]