Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγ agonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates it with clinical and laboratory outcomes in the published literature. In addition, this review article attempts to discuss some of the molecular mechanisms regarding the association between TZDs therapy and the nontraditional cardiovascular risks

The Impact of the Board of Directors' Characteristics and Ownership Structure on the Sustainable Development Disclosure in the Banks Listed on the Amman Stock Exchange

Purpose: This study tries to comprehend how corporate governance (CG) affects disclosures on economic, social, and environmental sustainability.   Theoretical framework: Recent literature has reported that CG has significant impact on disclosures on economic, social, and environmental sustainability. However, there is still much to investigate and learn about CG in sustainability process.   Design/methodology/approach: For the time period spanning 2015 to 2021, information about study variables was gathered from thirteen (13) banks listed on the Amman Stock Exchange (ASE) through annual reports and quantitative approach.   Findings: Study findings showed that CG components improve sustainability disclosures in general. The study results indicated that, a large board with a female director and a Corporate Social Responsibility Committee (CSRC) is better able to audit and control management choices related to sustainability issues (whether they be economic, environmental, or social) and produces better sustainability disclosure.   Research, Practical and Social implications: This study is proposed to help bank managers understand the real impact of corporate governance practices on sustainability, especially economic, environmental and social indicators of sustainability and how to improve and develop them.   Originality/value: Through quantitative and qualitative analysis, this study contributes methodologically and empirically to the literature on corporate governance and sustainability reporting in emerging and developing economies

Differential Expression of Human Peripheral Mononuclear Cells Phenotype Markers in Type 2 Diabetic Patients and Type 2 Diabetic Patients on Metformin

Background: Although peripheral blood mononuclear cells (PBMC) have been demonstrated to be in a pro-inflammatory state in obesity and type 2 Diabetes Mellitus (T2DM), characterization of circulating PBMC phenotypes in the obese and T2DM and the effect of Metformin on these phenotypes in humans is still ill-defined and remains to be determined.Methods: Thirty normal healthy adult volunteers of normal weight, 30 obese subjects, 20 obese newly diagnosed diabetics and 30 obese diabetics on Metformin were recruited for the study. Fasting blood samples were collected and PBMC were isolated from whole blood. Polarization markers (CD86, IL-6, TNFα, iNOS, CD36, CD11c, CD169, CD206, CD163, CD68, CD11b, CD16, and CD14) were measured by RT-qPCR. Gene expression fold changes were calculated using the 2−ΔΔCT method for RT-qPCR.Results: Obesity and T2DM are associated an increased CD68 marker in PBMC. mRNA expression of CD11b, CD11c, CD169, and CD163 were significantly reduced in PBMC from T2DM subjects whereas CD11c was significantly inhibited in PBMC from obese subjects. On the other hand, macrophage M1-like phenotype was observed in T2DM circulation as demonstrated by increased mRNA expression of CD16, IL-6, iNOS, TNFα, and CD36. There were no significant changes in CD14 and CD86 in the obese and T2DM when compared to the lean subjects. Metformin treatment in T2DM reverted CD11c, CD169, IL-6, iNOS, TNFα, and CD36 to levels comparable to lean subjects. CD206 mRNA expression was significantly upregulated in PBMC of T2DM while Metformin treatment inhibited CD206 expression levels.Conclusions: These data support the notion that PBMC in circulation in T2DM express different pattern of phenotypic markers than the patterns typically present in M1 and M2 like cells. These phenotypic markers could be representative of metabolically activated macrophages (MMe)-like cells. Metformin, on the other hand, reduces MMe-like cells in circulation

Effect of Permissive Underfeeding with Intensive Insulin Therapy on MCP-1, sICAM-1, and TF in Critically Ill Patients

Purpose: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. Methodology: This was a substudy of a 2 × 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. Results: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value < 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value < 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value < 0.01). For TF, there was a significant association with age (P-value < 0.01). Conclusions: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied

RESEARCH Open Access

Modulation of insulin/IGFs pathways by sirtuin-7 inhibition in drug-induced chemoreistanc

Increase in Plasma Interleukin-10 Following Hydrocortisone Injection

In view of the fact that glucocorticoids have an immunosuppressive effect and the fact that interleukin-10 (IL-10) is inhibitory to T helper cell function, we have now investigated the effect of hydrocortisone on plasma IL-10 concentrations. Seven normal subjects were injected with 100 mg hydrocortisone intravenously between 8 and 9:00 a.m. Sequential blood samples were obtained prior to and 1, 2, 4, 8 and 24h after the injection. Plasma IL-10 concentrations increased significantly and consistently following the injection in all subjects. The peak increase of IL-10 occurred at 4h and the restoration to baseline by 8h. The sequential values were (mean±SD): 3.0±1.3 pg/ml at 2h, 9±4.2 pg/ml at 4h, 3.7±1.8 pg/ml at 8h and 3.7±1.4 pg/ml at 24h. The magnitude of increase was 436% of the basal at peak effect. This effect of hydrocortisone (and possibly other glucocorticoids) may contribute to the immunosuppressive effect of this drug. IL-10 may also be potentially useful in the assessment of Cushing’s Syndrome as a marker of end organ effect of glucocorticoids

Insulin as an anti-inflammatory and antiatherosclerotic hormone

Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic complications, namely heart attack and stroke, which has led to the concept that insulin may promote atherosclerosis despite the absence of any evidence that insulin is atherogenic either in humans or in experimental models. Recent evidence shows that insulin exerts vasodilatory, antiplatelet, and anti-inflammatory effects at the cellular level in vitro and in humans in vivo. Because atherosclerosis is an inflammatory process, insulin is probably antiatherosclerotic in the long-term. Recent data on experimental atherosclerosis in mice show that (a) insulin administration reduces the number and the size of atherosclerotic lesions in apolipoprotein E null mice; and (b) in insulin receptor substrate-2 null mice, the interruption in insulin signal transduction results in enhanced atherogenicity. The use of a low dose of insulin infusion in patients with acute myocardial infarction (AMI) has been shown to markedly improve clinical outcomes both in diabetic and nondiabetic patients. The authors' most recent data show that a low-dose infusion of insulin in patients with AMI induces a reduction in inflammation (C-reactive protein and serum amyloid A) and oxidative stress and may have a role in myocardial protection. The authors conclude that insulin is both anti-inflammatory and antiatherogenic and may be of use in the treatment of cardiovascular inflammatory conditions, including AMI