Iron overload increases the risk of diabetes via mechanisms of abnormal glucose metabolism: insulin deficiency, insulin resistance, and/or hepatic dysfunction. Iron reduction upregulates glucose uptake and improves hepatocytes insulin receptor activity. This study was conducted to examine the effects of iron depletion-via controlled phlebotomy-on the hypoglycemic treatment in poorly controlled type 2 diabetes mellitus (T2DM) patients with non-genetic iron overload. Forty three patients with poorly controlled T2DM and iron overload were divided into 2 groups: iron depletion group and control group. Regular phlebotomy was performed for iron depletion group on monthly basis until serum ferritin reached 20 μg/L or less. Both groups were examined and compared for blood pressure, serum ferritin, lipid profile, HFE-gene, HbA1c, HOMA-IR and number of medicines used for diabetic control. The results had revealed that group differences of HbA1c (−2.64, 95% CI −3.23 to 2.04, p < 0.001) and HOMA-IR (−0.68, 95% CI −0.98 to −0.37, p < 0.001) showed significant decreases in iron depletion group at end of study. Significant decrease in the numbers of hypoglycemic medicines in iron depletion group was shown at end of study (p < 0.001); 66.7% of iron depletion group patients were receiving 1 or 2 medicines at end of study versus none of the control group. Diastolic blood pressure (DBP), triglycerides and LDL-C decreased significantly while HDL-C levels showed significant rise after iron depletion. It can be concluded from the present study that iron depletion therapy is beneficial for improving the efficiency of glycemic control, DBP, and dyslipidemia in poorly controlled type 2 diabetics with iron over load.
Purpose: Erythroferrone (ERFE) is well acknowledged for its inhibitory function on hepcidin synthesis in the liver during stress erythropoiesis, thereby ensuring sufficient iron supply to bone marrow erythroblasts. Hepcidin plays an indispensable role in the pathogenesis of anemia of chronic disease (ACD). Thus, ERFE was suggested to protect against ACD in various diseases. Rheumatoid arthritis (RA) is commonly involved with ACD and high hepcidin levels, with a further increase of the latter in active states. The present study is a case-control study that aimed to determine the pattern of ERFE expression in RA patients with concomitant ACD and study its relationship with hepcidin, erythropoietin (EPO) and disease activity. Patients and Methods: Fifty-five RA patients with ACD were categorized into active and inactive RA using the disease activity score (DAS28); 15 healthy subjects were included as control subjects. ERFE was measured for patients and control subjects using quantitative real-time polymerase chain reaction, in addition to testing for CBC, ESR, CRP, iron profile parameters and hepcidin. EPO was assessed for patients of both active and inactive RA groups. Results: ERFE and hepcidin showed the highest levels in active RA; ERFE values were similar in control subjects and inactive RA patients, while hepcidin was significantly higher in inactive RA than control subjects. Patients with high ERFE levels had higher RBC, Hct, MCV, hepcidin and EPO levels. Stepwise regression analysis has identified DAS28 and disease duration as the best predictors of ERFE values, whereas ERFE and hepcidin were independent predictors of disease activity.
Conclusion:We introduce ERFE as a novel marker of RA activity. Although the inhibitory effect of ERFE on hepcidin is not evident, our results still indicate that ERFE may have a beneficial erythropoietic effect in the context of ACD in RA disease activity.
Background
DNA methylation is involved in pathogenesis of acute myeloid leukemia (AML). N6-methyladenosine (m6A) modification of mRNA, mediated by methyltransferase-like 3 (METTL3), is one of the well-identified mRNA modifiers associated with the pathogenesis of AML. High level of METTL3 mRNA is detected in AML cells, thus can be a potential target therapy for AML. This is a preliminary study that aimed at measuring METTL3 mRNA expression level in de novo AML patients and correlating it with clinicopathological, laboratory and prognostic markers. METTL3 expression was analyzed by quantitative reverse transcription polymerase chain reaction in 40 newly diagnosed AML adults and was re-measured in the 2nd month of chemotherapy. Patients were followed up for periods up to 6 months post-induction therapy.
Results
METTL3 expression was found to be significantly upregulated in AML patients compared to control subjects (p < 0.001). METTL3 gene was significantly expressed among non-responders compared to responders (p < 0.001). A cutoff value was assigned for normalized METTL3 values to categorize AML patients according to response to therapy. Statistically significant association was observed between high pretreatment normalized METTL3 gene level and failure to attain complete remission at 2nd, 4th and 6th month following therapy (p = 0.01, 0.02 and 0.003, respectively). However, insignificant correlation was found between pretreatment normalized METTL3 gene level and event free survival or clinicopathological prognostic factors.
Conclusion
METTL3 is overexpressed in AML patients and is associated with adverse prognostic effect and failure to attain hematological remission within 6 months post-induction therapy.
Background: Mutant isocitrate dehydrogenase (IDH) 1 and 2 alter the epigenetic landscape in acute myeloid leukemia (AML) cells through production of the oncometabolite (R)-2-hydroxyglutarate. Methods: We aimed to determine the prevalence and clinical and prognostic effect of IDH1rs11554137 and IDH2R140Q SNPs mutations, in 80 newly diagnosed cytogenetically normal AML (CN-AML), using real-time polymerase chain reaction (PCR). Results: Heterozygous mutations of IDH1 and IDH2 SNP were detected in 13.8% and 16.3% of patients, respectively. Both mutations were associated with older age, higher platelet count, and shorter overall survival. Survivors showed significantly younger age and lower mean platelet and blast counts, as well as negative IDH1 SNP (p = 0.001, 0.016, 0.002, and 0.003, respectively). Multivariate logistic regression analysis identified high bone marrow blast percentage as an independent prognostic predictor for 6-month mortality (p = 0.014, OR 1.049, 95% CI 1.010-1.090). Conclusion: IDH1/2 SNPs mutations are recurrent events in CN-AML associated with negative prognostic impact, representing a new subgroup for risk stratification and may indicate new treatment options.
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