UNASSIGNED: Type 2 diabetes (T2D) is a prevalent chronic disease associated with several comorbidities.
UNASSIGNED: This study investigated whether the risk of T2D varied with genetically predicted insulin (INS), insulin receptor (INS-R), or insulin-like growth factor 1 receptor (IGF-1R) using genetic variants in a Mendelian randomization (MR) study.
UNASSIGNED: A 2-sample MR study was conducted using summary statistics from 2 genome-wide association studies (GWASs). Genetic predictors of the exposures (INS, INS-R, and IGF-1R) were obtained from a publicly available proteomics GWAS of the INTERVAL randomized controlled trial of blood donation in the United Kingdom. For T2D, the study leveraged the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) consortium. The estimated associations of INS, INS-R, and IGF-1R proteins with T2D were based on independent single nucleotide polymorphisms (SNPs) strongly (P < 5 × 10-6) predicting each exposure. These SNPs were applied to publicly available genetic associations with T2D from the DIAMANTE case (n = 74,124) and control (n = 824,006) study of people of European descent. SNP-specific Wald estimates were meta-analyzed using inverse variance weighting with multiplicative random effects. Sensitivity analysis was conducted using the weighted median (WM) and MR-Egger.
UNASSIGNED: INS-R (based on 13 SNPs) was associated with a lower risk of T2D (OR: 0.95 per effect size; 95% CI: 0.92, 0.98; P = 0.001), with similar estimates from the WM and MR-Egger. Insulin (8 SNPs) and IGF-1R (10 SNPs) were not associated with T2D. However, 1 of the SNPs for INS-R was from the ABO blood group gene.
UNASSIGNED: This study is consistent with a causally protective association of the INS-R with T2D. INS-R in RBCs regulates glycolysis and thus may affect their functionality and integrity. However, a pleiotropic effect via the blood group ABO gene cannot be excluded. The INS-R may be a target for intervention by repurposing existing therapeutics or otherwise to reduce the risk of T2D.

BACKGROUND: Dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice. We here describe a new mutation of PIEZO1 gene, the most frequent mutated gene in DHS, in a family affected by hereditary hemolytic anemia.
METHODS: We describe the case of a 12-years-old girl with well-compensated chronic hemolysis, increased MCHC and a father who had the same hematological characteristics. After excluding secondary causes of chronic hemolysis and enzymatic defects of the RBCs, microscopic observation of the peripheral blood smear, tests of RBC lysis, ektacytometry, SDS-PAGE and in last instance genetic analysis has been performed. This complex diagnostic workup identified a new variant in the PIEZO1 gene, never described in literature, causative of DHS. This pathogenetic variant was also detected in the father.
CONCLUSIONS: This case report highlights the importance of a correct and exhaustive diagnostic-workup in patients with clinical suspicious for hemolytic anemia in order to make a differential diagnosis. This is relevant for the management of these patients because splenectomy is contraindicated in DHS due to high thrombotic risk.

BACKGROUND: Accumulated studies have shown that hematological parameters [e.g., red blood cell distribution width (RDW), hemoglobin, platelet count] and serum potassium level can impact the prognosis of patients with acute myocardial infarction (AMI). However, no previous study has evaluated the prognostic values of these laboratory tests simultaneously.
METHODS: This study is based on an intensive care unit (ICU) database named Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II). Adult patients with AMI were included, and their hematological parameters and serum ion levels on admission were extracted. The relationships between these laboratory tests and hospital mortality were evaluated using a logistic regression model and receiver operating characteristic (ROC) curve analysis. The effects of these laboratory tests on 1-year mortality were evaluated using a Cox hazard regression model and Kaplan-Meier curve analysis.
RESULTS: In univariable analysis, increased white blood cell (WBC), neutrophil percentage, mean corpuscular volume (MCV), RDW, potassium and decreased red blood cell (RBC), hemoglobin, mean corpuscular hemoglobin concentration (MCHC), hematocrit and percentage of lymphocyte, monocyte, basophil and eosinophil were significantly associated with hospital mortality. In multivariable analyses, basophil percentage, potassium, WBC and MCHC were independently associated with hospital morality, while WBC, RDW, MCHC, potassium and percentages of neutrophil and lymphocyte were associated with 1-year mortality.
CONCLUSIONS: Hematological parameters and serum potassium can provide prognostic information in AMI patients. MCHC is an independent prognostic factor for both short and long term outcomes of AMI.