Sodium-glucose cotransporter 2 (SGLT2) inhibitors have lately become the recommended treatment in patients with type 2 diabetes and high cardiovascular risk. Patients with posttransplant diabetes mellitus (PTDM) also have high cardiovascular risk. The aim of this study was to investigate the safety and efficacy of empagliflozin in renal transplant recipients with PTDM. RESEARCH DESIGN AND METHODSForty-nine renal transplant recipients were included in an investigator-initiated, single-center, prospective, double-blind study and randomized to receive either 10 mg empagliflozin or placebo once daily for 24 weeks. Patients transplanted >1 year ago, diagnosed with PTDM, with stable renal function (estimated glomerular filtration rate [eGFR] >30 mL/min/1.73 m 2 ), and with stable immunosuppressive therapy were studied. RESULTS Forty-four renal transplant recipients (22 empagliflozin/22 placebo, 34 males) completed the study. Median (interquartile range) change in glycated hemoglobin (HbA 1c ) was significantly reduced with empagliflozin compared with placebo: 20.2% (20.6, 20.1) (22.0 mmol/mol [26.5, 21.0]) vs. 0.1% (20.1, 0.4) (1.0 mmol/mol [20.75, 3.8]) (P = 0.025). The magnitude of glucose reduction was dependent on GFR and baseline HbA 1c. The treatment also resulted in a significant reduction in body weight of 22.5 kg (24.0, 20.05) compared with an increase of 1.0 kg (0.0, 2.0) in the placebo group (P = 0.014). There were no significant differences between the groups in adverse events, immunosuppressive drug levels, or eGFR. CONCLUSIONSEmpagliflozin appeared safe and improved glycemic control in renal transplant recipients with PTDM compared with placebo. A concomitant reduction in body weight was seen.Posttransplant diabetes mellitus (PTDM) is a serious condition that may follow renal transplantation. In the early posttransplant period, hyperglycemia is common in renal transplant recipients mainly due to high doses of immunosuppressive therapy (1,2). However, 10-20% of renal transplant recipients without a prior history of diabetes develop persisting hyperglycemia after renal transplantation, defined as PTDM (3-6).

IntroductionChemerin is a chemotactic peptide which directs leukocytes expressing the chemokine-like receptor ChemR23 towards sites of inflammation. ChemR23 is a G protein-coupled receptor which binds several different ligands, and it is also expressed by other cell types such as adipocytes. In addition to chemotaxis, recent reports suggest that ChemR23 is capable of mediating either inflammatory or anti-inflammatory effects, depending on the type of ligand it binds. In the present study, we aimed to clarify whether human chondrocytes express ChemR23 and chemerin, and whether chemerin/ChemR23 signalling could affect secretion of inflammatory mediators.MethodsTissue sections were taken from human knee joints and labelled with antibodies towards chemerin and ChemR23. Chondrocytes from cartilage tissue were isolated, cultured and assessed for chemerin and ChemR23 expression by PCR and immunolabelling. Receptor activation and intracellular signalling were studied by assessment of phosphorylated mitogen activated protein kinases (MAPKs) and phosphorylated Akt after stimulating cells with recombinant chemerin21-157. Biological effects of chemerin21-157 were investigated by measuring secretion of pro-inflammatory cytokines and metalloproteases in cell supernatants.ResultsBoth serially cultured human articular chondrocytes and resident cells in native cartilage expressed chemerin and ChemR23. Stimulating cells with chemerin21-157 resulted in phosphorylation of p44/p42 MAPKs (ERK 1/2) and Akt (Ser 473). Also, significantly enhanced levels of the pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and the matrix metalloproteases MMP-1, MMP-2, MMP-3, MMP-8 and MMP-13 were detected.ConclusionsThese results demonstrate that human chondrocytes express both the receptor ChemR23 and the ligand chemerin. Chemerin21-157 stimulation engaged signal-transduction pathways that further promoted inflammatory signalling in chondrocytes, as judged by an enhanced secretion of cytokines and metalloproteases. Taken together, the previously reported chemotaxis and the present findings suggest that the receptor and its ligand may play pivotal roles in joint inflammation.

BackgroundRed cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is associated with mortality and adverse outcome in selected populations with cardiovascular disease. It is scarcely known whether RDW is associated with incident myocardial infarction (MI). We aimed to investigate whether RDW was associated with risk of first‐ever MI in a large cohort study with participants recruited from a general population.Methods and ResultsBaseline characteristics, including RDW, were collected for 25 612 participants in the Tromsø Study in 1994–1995. Incident MI during follow‐up was registered from inclusion through December 31, 2010. Cox regression models were used to calculate hazard ratios with 95% confidence intervals for MI, adjusted for age, sex, body mass index, smoking, hemoglobin, white blood cells, platelets, and other traditional cardiovascular risk factors. A total of 1779 participants experienced a first‐ever MI during a median follow‐up time of 15.8 years. There was a linear association between RDW and risk of MI, for which a 1% increment in RDW was associated with a 13% increased risk (hazard ratio 1.13; 95% CI, 1.07 to 1.19). Participants with RDW above the 95th percentile had 71% higher risk of MI compared with those with RDW in the lowest quintile (hazard ratio 1.71; 95% CI, 1.34 to 2.20). All effect estimates were essentially similar after exclusion of participants with anemia (n=1297) from the analyses.ConclusionRDW is associated with incident MI in a general population independent of anemia and cardiovascular risk factors.