Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor’s glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.

To evaluate and compare tear secretion and tear film instability following photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Department of Ophthalmology, Yonsei University School of Medicine, Seoul, Korea. In a prospective study, 36 eyes (21 patients) had PRK and 39 eyes (25 patients) had LASIK to correct myopia. Tear secretion and tear film instability were tested preoperatively and 3 and 6 months postoperatively using Schirmer test values, tear breakup time (BUT) scores, and tear osmolarity. Six months after surgery, the change in Schirmer test values from preoperative levels was -14.57% +/- 6.39% (SD) in the PRK eyes and -23.40% +/- 5.94% in the LASIK eyes and the change in BUT scores, -12.54% +/- 8.28% and -18.79% +/- 13.01%, respectively. The change in tear osmolarity was 14.95% +/- 6.46% and 35.63% +/- 8.51%, respectively. The decrease in tear secretion was greater after LASIK than after PRK at 6 months. Proper treatment of dry eye is required after LASIK and PRK, particularly in the LASIK postoperative period.

Lee DC, et al. Yonsei Med J. 2005 Aug;46(4):471-479. http://dx.doi.org/10.3349/ymj.2005.46.4.471

Various automated chemiluminescence immunoassay (CLIA) analyzers for the detection of antibodies to hepatitis C virus (HCV) are now commercially available in clinical laboratories and are replacing conventional enzyme immunoassays. We investigated the performance of four anti-HCV CLIAs (the Architect Anti-HCV assay on the Architect i2000 system, the Vitros Anti-HCV assay on the Vitros ECiQ Immunodiagnostic System, the Access HCV Ab PLUS assay on the UniCel DxI 800 analyzer, and the newly developed Elecsys Anti-HCV assay on the Cobas e 411 analyzer). The total percent coefficient of variation values of imprecision were 3.5 to 5.7% with positive control materials and 7.2 to 10.2% with negative control materials. The agreement between the results of the Elecsys, Architect, Vitros, and Access CLIAs ranged from 94.5 to 98.1%. The clinical sensitivity of all CLIAs was 100%. Each CLIA showed excellent reproducibility and clinical sensitivity. The Elecsys, Architect, Vitros, and Access CLIAs showed clinical specificities of 98.2, 98.8, 96.5, and 98.2%.

Recently, several renal tubular damage markers have gained considerable attention because of their clinical implications as sensitive and specific biomarkers for early stage diabetic kidney disease. However, little is known about the demographic and glucometabolic factors affecting levels of urinary N-acetyl-β-D-glucosaminidase (NAG), a marker of proximal tubular damage, in type 2 diabetes mellitus (T2DM).The aim of this study was to investigate the clinical relevance of urinary NAG with regard to demographic and glucometabolic parameters, as well as nephropathic parameters, by comparing the glomerulopathic marker of albuminuria.In this retrospective cross-sectional study, we enrolled a total of 592 patients with either prediabetes (N = 29) or T2DM (N = 563). Glucometabolic parameters (glucose, hemoglobin A1c, glycated albumin [GA], insulin, C-peptide, homeostasis model assessment [HOMA] of insulin resistance, HOMA-β, postprandial C-peptide-to-glucose ratio [PCGR], and urinary glucose-to-creatinine ratio) and nephropathic parameters (urinary NAG, albumin-to-creatinine ratio [ACR], and estimated glomerular filtration rate) were measured.The levels of urinary NAG showed moderate positive correlation with the levels of urinary ACR in T2DM (r = 0.46). In correlation analysis, urinary NAG was more strongly correlated with body mass index (BMI) (r = -0.22; P < 0.001 vs. r = -0.02; P = 0.74), plasma stimulated glucose (r = 0.25; P < 0.001 vs. r = 0.08; P = 0.10), GA (r = 0.20; P < 0.001 vs. r = 0.13; P = 0.01), PCGR (r = -0.17; P = 0.001 vs. r = -0.09; P = 0.11), and HOMA-β (r = -0.10; P = 0.05 vs. r = -0.02; P = 0.79) than urinary ACR. In multiple regression analysis, age, lower BMI, stimulated glucose, GA, and urinary ACR predicted increased urinary NAG.In conclusion, increase in urinary NAG may be related to glycemic parameters reflecting glucose fluctuation and decreased insulin secretory capacity in patients with T2DM. Further longitudinal, prospective studies are needed to investigate a causal relationship between glucose fluctuations, renal tubular damage, and other vascular complications of diabetes.