Prolonged impacts of sodium glucose cotransporter-2 inhibitors on metabolic dysfunction-associated steatotic liver disease in type 2 diabetes: a retrospective analysis through magnetic resonance imaging.

The beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in people with type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) have been suggested in several reports based on serological markers, imaging data, and histopathology associated with steatotic liver disease. However, evidence regarding their long-term effects is currently insufficient. In this retrospective observational study, 34 people with T2D and MASLD, treated with SGLT2 inhibitors, were examined by proton density fat fraction derived by magnetic resonance imaging (MRI-PDFF) and other clinical data before, one year after the treatment. Furthermore, 22 of 34 participants underwent MRI-PDFF five years after SGLT2 inhibitors were initiated. HbA1c decreased from 8.9 ± 1.8% to 7.8 ± 1.0% at 1 year (p = 0.006) and 8.0 ± 1.1% at 5 years (p = 0.122). Body weight and fat mass significantly reduced from baseline to 1 and 5 year(s), respectively. MRI-PDFF significantly decreased from 15.3 ± 7.8% at baseline to 11.9 ± 7.6% (p = 0.001) at 1 year and further decreased to 11.3 ± 5.7% (p = 0.013) at 5 years. Thus, a 5-year observation demonstrated that SGLT2 inhibitors have beneficial effects on liver steatosis in people with T2D and MASLD.

Clinical feasibility of remote intermittently scanned continuous glucose monitoring in coronavirus disease 2019 patients with and without diabetes during dexamethasone therapy.

The clinical utility of intermittently scanned continuous glucose monitoring (isCGM) in patients with coronavirus disease 2019 (COVID-19) is unclear. Hence, we investigated the accuracy of isCGM in COVID-19 patients during dexamethasone therapy. We evaluated the accuracy of the FreeStyle Libre via smartphone isCGM device compared to point-of-care (POC) fingerstick glucose level monitoring in 16 patients with COVID-19 (10 with and 6 without diabetes, 13 men; HbA1c 6.9 ± 1.0%). Overall, isCGM correlated well with POC measurements (46.2% and 53.8% within areas A and B of the Parkes error grid, respectively). The overall mean absolute relative difference (MARD) for isCGM compared to POC measurements was 19.4%. The MARDs were 19.8% and 19.7% for POC blood glucose measurements ranging from 70 to 180 mg/dL and >180 mg/dL, respectively. When divided according to the presence and absence of diabetes, both groups of paired glucose measurements showed a good correlation (56.3% and 43.7%, and 27.1% and 72.9% within the A and B areas in patients with and without diabetes, respectively), but the MARD was not significant but higher in patients without diabetes (16.5% and 24.2% in patients with and without diabetes). In conclusion, although isCGM may not be as accurate as traditional blood glucose monitoring, it has good reliability in COVID-19 patients with and without diabetes during dexamethasone therapy.

Novel clinical associations between time in range and microangiopathies in people with type 2 diabetes mellitus on hemodialysis.

AIMS/HYPOTHESIS: We investigated associations among glucose time in range (TIR, 70-180 mg/dL), glycemic markers and prevalence of diabetic microangiopathy in people with diabetes undergoing hemodialysis (HD). METHODS: A total of 107 people with type 2 diabetes undergoing HD (HbA1c 6.4 %; glycated albumin [GA] 20.6 %) using continuous glucose monitoring were analyzed in this observational and cross-sectional study. RESULTS: HbA1c and GA levels significantly negatively correlated with TIR, and positively correlated with time rate of hyperglycemia, but not with time rate of hypoglycemia. TIR of 70 % corresponded to HbA1c of 6.5 % and GA of 21.2 %. The estimated HbA1c level corresponding to TIR of 70 % in this study was lower than that previously reported in people with diabetes without HD. The prevalence of diabetic neuropathy was not significantly different between people with TIR ≥ 70 % and those with TIR < 70 % (P = 0.1925), but the prevalence of diabetic retinopathy in people with TIR ≥ 70 % was significantly lower than in those with TIR < 70 % (P = 0.0071). CONCLUSION/INTERPRETATION: TIR correlated with HbA1c and GA levels in people with type 2 diabetes on HD. Additionally, a higher TIR resulted in a lower rate of diabetic retinopathy. RESEARCH IN CONTEXT: What is already known about this subject? What is the key question? What are the new findings? How might this impact on clinical practice in the foreseeable future?

ATP6AP2 is robustly expressed in pancreatic ß cells and neuroendocrine tumors, and plays a role in maintaining cellular viability.

ATP6AP2, also known as (pro)renin receptor, has been shown to be expressed in several tissues including pancreatic ß cells. Whereas ATP6AP2 plays an important role in regulating insulin secretion in mouse pancreatic ß cells, the expression profiles and roles of ATP6AP2 in human pancreatic endocrine cells and neuroendocrine tumor cells remain unclear. Here in this study, we investigated the expression profiles of ATP6AP2 in pancreatic endocrine cells, and found that ATP6AP2 is robustly expressed in pancreatic insulinoma cells as well as in normal ß cells. Although ATP6AP2 was also expressed in low-grade neuroendocrine tumors, it was not or faintly detected in intermediate- and high-grade neuroendocrine tumors. Knockdown experiments of the Atp6ap2 gene in rat insulinoma-derived INS-1 cells demonstrated decreased cell viability accompanied by a significant increase in apoptotic cells. Taken together, these findings suggest that ATP6AP2 plays a role in maintaining cellular homeostasis in insulinoma cells, which could lead to possible therapeutic approaches for endocrine tumors.

Three-wavelength parallel optical fiber dispersion measurement using dual-heterodyne mixing.

We propose a novel optical dispersion measurement system using dual-heterodyne mixing to measure the relative phase. The system can realize parallel measurement of the relative phases between adjacent frequencies by introducing optical modulators to generate optical sidebands from a laser light source and an arrayed waveguide grating to separate the sidebands. To realize a wide dispersion range, different frequency intervals for the adjacent frequencies were combined in the system. One is the three-frequency optical dispersion measurement system (three-frequency measurement), which has been developed to measure the relative phase between adjacent peaks of an optical frequency spectrum with intervals of 25 GHz generated without any frequency scanning. The other is the four-frequency optical dispersion measurement system (four-frequency measurement) with intervals of 2 GHz generated from the three-frequency sets to expand the measurement range. The experimental results using single-mode optical fibers of different lengths from 0 to 90 km indicated the dispersion slope to be 16.8 ps/nm/km with a measurement range of 2500 ps/nm and an uncertainty of less than 1 ps/nm. The proposed system provides advantages to enable parallel measurement on a frequency axis without a high-speed (GHz) photodetector, even though GHz spacing on the optical scale is used, thus reflecting the dual-heterodyne mixing.

Discordance in the reduction rate between glycated albumin and glycated hemoglobin levels in type 2 diabetes patients receiving SGLT2 inhibitors.

AIMS: Although the difference in HbA1c reduction between sodium-glucose cotransporter 2 (SGLT2) inhibitors and other oral glucose-lowering agents is relatively small, SGLT2 inhibitors exhibit beneficial cardiorenal protection. This study was based on the hypothesis that changes of HbA1c in patients treated with SGLT2 inhibitors may not accurately reflect an improved glycemic profile. METHODS: Two studies were conducted: 1) a retrospective cohort study of 3039 patients administered with either an SGLT2 or a dipeptidyl peptidase-4 (DPP4) inhibitor for 12 months comparing the changes in glycated albumin (GA) and HbA1c levels and 2) a pilot study of 10 patients whose glycemic dynamics were evaluated using flash glucose monitoring at baseline and 2 months after treatment with an SGLT2 inhibitor. RESULTS: SGLT2 inhibitors reduced GA more markedly than HbA1c in both studies. DPP4 inhibitors decreased both GA and HbA1c to a comparable degree. The mean glucose levels and glycemic standard deviation were significantly reduced after treatment with an SGLT2 inhibitor, in concordance with GA decline, although the lowering of HbA1c was marginal. CONCLUSIONS: Changes in HbA1c levels underestimated the glucose-lowering effect and the diminished glycemic fluctuation induced by SGLT2 inhibitors. Thus, the distinct biomarker roles of GA and HbA1c should be reevaluated.

Hemodialysis-Related Glycemic Disarray Proven by Continuous Glucose Monitoring; Glycemic Markers and Hypoglycemia.

OBJECTIVE: There is a high risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate; therefore, the inclusion of glucose in the dialysate is believed to prevent intradialytic hypoglycemia. However, the exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia using dialysates containing >100 mg/dL glucose have not been determined. RESEARCH DESIGN AND METHODS: We evaluated the glycemic profiles of 98 patients, 68 of whom were men, with type 2 diabetes undergoing HD (HbA1c 6.4 ± 1.2%; glycated albumin 20.8 ± 6.8%) with a dialysate containing 100, 125, or 150 mg/dL glucose using continuous glucose monitoring. RESULTS: Sensor glucose level (SGL) showed a sustained decrease during HD, irrespective of the dialysate glucose concentration, and reached a nadir that was lower than the dialysate glucose concentration in 49 participants (50%). Twenty-one participants (21%) presented with HD-related hypoglycemia, defined by an SGL <70 mg/dL during HD and/or between the end of HD and their next meal. All these hypoglycemic episodes were asymptomatic. Measures of glycemic variability calculated using the SGL data (SD, coefficient of variation, and range of SGL) were higher and time below range (<70 mg/dL) was lower in participants who experienced HD-related hypoglycemia than in those who did not, whereas time in range between 70 and 180 mg/dL, time above range (>180 mg/dL), HbA1c, and glycated albumin of the two groups were similar. CONCLUSIONS: Despite the use of dialysate containing 100-150 mg/dL glucose, patients with diabetes undergoing HD experienced HD-related hypoglycemia unawareness frequently. SGL may fall well below the dialysate glucose concentration toward the end of HD.

Comparison of accuracy between flash glucose monitoring and continuous glucose monitoring in patients with type 2 diabetes mellitus undergoing hemodialysis.

INTRODUCTION: We evaluated the accuracy and clinical utility of flash glucose monitoring (FGM) in comparison with continuous glucose monitoring (CGM) and self-monitoring blood glucose (SMBG) in patients with type 2 diabetes (T2D) undergoing hemodialysis (HD). METHODS: Simultaneous FGM (FreeStyle LibrePro), CGM (iPro2) and SMBG were performed on 13 T2D research subjects. RESULTS: There were good overall correlations between SMBG and FGM (64.7% and 30.8% within the A and B of Parkes Error Grid, respectively) and between SMBG and CGM (87.9% and 11.0% within the A and B, respectively). However, during HD, correlations between SMBG and FGM were only 49.7% and 37.2% within the A and B, respectively, while correlations of SMBG and CGM were 72.8% and 22.2% within the A and B, respectively. The percentage of FGM not in Zone A + B was more than 4 times higher than for CGM. The overall mean absolute relative difference (MARD) for FGM was 18.2%, this significantly higher than 11.2% for CGM. During HD, MARD for FGM was 22.8%, significantly higher than 15.0% for CGM. CONCLUSION: FGM has good clinical agreement in T2D patients undergoing HD. However, the accuracy of FGM relative to SMBG was worse than that of CGM.

Case of cutaneous botryomycosis in an 8-year-old immunocompetent boy with a review of the published work.

Botryomycosis is a rare chronic suppurative granulomatous infection caused by several genera of non-filamentous bacteria. The clinical and histopathological findings are similar to those of mycetoma caused by true fungi or aerobic actinomycetes. Botryomycosis is divided into cutaneous and visceral disease, with the cutaneous form being more common. Histopathology shows granules of etiologic bacteria called "sulfur granules". Botryomycosis occurs more commonly among immunocompromised patients, although some cases have also been reported in immunocompetent patients. We report the case of an 8-year-old immunocompetent boy who visited our hospital with a 4-mm diameter subcutaneous tumor with mild tenderness on his right heel for several months. We surgically removed the tumor with an initial diagnosis of epidermal cyst. Histopathology showed sulfur granules surrounded by an eosinophilic matrix, indicating the Splendore-Hoeppli phenomenon. The granules consisted of Gram-positive cocci, leading to a diagnosis of botryomycosis. The patient was successfully treated by excision and oral trimethoprim/sulfamethoxazole (240 mg b.i.d.) for 2 weeks as adjuvant therapy. No recurrence was noted following treatment. The subcutaneous tumor in this case was smaller than the typical in botryomycosis infections. We reviewed the infection duration and tumor size in reported cases of botryomycosis in immunocompetent patients. Small tumor size may suggest that the case is in an early stage; therefore, it is important to remove and investigate these lesions proactively.