ABSTRACT
Objective Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) treatment guidelines recommend sodium glucose cotransporter 2 inhibitor (SGLT2I) and glucagon-like peptide-1 agonist (GLP-1A) therapy in patients with type 2 diabetes mellitus (T2DM). SGLT2I improves the pathological condition of NAFLD/NASH in T2DM patients. However, cases of rebound during long-term SGLT2I treatment have been reported. This study investigated the efficacy of SGLT2I and GLP-1A combination therapy in diabetic patients with NAFLD by examining changes in computed tomography (CT)-based body composition and clinical outcomes. Methods Fifteen patients (5 men/10 women) with T2DM-associated NAFLD who had not responded to SGLT2I treatment and were being treated with GLP-1A combination therapy were included. Changes in the liver function, visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were compared using CT to evaluate the body composition. Results SGLT2I significantly improved alanine aminotransferase (28.0 to 13.0 IU/L), alkaline phosphatase (250.0 to 77.0 IU/L), and gamma glutamyl transpeptidase (23.0 to 12.0 IU/L) levels. The body mass index (BMI) decreased from 25.7 to 25.2 kg/m2. A CT-based analysis showed a significant improvement in SATI (80.9 to 66.1, p=0.002), with no significant change in VATI (53.2 to 51.5). GLP-1A addition improved the BMI (25.2 to 23.5 kg/m2) and hemoglobin A1c (6.5% to 6.2%, p=0.001). A further analysis revealed additional improvement in SATI (66.1 to 56.6, p=0.007) and a significant decrease in VATI (51.5 to 48.3, p=0.001). Conclusion SGLT2I and GLP-1A combination therapy improved the liver function, body composition, and glycemic control in diabetic patients with NAFLD/NASH, as well as SATI and VATI. The optimal timing of combination therapy remains to be determined.
ABSTRACT
Aim of the study: Owing to the association between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia, there is a need for new treatment strategies to manage both conditions concomitantly. Our aim in this study was to evaluate the effectiveness of pemafibrate in alleviating dyslipidemia-associated NAFLD, including the evaluation of its effects on liver function and body composition. Material and methods: The study sample included 67 patients with dyslipidemia-associated NAFLD (29 males, mean age 65.7 years [range, 58.4-73.7]) who were administered pemafibrate continuously for a period of at least 12 months, between June 2019 and January 2022. Outcomes were the change in body composition indices (visceral adipose tissue index - VATI, subcutaneous adipose tissue index - SATI, and skeletal muscle index - SMI), lipid biochemistry, and liver function, reserve, and fibrosis score, from baseline to the 12-month time point of pemafibrate treatment. Results: Pemafibrate treatment improved liver function (alanine aminotransferase, aspartate aminotransferase, g-glutamyl transpeptidase, and alkaline phosphatase), and lipid biochemistry (triglycerides and total cholesterol). Improvements in ferritin and hepatic reserve (Mac-2 binding protein, albumin-to-bilirubin score, and NAFLD fibrosis score) were also observed, as well as a decrease in SATI. Conclusions: Pemafibrate improved dyslipidemia, liver function, and hepatic reserve. The positive effects of pemafibrate on body composition likely contributed to the improvements in liver function. Longer-term treatment may be necessary to influence VATI and thus to further evaluate the relationship between improved body composition and NAFLD with pemafibrate treatment.
ABSTRACT
The vagina is the site of copulation and serves as the birth canal. It also provides protection against external pathogens. In mice, due to the absence of cervical glands, the vaginal epithelium is the main producer of vaginal mucus. The development and differentiation of vaginal epithelium-constituting cells and the molecular characteristics of vaginal mucus have not been thoroughly examined. Here, we characterized vaginal mucous cell development and the expression of mucus-related factors in pregnant mice. The vaginal mucous epithelium layer thickened and became multilayered after Day 12 of pregnancy and secreted increasing amounts of mucus until early postpartum. Using histochemistry and transmission electron microscopy, we found supra-basal mucous cells as probable candidates for precursor cells. In vaginal mucous cells, the expression of TFF1, a stabilizer of mucus, was high, and some members of mucins and antimicrobial peptides (MUC5B and DEFB1) were expressed in a stage-dependent manner. In summary, this study presents the partial characterization of vaginal epithelial mucous cell lineage and expression of genes encoding several peptide substances that may affect vaginal tissue homeostasis and mucosal immunity during pregnancy and parturition.
