The expansion of life-style related diseases, such as metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM), appears to be unstoppable. It is also difficult to cease their complications in spite of many antidiabetic medications or intervention of public administration. We and our collaborators found that physical medicine using simultaneous stimulation of heat with mild electric current activates heat shock response, thereby reducing visceral adiposity, insulin resistance, chronic inflammation and improving glucose homeostasis in mice models of T2DM, as well as in humans with MS or T2DM. This combination therapy exerts novel action on insulin signaling, beta-cell protection and body compositions, and may provide a new therapeutic alternative in diabetic treatment strategy.
Adiposity ; Animals ; Body Composition ; Cytoprotection ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Glucose ; Heat-Shock Response* ; Homeostasis ; Hot Temperature* ; Humans ; Inflammation ; Insulin Resistance* ; Insulin* ; Mice ; Physical and Rehabilitation Medicine

Background/Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study. Methods: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD. Results: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4). Conclusions Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.