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.

Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide.

Patients with diabetic nephropathy develop nephrotic syndrome and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure.

Identification and quantification of plasma free salusin-ß, an endogenous parasympathomimetic peptide.

Salusin-ß is an endogenous parasympathomimetic proatherosclerotic peptide. Salusin-ß was initially predicted from bioinformatic analyses and later immunologically detected in human biofluids. However, elucidation of salusin-ß bioactivity has faced enormous challenges because of its unique physicochemical characteristics that cause it to strongly adhere to laboratory apparatus materials. In the strictest sense, the discovery of bioactive peptides is not complete until their exact native sequences have been confirmed in the peripheral circulation. In this study, we determined the plasma molecular form and levels of free salusin-ß to determine its pathophysiological significance. Ultra-high-yield enrichment and preseparation of non-tryptic human plasma was followed by LC-MS/MS, and full-length salusin-ß and seven different endogenous fragment sequences were identified. We established a new ELISA that specifically detects plasma free salusin-ß without cross-reacting with any of its identified endogenous fragments. Free salusin-ß levels exhibited a profound early morning nadir and rapidly decreased in response to parasympathetic nervous augmentation. Our technical advance in plasma native peptide analysis successfully identified a hard-to-detect bioactive peptide, salusin-ß, together with its formerly unrecognized fragments, and further suggests that conventional immunological measurements of target peptides may not be fully representative.