Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science.

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments.

Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.

Fibroblast growth factor 21 (FGF21) controls metabolic organ homeostasis and eating/drinking behavior via FGF receptor 1/Klothoβ (FGFR1/KLB) complexes expressed in adipocytes, pancreatic acinar cells, and the nervous system in mice. Chronic administration of recombinant FGF21 or engineered variants improves metabolic health in rodents, nonhuman primates, and humans; however, the rapid turnover of these molecules limits therapeutic utility. Here we show that the bispecific anti-FGFR1/KLB agonist antibody BFKB8488A induced marked weight loss in obese cynomolgus monkeys while elevating serum adiponectin and the adipose expression of FGFR1 target genes, demonstrating its action as an FGF21 mimetic.

Serum sclerostin and risk of hip fracture in older Caucasian women.

Context: Sclerostin, a protein secreted by osteocytes, inhibits bone formation. Individuals with genetic mutations that decrease the availability of sclerostin have very high bone mass.

Objective: The aim of this study was to examine the hypothesis that elevated serum sclerostin levels are associated with increased risk of hip fracture in older women.

Effects of duration of type 2 diabetes mellitus on insulin secretion.

Objective: To gain insight into the effects of duration of type 2 diabetes on insulin secretion in patients with type 2 diabetes mellitus.

Methods: C-peptide concentrations were measured every 2 years before and after intravenous injection of 1 mg of glucagon in 89 patients with type 2 diabetes (51 men and 38 women) as part of the Rochester Diabetic Neuropathy Study in those subjects who participated in follow-up (median, 12 years; range, 6 to 14).

Results: Although insulin secretion decreased over time (P<0.