INS and type 2 diabetes mellitus: The possibility exists that type 2 diabetic patients are able to increase systemic GDF15, perhaps via mitochondrial stress in liver or skeletal muscle, as a compensatory attempt to enhance insulin sensitivity and restore glucose control but were unable to concurrently increase FGF21, which also improves insulin sensitivity and hepatic steatosis common to type 2 diabetes (Kang, Choi, et al., 2021).